Celebrate DNA Day 2018 with ASHG

Posted By: Jannine Cody, PhD, Chair, ASHG Information & Education Committee

Happy DNA Day! Every April 25, we commemorate the discovery of DNA’s double helix structure in 1953 and the completion of the Human Genome Project in 2003, two key milestones in genetics. A variety of DNA Day events are taking place worldwide and online, including the debut of our ’15 for 15′ infographics on recent advances in human genetics – check them out!

ASHG marks this date each year by announcing the winners of our Annual DNA Day Essay Contest. Open to high school students worldwide, this year’s contest asked students to share their views on whether medical professionals, such as medical geneticists or genetic counselors, should be required for all genetic testing, or if consumers should have direct access to predictive genetic testing.

We received over 1000 entries from 43 U.S. states and 23 countries. Essays went through three rounds of scoring by ASHG members, who selected a first, second, and third place winner as well as 10 honorable mentions. (Want to participate next year? Read Dennis Drayna’s blog post on the judging experience.)

The winning essays were thoughtful and nuanced, reflecting a variety of views and a sophisticated consideration of the issues, and we were excited to see high-quality entries from several countries around the world. We awarded first place to Diane Zhang, a junior at Fox Lane High School in Bedford, N.Y.; second place to Ilan Bocia, a senior at YULA-Boys in Los Angeles, Calif.; and third place to Nadia O’Hara, a freshman at Pechersk School International in Kyiv, Ukraine.

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For a full list of winners, honorable mentions, and teachers, and to read the winning essays, check out the DNA Day 2018 Winners. Through this contest and our other K-12 initiatives, we hope to encourage young people to explore genetics and inspire the next generation of ASHG members and leaders.

Jannine Cody, PhD, Professor of Pediatrics at the University of Texas Health Science Center at San Antonio, is Chair of ASHG’s Information & Education Committee. Learn more about ASHG’s K-12 education programs.

ASHG and FASEB: Working Together to Make a Difference in Advocacy & Policy!

Posted By: Jennifer Zeitzer, FASEB Director of Legislative Relations

The Federation of American Societies for Experimental Biology (FASEB) is the nation’s largest coalition of biomedical researchers, representing 30 scientific societies and more than 130,000 researchers from around the world. As a member of FASEB, ASHG works closely with FASEB and the other member societies to advance research and education in biological and biomedical sciences and advocate for increased funding for biomedical research. Through FASEB, ASHG also monitors and regularly speaks out on science policy issues impacting the scientific community.

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Jennifer Zeitzer, FASEB Director of Legislative Relations

For example, ASHG recently joined FASEB in celebrating the historic $3 billion dollar increase for the National Institutes of Health (NIH) approved by Congress in late March. Securing the increase was a collaborative effort between many organizations. ASHG urged its members to email and call their elected officials and sent two Board members to FASEB’s Capitol Hill Day to make the case for NIH funding with their members of Congress.

This month, Congress began consideration of the fiscal year (FY) 2019 budget, and ASHG and FASEB are again working together to advocate for increased NIH funding. There is a good chance NIH will receive another significant funding increase in FY 2019, thanks to legislation passed in February to raise strict spending caps that were enacted in 2011. The appropriations committees will determine how that additional funding is divided among federal agencies.

Making sure NIH gets another increase will require additional coordinated advocacy between ASHG and FASEB over the next few months. More information is forthcoming, but ASHG members should expect to receive e-alerts from FASEB as well as reminders to check out the resources and tools in the ASHG Advocacy Center.

ASHG members also have access to FASEB’s Advocacy Toolbox, which includes instructions for requesting a meeting with a member of Congress at home and tips for communicating with elected officials through social media. The Washington Update newsletter provides the latest news on science policy and advocacy inside the Beltway and from federal agencies (click here to subscribe).

Communicating about science is another area where ASHG partners with FASEB. The Human Microbiome and Individualized Medicine: Genetically Fine-Tuning Prevention, Diagnosis, and Treatment of Disease are articles in FASEB’s Breakthroughs in Bioscience series that illustrate genetics-related developments in biomedical research and their importance to society. Similarly, the Horizons in Bioscience one-pagers, including articles on liquid biopsies, CRISPR/Cas gene editing, epigenetics, and optogenetics, summarize scientific discoveries on the brink of clinical application and supplement the longer Breakthroughs.

The recent $3 billion increase for NIH and other advocacy successes would not have been possible without the joint effort between FASEB and its member societies. As Congress makes decisions about the 2019 budget, FASEB is proud to have a strong partnership with ASHG to ensure that the voices of scientists are heard on Capitol Hill and in congressional districts across the country.

Jennifer Zeitzer has been the Director of Legislative Relations at FASEB since 2008. She coordinates advocacy efforts with FASEB member societies and others in the biomedical research community, including organizing FASEB’s annual Capitol Hill Day.

FASEB offers free webinars on advocacy and policy issues. Sign up to receive notifications about future FASEB webinars here.

Following the Path of ASHG’s Statement on Pediatric Genetic Testing

Posted By: Cara Cavanaugh, MSc, Cell Press

What happens to a paper once it is published? After the research is over, the proofs are reviewed, and the paper is out in the world, how is it used and by whom?

To answer these questions, we traced the post-publication trajectory of ASHG’s position statement, “Points to Consider: Ethical, Legal, and Psychosocial Implications of Genetic Testing in Children and Adolescents.” The statement was published in The American Journal of Human Genetics (AJHG) in 2015 and was an update from two decades earlier. Following the history of the paper since its publication shows us the reach that an ASHG position statement can have over three years.

About the Position Statement

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Published in 2015, the statement has been cited by a variety of sources, including academic, legal, and public discourse.

The position statement gives recommendations for when and why families should decide to perform genetic tests on children and adolescents. “We felt that it was timely to update the statement across a range of issues,” says first author Jeffrey Botkin, MD, MPH, a professor and chief of the Division of Medical Ethics and Humanities at the University of Utah. “Our primary focus was genetically testing children for adult-onset conditions when there is no intervention during childhood. There hasn’t been a lot of research on the impact of such testing because folks felt that it was unethical under any context. We wanted to soften the perceived stance that such testing should never be conducted and have the position of the society be a little more flexible. We recognize that there may be circumstances when such testing might be appropriate for the child and family. We also wanted to encourage more research on these issues.”

Academic Citations and Public Conversation

Since its publication, the position statement is one of the top downloaded papers in AJHG’s history, with over 5,000 downloads as of 2018. After publication, to make the content more accessible to readers, ASHG created infographics that explain the issues and intricacy around childhood genetic testing. The paper has been cited by Genetics in Medicine, Pediatrics, Blood, Nature Reviews Genetics, and more than 80 other academic titles.

The statement has also been cited outside of the scientific research context. For example, it has impacted legal academic discourse. In one 2016 paper, Sénécal et al. discuss the legal approaches to healthcare decisions for minors in the European Journal of Human Genetics to the ASHG position statement as a “more nuanced approach” to how genetic testing should be pursued. They praise the statement for advising that physicians should inform families of all genetic testing options, even if the family has decided not to pursue any tests. Another paper by Otero in the European Journal of Health Law uses the position statement in a narrower context, specifically to analyze European and Spanish legal frameworks. These papers are just two of several examples of how one position statement from scientists can contribute to legal analysis internationally.

In addition to the academic studies discussed above, the position paper was also featured in the mainstream media. It gained coverage in NPR, VICE, and Pacific Standard. Exposure in these news sources helped engender public conversations online about the ethics of genetic testing in children.

What’s Next?

This paper shows the broad reach the ASHG community has in important societal and cultural issues of our time. As genetic testing appears more frequently in the news and becomes increasingly controversial, especially with products like direct-to-consumer genetic testing kits, it is imperative that we fully debate and consider how this could affect children and adolescents. ASHG policy statements, like the one published in 2015, provide us with long-lasting resources for continuing those discussions.

Cara Cavanaugh, MSc, is a Marketing Contractor at Cell Press. She earned a BA in History of Science from Princeton University and a MSc in Science Communication from Dublin City University while on a Fulbright Award.

Inside AJHG: A Chat with Alice Davidson

Posted By: Sarah Ratzel, PhD, Science Editor, AJHG

Each month, the editors of The American Journal of Human Genetics interview the authors of a recently published paper. This month, we check in with Alice Davidson, PhD, to discuss her paper, “Antisense therapy for a common corneal dystrophy ameliorates TCF4 repeat expansion-mediated toxicity.

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(L-R) Kirithika Muthusamy, Christina Zarouchlioti, Alison Hardcastle, Alice Davidson, and Beatriz Sanchez-Pintado (courtesy Dr. Davidson)

AJHG: What caused you to start working on this project?

Alice: I work in the ophthalmic genetics field. Back in 2012, I was hugely intrigued by Eric Wieben and colleagues’ discovery that Fuchs endothelial dystrophy (FECD) was associated with a non-coding triplet repeat expansion within an intron of TCF4. I have always been fascinated by repeat expansion-mediated diseases and their respective pathophysiology. I also similarly have a longstanding interest in non-coding mutations and their contribution to human disease. The discovery that this non-coding repeat expansion was associated with a corneal endothelial disease, a group of conditions I had already begun to research with my mentor Alison Hardcastle and clinical collaborator Steve Tuft, gave me the impetus I needed to begin to develop my own independent research program. In 2015, I was awarded a Fight for Sight fellowship to work on the genetics of primary corneal endothelial disease and decided to initially focus my effort on developing endothelial cell culture methods to study the pathophysiology of TCF4 triplet expansion-mediated FECDs. Alison, Steve, and I subsequently partnered with Pete Adamson at ProQR therapeutics to explore the therapeutic potential of antisense oligonucleotides (ASO) therapy to treat this repeat expansion-induced pathology.

AJHG: What about this paper most excites you?

Alice: I find the translational potential of this project hugely exciting. FECD is a common, age-related disease. The non-coding TCF4 repeat expansion is now recognized as by far the most common genetic cause of the disease in a wide range of ethnically diverse populations. Invasive corneal transplantation surgery is the currently the only treatment option available to restore vision and prevent blindness for FECD patients. This treatment relies upon specialist facilities, can be associated with operative complications, and is dependent on the availability of healthy donor material, of which there is currently a global shortage. These issues, in addition to the global aging population, highlight the need for alternative and effective treatment strategies to be developed for FECD. Our paper highlights the potential of an ASO mediated therapy to treat this common, sight-threatening disease.

AJHG: Thinking about the bigger picture, what implications do you see from this work for the larger human genetics community?

Alice: Our study has impact beyond the ophthalmic research field, given that a wide range of neurological and neuromuscular diseases are caused by similar repeat expansion mutations, such as Huntington disease, myotonic dystrophy, and amyotrophic lateral sclerosis/frontotemporal dementia. Using our patient-derived corneal endothelial cell model has enabled us to study the cellular consequences of the repeat expansion within its native genomic and cellular context. The cornea is an easily accessible tissue that can be readily monitored for pathological and sub-symptomatic signs, unlike many of the neuronal tissues affected by other repeat-mediated diseases. We hope that any future therapeutic advances regarding TCF4 repeat expansion-mediated FECD and using the eye as a model system could be adopted for other, less tractable, non-coding repeat expansion mediated disease.

AJHG: What advice do you have for trainees/young scientists?

Alice: Don’t be scared to just give things a try. Often, as scientists, we can feel overwhelmed by the enormity of what we are trying to achieve and it is easy to focus on the problems and limitations associated with our experiments. Overcoming our personal fears of failure and giving ‘the impossible’ a try can often lead to unexpected and rewarding outcomes. I believe that the saying ‘it is always better to have tried and failed than to have never tried at all’ is very applicable to science.

AJHG: And for fun, tell us something about your life outside of the lab.

Alice: I gave birth to my first child in October 2016 and since then my life has been a real juggling act between work and family. At the moment nothing makes me happier than spending quality time with my little boy and husband outside of work. I love to do bikram (hot) yoga to help me relax and generally lift my spirits, especially on dark, cold winter days – which are plentiful, living in London!

Alice Davidson, PhD, is a Senior Research Associate at the Institute of Ophthalmology at University College of London. She has been an ASHG member since 2018.

Inside AJHG: A Chat with Andy McCallion, Loyal Goff, and Paul Hook

Posted By: Sara Cullinan, PhD, Deputy Director, AJHG

Each month, the editors of The American Journal of Human Genetics interview the authors of a recently published paper. This month, we check in with Andy McCallion (@FunctionalDNA), Loyal Goff (@loyalgoff), and Paul Hook (@paul_hook_HuGen) of Johns Hopkins University to discuss their paper, “Single-cell RNA-seq of mouse dopaminergic neurons informs candidate gene selection for sporadic Parkinson’s disease.”

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(L-R) Paul Hook, Andy McCallion, and Loyal Goff

AJHG: What prompted you to start working on this project?

Andy: The challenge presented by endeavoring to connect common variation identified through genome wide association studies (GWAS) to affected genes and ultimately to the mechanistic understanding of disease gives all of us a headache. Where to start?

Although powerful, GWAS are inherently biologically agnostic. Despite the wealth of loci they implicate in disease, GWAS tell us nothing of the cellular context of disease or how variants mediate their effect/s. This, and the significant distances over which regulatory sequences/variants can act, complicates efforts to systematically identify gene candidates. We wanted to ask whether, beginning with an underlying biological insight into a pathologically vulnerable cell population, we could make progress on this challenge.

AJHG: What about this paper/project most excites you?

Andy: Perhaps the most exciting thing is that this work provides a biologically informed framework that systematically prioritizes candidate genes for an entire field, Parkinson’s Disease (PD). We were able to ask what (if anything) makes the transcriptomes of neurons in the substantia nigra unique among central nervous system dopamine neurons. We reasoned that any differences may contribute to their preferential vulnerability of this population in PD. The data we generated facilitated the exploration of gene networks underpinning the identity of all assayed dopamine subpopulations and in turn revealed that networks most associated with PD are active in the nigral population.

Stepwise integration of this data allowed us to establish a rubric, filtering over 1000 potential genes in 49 PD GWAS intervals to approximately 100. The genuine excitement was driven by the fact that the data holds up! Among these candidates are many established familial/syndromic PD genes. Further, we validate the functional requirement of a gene not previously known to be mutated in PD.

AJHG: Thinking about the bigger picture, what implications do you see from this work for the larger human genetics community?

Andy: Our work demonstrates that starting from an informed biological hypothesis of (one) cellular context in which a subset of variation might be expected to mediate their effect, can yield robust, testable hypotheses of the genes modulated in disease. We’re not naïve enough to think this story is complete; we recognize that much more work needs to be done – similarly evaluating other cell populations, conditions, etc. Many others are similarly seeking ways to reveal what cellular contexts are most pertinent to a range of disorders. We see this as a proof of principle whose observations will (hopefully) synergize with those from other groups.

AJHG: What advice do you have for trainees/young scientists?

Andy: That’s a tough one! My advice would not be technical. I frequently joke with my trainees that life is not complicated – we all have only two responsibilities. First, you need to get the best out of yourself – work hard, be curious, invest in the intellectual and technical platform you create for your science, think rigorously and creatively. Second, you need to get the best out of everyone else – be fair, honest, empathetic; share information generously, recognize what you can learn from the experiences of others.

Hold those things in tension and you will reach for your success, want to ensure the success of others, and simultaneously avoid being a jerk­. The field of genetics/genomics has become so multi-disciplinary that throughout your career, you will need to develop many relationships – networks of colleagues. Hold yourself accountable for how you work and how you build and maintain relationships.

AJHG:  And for fun, tell us something about your life outside of the lab.

Andy: Outside of the lab, Paul is an avid cook and enjoys time in the kitchen. Loyal is a talented photographer and musician but currently spends most of his time chasing after his two young children. I spend much of my free time woodworking – both at home and as the carpenter on the restoration of an active second world war Liberty Ship and living museum, working alongside my teenage son. Collectively our labs (Goff and McCallion) enjoy almost anything that involves food, drink, our families, and a great laugh.

Andy McCallion, PhD; Loyal Goff, PhD; and Paul Hook, BS, study neurogenetics at the Johns Hopkins University McKusick-Nathans Institute of Genetic Medicine. Dr. McCallion, an ASHG member since 2001, served on the Society’s Program Committee from 2012-13 and as its Chair in 2014. Dr. Goff and Mr. Hook have been ASHG members since 2015.

 

 

Representing ASHG and Genetics at FASEB’s Capitol Hill Day

Posted by: Neil Hanchard, MD, PhD, ASHG Board Member

I don’t consider myself to be particularly ‘political’; however, the last two Presidential budgets have included closing the U.S. Department of Agriculture-funded building that houses my lab and office. This has made me keenly aware that the science we do doesn’t occur in a vacuum. I thus consider myself particularly fortunate to have had the opportunity to participate in FASEB’s Capitol Hill Day (March 8) as a representative of ASHG. This now annual event brings scientists from across FASEB’s 31 experimental biology societies – including ASHG – to the Capitol to lobby for their own science. It’s timed to coincide with annual budget making season and, since it’s been going on longer than any of the more than 50 fellow scientists in the room knew for sure, it’s a central piece of FASEB’s public policy engagement.

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L-R: James Musser, FASEB President-elect; Sharma Prabhakar, AFMR; and Neil Hanchard, ASHG Board Member.

For me, getting up close and personal with the machinations that enable the science engine was a truly fascinating experience. The DC-based staff of FASEB and ASHG essentially do this all the time and, accordingly, were like a well-oiled sequencer. They did an amazing job of prepping first time scientists-come-lobbyists (like myself) – hosting prep sessions well before the event, as well the night before and morning of. Plus, they ensured that everyone was suitably armed with critical talking points for their State representatives and glossy summary pamphlets to go along with them. After a day running around (literally) meeting with State representatives’ aides in the halls and offices of the National’s Capitol, here are my top 5 takeaways:

  1. There is strength (and comfort) in numbers. FASEB represents ~130,000 scientists in the U.S. and around the world – that’s not a trivial number and the powers-that-be know it.
  2. The Capitol is very large. It’s a mind-boggling maze of offices and hallways, with a subway linking the two houses to boot. With multiple 10-15 minute meetings strewn across the “The Hill”, there’s no way we could have done it on our own – the FASEB facilitators, who included our own ASHG staff, knew not only where we were going, but each of the representatives’ voting and stances on science issues as well.
  3. There is an art to the lobby. There’s an etiquette to lobbying, with polite, often unwritten rules of how to deal – the mandatory exchange of business cards (which I forgot – whoops!); the pitch, the pivot (when you’ve lost your audience); the parting promises and closing invitations – a well-rehearsed dance that, performed well, can be the difference between a “yea” and a “nay”.
  4. Everyone wants their piece of the pie. The Lobby dance is performed by umpteen groups this time of year – if there’s a group you can think of, they were probably there. For scientists to get the funding they need to continue doing good science, they should remember that “the squeaky wheel gets the grease.”
  5. Science is bipartisan. Somewhat surprisingly for me, the pitch for NIH, NSF, and USDA science was well-received at all of the Texas representatives’ offices we visited, irrespective of party affiliation. I also learned of several unheralded champions for science from both sides of the political aisle.
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After a chance hallway meeting with Rep. Al Green, the Texas group sat down with Rep. Green’s staffer to discuss the importance of biomedical research.

All in all, this was a truly enlightening and emboldening experience; honestly, if I can do it, pretty much anyone can, and there’s a strong argument that any and all scientists should – host a representative in your lab, visit your local representative’s office, make the phone call/sign the email – as jaded as I was about the process at the start, it was heartening to know that it can actually make a difference.

Neil Hanchard, MD, PhD, FACMG, serves as Early-Career Member of the ASHG Board of Directors. He is an Assistant Professor and Clinical Geneticist at Baylor College of Medicine and Texas Children’s Hospital, and has been a member of ASHG since 2010.

Networking Session was Great! What’s Next?

Posted By: Rohit Thakur, Marie Sklodowska-Curie research fellow, University of Leeds, United Kingdom

During ASHG 2017, I participated in the Conference to Career program, organized by ASHG in collaboration with The Jackson Laboratory. The program taught various skills such as networking, elevator pitches, informational interviewing, and how to follow up effectively, some of which I highlighted on the MELGEN blog last month. Today, I wanted to focus on the aftermath of networking: The art of following up! Before I start recommending strategies, I wanted to share my experience of how effective follow-up can lead to wonderful opportunities.

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Rohit Thakur (left) and colleague Joey Mark Diaz (right), participants in the ASHG/JAX Conference to Career Program (courtesy Mr. Thakur)

During the ASHG meeting, I was intrigued by a talk by Manolis Kellis, PhD, after which I prepared my elevator speech and talked to him about his group’s ongoing research. I was very interested in their machine learning approaches. Dr. Kellis was very kind and put me in touch with his graduate student. After returning from the conference, I followed up with Dr. Kellis, and that led to potential talks of collaboration between our groups. Dr. Kellis also offered to host me for a month-long internship in his group at MIT, which I accepted.

From my limited experience, I can say that effective follow-up is a necessary step towards building a strong network. Here are some recommended strategies.

Write an Email – 24 Hours’ Countdown

Follow up with people after networking by sending a personalized email within the next 24 hours, while the meeting is fresh in their minds. This email should include a thank you note and all the relevant information – articles, programming scripts, and anything else you had agreed to share after the networking session – and express interest in scheduling another meeting.

Connect with Them on Social Media

Social media has made it easy to connect with people from around the world, through platforms like Twitter, LinkedIn, and ResearchGate. You can keep in touch by congratulating them for their recent achievements and recognitions, and wish them on other occasions such as birthdays, and the New Year.

Invite Them to Give a Seminar

If you are fascinated by someone’s work, you can always invite them for a department seminar. As a trainee, you can recommend speaker names to the head of your department suggesting why they should be invited and how it will benefit your department’s research. Not only will this strengthen your relationship with the speaker, but will also help in fostering collaborations between other trainees/researchers and the speaker.

Always Give First and Expect Nothing in Return

Networking is a team sport. You can follow up with people by offering them your help and suggestions in a constructive manner. If following up leads to a successful collaboration, then you should always give equal opportunity in decision making, leadership, responsibilities, and benefits.

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L-R: Manolis Kellis, PhD; Mr. Thakur; and Alvin Shi, PhD Candidate at MIT (courtesy Mr. Thakur)

Acknowledgements: My project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 641458. I am highly thankful to my supervisors Jenny Barrett, PhD, Julia Newton-Bishop, MD, MBChB, FMedSci, Jeremie Nsengimana, PhD, and Göran Jönsson, PhD, for their exceptional mentorship and encouragement to expand my horizons. I am thankful to the organizers of the Conference to Career Program for developing networking skills of ASHG trainees and to Dr. Kellis for providing me with a wonderful learning opportunity in his group at MIT.

Rohit Thakur, B. Tech, is a PhD Candidate at the University of Leeds. He has been an ASHG member since 2017.