March 26, 2015
On March 25, the journal Nature Genetics published a collection of four studies based on whole-genome sequencing information from 2,636 Icelandic individuals. The papers, written by researchers from Reykjavik’s deCODE, represent a significant population sequencing initiative that will form the basis of delivering precision medicine, as well as shed light on basic human genetics.
The central paper, “Large-scale whole-genome sequencing of the Icelandic population,” provides an interpretation of the genome variants in relation to their function and traces how variations in Icelandic geography affect sequence diversity. The researchers also show how, with this new sequence information, rare genome variants can be predicted in more than 100,000 individuals who have been genotyped but not sequenced, and together how these rare variants may contribute to clinical diagnoses. An example of how this data may be used is published as a brief communication: "Loss-of-function variants in ABCA7 confer risk of Alzheimer's disease." Looking at the fully sequenced Icelandic individuals, genotyped individuals, and patterns of family inheritance, the researchers located new, rare gene variants that when absent, confer increased risk of Alzheimer’s disease.
Two additional papers in the Icelandic Genomes collection use the detailed genetic information to offer new insights into functional genome diversity and evolution. The study "Identification of a large set of rare complete human knockouts" revealed that a rather surprising 7.7% of the examined population has a knocked-out, or non-functional gene, the effects of which are largely unknown but may have negative effects on health. Continued study of these individuals will boost understanding of the effects of specific genes on human biology. The final work on "The Y-chromosome point mutation rate in humans" uses more than 50,000 years of Icelandic male ancestry to provide estimates of the mutation and gene repair rate in different regions of the Y chromosome.
The comprehensive research collection represents the most detailed portrait of population genomics to date. Further, it was a demonstration of how large-scale genome sequencing projects can advance both the basic understanding of human genetics and provide detailed context for disease risk and potential therapies. Other population sequencing efforts, including those from Genomics England and The Scottish Genomes Partnership, are underway to achieve similar goals.