Building a better human genome

Today we take for granted that the entire human genome is available at a mouse click, thanks to the Genome Reference Consortium (http://www.ncbi.nlm.nih.gov/projects/genome/assembly/grc), which maintains the most complete publicly available sequence information. The human genome reference is, by definition, the standard against which all other genomic information is compared. But even with constant correction and updating, the reference genome contains artifacts of its origin in the Human Genome Project. It is, contrary to myth, not the sequence of genome pioneer Craig Venter but an amalgam from several sources. There is now a move to create a reference genome from a single source, a so-called “platinum genome.” Its origin and evolution are described in a long feature in Bio-IT World (30 June 2014). The Genome Institute at Washington University in St. Louis is assembling the platinum genome from a haploid cell line called CHM1, which is already an industry standard. CHM1 clones have never been assembled into a complete genome, but recent progress in producing longer and longer stretches of unbroken sequence from a single sequencing read is enabling researchers to come closer to complete assembly. When finished, the sequence will have advantages over the current reference genome in that it will be from a single individual and will have been assembled from longer fragments with fewer gaps than the current reference genome. The Genome Institute plans to deposit the full sequence in GenBank for public use as soon as it is ready. Researchers involved in the project say that it will be particularly useful in haplotype studies, where it is important to know which variants are often inherited together. In the longer term, a second publicly available reference genome should be an invaluable resource for everyone involved in genomic research. —Karyn Hede, News Editor

As genome sequencing enters the clinic, insurers opt out

A recent investigation by Reuters News Service revealed that insurance companies are beginning to refuse to pay for whole-genome and whole-exome sequencing just as these technologies begin to enter clinical use. Reporter Julie Steenhuysen followed the medical odyssey of one family seeking an explanation for their infant son’s baffling and debilitating symptoms. Standard single-gene tests revealed nothing useful, and the family had exhausted its resources. Like many families dealing with an undiagnosed condition, they pursued whole-exome sequencing, but their insurance company refused to pay for the test. Additional reporting revealed that many of the largest insurers in the United States are now routinely refusing to pay for whole-genome or whole-exome sequencing absent definitive evidence of clinical benefit. The Reuters report noted that Cigna, Blue Cross, Aetna, and other providers are demanding proof of clinical benefit in terms of improved outcomes, a standard of evidence that is often difficult to meet. The consensus among insurers seems to be, as James Cross, vice president of national medical policy and operations at Aetna, told Reuters, that the ability to sequence has gotten ahead of the evidence. He said coverage decisions are based on an individual test and whether it affects patient outcomes. At this point, it is going to be up to the clinical sequencing industry to prove to insurers that the tests provide value to patients and save money in the long run. Until then, as far as insurers are concerned, the tests may remain “investigational,” i.e., not covered. —Karyn Hede, News Editor

Genetics in Medicine | Mission Statement

Genetics in Medicine is a monthly journal committed to the timely publication of:

  • Original reports which enhance the knowledge and practice of medical genetics

  • Strategies and innovative approaches to the education of medical providers at all levels in the realm of genetics

As the official journal of the American College of Medical Genetics and Genomics (ACMG), the journal will:

  • Provide a forum for discussion, debate and innovation concerning the changing and expanding role of medical genetics within the broader context of medicine

  • Fulfill our responsibility to the College membership through the publication of guidelines, policy statements and other information that enhances the practice and understanding of medical genetics

Finally, as genetics becomes increasingly important in the wider medical arena, we will be an accessible and authoritative resource for the dissemination of medical genetic knowledge to providers outside of the genetics community through appropriate reviews, discussions, recommendations and guidelines.