genome medical essay contest

SCHOLARSHIP OPPORTUNITY

Force For Good High School Essay Contest

Who can apply to the scholarship.

• Eligible students must currently be sophomores or juniors in high school in the United States and identify as a member of one or more underrepresented population based on race, ethnicity, sex, gender, sexual orientation, socioeconomic status, country of origin, culture, language, religion, spiritual beliefs, health history, disability, financial hardship, and/or others. Students must submit their essay online in English.
• 1st, 2nd and 3rd place awards of $2500, $1000 and $500, respectively, to go to the winning essays which are picked by our diverse essay review committee made up of both clinical genetic and genomic healthcare providers and non clinical employees of Genome Medical. Monetary prizes to be awarded in addition to a public congratulations and post of the winning essays/students on our social media. Finalists will be contacted and their personal and school information will be confirmed. In addition, a photo will be requested (optional) for the purposes of announcing the winners.

We are revising our scholarship program in 2024. If you would like to be notified when we re-launch it, please provide your contact information.

GeneMatters is now a Genome Medical company.   Learn more .

If you are a current GeneMatters client or patient, you can now access your account using the "Login" section in the top right area of our website.

The European Society of Human Genetics

News details, eshg dna day essay & video contest 2024: submission now open.

Essays and Videos can be submitted electronically between January and April 25 (Deadline for submission).

This year’s question: 'Ask an Artificial Intelligence chat of your choice to write a 350 word essay on the topic: “Is the human Y-chromosome vanishing in the future?” In a 750 word essay of your own, discuss the result and its consequences, should the public believe the content of the A.I. essay was actually true.'

Finally, we are looking for a number of judges volunteering to evaluate the submissions. Please email us if you would like to contribute as a judge, your help would be greatly appreciated.

With almost 180 submissions from 22 countries, 2023 was another great year for our DNA Day Essay and Video contest. The “top five” participating countries were Turkey, United Kingdom, Albania, Italy, and France. The number of submissions has grown from about 90 in the first year the event was held. For the 16th year, the European Society of Human Genetics (ESHG) will be sponsoring a DNA Day Essay contest in European high schools as part of International DNA Day activities. Given the growing impact of Artificial Intelligence on our lives, the Education Committee has decided to make A.I. part of the contest instead of banning it. This year’s question is:

' Ask an Artificial Intelligence chat of your choice to write a 350 word essay on the topic: “Is the human Y-chromosome vanishing in the future?” In a 750 word essay of your own, discuss the result and its consequences, should the public believe the content of the A.I. essay was actually true.'

More information: DNA Day website ( www.dnaday.eu )

Finally, we are looking for a number of judges volunteering to evaluate the submissions. Judging will be made between May 1 and May 20 and is great fun! Please let us know if you would like to contribute as a judge, your help would be greatly appreciated.

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DNA Day Essay Contest

Ages: High School

Type: Submission

Scope: International

Evelyn Mantegani [email protected] 301-634-7351

Participate

National DNA Day commemorates the completion of the Human Genome Project in April 2003 and the discovery of the double helix of DNA in 1953. Teachers and students around the world are encouraged to celebrate by participating in the American Society of Human Genetics' (ASHG) annual DNA Day Essay Contest! The question each year aims to cover a current topic in genetics that may not be covered in biology class. Students are encouraged to work with their science and language arts teachers. Essays should be 750 words maximum. Winners and honorable mentions are announced on Friday, April 24, 2020.

This contest is open to students in grades 9-12 worldwide and asks students to examine, question, and reflect on important concepts in genetics. Essays are expected to be well-reasoned arguments indicative of a depth of understanding of the concepts related to the essay question.

2020 Question

• Essays must be the product of an individual student's work;  group submissions are not permitted .
• All essays must be written in  English  and are limited to  750 words . Word count includes in-text citations, but does not include reference lists.
• Essay titles are optional and  will  be counted towards the word limit.
• Word count is best determined by Microsoft Word's count. The submission page will give an official word count when submitters enter the essay.
• Essays should  not  include a student's name.
• Essays must include  at least one reference . References must be clearly documented with both in-text citations and in the references list (the reference list should be separately entered into the "References" section of the submission page). Students may use either  APA  or  MLA  style citations. There is no restriction on how many references students may use. However, please keep in mind that students should avoid having too many references, as we want to know the student's opinion on the question and not the opinion of the student's sources.
• Low quality sources  = Wikipedia.
• High quality sources  = Research journals (for example, from  PubMed )

Website: http://www.ashg.org/education/dnaday.shtml

Managing Organization: American Society of Human Genetics

Contact: Evelyn Mantegani [email protected] 301-634-7351

Eligibility: Essays that will be accepted must be submitted by a teacher and written by high school students (grades 9-12) in the U.S. and internationally.

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HGSA DNA day essay contest winner 60 years on: still coding for cutting-edge science

Affiliation.

• 1 Melbourne High School, Melbourne, VIC, Australia.
• PMID: 23870684
• DOI: 10.1017/thg.2013.45

MESSAGE FROM THE EDUCATION COMMITTEE: In 2013, the Education Committee of the Human Genetics Society of Australasia (HGSA) established the DNA Day Essay Contest in Australia and New Zealand. The contest was first established by the American Society of Human Genetics in 2005 and the HGSA DNA Day Essay Contest is adapted from this contest via a collaborative partnership. The aim of the contest is to engage high school students with important concepts in genetics through literature research and reflection. As 2013 marks the 60th anniversary of the discovery of the double helix of DNA by James Watson and Francis Crick and the 10th anniversary of the first sequencing of the human genome, the essay topic was to choose either of these breakthroughs and explain its broader impact on biotechnology, human health and disease, or our understanding of basic genetics, such as genetic variation or gene expression. The contest attracted 87 entrants in 2013, with the winning essay authored by Patrick Yates, a Year 12 student from Melbourne High School. Further details about the contest including the names and schools of the other finalists can be found at http://www.hgsa-essay.net.au/. The Education Committee would like to thank all the 2013 applicants and encourage students to enter in 2014.

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ASHG announces DNA Day essay contest winner

By john daniels assistant public affairs specialist.

By the time, high school students reach their senior year, they've learned about DNA, RNA and scientific theories about evolution and genetic variation. This year, more than 750 students went beyond those basic biology lessons to find topics they would write about and submit to an international essay contest sponsored by the American Society of Human Genetics (ASHG).  Held every year, the contest coincides with National DNA Day, which was established by the National Human Genome Research Institute (NHGRI) to commemorate the 1953 discovery of DNA's double helix structure and the 2003 completion of the Human Genome Project. Rachel Gleyzer, a tenth grade student at Bergen County Academies in Hackensack, N.J., took first place this year with her essay on the role genetics and the environment play in absolute pitch (AP), a person's ability to accurately and instantly identify a musical tone's pitch without hearing a preceding reference note. Ms. Gleyzer chose this topic because she wanted to know why some people she knew had AP, but she did not. "I was so happy when I found out I was a finalist in the contest. It was exciting, but a little unexpected," said Ms. Gleyzer, adding that writing the essay was not easy. "I had to read a lot of complex technical information and try to make it interesting and accessible, but it really improved my writing," she said. "It's very important that good scientists are good communicators," said Carol Zepatos, Ms. Gleyzer's biology teacher. "This is a great opportunity for students to hone their technical writing skills." Ms. Zepatos requires all of her biology students to write an essay for the contest. ASHG encourages participation in the contest by marketing it to teachers, rather than to students. Teachers, in turn, equip their students to write the essays by educating their classes on that year's topic. This year, students were asked to identify and describe at least one genetic factor and one environmental factor that contribute to a particular complex trait, such as blood pressure or height. The essays went through three rounds of judging, during which more than 530 ASHG members judged them on accuracy, quality of writing and supporting arguments. The annual contest, which began in 2006, has grown significantly over the past few years. The 750 submissions in this year's contest is more than double the total number since 2009.  All winners are awarded a monetary prize. The teachers of the top three winners receive grants for genetic teaching materials. "The contest helps high school students to not only learn about genetics in the classroom, but it helps them use that knowledge in a meaningful way," said Katherine Lontok, Ph.D., ASHG's educational programs manager.  "We were glad to see so many great essays from students who have a passion for genetics." Ms. Gleyzer hopes to turn her passion into a career that combines molecular biology with the humanities. "I want to take the skills I'd learn in a lab and be more creative with them," she said. For high school students thinking about entering next year's contest, she said, "Go for it! It'll pay off in the future. Just because something's challenging doesn't mean it's not worth doing."

Congratulations to this year's essay contest winners:

Honorable mention.

Arwa Abdelhamid , Staten Island Technical High School in Staten Island, N.Y. . Samantha Burns , Lely High School in Naples, Fla. Vivien Chen , Richard Montgomery High School in Rockville, Md Hussein Elghazaly , El Alsson British & American International School in Haraniya, Giza Lucas Lin , Thomas Jefferson High School for Science and Technology in Alexandria, Va. Sangho Myung , Montgomery Blair High School in Silver Spring, Md. Rosie Nagele , Springside Chestnut Hill Academy in Philadelphia, Pa. Allison Rerick , Staten Island Technical High School in Staten Island, N.Y. Karl Tayeb , Bergen County Academies in Hackensack, N.J. Eytan Weinstein , Tichon Ramah Yerushalayim in Jerusalem, Israel The National Human Genome Research Institute (NHGRI) will celebrate National DNA Day at the USA Science and Engineering Festival in Washington, D.C., from Saturday, April 26 to Sunday, April 27. For more information go to: http://www.genome.gov/DNADay . Attendees will be able to participate in family-friendly activities on genetics and DNA with NHGRI staff and volunteers. NHGRI will also post on the National DNA Day Facebook and Twitter pages from the festival.

Posted: April 25, 2014

Last updated: April 25, 2014

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UKCGG Essay Competition

UKCGG Essay Competition 2023

The topic for the 2023 UKCGG Essay Competition was " Increasing use of artificial intelligence in genomic medicine for cancer care – the promise and potential pitfalls. " We had essays on a similar theme in 2018, but given the huge advances in this space since then, we thought it worth revisiting! The submissions were of a high standard, with some fantastic ideas and insights.

Hearty congratulations to our winners!

• Medical student: Eva Hanlon
• Junior doctors: Olivia O'Connor (Overall winner) 
• Clinical scientist trainee: Rasha Bensabai 

Read the winning entries here . 

UKCGG Essay Competition 2022: What will enable personalised cancer risk assessments ten years from now?

The topic for the 2022 Essay Prize was: What will enable personalised cancer risk assessments ten years from now?

As usual we had some fantastic submissions. 

Huge congratulations to our overall winner, Dr Eunice Xing, and to our winners in all categories. We were disappointed that we had no submissions from Trainee Genetic Counsellors, so expect lots of submissions from this group in 2023!!

We also awarded commendations to: Amber Corrigan, Joseph Christopher, Samira Ahmad Bawany

Download and read the winning essays by clicking here.

2021: "Delivering cancer genetics services in the post-pandemic era – are we ready for a virtual model of care?"

The topic for the 2021 Essay Prize was:  "Delivering cancer genetics services in the post-pandemic era – are we ready for a virtual model of care?"

The submissions for this year's competition were fantastic, and gave us lots of food for thought in how we can continue to deliver services in the midst of yet another wave - we're not quite "post" pandemic yet. 

The overall winner, and first prize in the junior doctor category was Melody Redman, who also presented an overview of her essay at the recent UKCGG winter meeting. 

Other winners included 

• Medical student - Jen Lim 
• Genetic counsellor trainees - Vernie Aguda 
• Junior Doctor (commendation) - Rhys Dore 

Read all of their wonderful submissions here . 

2020: "Horizon scanning in cancer genomics"

We had some phenomenal entries in our 2020 UKCGG essay competition, on the topic of "Horizon Scanning in Cancer Genomics". Participants were tasked with writing an essay based on the following scenario: 

Imagine two patients - one being diagnosed with cancer now and one being diagnosed with the same cancer in 10 years time. How and why do you think advances in genomic medicine will change the care we offer now and then for cancer patients and their families?

Some stellar entries were received. Massive congratulations to all participants, and to our winners! 

Overall winner, and first prize Medical Student category - Lydia Seed 

Lydia gave a fantastic presentation summarising her essay at the UKCGG Winter meeting, and was so impressive that she was also invited to speak as part of the ICR-led module "Molecular Pathology of Cancer and Application in Cancer Diagnosis, Screening and Treatment" on the MSc Genomic Medicine, Imperial College London. 

Winners in the other categories included:

Doctor category: Melody Redman 

Genetic counsellor category: Xavier Bracke-Manzanares

Scientist category: Robert Pigott

Runners up included:

Doctor category: Emily Ferguson 

Medical student category: Tom Hampshire 

Genetic Counsellor category: Courtney Elliot

Scientist category: Seemu Ali

Read the winning essays! All available here .

2019: "Should All Individuals be screened for Genetic Predisposition to Cancer"

The topic for the essay competition in 2019 was ""Should All Individuals be screened for Genetic Predisposition to Cancer". Again, we had some fantastic submissions. 

Congratulations to all participants and to our winners! 

Overall Winner and First Prize Junior Doctor Category  - Sarah Wedderburn

Sarah said "I am currently an ST5 in Clinical Genetics based at the Queen Elizabeth University Hospital, Glasgow. I have always wanted to work in clinical genetics but it was my time as a core medical trainee on the oncology unit which focused my interest towards cancer genetics. The role of the clinical geneticist evolves with the specialty.  Questions such as that asked by the essay will become ever more frequent and answering them will be part of our role. This essay has made me consider many of the current and future challenges facing clinical genetics and genomics."  

Second Prize Junior Doctor Category - Lucy Loong

Special Commendations Junior Doctor Category  -  Tom Webb and Christopher Harlow

First Prize Medical Student Category - Francesco Dernie

Second Prize Medical Student Category  - Wassem Hasan

You can read the winning entries here .

2018: "Will Artificial Intelligence Eventually Replace Cancer Geneticists"

We had some excellent entries in the CGG Essay Prize in 2018, on the topic "Will Artificial Intelligence Eventually Replace Cancer Geneticists"

Huge congratulations to all our winners:

Overall Winner and First Prize Medical Student Category  - Olivia Greatbatch

Olivia said " I am currently in my second year of medicine at University College London, and so am in the process of deciding which intercalated BSc I wish to pursue. Given just how topical the future of artificial intelligence is across all medical specialities, it is an area which I have recently been trying to learn more about. Since both oncology and genetics are options that I am considering for intercalation, I felt that the essay competition would be a great way to gain an appreciation of what a career in these two fields may entail in the future, whilst also exploring my own interests."  

Second Prize Medical Student Category  - Rashmi  Saincher

Third Prize Medical Student Category  - Ayan Basu

First Prize Junior Doctor Category  - Alice Garrett

Second Prize Junior Doctor Category - Lara Hawkes

Third Prize Junior Doctor Category  - George Morrissey

First Prize Scientist Trainee Category  - Nana Mensah

 You can read their winning entries here .

Essay Contest

The 2024 Essay Contest is now closed. Winners will be announced in July.

About the Contest

The Lasker Essay Contest engages early career scientists and clinicians from the US and around the globe in a discussion about big questions in biology and medicine and the role of biomedical research in our society today. The Contest aims to build skills in communicating important medical and scientific issues to broad audiences. The topic is announced annually in early February, and winners are announced in mid-July.

Eligibility

The Contest is open to medical school students, interns, residents, and fellows; doctoral students and postdoctoral fellows in biomedical sciences; and graduate students training in health professions programs e.g., public health, dental, pharmacy, etc who are currently doing research. Applicants (from the US or any other countries) must be currently participating in an educational program. This program may be located in any country.

Winners will receive up to $5,000. Monetary prizes will be directed to the winner’s university to be used towards the winner’s educational expenses.

Essays should be 800 words or less and must be written in English. We allow only one essay submission per applicant, and the essay must be written by a single author. The use of any generative AI tool (e.g. ChatGPT) in composing an entry is prohibited – all essays will be screened with software designed to detect use of AI. Essays need to be original; content previously published will be disqualified.The file containing the essay should include the essay title and the applicant’s name, email, and institutional affiliation. The 800-word limit applies to the body of the essay. Field-specific scientific jargon should be avoided or explained.

Evaluation Criteria

Essays will be evaluated based on their originality, quality of writing, style, and clarity. Essays that are not written in English or are longer than 800 words will not be considered.

Publication

The winning essays will be published in the July issue of The Journal of Clinical Investigation .

All Winners

Meet the Winners of the 2023 Essay Contest and Read the Essays

Meet the Winners of the 2022 Lasker Essay Contest

The 2022 Lasker Essay Contest

Meet the Winners of the 2021 Lasker Essay Contest

The 2021 Lasker Essay Contest

Winners of the 2020 Lasker Essay Contest

Winners of the 2019 Lasker Essay Contest

Winners of the 2018 Essay Contest

Winners of the 2017 Essay Contest

Winners of the 2016 Essay Contest

Winners of 2015 Essay Contest: The “Research Challenge”

2014 Essay Contest: Supporting Medical Research

Read the winning essays.

Allison R. Chen Research Training in an AI World

Louise O. Downs Is a Test Better Than No Test When There Is No Treatment?

Ayush Kumar Using HG1222 — A Perspective Into the Ethics of Collecting Biospecimens

Salman E. Qasim The Human Brain: The Final Frontier and the Wild West

Sneha P. Rath Cementing the Bricks

Kaelyn Cummins Microbes, Medicine, and Astronauts: Reflections on a Collaborative Project

Azmina Karukappadath Two Fields, One Dream

Hussain Lalani I Would Be Scared if I Heard That Too

Rutvij Merchant Pathways to Global Health Equity: More Seats, Fresh Perspectives

Kirti Nath Puzzles

Avik Ray Unified Diversity: The Team Game

Ziad Ali What Happens Now?

Banafsheh Nazari Embracing Technology, the Pandemic’s Lesson for Us

Trisha Pasricha One more question

Miriam Saffern My Mother is a Layperson

Adina Schonbrun The Cornerstone of Scientific Success: Unsung Frontline Heroes of the COVID-19 Pandemic

Emily Ashkin Michael Bishop: A Scientist for the Next Generation

David Basta For the Love of Science

Avash Das Michael Brown and Joseph Goldstein: Tribute to My Inspiration

William Dunn Sweet Are the Uses of Adversity

Safwan Elkhatib Salk, Sabin, and the Crown of Health

Laurel Gabler Putting “People’s Health in People’s Hands”: How the Bangs Inspired my Personal Journey

Kwabena Kusi-Mensah As One Single Tribe: Thinking Globally and Locally

Lisa Learman With the Corn, Against the Grain

Olivia Lucero Genetics as a Tool for Generational Empowerment

Hannah Mason My Gym Genie: Gathering Inspiration from Dr. John Schiller

Samantha Wong Fauci: Science as a Voice of Reason

Grace Beggs Game On: Smartphone Technology for Science Education

Peter John Making it All Fun and Games in the Biomedical Sciences

Dereck Paul Pathways: A National Mentorship Program for High School Students Underrepresented in Science and Medicine

David Hartmann Cancer Survivors: Outstanding Advocates for Trust in Science

Debra Karhson A Verification Vaccine for Social Contagion

Caroline Vissers Diversity at the Top of the Social Media Signaling Cascade

Abigail Cline Science and Cinema: From the Benchtop to the Big Screen

Tammy Tran Science Is Everywhere: Unexpected Science Encounters in the Course of Everyday Life

Michael Wu Search for Science: Smart Search-Linked Discussion Forums

Jennifer Bratburd Breaking through Barriers to Science with Citizen Science

Apurva Lunia Dissemination of Biomedical Research Via Multimedia Platforms Using Existing Healthcare Frameworks

Jessica Sagers Let’s Get Real: (Re)making Scientists Into People

David Ottenheimer Modern Neuroscience Has the Tools to Treat Psychiatric Illness

Therese Woodring (Korndorf) Hacking the Bacterial Social Network: Quorum Sensing and the Future of Microbial Management

Unikora Yang The Cutting Edge of DNA Editing: Translating CRISPR to Improve Human health

David Hill Mutual Understanding: Uncovering the Mechanistic Basis of the Host-Symbiont Relationship in Human Health

Joseph Rathkey In Silico Modeling as an Ideal Platform for Future Biological Research and Discovery

Stephanie Ng Depression and the Final Frontier

Omar Toubat Mastering the Genetic Reprogramming of Cells

Peter Soh Offering Incentives for Future Scientists

Michael Burel Catalyzing Broad Public Interest in Scientific Research

Nick Andresen Crowdsourcing a Medical Research Donation Database

Gregg Gonsalves Researchers as Advocates and Activists

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NEWS Pirogov Medical University

A delegation from the Ministry of Education and Training of the Socialist Republic of Vietnam, led by Deputy Minister Hoang Minh Son, visited the Pirogov Russian National Research Medical University by the Ministry of Health of Russia

Specialists from the Pirogov Russian National Research Medical University of the Ministry of Health of Russia took part in the Conference "Current Issues in the Implementation of Innovative Technologies in Emergency Medical Care Practice."

A delegation from the Ministry of Health of the Democratic People's Republic of Korea visited the Pirogov Russian National Research Medical University by the Ministry of Health of Russia

International Pirogov Scientific Medical Conference

University staff visited an educational exhibition in Samarkand

“My opponent is the me from last year” says the first participant of the intership program for foreign practicing doctors at leading medical and scientific centers of Russia, Nairi Melkonyan, a doctor from Armenia

At the end of 2023, INTERDOCTOR: a project implemented by Ministry of Health of the Russian Federation and Pirogov Russian National Research Medical University, had begun. The first participant was Doctor Nairi Melkonyan, a...

Emerging technologies: advancing rehabilitation projects

Yana Olegovna Grigoryeva and Irina Igorevna Karpeeva , delegates from the Pirogov Russian National Research Medical University's international department under the auspices of Russia's Ministry of Health, took an active part...

Representatives of the Embassy and of the Consulate General of the I. R. of Iran met with students at Pirogov Russian National Research Medical University

Preparatory Courses Invite Future Applicants

TRAINING IN RUSSIAN, CHEMISTRY AND BIOLOGY.

Admission for International Students

Moscow, Russia

See the official Rolling Stones web site in Russia , also having info in English!

How "the rolling stones" solve the problem of unemployment in moscow, their own uncompetence, their own openess, thanks to constantin preobrazhensky (moscow) for supplying info about the web site and the stones show in russia. also thanks to leonid ulitsky , italy, for info..

Healthcare in Moscow

This guide was written prior to Russia's 2022 invasion of Ukraine and is therefore not reflective of the current situation. Travel to Russia is currently not advisable due to the area's volatile political situation.

Healthcare in Moscow is organised by the Moscow Health Department. While public healthcare facilities are available, most expats seek out private healthcare at international medical centres. Expats are advised to take out private medical insurance if it is not provided to them by their company.

Subsidised healthcare is provided to everyone living in the country, paid for by the state and the mandatory health insurance system. That said, professionals in the state system are likely to speak little to no English. 

There are several private medical centres in Moscow where English is spoken and where the healthcare is on par with expat standards. These clinics are generally very expensive, so it is highly recommended that expats take out private medical insurance to cover medical costs in Moscow. Most insurance coverage plans will also include evacuation cover for emergencies or life-threatening situations. 

Recommended hospitals in Moscow

Alliance medicale.

www.alliancemedicale.ru Address: Kutuzovsky Ave, 1/7

Intermed Center American Clinic

www.en.intac.ru Address:  4 Monetchikovsky Lane, 1/6, Building 3

International Clinic MEDSI

www.medsi.ru Address:  26 Prospekt Mira, Building 6

European Medical Center

www.emcmos.ru Address:   5 Spiridon'yevskiy Pereulok, Building 1

Further reading

►For more on the Russian healthcare system see our Healthcare in Russia page.

Expat Interviews " The standard is high, but health insurance is essential − both international and local cover tend to be adequate and similar for routine things." Read more about Stephen, a British expat, and his  experience living in Moscow . 

Are you an expat living in Moscow?

Expat Arrivals is looking for locals to contribute to this guide, and answer forum questions from others planning their move to Moscow. Please contact us if you'd like to contribute.

Expat Health Insurance

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Moscow, Russia – Architectural Splendor at the Heart of Eurasia

Moscow, Russia – Most Populated Cities in the World

Moscow, the capital city of Russia, stands as an architectural testament to the country’s rich history and cultural legacy. This article explores the architectural landscape of Moscow, uncovering its unique blend of historical monuments, Soviet-era structures, and contemporary designs that define this vibrant metropolis.

Population Dynamics of Moscow

From medieval roots to megacity.

Moscow, with a population exceeding 12 million, has evolved from its medieval roots into a bustling megacity. The city’s demographic dynamism reflects its historical significance as a political, economic, and cultural center. Moscow’s urban growth presents challenges and opportunities for architects and urban planners, requiring a delicate balance between preservation and modernization.

Architectural Diversity in Moscow

Kremlin, red square, and the modern skyline.

Moscow’s architectural diversity is a harmonious blend of historical landmarks and contemporary structures. The iconic Kremlin, with its cathedrals and palaces, dominates the cityscape, while the neighboring Red Square provides a historical focal point. Beyond the historical core, Moscow’s skyline is adorned with modern skyscrapers like the Moscow International Business Center, symbolizing the city’s economic and architectural evolution.

Sustainable Architecture Initiatives

Green innovations amidst urban density.

As Moscow confronts environmental challenges and urban density, architects have championed sustainable solutions. Green building practices, energy-efficient designs, and eco-friendly materials are integral to Moscow’s architectural discourse. The city’s commitment to sustainability is evident in projects like Zaryadye Park, a green oasis in the heart of the city.

Urban Planning and Zoning Strategies

Preserving heritage amidst modernization.

Moscow’s urban planning endeavors to preserve its historical heritage while accommodating modern developments. The preservation of architectural gems like St. Basil’s Cathedral and the Pushkin Museum coexists with contemporary urban projects such as the Moscow City residential complexes. Urban planners in Moscow face the challenge of balancing the demands of a growing population with the need to protect the city’s cultural legacy.

Resilience in the Face of Urban Challenges

Adaptable architecture for harsh climates.

Moscow’s architectural resilience is tested by the city’s harsh climate and urban challenges. Architects prioritize designs that can withstand extreme temperatures and adapt to the evolving urban landscape. The use of durable materials and innovative construction techniques showcases Moscow’s commitment to architectural adaptability.

Technological Integration in Moscow’s Architecture

Smart city initiatives and futuristic designs.

Moscow’s architectural landscape seamlessly integrates cutting-edge technology for enhanced urban living. Smart city initiatives, digital infrastructure, and futuristic designs like the Moscow Central Diameters (MCD) showcase the city’s commitment to technological innovation. Moscow positions itself as a global hub for modern architectural practices, leveraging technology to improve efficiency and sustainability.

Architectural Icons of Moscow

Kremlin and red square.

The Kremlin and Red Square, UNESCO World Heritage Sites, symbolize Moscow’s historical and political significance. The architectural ensemble, including the iconic St. Basil’s Cathedral and the State Historical Museum, reflects Russia’s cultural and religious heritage.

Moscow International Business Center (Moscow City)

Moscow City, with its futuristic skyscrapers, represents the city’s economic prowess and modern aesthetic. The complex includes iconic structures like the Federation Tower and Mercury City Tower, showcasing Moscow’s status as a global financial and architectural hub.

Moscow’s Future Architectural Landscape

As Moscow continues to evolve, the city’s architectural landscape is poised for further transformation. Urban planners and architects are exploring innovative solutions to accommodate the growing population while preserving the city’s unique identity. Moscow’s commitment to sustainable practices, technological integration, and resilient design will shape its architectural future.

In conclusion, Moscow, Russia, stands as a city where architectural marvels narrate the story of a nation’s history and progress. From medieval fortifications to contemporary skyscrapers, Moscow’s architectural landscape is a testament to its resilience and adaptability. As the city looks toward the future, its architectural canvas promises to be a captivating blend of tradition, modernity, and technological innovation at the heart of Eurasia.

Rethinking The Future (RTF) is a Global Platform for Architecture and Design. RTF through more than 100 countries around the world provides an interactive platform of highest standard acknowledging the projects among creative and influential industry professionals.

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Realizing the benefits of human genetics and genomics research for people everywhere.

2022 DNA Day Essay Contest: Full Essays

1 st  Place : Man Tak Mindy Shie, Grade 12 Teacher:  Dr. Siew Hwey Alice Tan School:  Singapore International School (Hong Kong) Location:  Hong Kong, China

Many would say that the most significant stride in recent genetics has been the completion of the human genome, which laid the basis for studying genetic variation. However, let us not forget that this began with the understanding of heredity based on Gregor Mendel’s observations in 1857.

Observations from Mendel’s pea plant hybridization experiments led to two fundamental principles of inheritance (1). The first was the Law of Segregation, which states that reproductive gamete cells transmit only one allele to their offspring. This means that a diploid offspring will inherit one allele from each parent. We now understand genes to be the units of heredity that carry genetic information and alleles to be different variants of a gene (2). Mendel’s second principle, the Law of Independent Assortment, states that alleles are assorted independent of each other during gamete formation, leading to individual traits being inherited independently (1). Additionally, Mendel discovered that alleles could either be dominant or recessive. An allele that constituted a phenotypic trait over the other in a heterozygous genotype was labeled dominant, while the other phenotypically unexpressed allele was called recessive (3). A class of diseases was subsequently named after Mendel as they follow the same observations; Mendelian disorders are inherited monogenic diseases that result from mutation at a single gene locus (4). A notable example is phenylketonuria, where loss-of-function mutations in the PAH gene cause systemic excess phenylalanine, resulting in behavioral abnormalities (5).

Mendel’s Laws still provide important insight in understanding Mendelian traits. For example, the Law of Segregation created the basis of dominant and recessive phenotypic ratios (6). The phenotypic ratios in family pedigrees thus allow inference of dominant and recessive traits. This is additionally helpful when an unknown disorder is found to be a Mendelian trait. Since Mendelian traits have complete penetrance, i.e. individuals carrying the pathogenic variant always express the associated trait, it is possible to search for the gene-of-interest when parental genomes are also sequenced. In present-day analysis, Whole Exome Sequencing leverages the fact that most complete penetrance genes lie in the coding region of the genome; this reduces cost and search space for identifying novel diseases (7).

We now know that the Law of Independent Assortment is applicable only when traits are located on different chromosomes. Therefore, it is important in laying the assumption of the lack of linkage between different traits whose loci are genetically far apart. Traditionally, linkage analysis used this prerequisite to identify specific loci within the disease-causing organism, as genes in proximity are often in linkage and do not sort independently (7). Regardless, this stipulation could lead to the belief that the Law of Independent Assortment has less direct value in understanding Mendelian disorders.

In contrast to monogenic diseases, complex diseases arise from multiple genetic and/or environmental factors, displaying complicated inheritance and genetics (1,8). Asthma, for example, was shown to be associated with more than 100 genes with significant inter-population variation (9), and is clinically associated with environmental allergens. Researchers are still looking for contributing variants of many common complex diseases as, unlike Mendelian Disorders, the additive inheritance explained by the associated variants does not explain the genetic contribution to the disease determined by twin studies (8). This is known as the ‘missing heritability problem’, and has prompted scientists to look for other clues.

One way to unravel complex disease genetics lies in the functional characterization of gene variants. Mendelian Diseases thus became an important way to study the link between the genotype-phenotype relationship due to a clear causal relationship and complete penetrance. This puts us in a better position to understand why a variant results in a phenotypic trait (6). Moreover, Mendelian traits allow us to elucidate the functional perturbation due to the mutation itself, providing an excellent opportunity to understand how a change in RNA/protein function caused by mutations can contribute to pathogenesis (6). When variants within complex traits, whether rare or common, are involved within neighboring variants of Mendelian traits, molecular insight may be provided regarding the pathways involved in pathogenesis. Therefore, studying the molecular basis of Mendelian traits could provide essential clues to the bigger puzzle of complex disease.

In the late 2000s, Genome-Wide Associated Studies focused on complex traits and forced Mendelian Diseases to take a back seat; yet today we find that many genetic variants must first be understood through studying Mendelian Diseases. While most Mendelian Diseases are low in incidence, they nonetheless provide valuable lessons as we continue on our journey to understand human genetics.

Citations/References:

• Kennedy, M.A. (2005). Mendelian Genetic Disorders. In eLS, (Ed.). https://doi.org/10.1038/npg.els.0003934
• Cooper, G. M. (2000). The Cell: A Molecular Approach. 2nd edition. NCBI. Retrieved 2022, from https://www.ncbi.nlm.nih.gov/books/NBK9944/
• Wanjin, X., & Morigen, M. (2015). Understanding the cellular and molecular mechanisms of dominant and recessive inheritance in genetics course. Yi chuan = Hereditas, 37(1), 98–108. https://doi.org/10.16288/j.yczz.2015.01.014
• Prosen, T., & Hogge, W. (2008). Molecular and Mendelian Disorders. The Global Library of Women’s Medicine. https://www.glowm.com/section-view/heading/Molecular%20and%20Mendelian%20Disorders/item/223#.YhygEJNBzAN
• MedlinePlus. (2021). Phenylketonuria. https://medlineplus.gov/genetics/condition/phenylketonuria/
• Mendel, G., & Bateson, W. (2013). Mendel’s Principles of Heredity Dover Books on Biology. Courier Corporation.
• Antonarakis, S. E., Chakravarti, A., Cohen, J. C., & Hardy, J. (2010). Mendelian disorders and multifactorial traits: the big divide or one for all?. Nature reviews. Genetics, 11(5), 380–384. https://doi.org/10.1038/nrg2793
• What are complex or multifactorial disorders?: MedlinePlus Genetics. (2021). Medline Plus. https://medlineplus.gov/genetics/understanding/mutationsanddisorders/complexdisorders/
• Allergic asthma: MedlinePlus Genetics. (2020). MedlinePlus. https://medlineplus.gov/genetics/condition/allergic-asthma/

2 nd  Place: Gillian Wells, Grade 11 Teacher:  Mrs. Rebecca Hodgson School:  Ulverston Victoria High School Location:  Ulverston, England, UK

Mendel is often referred to as the “Father of Modern Genetics” (1). Prior to his experiments in plant hybridization, it was believed inherited traits resulted from blending the traits of each parent (2). From his studies, Mendel derived three principles of inheritance: the laws of dominance (in a heterozygote, the dominant allele conceals the presence of the recessive allele), segregation (each individual possesses two alleles for a specific trait, one inherited from each parent, and segregated during meiosis) and independent assortment (alleles for separate traits are inherited independently) (3, 4).

These principles give a pattern of inheritance followed by Mendelian or monogenic disorders – disorders caused by variation in a single gene (5). Mendel’s law of dominance explains the pattern of inheritance for autosomal dominant monogenic disorders, which present in individuals with only one dominant mutated allele (2). The heredity of dominant disorders – for example, Huntington’s disease and myotonic dystrophy – therefore follow the same pattern as the dominant traits Mendel observed in pea plants (4, 6). Mendel’s law of dominance also explains the pattern of inheritance for autosomal recessive monogenic disorders, which are not expressed in heterozygous individuals (carriers) as the dominant allele ‘hides’ the mutated recessive allele. Therefore, in families with multiple affected generations, the disorder will appear to ‘skip’ generations, only presenting in individuals that inherit two recessive mutated alleles of the same gene, one from each parent, as explained by Mendel’s law of segregation (2). The heredity of recessive disorders – for example, phenylketonuria and cystic fibrosis – therefore follow the same pattern as the recessive traits Mendel observed in pea plants (4, 6).

This understanding of inheritance patterns establishes the causal relationship between genes and Mendelian disorders, between genotype and phenotype (7). From this, many Mendelian disorder gene identification approaches have been developed, from positional cloning and linkage mapping to whole exome and genome sequencing (8, 9). The results are compiled in Online Mendelian Inheritance in Man (OMIM), a comprehensive database of human genes and genetic disorders, with over 26,000 entries describing over 16,000 genes and 9,000 Mendelian phenotypes (10, 11). Identifying these causal genes improves understanding of specific Mendelian disorders, allowing for molecular diagnosis and carrier testing (9).

In contrast, complex or polygenic diseases are caused by variation in multiple genes interacting with environmental and lifestyle factors, and so do not follow Mendelian inheritance patterns (12). However, widespread comorbidity between Mendelian disorders and complex diseases has been identified, suggesting a genetic association (14). Recent studies have shown that nearly 20% of the identified genes underlying Mendelian disorders contain variants responsible for genome-wide association study (GWAS) signals that cause complex diseases. 15% of all genes underlie Mendelian disorders. Mendelian genes are therefore enriched in GWAS signals and so contribute to the etiology of corresponding complex diseases (13, 14).

Given that different variants of the same gene can give rise to several different phenotypes, some Mendelian genes carry variants that contribute to complex diseases as well as causal variants for Mendelian disorders (13, 15). For example, the gene ABCA4 causes the monogenic conditions retinitis pigmentosa and Stargardt disease, as well as the complex disease age-related macular degeneration (15). Therefore, selecting genes that cause Mendelian disorders for candidate gene association studies can reveal variants that contribute to the etiology of complex diseases, allowing their genetic basis to be understood (10).

Given this genetic association between Mendelian disorders and complex diseases, the identification of Mendelian genes and knowledge of their expression can be used to further understand the mechanisms of associated complex diseases. An example in cardiovascular disease (CVD) research is the identification of causal genes for the monogenic disorder severe hypercholesterolemia. This has provided invaluable insights into lipid transport, leading to an improved understanding of CVD. From this, successful therapies have been developed for CVD using knowledge of the relevant genes and pathways (16). Mutation mechanisms observed in Mendelian disorders that can provide insight into complex disease include anticipation, gene dosage effects, and uniparental disomy (10).

Overall, Mendel’s discoveries revolutionized genetics, creating a model of inheritance that led to advancements in the diagnosis, treatment, and genetic understanding of inherited Mendelian disorders. In turn, research of Mendelian disorders has provided an understanding of the causes and mechanisms of complex diseases through genetic association – up to 23% of genes known to cause Mendelian disorders have been associated with a complex disease (17). The study of Mendelian phenotypes has and will continue to provide breakthroughs in the development of treatments and therapies of all genetic disorders (10).

References/Citations:

• Dastur, AdiE, and PD Tank. “Gregor Johann Mendel: The Father of Modern Genetics.” Journal of Prenatal Diagnosis and Therapy, vol. 1, no. 1, 2010, p. 3, https://doi.org/10.4103/0976-1756.62132.
•  Reyna, Barbara, and Rita Pickler. “Patterns of Genetic Inheritance.” Neonatal Network, vol. 18, no. 1, Feb. 1999, pp. 7–10, https://doi.org/10.1891/0730-0832.18.1.7.
•  Miko, Ilona. “Gregor Mendel and the Principles of Inheritance | Learn Science at Scitable.” Nature.com, 2014, www.nature.com/scitable/topicpage/gregor-mendel-and-the-principles-of-inheritance-593/#.
• Mendel, Gregor. “Versuche Über Pflanzen-Hybriden.” Der Züchter, vol. 13, no. 10-11, Oct. 1941, pp. 221–68, https://doi.org/10.1007/bf01804628.
• Jensen, Peter K. A. “[Monogenic Hereditary Diseases].” Ugeskrift for Laeger, vol. 165, no. 8, Feb. 2003, pp. 805–9, pubmed.ncbi.nlm.nih.gov/12625123/.
• Chial, Heidi. “Gregor Mendel and Single-Gene Disorders | Learn Science at Scitable.” Nature.com, 2014, www.nature.com/scitable/topicpage/mendelian-genetics-patterns-of-inheritance-and-single-966/.
• Hansen, Adam W., et al. “A Genocentric Approach to Discovery of Mendelian Disorders.” The American Journal of Human Genetics, vol. 105, no. 5, Nov. 2019, pp. 974–86, https://doi.org/10.1016/j.ajhg.2019.09.027.
•  Botstein, David, and Neil Risch. “Discovering Genotypes Underlying Human Phenotypes: Past Successes for Mendelian Disease, Future Approaches for Complex Disease.” Nature Genetics, vol. 33, no. S3, Mar. 2003, pp. 228–37, https://doi.org/10.1038/ng1090.
• Gilissen, Christian, et al. “Unlocking Mendelian Disease Using Exome Sequencing.” Genome Biology, vol. 12, no. 9, 2011, p. 228, https://doi.org/10.1186/gb-2011-12-9-228.
• Antonarakis, Stylianos E., and Jacques S. Beckmann. “Mendelian Disorders Deserve More Attention.” Nature Reviews Genetics, vol. 7, no. 4, Mar. 2006, pp. 277–82, https://doi.org/10.1038/nrg1826.
• Hamosh, Ada. “OMIM Entry Statistics.” Omim.org, omim.org/statistics/entry#.
• SCHORK, NICHOLAS J. “Genetics of Complex Disease.” American Journal of Respiratory and Critical Care Medicine, vol. 156, no. 4, Oct. 1997, pp. S103–9, https://doi.org/10.1164/ajrccm.156.4.12-tac-5.
• Blair, David R., et al. “A Nondegenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk.” Cell, vol. 155, no. 1, Sept. 2013, pp. 70–80, https://doi.org/10.1016/j.cell.2013.08.030.
• Chong, Jessica X., et al. “The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities.” The American Journal of Human Genetics, vol. 97, no. 2, Aug. 2015, pp. 199–215, https://doi.org/10.1016/j.ajhg.2015.06.009.
• Dean, Michael. “Approaches to Identify Genes for Complex Human Diseases: Lessons from Mendelian Disorders.” Human Mutation, vol. 22, no. 4, Aug. 2003, pp. 261–74, https://doi.org/10.1002/humu.10259.
• Kathiresan, Sekar, and Deepak Srivastava. “Genetics of Human Cardiovascular Disease.” Cell, vol. 148, no. 6, Mar. 2012, pp. 1242–57, https://doi.org/10.1016/j.cell.2012.03.001.
• Spataro, Nino, et al. “Properties of Human Disease Genes and the Role of Genes Linked to Mendelian Disorders in Complex Disease Aetiology.” Human Molecular Genetics, vol. 26, no. 3, Feb. 2017, pp. 489–500, https://doi.org/10.1093/hmg/ddw405.

3 rd  Place:  Yiyang Zhang, Grade 11 Teacher:  Dr. Qiongyu Zeng School:  Shanghai High School International Division Location:  Shanghai, China

Natural populations are characterized by astonishing phenotypic diversity determined by genes and dynamic environmental factors. In 1865, Gregor Mendel showed how traits are passed between generations through his classical pea crosses, giving us the first insight into the heritable basis of phenotypic variation [1]. Mendel’s findings revolutionized the concept of genotype-phenotype relationships and laid the foundation for modern genetics. However, our understanding of the spectrum and continuum between Mendelian and non-Mendelian diseases remains incomplete, and more work is needed to fully unravel the mechanisms underlying human diseases [2].

Mendelian diseases such as sickle cell anemia are characterized by monogenic genetic defects that result in discrete phenotypic differences [3]. Such Mendelian mutations are thought to segregate in predictable patterns, similar to the simple traits Mendel demonstrated in his pea crosses. Indeed, genetic mapping in family-based studies has led to remarkable discoveries of rare chromosomal abnormalities in patients with Mendelian diseases such as Duchenne muscular dystrophy [4]. However, even monogenic diseases follow a Mendelian inheritance pattern only sporadically. For example, in cystic fibrosis (CF), which has nearly 2000 mutant alleles in the primary causative gene Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and six other loci associated with but not causing the disease, patients exhibit considerable interindividual variability in symptom severity [5, 6]. Thus, there is no pure Mendelian inheritance [7] or, in other words, there are essentially no simple diseases [8].

In Mendelian diseases, mutations in critical genes are usually embryologically lethal, which explains the low prevalence of Mendelian disorders in natural populations [9]. In contrast, common forms of human disease such as diabetes, heart disease, and cancer occur in previously healthy individuals, and instead of dominant disease-causing alleles, many weak genetic factors exert miniscule and accumulative effects on phenotypic outcomes. This multifactorial nature of complex diseases, which are either oligogenic or polygenic [10], means that they do not strictly adhere to Mendelian inheritance patterns in conventional mapping analyses, as segregation of genetic variants in the recombinant offspring of genetically distinct parents can easily hide extreme phenotypes and mask association signals. Therefore, researchers have developed a threshold model that assumes that there is a distribution of susceptibility for a particular trait in the population and that the trait only occurs when a threshold is exceeded [11]. This model could explain ‘all or none’ phenotypes such as cleft palate and why relatives of affected individuals are at higher risk of multifactorial traits such as hypertension or diabetes than the general population [12].

With the advent of genome-wide association studies (GWAS), which use a large sample of unrelated individuals, significant progress has been made in reliably identifying genes that influence the risk of complex diseases [13]. However, even though many thousands of disease susceptibility loci have been characterized, challenges remain, such as the ‘dark matter of inheritance’ that cannot be assigned for most complex traits [14]. Several explanations have been proposed for this, including numerous low-influence variants, rare variants, poorly recognized structural variants, and inadequate estimation of gene-gene and gene-environment interactions [15].

Gene interaction was first demonstrated in retinitis pigmentosa (RP). Since the structural integrity of retinal photoreceptors depends on the functional complexes formed by Retinal Degeneration Slow (RDS) and Rod Outer segment Membrane protein 1 (ROM1), mutations at discrete loci disrupt digenic interactions and produce the same phenotype as alleles of the same locus [16, 17]. This is a perfect example of how pushing the boundaries of Mendelian genetics can help us unravel the true physiological and cellular nature of complex diseases.

In addition to gene-gene interactions, gene-environment interactions also contribute to quantitative traits and trigger the occurrence of complex diseases such as asthma, which are influenced by numerous genetic and nongenetic factors [18]. Environmental factors can also influence traits epigenetically. For example, the more methyl donors such as folic acid or vitamin B12 are present in the diet of young mice, the higher the frequency of methylation at the CpG site of the agouti gene and the darker the coat coloration in adulthood [19, 20].

Our understanding of the causes of disease has evolved from a simplified paradigm of the Mendelian model (one variant-one disease) to a more sophisticated polygenic model. Expanding Mendelian concepts and constructing theoretical models with higher complexity is the first step toward creating a conceptual continuum between Mendelian and non-Mendelian genetic traits. In the long term, genomics and phenomics will continue to be inexhaustible sources of information to elucidate the genetic architecture of both single gene anomalies and complex diseases and to enable more personalized diagnosis and treatment.

• Mendel, J.G., Versuche u ̈ber Pflanzenhybriden Verhandlungen des naturforschenden Vereines in Brünn, Bd. IV für das Jahr, Abhandlungen. 1865: p. 3-47.
• Badano, J.L. and N. Katsanis, Beyond Mendel: an evolving view of human genetic disease transmission. Nat Rev Genet, 2002. 3(10): p. 779-89.
• Steinberg, M.H. and A.H. Adewoye, Modifier genes and sickle cell anemia. Curr Opin Hematol, 2006. 13(3): p. 131-6.
• Monaco, A.P., et al., Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene. Nature, 1986. 323(6089): p. 646-50.
• Drumm, M.L., A.G. Ziady, and P.B. Davis, Genetic variation and clinical heterogeneity in cystic fibrosis. Annu Rev Pathol, 2012. 7: p. 267-82.
• Emond, M.J., et al., Exome sequencing of extreme phenotypes identifies DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis. Nat Genet, 2012. 44(8): p. 886-9.
• Van Heyningen, V. and P.L. Yeyati, Mechanisms of non-Mendelian inheritance in genetic disease. Hum Mol Genet, 2004. 13 Spec No 2: p. R225-33.
• Dean, M., Approaches to identify genes for complex human diseases: lessons from Mendelian disorders. Hum Mutat, 2003. 22(4): p. 261-74.
• Quintana-Murci, L. and L.B. Barreiro, The role played by natural selection on Mendelian traits in humans. Ann N Y Acad Sci, 2010. 1214: p. 1-17.
• Assimes, T.L. and P.S. de Vries, Making the Most out of Mendel’s Laws in Complex Coronary Artery Disease. J Am Coll Cardiol, 2018. 72(3): p. 311-313.
• Wright, S., An Analysis of Variability in Number of Digits in an Inbred Strain of Guinea Pigs. Genetics, 1934. 19(6): p. 506-36.
• Korf, B.R., Basic genetics. Prim Care, 2004. 31(3): p. 461-78, vii.
• Crawford, N.P., Deciphering the Dark Matter of Complex Genetic Inheritance. Cell Syst, 2016. 2(3): p. 144-6.
• Kere, J., Genetics of complex disorders. Biochem Biophys Res Commun, 2010. 396(1): p. 143-6.
• Zuk, O., et al., The mystery of missing heritability: Genetic interactions create phantom heritability. Proc Natl Acad Sci U S A, 2012. 109(4): p. 1193-8.
• Clarke, G., et al., Rom-1 is required for rod photoreceptor viability and the regulation of disk morphogenesis. Nat Genet, 2000. 25(1): p. 67-73.
• Travis, G.H., et al., Identification of a photoreceptor-specific mRNA encoded by the gene responsible for retinal degeneration slow (rds). Nature, 1989. 338(6210): p. 70-3.
• Papi, A., et al., Asthma. Lancet, 2018. 391(10122): p. 783-800.
• Wolff, G.L., et al., Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice. FASEB J, 1998. 12(11): p. 949-57.
• Waterland, R.A. and R.L. Jirtle, Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol, 2003. 23(15): p. 5293-300.

Honorable Mentions

Lena Chae Glenbrook South High School Glenview, Illinois Teacher: Mrs. Marianne Gudmundsson

Angelina Jolie, a famous actress, underwent bilateral mastectomy and oophorectomy to prevent hereditary breast and ovarian cancer that is prevalent in her family [1]. This was only possible because she was able to predict her risk of developing these cancers in her lifetime, which was substantially high enough to warrant prevention surgery. We now know that germline mutations found in BRCA1/2 genes are responsible for hereditary breast and ovarian cancer syndrome transmitted in an autosomal dominant fashion [2]. This discovery was made possible through progress in genetics which began with Mendel’s experiments in the 1800s [3].

Mendel’s discovery helped us better understand Mendelian disorders that involve single-gene mutations. First, the principles of inheritance found in plants opened up opportunities for scientists to apply their observations to patterns they noticed across human generations. This progress towards human studies from plants, helped scientists dissect human diseases that are inherited in a systematic manner. Second, Mendel’s discoveries allowed us to discover and understand the genetic material known as DNA. Because of Mendel’s observations, Watson and Crick were able to demonstrate the structure of the DNA molecule through their discovery of the double helix [4]. The Human Genome Project led by Craig Venter and Francis Collins laid the foundation for us to locate genes responsible for pathogenesis [5]. Third, understanding both the inheritance pattern of specific human hereditary diseases, along with the knowledge of the sequences in the human genome, contributed to the specific discovery of the mutations in such hereditary diseases. For instance, mutations in the HTT gene can cause Huntington’s disease [6], while mutations in the CFTR gene can cause cystic fibrosis [7]. Due to Mendel’s original discovery and experiments, scientists have been able to link genetics to human pathology.

The study of Mendelian disorders aided in a better understanding of complex diseases in two different ways. First, pedigree studies, or family tree analysis, were used to study monogenic Mendelian disorders with high penetrance; this led to a realization that many human diseases cannot be explained by the Mendelian principle of inheritance. Except for a few hereditary diseases, most human diseases involve more than one gene abnormality when comparing the affected versus unaffected members within a family. This finding led to the concept of stepwise multigene abnormalities and environmental interaction with respect to pathogenesis. Second, Genome-Wide Association Studies (GWAS), which is the population-level study of genes and human diseases, could be understood as an aggregate of linkage analyses based on Mendelian principles [8]. It also extended the field of genetics. GWAS made it possible for scientists to define the role of single DNA mutations in complex diseases. Hundreds of thousands of single-nucleotide polymorphisms (SNPs) can be tested to explore the associations between these variants and disease in larger populations. For example, through the GWAS study, over 40 loci have been found to be associated with Type 2 Diabetes Mellitus (DM) [9]. Another highly heritable psychiatric disorder, schizophrenia, is linked with 108 genetic loci according to a GWAS consisting of more than 150,000 samples [10]. An improved understanding of comprehensive genomic mutations involved in such complex diseases led to the creation of a risk profile score (RPS), which is currently used to predict the risk of such disease development [11].

However, human diseases can sometimes be more than just changes in DNA. Both pedigree analysis and GWAS assume that hereditary diseases can fully be explained by genetic mutations. But epigenetic changes can be equally or more important [12]. Epigenetic processes such as DNA methylation or histone modifications, triggered by environmental and behavioral changes, may turn the target gene expressions “on” or “off”. Furthermore, protein modification may also play a role in pathogenesis. Therefore, to better understand complex diseases, it is critical to utilize both the study of genetics stemming from Mendel’s discoveries, and the non-genetic processes including epigenetics, transcriptomics, and proteomics [12].

In summary, Mendel’s discovery helped us better understand Mendelian disorders but also more complex diseases. Owing to Mendel’s principles of inheritance, scientists are now equipped with platforms and techniques to analyze both Mendelian disorders and complex diseases. Individualized treatments are now made possible through accurate diagnoses including identification of mutations leading to disease. Just as Angelina Jolie was able to prevent hereditary breast and ovarian cancer through germline DNA profiling, further in-depth DNA screening in a population can lead to a significant reduction in the risk of various hereditary and complex diseases.

• Jolie, A. (2013, May 14). My Medical Choice. New York Times, pp. 25–25.
• Rebbeck, T. R., Friebel, T., Lynch, H. T., Neuhausen, S. L., van ’t Veer, L., Garber, J. E., Evans, G. R., Narod, S. A., Isaacs, C., Matloff, E., Daly, M. B., Olopade, O. I., & Weber, B. L. (2004). Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: THE PROSE Study Group. Journal of Clinical Oncology, 22(6), 1055–1062. https://doi.org/10.1200/jco.2004.04.188
• B. (2021, May 21). Gregor Mendel. Biography. https://www.biography.com/scientist/gregor-mendel
• Pray, L. (2008) Discovery of DNA structure and function: Watson and Crick. Nature Education 1(1):100
• Adams, J. (2008) Sequencing human genome: the contributions of Francis Collins and Craig Venter. Nature Education 1(1):133
• Conneally P. M. (1984). Huntington disease: genetics and epidemiology. American journal of human genetics, 36(3), 506–526.
• Gallati S. (2003). Genetics of cystic fibrosis. Seminars in respiratory and critical care medicine, 24(6), 629–638. https://doi.org/10.1055/s-2004-815659
• Manolio T. A. (2010). Genomewide association studies and assessment of the risk of disease. The New England journal of medicine, 363(2), 166–176. https://doi.org/10.1056/NEJMra0905980
• Hakonarson, H., & Grant, S. F. (2011). Genome-wide association studies (GWAS): impact on elucidating the aetiology of diabetes. Diabetes/metabolism research and reviews, 27(7), 685–696. https://doi.org/10.1002/dmrr.1221
• Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature, 511(7510), 421–427. https://doi.org/10.1038/nature13595
• Xiao, E., Chen, Q., Goldman, A. L., Tan, H. Y., Healy, K., Zoltick, B., Das, S., Kolachana, B., Callicott, J. H., Dickinson, D., Berman, K. F., Weinberger, D. R., & Mattay, V. S. (2017). Late-Onset Alzheimer’s Disease Polygenic Risk Profile Score Predicts Hippocampal Function. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2(8), 673–679. https://doi.org/10.1016/j.bpsc.2017.08.004
• Centers for Disease Control and Prevention. (2020, August 3). What is epigenetics? Centers for Disease Control and Prevention. Retrieved March 1, 2022, from https://www.cdc.gov/genomics/disease/epigenetics.htm

  Aadit Jain International Academy Bloomfield Hills, Michigan Teacher: Mrs. Suzanne Monck

Nearly two centuries ago, Gregor Mendel launched the scientific community into the vast world of genetics and diseases with his experiments on the common pea plant (1,2). Specifically, his principles have been instrumental in the plethora of discoveries that have been made in Mendelian disorders. With around 400 million people worldwide suffering from one of the 7,000 Mendelian disorders, much research today centers on identifying the genetic causes of these diseases (3). While Mendel was unaware of genes and DNA when he conducted his study (2), his discoveries kickstarted the substantial research that scientists have undertaken on Mendelian disorders.

Mendel’s principles have directly allowed scientists to understand how Mendelian disorders are inherited. For example, his notable discovery that phenotypes of recessive traits can skip generations (2) applies to Mendelian disorders in the case of carriers (4). These are individuals who may not display the disorder phenotype but still carry and can pass on the altered gene (4). Therefore, it is essential to analyze pedigrees of affected families to determine whether the disease-causing gene has a dominant or recessive phenotype. Importantly, this knowledge helps genetics professionals understand the risk that individuals have of passing on a disorder (5). For example, a person who suffers from an autosomal dominant disorder bears a 50% chance of passing the affected gene to each offspring (5). In contrast, two heterozygous parents for an autosomal recessive disorder have a 25% chance of having an offspring affected with the disorder with each pregnancy (5).

Mendel’s principles of uniformity, segregation, and independent assortment demonstrate how genes and alleles are inherited (2). However, subsequent research revealed exceptions such as the sex-linked pattern of inheritance (2,6). Contrary to inheritance of autosomal single-gene diseases, males and females receive a different number of copies of the implicated gene for sex-linked disorders due to their respective pairs of sex chromosomes (1). As a result, sex-linked diseases tend to be prevalent in only one gender (1). For example, Hemophilia A, a blood clotting disorder, typically affects only males because it is an X chromosome-linked recessive disease (1). It is evident that although Mendel’s principles have laid a strong foundation of inheritance patterns, the scientific community’s understanding of Mendelian disorders is greatly enhanced through new research.

Mendel’s discoveries have been fundamental in developing effective methods to test for disorders. With the understanding that the same allele codes for a specific phenotype, researchers have individuals with the same phenotype disorder undergo sequencing in order to identify the defective gene (7). Such was the case in 2010, when scientists discovered that the MLL2 gene was responsible for Kabuki syndrome: 7 out of 10 individuals in the group suffered from a loss of function in that gene (7). Since then, with the Matchmaker Exchange (MME) and the Monarch Initiative, there has been an emphasis on sharing phenotype and genotype data in order to discover new Mendelian disorders (7).

Although complex diseases are influenced by several factors and do not fully follow the inheritance patterns (8), investigating Mendelian disorders can provide insight into the implicated genes and pathways in them. By analyzing data from established databases, genetic researchers found that in fact 54% of Mendelian disease genes play a notable role in complex diseases as well (9). Genes underlying both diseases tend to be associated with more phenotypes and protein interactions, so studying them can be quite useful in understanding Mendelian disorders and consequently complex diseases (9). In some cases, individuals diagnosed with complex diseases have an underlying monogenic condition that is the cause (10). This specifically highlights the significance of research techniques for single-gene disorders to investigations of complex diseases. In the case of hypercholesterolemia, for example, monogenic forms of the disease were used to determine the impact of lipid transport and to identify the involved pathways in the development of this complex disease (10).

Research on Mendelian disorders has helped scientists understand gene function and mechanisms overall. Studying single-gene disorders can further provide insight into the genetic pathways of complex diseases (9). In fact, with genome-wide association studies (GWAS) into single nucleotide polymorphisms (SNP), thousands of genes implicated in complex diseases have been identified (9). Although many details of complex diseases have been established, heritable aspects still remain uncertain (9). Overall, knowledge of Mendel’s principles and Mendelian disorders will be essential in this case and others as research delves further into disease processes.

• Chial, Heidi. “Mendelian Genetics: Patterns of Inheritance and Single-Gene Disorders.” Edited by Terry McGuire. Nature Education, 2008, www.nature.com/scitable/topicpage/mendelian-genetics-patterns-of-inheritance-and-single-966/.
• Miko, Ilona. “Gregor Mendel and the Principles of Inheritance.” Edited by Terry McGuire. Nature Education, 2008, www.nature.com/scitable/topicpage/gregor-mendel-and-the-principles-of-inheritance-593/.
• Ganguly, Prabarna. “NIH funds new effort to discover genetic causes of single-gene disorders.” National Human Genome Research Institute, 15 July 2021, www.genome.gov/news/news-release/NIH-funds-new-effort-to-discover-genetic-causes-of-single-gene-disorders.
• “Carrier.” National Human Genome Institute, www.genome.gov/genetics-glossary/Carrier.
• “If a genetic disorder runs in my family, what are the chances that my children will have the condition?” MedlinePlus, medlineplus.gov/genetics/understanding/inheritance/riskassessment/.
• Nickle, Todd, and Isabelle Barrette-Ng. “3.5: Sex-Linkage- An Exception to Mendel’s First Law.” Biology LibreTexts, 3 Jan. 2021, bio.libretexts.org/Bookshelves/Genetics/Book%3A_Online_Open_Genetics_(Nickle_and_Barrette-Ng)/03%3A_Genetic_Analysis_of_Single_Genes/3.05%3A__Sex-Linkage-_An_Exception_to_Mendels_First_Law.
• Seaby, Eleanor G., et al. “Strategies to Uplift Novel Mendelian Gene Discovery for Improved Clinical Outcomes.” Frontiers in Genetics, 17 June 2021, www.frontiersin.org/articles/10.3389/fgene.2021.674295/full.
• Craig, Johanna. “Complex Diseases: Research and Applications.” Edited by Alexandre Vieira. Nature Education, 2008, www.nature.com/scitable/topicpage/complex-diseases-research-and-applications-748/.
• Jin, Wenfei, et al. “A systematic characterization of genes underlying both complex and Mendelian diseases.” Human Molecular Genetics, vol. 21, no. 7, 20 Dec. 2011, academic.oup.com/hmg/article/21/7/1611/2900796.
• Chong, Jessica X., et al. “The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities.” Science Direct, www.sciencedirect.com/science/article/pii/S0002929715002451.

  Sharanya Ravishanker Conestoga High School Berwyn, Pennsylvania Teacher: Mrs. Liz Gallo

Through his genetic experimentations with pea plants, Gregor Mendel established the following Laws of Inheritance that remain critical to our understanding of heredity: The Law of Segregation, The Law of Independent Assortment, and The Law of Dominance (1, 2). In summation, phenotypes—expressed characteristics—are correlated with the type of allele inherited from each parent during gamete formation when genes randomly separate. If an allele is dominant, it is expressed; if an allele is recessive, the associated characteristic will not be displayed unless a matching recessive allele is inherited from the other parent.

These laws and inheritance patterns form the basis of our understanding of Mendelian disorders, rare monogenic diseases caused by alterations—often single-nucleotide polymorphisms (SNPs) and corresponding amino-acid substitutions resulting in the production of unwanted or malfunctioning proteins—in just one of the 25,000 genes in a human genome (3, 4, 5). These mutations typically occur in germline cells, and are thus passed down through DNA to every cell of the offspring (6). Well known Mendelian diseases include cystic fibrosis, sickle cell anemia, and Huntington’s disease.

Through the application of Mendel’s Laws, geneticists have identified five modes of inheritance for Mendelian disorders: autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, and mitochondrial (7), paving the way for geneticists to accurately diagnose Mendelian disorders, a step crucial in providing patients with the treatment and specific care they require, as well as revealing significant information vital to the family planning of individuals who carry recessive alleles for threatening disorders. Genealogical records and pedigree analyses have been utilized to trace inheritance through families, but next-generation sequencing technology has gained traction as a method to detect changes in nucleotide orders. Exome-sequencing, for example, focuses on identifying variants in the protein-coding region (exons), and is regarded as cost-effective due to its specificity, focusing on only 1% of the human genome (8, 9, 10). On the other hand, whole genome sequencing can be advocated for due to its capture of DNA variations outside of exons as well as within. Still, as benign polymorphisms are highly prevalent and frequent, entire genome sequencing can make it difficult to prioritize harmful mutations due to the sheer amount of variants shown (9, 11). RNA sequencing can provide support here by quantifying the effect to which a gene is expressed (11, 12 ).

Information gathered from these methods and Mendelian principles regarding dominance also enable geneticists to determine trait-associated gene loci, allowing for a better understanding of protein formation, modification, and function (13). In fact, as Rockefeller University president and accomplished biochemist Dr. Richard Lifton notes, understanding the connection between genes and expressed traits—SNP and product—has served as “starting points for understanding disease and human biology in general”. For example, analysis of a Mendelian form of hypertension resulted in the discovery of a pathway regulating salt reabsorption and potassium secretion in the kidney (14). Similar discoveries of pathways as a result of studies into Mendelian disorders can increase our understanding and ability to treat complex disorders such as cancer, even if these diseases disregard Mendelian principles of inheritance on account of being caused by numerous genetic and environmental factors interacting with one another.

In the same vein, understanding the results of SNP modification allows for research into the genetic susceptibility for various complex disorders and its correlation with environmental exposure. For example, it was determined that individuals whose genotype is homozygous recessive for xeroderma pigmentosum are highly susceptible to UV light related disorders due to mutations in DNA-repairing genes. Similarly, individuals with a mutation in the Alpha-1 gene are at a greater risk for emphysema, especially through smoking, though the mutation itself isn’t causative of the disease (15). The aforementioned linkages between genes and phenotypes would not be possible without the research into Mendelian disorders that revealed crucial information regarding the impacts of individual genes on expressed phenotypes.

Overall, studies into Mendelian diseases—in turn impacted by the understanding of Mendel’s Laws of Inheritance—have contributed significantly to our knowledge of more complex disorders. This knowledge will prove beneficial in developing more efficient medicinal drugs and therapies that effectively target detrimental proteins or alter gene expression to receive desired results (16). As Dr. James Luspki, Professor of Molecular and Human Genetics at Baylor College of Medicine says, “We’re on the threshold of new explanations of disease inheritance and development” (14). Resulting discoveries from studies into Mendelian principles and disorders will undoubtedly clear the way towards greater advancements in our ability to treat complex disorders.

References/Citations: Mendel’s Law of Segregation. 15 Aug. 2020, https://bio.libretexts.org/@go/page/13271. “Inheritance of Traits by Offspring Follows Predictable Rules.” Nature. Scitable by Nature Education, www.nature.com/scitable/topicpage/inheritance-of-traits-by-offspring-follows-predictable-6524925/#:~:text=One%20allele%20for%20every%20gene,same%22)%20for%20that%20allele. Accessed 22 Feb. 2022. Jackson, Maria et al. “The genetic basis of disease.” Essays in biochemistry vol. 62,5 643-723. 2 Dec. 2018, doi:10.1042/EBC20170053 Coding single-nucleotide polymorphisms associated with complex vs. Mendelian disease: Evolutionary evidence for differences in molecular effects. Paul D. Thomas, Anish Kejariwal. Proceedings of the National Academy of Sciences Oct 2004, 101 (43) 15398-15403; DOI: 10.1073/pnas.0404380101 The 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature 526, 68–74 (2015). https://doi.org/10.1038/nature15393 “Germline Mutation.” National Cancer Institute, www.cancer.gov/publications/ dictionaries/cancer-terms/def/germline-mutation. Accessed 22 Feb. 2022. Genetic Alliance; District of Columbia Department of Health. Understanding Genetics: A District of Columbia Guide for Patients and Health Professionals. Washington (DC): Genetic Alliance; 2010 Feb 17. Appendix B, Classic Mendelian Genetics (Patterns of Inheritance) Available from: https://www.ncbi.nlm.nih.gov/books/NBK132145/ “Exome Sequencing.” Science Direct, 2018, www.sciencedirect.com/topics/ agricultural-and-biological-sciences/exome-sequencing. Accessed 22 Feb. 2022. “What are whole exome sequencing and whole genome sequencing?” MedlinePlus, 28. July 2021, medlineplus.gov/genetics/understanding/testing/sequencing/. Accessed 22 Feb. 2022. Bamshad, M., Ng, S., Bigham, A. et al. Exome sequencing as a tool for Mendelian disease gene discovery. Nat Rev Genet 12, 745–755 (2011). https://doi.org/10.1038/nrg3031 Byron, S., Van Keuren-Jensen, K., Engelthaler, D. et al. Translating RNA sequencing into clinical diagnostics: opportunities and challenges. Nat Rev Genet 17, 257–271 (2016). https://doi.org/10.1038/nrg.2016.10 Wang, Zhong et al. “RNA-Seq: a revolutionary tool for transcriptomics.” Nature reviews. Genetics vol. 10,1 (2009): 57-63. doi:10.1038/nrg2484 Chial, H. (2008) Rare Genetic Disorders: Learning About Genetic Disease Through Gene Mapping, SNPs, and Microarray Data. Nature Education 1(1):192 Benowitz, Steven. “Centers for Mendelian Genomics uncovering the genomic basis of hundreds of rare conditions.” National Human Genome Research Institute, 6 Aug. 2015, www.genome.gov/news/news-release/ Centers-for-Mendelian-Genomics-uncovering-the-genomic-basis-of-hundreds-of-rare-conditions. Accessed 22 Feb. 2022. Craig, J. (2008) Complex diseases: Research and applications. Nature Education 1(1):184 Heguy, A et al. “Gene expression as a target for new drug discovery.” Gene expression vol. 4,6 (1995): 337-44.

Zhiyuan Shi BASIS International School Hangzhou Hangzhou, China Teacher: Dr. Dongchen Xu

Mendelian theories provided the foundations for the contemporary understanding of heredity. Mendel’s legacy has been particularly beneficial to medical sciences, where research on inheritance patterns of Mendelian disorders has been made possible through utilizing Mendel’s theory. Mendelian theories serve as robust models for evaluating and verifying the inheritance patterns of particular diseases. Even though our current understanding of genetics has moved beyond the Mendelian model, studying certain Mendelian disorders such as oculocutaneous albinism can lead to an improved understanding of complex disorders with polygenic inheritance.

Oculocutaneous albinism is an autosomal-recessive condition caused by the extremely low level of melanin biosynthesis due to mainly four genes (1, 2). Individuals with this illness will also experience whitening of the skin, certain degrees of vision deterioration, and a higher risk of contracting skin cancer due to the lack of dermal melanin (1, 2); understanding the underlying inheritance pattern of albinism would be advantageous towards the prevention of skin cancers. The genetic cause of oculocutaneous albinism can be explained by Mendelian genetics. The disorder is autosomal, meaning neither the gender of the parents nor the gender of the offspring plays a role in its inheritance. The disorder is recessive, meaning both parents must be carriers for birthing an Albino child (3). Through examination of information like the ones above and specific pathology of the disorder, one can establish critical predictions of an offspring’s genotype based on the family’s history. Such analyses enable us to speculate and reconstruct pedigrees for Mendelian disorders using family history. Information regarding Mendelian disorders running in the family and the possible genotypes for offsprings (50% risk of being carriers and 25% risk of being affected) are important to parents seeking family planning suggestions, reinforcing prevention.

Mendelian and non-Mendelian diseases are often regarded as segregated families of genetic disorders. Complex non-Mendelian disorders involve polygenic traits that don’t follow Mendelian disorders’ monogenic properties. However, genes responsible for monogenic diseases correspondingly contribute to the expression of polygenic traits (4). Mendelian disorders are key in providing the individual monogenic components that contribute to complex disease’s polygenic causes. Some of the gene variants responsible for skin pigmentation disorder and skin cancer are the exact genes responsible for the pigment deficiency in the Mendelian disorder oculocutaneous albinism. The 2 most notable ones are variants of the gene TYRP1, a gene coding for the protein tyrosinase-related protein 1, which contributes to melanosome integrity; and gene SLC45A2, which code for a cation exchange protein that transports material required for melanin synthesis into the melanosome (2, 6, 7). Variants of these genes are inherited as monogenic traits, and studies show they contribute to the formation of polygenic skin cancers such as squamous skin cell carcinoma (8). Mendelian inheritance of other variants of the 2 listed genes can even cause other polygenic skin cancers such as melanoma, exhibiting excessive melanin levels. Research showed that heterozygous variants of TYRP1 and SLC45A2 are overrepresented in families with multiple cases of melanoma (9).

Although overrepresentation of SLC45A2 is found in cases of melanoma, variants of the gene can have the opposite effect. A meta-analysis conducted by Ibarrola-Villava et al., 2012, revealed that the SLC45A2 p.Phe374Leu variant had an odds ratio of 0.41 for melanoma (p = 3.50 * 10^-17), enough for concluding that SLC45A2 p.Phe374Leu negatively correlates with melanoma formation (13). This and the previous evidence suggest that factors affecting melanin concentration, one of the key determinants for the presence of different types of polygenic skin cancers, could be partially attributed to the variants of TYRPI and SLC45A2 genes that involve Mendelian inheritance mechanisms.

Another polygenic disorder with Mendelian roots is growth disorder, in which several genes that contribute to the complex disorder of growth disorders are monogenic. For instance, one factor contributing to the common short stature in growth disorders such as dwarfism is the autosomal dominant Mendelian disorder achondroplasia, resulting from the Mendelian inheritance of the mutated FGFR3 gene (10,11). Another monogenic disorder that contributes to growth disorders such as dwarfism is growth hormone deficiency, an autosomal recessive disorder resulting from the mutation and Mendelian inheritance of the mutated GH1 or GHRHR gene (12).

The Mendelian factors underlying both skin cancer and growth disorders demonstrated the value of studying Mendelian inheritance patterns in complex disorders. Although Mendelian diseases only contribute to a small proportion of all known human disorders, understanding their underlying mechanism and pattern, and utilizing them alongside conventional methods for the investigation of complex diseases is of great importance(5), and would produce spectacular innovations in the field of genetics.

• Marçon, C. R., & Maia, M. (2019). Albinism: Epidemiology, genetics, cutaneous characterization, psychosocial factors. Anais brasileiros de dermatologia. Retrieved March 1, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857599/
• Grønskov, K., Ek, J., & Brondum-Nielsen, K. (2007, November 2). Oculocutaneous albinism. Orphanet journal of rare diseases. Retrieved March 1, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211462/
• Gulani, A. (2021, May 8). Genetics, autosomal recessive. StatPearls [Internet]. Retrieved March 1, 2022, from https://www.ncbi.nlm.nih.gov/books/NBK546620/
• Franić, S., Groen-Blokhuis, M. M., Dolan, C. V., Kattenberg, M. V., Pool, R., Xiao, X., Scheet, P. A., Ehli, E. A., Davies, G. E., van der Sluis, S., Abdellaoui, A., Hansell, N. K., Martin, N. G., Hudziak, J. J., van Beijsterveldt, C. E. M., Swagerman, S. C., Hulshoff Pol, H. E., de Geus, E. J. C., Bartels, M., … Boomsma, D. I. (2015, October). Intelligence: Shared genetic basis between Mendelian disorders and a polygenic trait. European journal of human genetics : EJHG. Retrieved March 1, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592100/
• Lango Allen, H., Estrada, K., Lettre, G., Berndt, S. I., Weedon, M. N., Rivadeneira, F., Willer, C. J., Jackson, A. U., Vedantam, S., Raychaudhuri, S., Ferreira, T., Wood, A. R., Weyant, R. J., Segrè, A. V., Speliotes, E. K., Wheeler, E., Soranzo, N., Park, J.-H., Yang, J., … Hirschhorn, J. N. (2010, October 14). Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature. Retrieved March 1, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955183/
• Del Bino, S., Duval, C., & Bernerd, F. (2018, September 8). Clinical and biological characterization of skin pigmentation diversity and its consequences on UV impact. International journal of molecular sciences. Retrieved March 1, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163216/
• Federico, J. R. (2021, August 27). Albinism. StatPearls [Internet]. Retrieved March 1, 2022, from https://www.ncbi.nlm.nih.gov/books/NBK519018/
• Board, P. D. Q. C. G. E. (2009, July 29). Genetics of Skin Cancer (PDQ®). PDQ Cancer Information Summaries [Internet]. Retrieved March 1, 2022, from https://www.ncbi.nlm.nih.gov/books/NBK65895/
• Nathan, V., Johansson, P. A., Palmer, J. M., Howlie, M., Hamilton, H. R., Wadt, K., Jönsson, G., Brooks, K. M., Pritchard, A. L., & Hayward, N. K. (2019). Germline variants in oculocutaneous albinism genes and predisposition to familial cutaneous melanoma. Pigment Cell & Melanoma Research, 32(6), 854–863. https://doi.org/10.1111/pcmr.12804
• Krakow, D., & Rimoin, D. L. (2010, April 27). The skeletal dysplasias. Nature News. Retrieved March 1, 2022, from https://www.nature.com/articles/gim201054
• U.S. National Library of Medicine. (2020, August 18). Achondroplasia: Medlineplus genetics. MedlinePlus. Retrieved March 1, 2022, from https://medlineplus.gov/genetics/condition/achondroplasia/#inheritance
• U.S. National Library of Medicine. (2020, August 18). Isolated growth hormone deficiency: Medlineplus Genetics. MedlinePlus. Retrieved March 1, 2022, from https://medlineplus.gov/genetics/condition/isolated-growth-hormone-deficiency/
• Ibarrola-Villava, M., Hu, H.-H., Guedj, M., Fernandez, L. P., Descamps, V., Basset-Seguin, N., Bagot, M., Benssussan, A., Saiag, P., Fargnoli, M. C., Peris, K., Aviles, J. A., Lluch, A., Ribas, G., & Soufir, N. (2012). MC1R, SLC45A2 and Tyr genetic variants involved in melanoma susceptibility in southern European populations: Results from a meta-analysis. European Journal of Cancer, 48(14), 2183–2191. https://doi.org/10.1016/j.ejca.2012.03.006

Audric Thakur Reading School Reading, United Kingdom Teacher: Ms. Francis Howson

Mendel’s research intended to determine how characteristics of an individual were inherited by their offspring. At the time, the scientific community lacked the genotypic knowledge required to explain how genetic information was transferred to an individual¹. Only in 1826 did Augustin Sageret discover the idea of trait dominance³ (amid a cultural resurgence of Preformation Theory²), and so it was through observational study that Mendel developed the laws of heredity which ground our understanding of Mendelian disorders today.

Most famous of Mendel’s work are those regarding the rugosus locus and the presence or absence of the SBE1 gene⁴, phenotypically expressed by the distinctive ’round’ or ‘wrinkled’ shapes of pea pods respectively⁵. Specifically, he determined the recessive nature of the wrinkled trait through his monohybrid crossing of a uniformly heterozygous generation of pea plants (which themselves were the progeny of a homozygous-dominant and homozygous-recessive cross)⁵. Naturally, this uniform generation of heterozygous peas all possessed the round characteristic. However, Mendel proved that these peas retained their parents’ ‘elementen’⁵ (or more accurately, DNA), since they went on to produce offspring with characteristics from the grandparent generation, evidenced by the 3:1 ratio of round to wrinkled offspring – clear to us now through use of a Punnett square⁶. Of course, these results were the aggregate of a large sample size across several iterations⁵, and therefore incredibly precise (to the point of controversy⁷). As such, they formed the basis for his laws of heredity.

Deriving Mendel’s laws from his work on pea plants is critical to understanding monogenic conditions because their inheritance patterns are often identical⁸, enabling us to make accurate comparisons between the two. This is demonstrated by the Mendelian condition phenylketonuria (PKU)⁹-¹⁰, an autosomal recessive disorder caused by an absent PAH gene at the genetic locus 12q23.2¹⁰.

Citing national Newborn Screening Reports¹¹, 1.7606% of Caucasian-Americans (1996-2000) are heterozygous carriers of PKU. If I apply some simplified mathematics (i.e. ignoring lifestyle factors), the probability of both parents in a Caucasian-American household being carriers of PKU is 0.0310% (0.017606²). Therefore, as per the rules of inheritance followed by Mendel’s pea plants, 0.0077% (0.0310*0.25) of the Caucasian-American population should be expressors of PKU. According to the National Library of Medicine¹¹, the official estimate is 0.0075% – a remarkable example of the accuracy and utility of Mendel’s work, and how understanding and implementing his discoveries has relevant real-world significance, being comparable to large-scale medical statistics to this day.

Unfortunately, it must be noted that Mendelian disorders are an exceptional minority of genetic conditions – the emerging consensus that most exist on a spectrum from Mendelian conditions¹² (high gene penetrance and low gene-environment interaction¹³) to increasingly complex conditions (incomplete or varying gene penetrance and high gene-environment interaction¹³), and that complex disorders are influenced by a multitude of interconnected factors¹⁴. This is why scientists approach complex disorders by assessing risk of onset, rather than applying Mendelian rules of inheritance. Nevertheless, links between the genotypic expression of Mendelian conditions in an individual and the onset of associated complex disorders have been established in the last decade or so of scientific inquiry¹³.

Studies regarding Mendelian comorbidities alongside complex disorders have proved that genetic loci containing causal variants for both Mendelian disorders and complex disease tend to have a greater influence on the onset of a complex disorder compared to genes that pertain to risk factors for only that complex disorder¹³. This means, for an individual afflicted by a series of Mendelian disorders, the probability that they will develop a complex disorder whose determinant genes are simultaneously involved in expressing those Mendelian disorders is significantly higher¹³. For example, an increased risk of schizophrenia is involved with patients who carry genetic variants of Lujan-Fryns and velo-cardio-facial syndromes¹⁷ (clear correlation), and a higher likelihood of developing type-2 diabetes mellitus if the patient suffers from Huntington’s disease, Friedreich’s ataxia and beta-thalassemia¹⁵-¹⁶ (partially supported correlation). This demonstrates that Mendelian-associated genes are certainly influential in determining emergence of a complex disorder. Therefore, understanding inheritance patterns of these Mendelian conditions is essential to create an accurate way of ascertaining the risk of onset for more complex conditions.

Despite the elusive nature of inheritance patterns surrounding several complex disorders, insight can nevertheless be found in studying genes associated with Mendelian conditions. Due to their high penetrance and straightforward inheritance patterns¹³, these monogenic conditions are easy to diagnose and engage in research with, providing a unique foothold to better understand many complex conditions, and allowing us to form more realistic models to predict their onset¹⁸.

Note: citations from sources published prior to 2015 have been used for historical knowledge or to explain/discuss historical scientific experiments only. The exception to this is reference 15.

• Durmaz, A. A., Karaca, E., Demkow, U., Toruner, G., Schoumans, J., & Cogulu, O. (2015). Evolution of genetic techniques: Past, present, and beyond. BioMed research international. Retrieved February 28, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385642/
• Maienschein, J. (2005, October 11). Epigenesis and Preformationism. Stanford Encyclopedia of Philosophy. Retrieved February 28, 2022, from https://plato.stanford.edu/entries/epigenesis/#8
• Zirkle, C. (1951, June). Gregor Mendel & his Precursors. Retrieved February 28, 2022, from https://www.mun.ca/biology/scarr/Zirkle_%281951%29_Gregor_Mendel_&_his_Precursors,%20Isis_42,97-104.pdf
• Smith, A., & Martin, C. (2020, December 11). A history of wrinkled-seeded research in PEA. John Innes Centre. Retrieved February 28, 2022, from https://www.jic.ac.uk/advances/a-history-of-wrinkled-seeded-research-in-pea/
• Miko, I. (2008). Gregor Mendel and the Principles of Inheritance. Nature news. Retrieved February 28, 2022, from https://www.nature.com/scitable/topicpage/gregor-mendel-and-the-principles-of-inheritance-593/
• (while the citation doesn’t reference the SBE1 gene in particular, it does discuss other recessive pea plant traits, making it useful nevertheless) LibreTexts, O. S. (2021, September 22). 8.2: Laws of inheritance. Biology LibreTexts. Retrieved February 28, 2022, from https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_Concepts_in_Biology_(OpenStax)/08%3A_Patterns_of_Inheritance/8.02%3A_Laws_of_Inheritace
• Radlick, G. (2015, October 9). Beyond mendelfisher – eprints.whiterose.ac.uk. Beyond the “Mendel-Fisher controversy”. Retrieved February 28, 2022, from https://eprints.whiterose.ac.uk/91201/2/BeyondMendelFisher091015%5B1%5D.pdf
• Chial, H. (2008). Mendelian Genetics: Patterns of Inheritance and Single-Gene Disorders. Nature news. Retrieved February 28, 2022, from https://www.nature.com/scitable/topicpage/mendelian-genetics-patterns-of-inheritance-and-single-966/
• NHS. (2019, December 3). Phenylketonuria. NHS choices. Retrieved February 28, 2022, from https://www.nhs.uk/conditions/phenylketonuria/
• Hillert, A., Anikster, Y., Belanger-Quintana, A., Burlina, A., Burton, B. K., Carducci, C., Chiesa, A. E., Christodoulou, J., Đorđević, M., Desviat, L. R., Eliyahu, A., Evers, R. A. F., Fajkusova, L., Feillet, F., Bonfim-Freitas, P. E., Giżewska, M., Gundorova, P., Karall, D., & Blau, N. (2020, July 14). The genetic landscape and epidemiology of phenylketonuria. The American Journal of Human Genetics. Retrieved February 28, 2022, from https://www.sciencedirect.com/science/article/pii/S0002929720301944
• Arbesman, J., Ravichandran, S., Funchain, P., & Thompson, C. L. (2018, July 1). Melanoma cases demonstrate increased carrier frequency of phenylketonuria/hyperphenylalanemia mutations. Pigment cell & melanoma research. Retrieved February 28, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013363/
• 12.Freund, M. K., Burch, K. S., Shi, H., Mancuso, N., Kichaev, G., Garske, K. M., Pan, D. Z., Miao, Z., Mohlke, K. L., Laakso, M., Pajukanta, P., Pasaniuc, B., & Arboleda, V. A. (2018, October 4). Phenotype-specific enrichment of mendelian disorder genes near gwas regions across 62 complex traits. The American Journal of Human Genetics. Retrieved February 28, 2022, from https://www.sciencedirect.com/science/article/pii/S0002929718302854
• Spataro, N., Rodríguez, J. A., Navarro, A., & Bosch, E. (2017, February 1). Properties of human disease genes and the role of genes linked to mendelian disorders in complex disease aetiology. Human molecular genetics. Retrieved February 28, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409085/
• Yong, S. Y., Raben, T. G., Lello, L., & Hsu, S. D. H. (2020, July 21). Genetic architecture of complex traits and disease risk predictors. Nature News. Retrieved February 28, 2022, from https://www.nature.com/articles/s41598-020-68881-8
• Blair, D. R., Lyttle, C., Mortensen, J., Bearden, C., Jensen, A., Khiabanian, H., Melamed, R., Rabadan, R., Bernsdam, E., Brunak, S., Jensen, L., Nicolae, D., Shah, N., Grossman, R., Cox, N., White, K., & Rzhetsky, A. (2013, September 26). A Nondegenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk. Define_me. Retrieved February 28, 2022, from https://www.cell.com/fulltext/S0092-8674(13)01024-6
• (not disproving, but cautioning the results of 15) Montojo, M. T., Aganzo, M., & González, N. (2017, September 29). Huntington’s disease and diabetes: Chronological sequence of its association. Journal of Huntington’s disease. Retrieved February 28, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676851/
• Rizvi, S., Khan, A. M., Saeed, H., Aribara, A. M., Carrington, A., Griffiths, A., & Mohit, A. (2018, August 14). Schizophrenia in digeorge syndrome: A unique case report. Cureus. Retrieved February 28, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188160/
• Jordan, D., & Do, R. (2018, April 11). Using full genomic information to predict disease: Breaking down the barriers between complex and Mendelian Diseases. Annual Reviews. Retrieved February 28, 2022, from https://www.annualreviews.org/doi/10.1146/annurev-genom-083117-021136

Emma Tse Cheltenham Ladies’ College Cheltenham, United Kingdom Teacher: Ms. Helen Stuart

Between 1856 and 1865, Gregor Mendel conducted experiments on garden peas to investigate inheritance (1). His observations, notably his three principles of inheritance, form the basis of scientists’ grasp of monogenic (Mendelian) disorders today, which are caused by mutations in a single gene (2). Before Mendel’s discoveries, it was widely accepted that traits of progeny were a combination of those of each parent. However, when he cross-pollinated smooth-seeded peas with wrinkled-seeded peas, the offspring (F1 generation) only had smooth seeds as opposed to semi-wrinkled seeds. This gave rise to the concept of dominant traits, as well as his first principle: the principle of uniformity, which states that all offspring of parents with two distinct traits will inherit the same (dominant) trait of one parent (3). Mendel discovered recessive traits by self-pollinating a plant from the F1 generation, noting that its offspring (F2 generation) displayed a 3:1 ratio of smooth to wrinkled seeds (3). This proportion indicated that there was a hidden form of the trait, which Mendel acknowledged passed down to the F2 generation. Mendel also proposed the idea of each parent giving their offspring one heritable unit which he called “elementen”, and scientists now recognise this as genes – more specifically, alleles (2). Sickle-cell anaemia is a well-characterised autosomal recessive disease; those affected inherit two copies of a mutant beta-globin gene (1). Huntington’s disease, on the other hand, is an autosomal dominant disorder in which affected individuals possess at least one copy of the mutant HTT gene (1).

Mendelian disorders are relatively uncommon; on the other hand, complex diseases such as asthma and multiple sclerosis are more prevalent and arise from a combination of genetic, environmental and lifestyle factors (4). Therefore, complex diseases do not entirely adhere to Mendelian inheritance. They can be oligogenic or polygenic, meaning there are multiple genes each with their own mutations contributing to the disease’s phenotype (5). Studying Mendelian disorders allows researchers to examine the mutant gene’s effects on human biochemistry and physiology, thus furthering our understanding of the aetiology of complex, multifactorial diseases (4). An example is obesity, an increasingly pressing medical issue in developed countries. In congenital leptin disorder, a rare disease exhibiting an autosomal recessive inheritance pattern, severe obesity is a typical clinical feature. Affected individuals are unable to produce leptin because of mutations in the leptin encoding gene. Leptin acts on the hypothalamus to halt the production of neuropeptide Y, a neurotransmitter responsible for stimulating food, specifically carbohydrate, intake (6). Thus, studying congenital leptin disorder and other related Mendelian obesity disorders has helped scientists gain deeper insight into the complexity of the underlying causes behind obesity, one of which is the effects of leptin on the human body.

Another example is Van der Woude syndrome, an autosomal dominant condition caused by mutations in the IRF6 gene. It is characterised by a cleft lip and palate, hypodontia and lower lip pits (7). Interestingly, IRF6 mutations were also shown to be associated with non-syndromic isolated cleft lips and palates, which are complex traits and more prevalent in the general population than Van der Woude syndrome (8). This illustrates how the same defective gene could be responsible for rare inherited diseases and common medical conditions simultaneously. In essence, this shows Mendelian disorders and complex diseases that share overlapping phenotypes could be caused by the same sets of genetic aberrations (4).

Furthermore, systematic analyses using statistical methodologies have demonstrated that certain Mendelian disorders and complex diseases share a common genetic foundation. A study examining patients with concomitant Mendelian disorders and cancer revealed genetic connections between the two (9). The researchers’ initial hypothesis was that genetic mutations responsible for certain Mendelian disorders may predispose to the development of cancer. They found that genes associated with melanoma (MC1R and TYR), for instance, are also mutated in patients with oculocutaneous albinism, a Mendelian recessive disorder in which patients lack pigment in their skin, hair or eyes (10). Identifying cancer-driving genes that are found in Mendelian disorders enables scientists to understand the genetic basis of cancer development as well as various clinical presentations in cancer patients.

Although Mendel’s legacy has undoubtedly shaped our present understanding of inheritance, his discoveries alone cannot fully encapsulate the science behind complex diseases. The study of Mendelian disorders has given scientists a strong grounding for further research using advanced technologies such as whole genome sequencing and genome-wide association studies (11, 12), enhancing our knowledge of the genetic mechanisms and pathogenesis underlying polygenic diseases which would have been impossible in the 19th century.

• Molnar, Charles. Concepts Of Biology – 1st Canadian Edition. 1st ed., 2019, pp. Chapter 8.1.
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• Miko, Ilona. “Gregor Mendel And The Principles Of Inheritance”. Scitable By Nature Education, 2008, https://p75fz1.nbcnews.top/scitable/topicpage/gregor-mendel-and-the-principles-of-inheritance-593.
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• Collins, Samuel et al. The Genetics Of Allergic Disease And Asthma. 4th ed., Elsevier, 2016, pp. 18-30, https://www.sciencedirect.com/science/article/pii/B9780323298759000033, Accessed 25 Feb 2022.
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• Chial, Heidi. “Human Genetic Disorders: Studying Single-Gene (Mendelian) Diseases | Learn Science At Scitable”. Nature.Com, 2008, https://www.nature.com/scitable/topicpage/rare-genetic-disorders-learning-about-genetic-disease-979/.
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• “Oculocutaneous Albinism – NORD (National Organization For Rare Disorders)”. NORD (National Organization For Rare Disorders), https://rarediseases.org/rare-diseases/oculocutaneous-albinism/.
•  “Genome-Wide Association Studies Fact Sheet”. National Human Genome Research Institute, 2020, https://www.genome.gov/about-genomics/fact-sheets/Genome-Wide-Association-Studies-Fact-Sheet.
•  Benowitz, Steven. “Centers For Mendelian Genomics Uncovering The Genomic Basis Of Hundreds Of Rare Conditions”. National Human Genome Research Institute, 2015, https://www.genome.gov/news/news-release/Centers-for-Mendelian-Genomics-uncovering-the-genomic-basis-of-hundreds-of-rare-conditions.

  Hannah Wilson Raphael House Rudolf Steiner School Lower Hutt, New Zealand Teacher: Ms. Sarah McKenzie

From his study of pea plants, Gregor Mendel developed three fundamental principles of inheritance: the principle of uniformity, the principle of segregation, and the principle of independent assortment (1). All monogenic traits follow these principles and are thus called Mendelian traits (1,2). Therefore, Mendel’s principles can be used to study Mendelian diseases, notably through pedigree analysis (1,2). The study of Mendelian diseases can in turn provide valuable insight into complex (non-Mendelian) diseases due to genetic correlations between Mendelian and complex diseases (3-6).

Mendel’s principles enable us to both decipher the past inheritance and predict the future inheritance of Mendelian diseases through pedigree analysis. Pedigree charts are diagrams based on Mendel’s principles that visually represent a family’s inheritance history of a Mendelian trait (1,2). Analysis of pedigree charts reveals whether the allele responsible is dominant or recessive, autosomal or sex-linked, due to the specific inheritance pattern exhibited by each allele type (2). Autosomal recessive diseases such as phenylketonuria (PKU) and sickle cell anemia can skip generations because two heterozygous (carrier) parents can give rise to progeny with either the affected or wild-type phenotype (2). Autosomal dominant diseases never skip generations unless random mutation occurs (2). Conversely, sex-linked Mendelian diseases display unique inheritance patterns depending on whether the disease is X-linked or Y-linked, dominant or recessive (2).

Pedigree analysis is applied in genetic counselling (7). Genetic counsellors presented with the family history of two individuals can predict the probability of each possible genotype and phenotype occurring in future offspring (7). These probabilities equip individuals with the information they need to make an informed reproductive decision. Furthermore, the simplicity of Mendel’s principles makes them accessible to the general public, better enabling individuals to understand the nature of their or their loved one’s disease. Nowadays, fetuses can be screened for common genetic defects during pregnancy, however, pedigree analysis maintains its value in that it can provide preliminary information before conception (8).

Although Mendel’s principles form the foundation of inheritance, most human diseases are complex, meaning they violate Mendel’s principles of inheritance (3). Examples of complex diseases include schizophrenia, hypertension, multiple sclerosis, and Alzheimer’s disease (3). Complex diseases are polygenic, meaning they are influenced by multiple genes, and are subject to environmental influence (3). Some also exhibit pleiotropy and epistatic interactions (9,10). Thus, unlike Mendelian diseases, complex diseases lack distinct inheritance patterns (3,4). This poses a challenge to geneticists when attempting to predict an individual’s risk of developing a complex disease.

In addition, there is now evidence that Mendelian and complex diseases are more interconnected than scientists formerly believed (11). For example, cystic fibrosis, typically categorized as an autosomal recessive Mendelian disease, is now believed to involve multiple loci (5,6). A mutation in the CTFR gene, which codes for a membrane channel protein for chlorine ions, forms the primary genetic basis for cystic fibrosis (6,12). However, variation in the severity of cystic fibrosis has been linked to potential modifier genes separate from the CTFR gene (5,6). As eukaryotic gene expression involves transcription factors as well as the structural gene(s) underlying a trait, it is highly likely that other Mendelian diseases also have complex aspects (13).

The study of Mendelian diseases can directly inform the study of complex diseases when a Mendelian disease acts as a model for a complex disease. Such is the case for Van der Woude syndrome, a rare autosomal dominant Mendelian disorder caused by mutations in the IRF6 gene (3,14). Symptoms of Van der Woude syndrome include cleft lip, a birth defect where the tissue in the lip does not join up completely before birth (3,14). Statistical studies provide evidence that one of the genes responsible for isolated cleft lip, a complex disorder, is IRF6, the same gene underlying Van der Woude syndrome (3). The discovery of links between other phenotypically similar Mendelian and complex diseases would be highly beneficial when considering that complex diseases are simultaneously challenging to study in isolation and highly prevalent in the general population (3,4).

Mendel’s abstract but fundamental principles of inheritance have paved the way for modern genetics. These principles directly enable both scientists and the general public to comprehend the inheritance of Mendelian diseases (1). The study of Mendelian diseases can also inform our understanding of complex diseases, especially in cases where a complex disease shares an element of its genetic basis with a Mendelian disease (ref). Therefore, despite their rarity, humankind as a whole is certain to benefit from the continued study of Mendelian diseases.

• Miko, I. (2008). Gregor Mendel and the Principles of Inheritance. Nature Education. https://www.nature.com/scitable/topicpage/gregor-mendel-and-the-principles-of-inheritance-593/
• Chial, H. (2008). Mendelian Genetics: Patterns of Inheritance and Single-Gene Disorders. Nature Education. https://www.nature.com/scitable/topicpage/mendelian-genetics-patterns-of-inheritance-and-single-966/
• Craig, J. (2008). Complex Diseases: Research and Applications. Nature Education. https://www.nature.com/scitable/topicpage/complex-diseases-research-and-applications-748/
• MedlinePlus. (2021, May 14). What are complex or multifactorial disorders? https://medlineplus.gov/genetics/understanding/mutationsanddisorders/complexdisorders
• O’Neal, W. K., & Knowles, M. R. (2018). Cystic Fibrosis Disease Modifiers: Complex Genetics Defines the Phenotypic Diversity in a Monogenic Disease. Annual review of genomics and human genetics, 19, 201–222. https://doi.org/10.1146/annurev-genom-083117-021329
• Buschman, H. (2019, December 10). Modifier Gene May Explain Why Some with Cystic Fibrosis are Less Prone to Infection. UC San Diego Health. https://health.ucsd.edu/news/releases/Pages/2019-12-10-modifier-gene-may-explain-why-some-with-cystic-fibrosis-less-prone-to-infection.aspx
• NBIAcure. (2014). Genetic Counselling. http://nbiacure.org/learn/genetic-counseling/
• MedlinePlus. (2021, September 29). Prenatal Testing. https://medlineplus.gov/prenataltesting.html
• Nagel R. L. (2005). Epistasis and the genetics of human diseases. Comptes rendus biologies, 328(7), 606–615. https://doi.org/10.1016/j.crvi.2005.05.003
• Gratten, J. & Visscher, P.M. (2016). Genetic pleiotropy in complex traits and diseases: implications for genomic medicine. Genome Med 8, 78. https://doi.org/10.1186/s13073-016-0332-x
• Jin, W et al. (2012, April 1). A systematic characterization of genes underlying both complex and Mendelian diseases. Human Molecular Genetics, Volume 21, Issue 7, Pages 1611–1624. https://doi.org/10.1093/hmg/ddr599
• MedlinePlus. (2021, July 6). Cystic Fibrosis. https://medlineplus.gov/genetics/condition/cystic-fibrosis/#causes
• Urry, Meyers, N., Cain, M. L., Wasserman, S. A., Minorsky, P. V., & Reece, J. B. (2018). Campbell Biology: Australian and New Zealand Version (11th edition. Australian and New Zealand version.). Pearson Australia.
• Children’s Hospital of Philadelphia. (2022). Van der Woude Syndrome. https://www.chop.edu/conditions-diseases/van-der-woude-syndrome

Emma Youngblood St. John Paul the Great Catholic High School Dumfries, Virginia Teacher: Dr. Clare Kuisell

“I am convinced that it will not be long before the whole world acknowledges the results of my work.” Gregor Mendel published the results of his pea plant experiments in 1865, but it wasn’t until the 1900s that people began to rediscover his work, and even then, it was controversial (Williams & Rudge, 2015). Now, nearly 200 years later, he is known as the father of the science of genetics, and students throughout the world learn about the laws of segregation and independent assortment which originated from Mendel’s observations. Mendel’s discoveries allow us to understand Mendelian disorders because they have been used to identify patterns of inheritance, which can be applied to genes that are known to have influence in complex diseases.

Single gene diseases are often referred to as Mendelian diseases–or disorders–and may be inherited in one of several patterns (Genetic Alliance, 2010). An example of such a disease is Marfan syndrome. With an incidence of approximately 1 in 5000 individuals, Marfan syndrome is an autosomal dominant disease that affects the body’s connective tissue (Coelho & Almeida, 2020). Using Mendel’s law of dominance and uniformity, which differentiates dominant and recessive alleles (Lewis & Simpson, 2021), one can predict the inheritance pattern of Marfan syndrome using the same calculations and ratios Mendel discovered in his pea plants. Because the mutated allele of the gene is dominant, a child who inherits Marfan syndrome must have a parent who also has it. This also means that Marfan syndrome, like other autosomal dominant diseases, would occur in every generation until the dominant allele is not inherited from either the mother or the father. Mendel’s work has allowed the identification of different types of inheritance patterns of single gene disorders to be very simple.

Complex diseases, while much less predictable than Mendelian disorders, are still influenced by genetics. Almost all complex diseases are affected by multiple genes and environmental factors, and examples include heart disease, cancer, and diabetes (National Human Genome Research Institute, 2013). Another well-known complex disease is Alzheimer’s Diseases (AD). Approximately 44 million people currently live with AD, and that number is expected to triple by 2050 (Lane et al., 2018). Aside from age, one of the highest risk factors for AD is the presence of the ε4 allele of the gene that codes for apolipoprotein E, also called ApoE (Yin & Wang, 2018). Recent studies have also shown that two of the most reliable biomarkers for AD are Aβ protein deposits and phosphorylated tau proteins (Mantzavinos & Alexiou, 2017). By studying the genes that code for these proteins and the gene that codes for, scientists may be able to identify a better way to treat or even cure AD. The multiple factors that affect complex diseases make it nearly impossible to determine exact patterns of inheritance, but if single genes that influence them can be isolated, the same patterns used to predict inheritance patterns in Mendelian disorders can be used to predict a high or low likelihood of developing or inheriting a complex disease.

Mendel’s discoveries have been essential in determining the inheritance patterns of Mendelian disorders, which can also be used to form a more accurate prediction of the inheritance of complex diseases. Interest in genetics-related careers is rapidly growing; the U.S. Bureau of Labor Statistics shows a job outlook of 26% from 2020 to 2030. This compares to the outlook of 14% for other healthcare occupations and 8% for all occupations (2021). Increased interest in the field of genetics may lead to new ways of applying the discoveries Mendel made nearly 200 years ago to solve modern questions and problems. It might have taken longer for the world to acknowledge the results of his work than he believed it would, but there is no doubt that once it did, Gregor Mendel’s work opened a realm of new scientific possibilities that will certainly endure for 200 years more.

Boyle, E. A., Li, Y. I., & Pritchard, J. K. (2017). An Expanded View of Complex Traits: From Polygenic to Omnigenic. Cell, 169(7), 1177–1186. https://doi.org/10.1016/j.cell.2017.05.038 Coelho, S. G., & Almeida, A. G. (2020). Marfan syndrome revisited: From genetics to the clinic. Síndrome de Marfan revisitada – da genética à clínica. Revista portuguesa de cardiologia, 39(4), 215–226. https://doi.org/10.1016/j.repc.2019.09.008 Genetic Alliance. (2010, February 17). Classic Mendelian Genetics (Patterns of Inheritance). Understanding Genetics: A District of Columbia Guide for Patients and Health Professionals. Retrieved January 20, 2022, from https://www.ncbi.nlm.nih.gov/books/NBK132145/ Lane, C. A., Hardy, J., & Schott, J. M. (2018). Alzheimer’s disease. European journal of neurology, 25(1), 59–70. https://doi.org/10.1111/ene.13439 Lewis, R. G., & Simpson, B. (2021). Genetics, Autosomal Dominant. In StatPearls. StatPearls Publishing. Mantzavinos, V., & Alexiou, A. (2017). Biomarkers for Alzheimer’s Disease Diagnosis. Current Alzheimer research, 14(11), 1149–1154. https://doi.org/10.2174/1567205014666170203125942 National Human Genome Research Institute. (2013, May 3). Genetic Analysis Tools Help Define Nature and Nurture in Complex Disorders. Genome.gov. Retrieved January 20, 2022, from https://www.genome.gov/10000865/complex-disorders-background U.S. Bureau of Labor Statistics. (2021, September 8). Genetic counselors : Occupational outlook handbook. U.S. Bureau of Labor Statistics. Retrieved January 21, 2022, from https://www.bls.gov/ooh/healthcare/genetic-counselors.htm Williams, C. T., & Rudge, D. W. (2015). Mendel and the Nature of Science. The American Biology Teacher, 77(7), 492–499. https://doi.org/10.1525/abt.2015.77.7.3 Yin, Y., & Wang, Z. (2018). ApoE and Neurodegenerative Diseases in Aging. Advances in experimental medicine and biology, 1086, 77–92. https://doi.org/10.1007/978-981-13-1117-8_5

  Vivian Yuan Ridgewood High School Ridgewood, New Jersey Teacher: Mr. Ryan Van Treuren

Complex Diseases Through the Lens of Mendelian Genetics

In 2001, the Human Genome Project reported that the human genome contains 20,000 to 25,000 protein-coding genes (1, 2). Among those genes, less than 10% are related to single gene diseases, also known as monogenic or Mendelian disorders (2). With the recent advances of genome-wide association studies (GWAS) and single nucleotide polymorphism (SNP) sequencing approaches, interest in human genetics has shifted from rare Mendelian disorders to more common complex diseases, which involve both genetic components and environmental factors (2, 3, 4). Although Mendelian disorders affect a small portion of the population, studying them has contributed greatly to our understanding of genetic mutations and the risk factors underlying the aetiology of complex diseases.

The foundation of all modern human genetic studies relies upon Gregor Mendel’s study with pea plants. Through his experiments, Mendel discovered three laws: the law of dominance, the law of segregation, and the law of independent assortment (5, 6). Mendelian laws aptly dictate Mendelian disorders, which allows scientists to better determine the inheritance pattern of diseases. Disease inheritance genes can be classified as autosomal or sex linked, dominant or recessive. Huntington’s disease, a progressive neurodegenerative disorder, is an example of autosomal dominant Mendelian disorder, because only one copy of the defective gene from one parent is needed for disease manifestation. Conversely, phenylketonuria (PKU), which causes the accumulation of the amino acid phenylalanine, is an autosomal recessive disease. Both parents must give the defective gene to the child for the disease to appear. If only one parent carries the mutated gene, the child will not be affected, but they could still be a carrier of the mutated gene. Luckily, doctors are now able to predict the genotype and phenotype of an individual using pedigree analysis. Now, PKU could be confirmed within three days after birth, and PKU babies will be switched to a low protein and phenylalanine diet, preventing cognitive abnormality.

Although complex diseases do not follow Mendelian inheritance, the mechanisms learned from Mendelian diseases can help scientists understand complex diseases (2). Initially, cystic fibrosis was characterized as an autosomal recessive monogenic disease because of the mutations in the Cystic Fibrosis Trans-membrane conductance Regulator (CFTR) gene. However, recent studies showed that not all CFTR mutations produce the same disease, and disease severity is associated with modifier genes (7, 8). The interactions between modifier genes and different CFTR mutations heavily affect the phenotypic complexity and expressivity of CFTR genes. Due to the discovery of these modifier genes, cystic fibrosis is now classified as an oligogenic disease, involving a few genes. In a study of several families with epilepsy, multiple members carrying the same SCN1A gene mutations showed varying phenotypes and disease severity. Like the case in cystic fibrosis, modifier genes were also identified in epilepsy. While they may not be pathogenic, those genes still account for the variability in SCN1A-related phenotype (9).

In addition, study of Mendelian diseases can provide useful information about individual gene’s contribution to the phenotypes in complex diseases. When comparing two databases, Online Mendelian Inheritance in Man database (OMIM) and Genetic Association database (GAD), scientists found that among the 968 Mendelian genes identified, 524 genes are also genetic risk factors for complex diseases (3); hence, those genes are called complex-Mendelian genes (CM genes). CM genes were found to have higher allelic Odds Ratios (ORs) than genes associated only with complex disease, suggesting that CM genes have stronger effects on the complex phenotypes they affect (10).​ ​​​​​​

Furthermore, some complex diseases, such as breast cancer and hypertension, have Mendelian subtypes that clearly display the inheritance patterns typical of monogenic diseases. Hereditary breast cancer, accounting for 5%-10% of all breast cancer, is mainly caused by a mutation in BRCA1 and BRCA2 genes (11). The inheritance of BRCA1 and BRCA2 follows an autosomal dominant pattern, and carriers of those two genes are at higher risk of developing other cancers, especially ovarian cancer. Similarly, scientists have found that some types of hypertension, called monogenic hypertension, are caused by distinct genetic mutations resulting in gain-of-function or loss-of-function in the mineralocorticoid, glucocorticoid, or sympathetic pathways (12).

The knowledge gained from studying genetic inheritance is surely invaluable to understanding diseases and finding treatments. Future applications of these basic principles laid out by Mendel over 150 years ago will lead doctors to predict disease manifestation and severity, working towards prevention and early treatment for all diseases, simple or complex.

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• O’Neal W.K. and Knowles M.R. Cystic Fibrosis Disease Modifiers: Complex Genetics Defines the Phenotypic Diversity in a Monogenic Disease. Annu. Rev. Genom. Hum. Genet. 2018. 19:201–22
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• Spataro N., Rodriguez J., Navarro A., Bosch, E. (2017) Properties of Human Disease Genes and the Role of Genes Linked to Mendelian Disorders in Complex Disease Aetiology. Human Molecular Genetics 26 (3): 489-500
• Mehrgou A. and Akouchekian M. (2016) The Importance of BRCA1 and BRCA2 gene mutations in breast cancer development. Med J Islam Repub Iran 30: 369
• Raina R, Krishnappa V, Das A, et al (2019) Overview of Monogenic or Mendelian forms of Hypertension. Frontiers in Pediatrics 7: 263

Xinyi Zhang South Brunswick High School Monmouth Junction, New Jersey Teacher: Ms. Jessica Pagone

Genetic mutations lend each person their individuality, but certain variations can cause adverse health effects. Mendelian, or monogenic, disorders arise from variations in just one of the over 4,000 protein-coding genes that are currently associated with these diseases (2). Using Mendel’s principles to trace the inheritance pattern and phenotypes of a specific genetic mutation forms the basis of studying monogenic disorders. In turn, these findings can elucidate the role of various genetic mutations in diseases with more complex causes (8).

Gregor Mendel’s laws of genetic inheritance establish the framework for Mendelian patterns of inheritance. Given that each parent provides an allele for every gene in their offspring, if one parent has a genetic mutation that may cause a certain monogenic disorder, their offspring may inherit the mutant allele (5). Whether the child will develop the disorder or be a carrier depends on the dominance of the alleles they inherit (11).

Coupling Mendel’s principles with pedigree analysis reveal predictable modes of inheritance that bring light to the genetic nature of Mendelian diseases (5). Consider, for example, the realization of the inheritance pattern of sickle cell disease (SCD). Both parents need to have at least one mutant allele in the hemoglobin beta (HBB) gene to produce offspring with SCD (6). However, if their offspring only has one mutant allele, they will not be afflicted with SCD (6). With these observations, scientists determined that SCD is an autosomal recessive disorder in which it could only develop in people with two mutant alleles of the HBB gene (11). The inheritance pattern of a Mendelian disease would be different in an autosomal dominant disorder, where one mutant allele is enough to cause the disease, or in a sex-linked disorder, where diseases are inherited through the X or Y chromosome (11). Using Mendel’s principles to identify Mendelian inheritance patterns often serves as the first step in assessing disease risk and pinpointing the responsible genotype.

In actuality, Mendelian disorders are much rarer than complex disorders, which are distinguished from monogenic conditions because many genes, environmental interactions, and lifestyle choices all contribute to disease development (8). These variables complicate the determination of inheritance patterns or causative factors of a complex disease.

Despite their inherent differences, some connections have been uncovered between Mendelian and complex diseases. Many monogenic diseases are comorbid with complex ones (4). Furthermore, over 20% of the gene variations that cause Mendelian disorders have been implicated in at least one complex disorder (8). For instance, mutations in the IRF6 gene can lead to Van der Woude syndrome, a rare Mendelian disorder that causes cleft lip, cleft palate, and other facial deformities (10). Intriguingly, IRF6 mutations have also been implicated in complex, isolated forms of cleft lip and palate (12). These overlaps highlight the importance of utilizing Mendelian diseases to understand complex disease etiology.

Techniques such as whole-exome sequencing can link the characteristics of a Mendelian disease with the mutant gene that causes them (9). These findings are recorded in the Online Mendelian Inheritance in Man (OMIM), an accessible catalog of thousands of genotype-phenotype links for monogenic disorders (3). Studying this data has led to the identification of mutations and pathways that play a role in producing similar phenotypes in complex diseases (3,4). To better understand the complexity of essential hypertension, researchers studied many Mendelian disorders that are associated with high blood pressure, such as Liddle’s syndrome (7). Many of these disorders are caused by genetic mutations that alter proteins involved in renal salt balance (7). These studies brought attention to the importance of the kidneys and adrenal glands in regulating blood pressure and revealed the genetic mutations that may be associated with essential hypertension (7). Better knowledge of the molecular pathways behind essential hypertension has opened up new targets in drug development, such as ROMK, a renal potassium channel that is altered by a monogenic disorder known as Bartter syndrome type II (1).

Overall, while insights gleaned from studying Mendelian disorders cannot account for the environmental or lifestyle risks that contribute to complex diseases, they can guide research on pinpointing the pathophysiological processes and susceptibility alleles that bring about complex disorders. Thus, despite the rarity of Mendelian disorders, research on them should not be undercut to prioritize the study of prevalent complex diseases. A more comprehensive understanding of Mendelian disorders allows for more efficient risk assessment, prevention measures, and diagnoses for Mendelian and complex diseases alike, rendering it a valuable tool that should be further explored in the field of medical genetics.

• Abdel-Magid, A. F. (2016, November 22). Potential of renal outer medullary potassium (ROMK) channel as treatments for hypertension and heart failure. American Chemical Society. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5238487/
• Antonarakis, S. E. (2021, June 23). History of the methodology of disease gene identification … Wiley Online Library. Retrieved from https://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.62400
• Brownlee, C. (n.d.). OMIM turns 50: A genetic database’s past, present, and future. Johns Hopkins Medicine. Retrieved from https://www.hopkinsmedicine.org/research/advancements-in-research/fundamentals/in-depth/omim-turns-50-a-genetic-databases-past-present-and-future
• Kumar Freund, M. (2018, October 4). Phenotype-Specific Enrichment of Mendelian Disorder Genes near GWAS Regions across 62 Complex Traits. Cell. Retrieved from https://www.cell.com/ajhg/fulltext/S0002-9297(18)30285-4
• Lewis, R. G. (2021, May 7). Genetics, autosomal dominant. StatPearls [Internet]. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK557512/
• Mangla, A. (2021, December 19). Sickle cell anemia. StatPearls [Internet]. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK482164/
• Seidel, E., Scholl, U. I. (2017, November 1). Genetic mechanisms of human hypertension and their implications for blood pressure physiology. Physiological Genomics. Retrieved from https://journals.physiology.org/doi/full/10.1152/physiolgenomics.00032.2017
• Spataro, N., Rodríguez, J. A., Navarro, A., & Bosch, E. (2017, February 1). Properties of human disease genes and the role of genes linked to mendelian disorders in complex disease aetiology. Human molecular genetics. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409085/
• Suwinski, P., Ong, C. K., Ling, M. H. T., Poh, Y. M., Khan, A. M., & Ong, H. S. (2019, February 12). Advancing personalized medicine through the application of whole exome sequencing and Big Data Analytics. Frontiers. Retrieved from https://www.frontiersin.org/articles/10.3389/fgene.2019.00049/full
• U.S. National Library of Medicine. (2020, August 18). Van der Woude Syndrome: Medlineplus Genetics. MedlinePlus. Retrieved from https://medlineplus.gov/genetics/condition/van-der-woude-syndrome/
• 11. U.S. National Library of Medicine. (2021, April 19). What are the different ways a genetic condition can be inherited?: Medlineplus Genetics. MedlinePlus. Retrieved from https://medlineplus.gov/genetics/understanding/inheritance/inheritancepatterns/
• Zhao, H., Zhang, M., Zhong, W., Zhang, J., Huang, W., Zhang, Y., Li, W., Jia, P., Zhang, T., Liu, Z., Lin, J., & Chen, F. (2018, July 20). A novel IRF6 mutation causing non-syndromic cleft lip with or without cleft palate in a pedigree. OUP Academic. Retrieved from https://academic.oup.com/mutage/article/33/3/195/5056500

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