Scimex: Scientists have sequenced the genomes of over 2,600 Icelanders, making it the biggest set of human genomes to be gleaned from a single population. The researchers have identified more than 20 million genetic variants that can be used, together with healthcare information and genealogical records, to understand the genetic basis of many diseases affecting humans globally. Their work, too large to be covered in just one report, has been published as four linked papers.
The largest set of human genomes sequenced from a single population is
reported in four linked papers published online this week in Nature Genetics. These data provide a comprehensive resource for the study of human disease and genetic diversity.
Kari Stefansson and colleagues sequenced the genomes of 2,636
Icelanders. They identified more than 20 million genetic variants that
can be used, together with national healthcare information and extensive
genealogical records, to better understand the genetic basis of many
diseases. To demonstrate the usefulness of this resource, the authors
combined the whole genome sequence data with less extensive genotype
data from over 104,000 additional Icelanders to strengthen their
association tests and identified a number of variants associated with a
variety of diseases. In one such test of the power of these data, the
researchers identified a variant of the gene ABCB4 that is significantly associated with the risk of developing liver disease.
In a separate study using these data, Stefasson and colleagues identified mutations in the ABCA7gene that are associated with an increased risk of Alzheimer's disease. Six of the eight mutations in ABCA7 were
also found to be present in other populations of European ancestry,
including the United States, indicating that the results are not
specific to the Icelandic population.
In a third study, Patrick Sulem and colleagues mined these data to
identify over 8,000 Icelandic individuals that have completely lost the
function of at least one gene. In all, they identified 1,171 of these
rare genetic "knockouts". Olfactory receptor genes, which are
responsible for our ability to discriminate between different smells,
were the most commonly knocked out class of genes, while genes expressed
highly in the brain were rarely knocked out, suggesting their loss
would be more harmful. Further mining of these data will help scientists
understand which genes are indispensable and which are linked to
The fourth linked study, by Agnar Helgason and colleagues, used
whole-genome sequence data from 753 Icelandic men from 274 groups of
related individuals to estimate the rate of mutations on the
Y-chromosome. The results represent the most accurate estimate of the
male-specific mutation rate to date. The study dates the most recent
common ancestor (MRCA) for human Y chromosomes to 174,000–321,000 years
ago. This estimate is much closer to that of the MRCA for mitochondrial
DNA, which is inherited exclusively from the mother, and may have
implications for understanding the evolution of our species.
Genetic and genomic variation data pertaining to the paper Sequence variants from whole genome sequencing of a large group of Icelanders are described in an accompanying Scientific Data article,
along with important methodological details and other information to
facilitate the use these data by other researchers.