A human genome sequencing project conducted among the population of Iceland has revealed important new insights into human evolution and susceptibility to disease.
Four related papers published in Nature Genetics by scientists from deCODE Genetics report a range of findings derived from whole-genome sequences of 2,636 Icelanders and less extensive genotyping of another 104,000 Icelandic people.
“This work is a demonstration of the unique power sequencing gives us for learning more about the history of our species and for contributing to new means of diagnosing, treating and preventing disease,” says Kari Stefansson, founder of deCODE and lead author of the papers.
One of the studies revealed a variant in the MYL4 gene that causes early-onset atrial fibrillation, several mutations in ABCB4 that increase risk of liver diseases and a variant in GNAS associated with thyroid-stimulating hormone levels[1]
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Another study identified eight loss-of-function mutations in the ABCA7 gene that are associated with a more than two-fold increased risk of Alzheimer’s disease[2]
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A third study catalogued 1,171 autosomal genes that had been completely knocked out by rare loss-of-function mutations[3]
. Olfactory receptor genes were the most frequently knocked out whereas genes highly expressed in the brain were rarely lost.
An accompanying editorial[4]
lauds the deCODE project for yielding clues about human disease and pointing to translational options in medicine but says it raises questions about how society – and the Icelanders in particular – should implement the knowledge gained.
References
[1] Gudbjartsson DF, Helgason H, Gudjonsson SA, et al. Large-scale whole-genome sequencing of the Icelandic population. Nature Genetics 2015 Mar 25; DOI:10.1038/ng.3247.
[2] Steinberg S, Stefansson H, Jonsson T, et al. Loss of function variants in ABCA7 confer risk of Alzheimer’s disease. Nature Genetics 2015 Mar 25; DOI: 10.1038/ng.3246.
[3] Sulem P, Helgason H, Oddson A, et al. Identification of a large set of rare complete human knockouts. Nature Genetics 2015 Mar 25; DOI:10.1038/ng.3243.
[4] Gudbjartsson DF, Sulem P, Helgason H, et al. Sequence variants from whole genome sequencing a large group of Icelanders. Nature Genetics 2015 Mar 25; DOI:10.1038/sdata.2015.11.
