NHGRI Celebrates Tenth Anniversary of Human Genome Sequence

Jacquelyn K. Beals, PhD

February 18, 2011

February 18, 2011 — Twenty years ago, the Human Genome Project was just getting underway — 10 years later, investigators had a draft sequence of the human genome.

To celebrate these landmark events, and to publicize its vision for the future, on February 11 the National Human Genome Research Institute (NHGRI) held a symposium on "A Decade with the Human Genome Sequence: Charting a Course for Genomic Medicine," on the campus of the National Institutes of Health (NIH). The same week, NHGRI unveiled its vision in Nature.

The symposium featured talks on topics that reflect the current — and projected — effect of genomics in diagnostic medicine and therapeutics, in personal genetics, and in ethical, legal, and social spheres.

The presentations included "Fevers, Genes, and Targeted Therapies: Adventures in the Genomics of Inflammation," by Daniel L. Kastner, MD, PhD, who runs the intramural research program at NHGRI.

"For many years, he's been studying the genetic basis of rare fever– or just inflammatory-related diseases," Eric D. Green, MD, PhD, director of NHGRI, told Medscape Medical News.

Over the last 20 years, Dr. Kastner's work has investigated the genes and pathways involved in regulating inflammation and how to target them for treatment.

Dr. Kastner "gave examples on how the field of genetics can reveal ways to treat disorders," attendee Nora Volkow, MD, told Medscape Medical News. Dr. Volkow is director of the National Institute on Drug Abuse.

"NHGRI has played a fundamental role in building infrastructure (methodological and knowledge) for understanding how information is stored in DNA and in the machinery that cells use to decode it," said Dr. Volkow, noting that "research supported by [the National Institute on Drug Abuse] builds upon this infrastructure."

Vision for the Future

Another symposium presentation, by David C. Page, MD, director of the Whitehead Institute, Cambridge, Massachusetts, discussed the evolution of sex chromosomes, and particularly the Y chromosome. This smallest human chromosome is evolving so rapidly that more than 30% of the human Y chromosome DNA differs from that of the chimpanzee.

"[Dr. Page] is showing...that there are clearly disorders that he's now finding related to structural rearrangements on the Y chromosome," said Dr. Green. "There are some things, for example, related to infertility, that have now been discovered to be related to structural changes on the Y chromosome."

A link to videos of the symposium talks is posted online.

NHGRI also marked the celebration by presenting its vision for the future in the February 10 issue ofNature. Dr. Green was lead author of a perspectives piece highlighting 5 research domains for NHGRI "from base pairs to bedside": understanding the structure of genomes, understanding the biology of genomes, understanding the biology of disease, advancing the science of medicine, and improving the effectiveness of healthcare.

A schematic in the article shows that most genomics research accomplishments from 2004 to 2010 dealt with the structure or biology of genomes. The period from 2011 to 2020 is projected as a time of intensifying research on the biology of disease. Beyond 2020, the research focus is expected to advance into the science of medicine and improving the effectiveness of healthcare.

The article repeatedly refers to the "importance of non-coding variants in human disease" or "illuminating the fundamental biology of non-coding sequence variation and its phenotypic implications."

A Lot More to Learn

Medscape Medical News asked Dr. Green to elaborate on this topic, which goes far beyond the familiar formula of "DNA to RNA to protein."

"Study of the human genome, since the end of the human genome project, has revealed that the minority of the functional parts of the human genome are protein-coding regions, which really are the regions we understand the best," said Dr. Green.

"Once upon a time we thought that most of the action, where the functional parts of our genome are going to be, was in the genes, the stuff that made information for coding proteins.

"What has been revealed, since the end of the genome project, is that's really important stuff — something like 21,000 genes or so — but in fact, that only represents about a third of the functional sequences in our genome," he added.

The remaining two thirds of the functional sequences do not code for protein, but have other functions.

"We have a lot to learn. We barely have scratched the surface in studying that part of the genome," said Dr. Green.

Some elements in this noncoding DNA regulate where and when and how much genes are turned on or off; Dr. Green refers to them as "dimmer switches" that can switch on, or switch off, or modulate how much a gene is expressed. That constitutes a whole circuitry of noncoding DNA that is very important.

"The more we study it, the more we realize how complicated it is. We are learning that these genetically complex diseases, which are diseases responsible for filling hospitals and clinics around the world — diabetes, cardiovascular disease, mental illness, some forms of cancer — that these disorders are complicated because they involve multiple different genetic changes that confer risk for disease. The majority of times, the noncoding DNA elements are the ones that contain variants conferring risk for these complex diseases," explained Dr. Green.

"So the reason [noncoding DNA elements] are so medically important is: number 1, it's probably where a lot of the variation is that confers risk for human disease. And number 2, we don't understand that very well. And yet we have to, because it's medically important," he added.

Dr. Green, his coauthors, and Dr. Volkow have disclosed no relevant financial relationships.

NHGRI symposium video.

Nature. 2011;470:204-213. Abstract


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: