Giant genome study generates new
understanding of human diseases and
genetic diversity
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NATURE GENETICS
& SCIENTIFIC DATA
Embargo
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London: Wednesday 25 March 2015 18:00 (GMT)
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New York: Wednesday 25 March 2015 14:00 (EDT)
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Tokyo: Thursday 26 March 2015 03:00 (JST)
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Sydney: Thursday 26 March 2015 05:00 (AEDT)
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 disease.
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.
Author details:
Please contact the deCODE authors via:
Edward Farmer (WuXi NextCODE, Cambridge, MA, USA)
E-mail: efarmer@wuxinextcode.com Tel: +1 781 775 6206
Jón Gústafsson (deCODE Genetics, Reykjavik, Iceland)
E-mail: jon@decode.com Tel: +354 664 1905
Article and author details
1. Large-scale whole-genome sequencing of the Icelandic
population
DOI
10.1038/ng.3247
Online paper*
http://nature.com/articles/doi:10.1038/ng.3247
2. Loss of function variants in ABCA7 confer risk of Alzheimer's
disease
DOI
10.1038/ng.3246
Online paper*
http://nature.com/articles/doi:10.1038/ng.3246
3. Identification of a large set of rare complete human knockouts
DOI
10.1038/ng.3243
Online paper*
http://nature.com/articles/doi:10.1038/ng.3243
4. The Y-chromosome point mutation rate in humans
DOI
10.1038/ng.3171
Online paper*
http://nature.com/articles/doi:10.1038/ng.3171
5. Sequence variants from whole genome sequencing a large
group of Icelanders
DOI
10.1038/sdata.2015.11
Online paper*
http://nature.com/articles/doi:10.1038/sdata.2015.11
* Please link to the article in online versions of your report (the URL will go live after the embargo ends).