Researchers have unveiled a human genome map with a twist. It details how large chunks of DNA differ between individuals.
In the November 23, 2006 issue of Nature (Vol. 444, No. 7118, pp. 444-454), Matthew E. Hurles and colleagues present a map of DNA segments, with each segment containing at least 1,000 base-pair differences between individuals. The map was drawn up by analysing DNA from 270 individuals from four populations with ancestry in Europe, Africa or Asia. Over 1,400 of these so-called copy number variants (CNVs) were found, covering 12% of the human genome. This makes them far more prevalent than was previously thought.
CNVs can influence gene expression and phenotype, and can cause disease. So unless they are analysed directly, the authors warn that they could be missed by present strategies to identify genes mutated in genetic diseases.
The study is hot on the heels of the International HapMap project, which detailed single-base-pair changes between individuals. Both projects seek to address how human genomes differ from one another, and how genetics contributes to the myriad differences seen between one person and the next.
In a related study to be published online by Nature Genetics, Stephen Scherer and colleagues show that a large number of new CNVs can be identified by directly comparing the whole-genome sequences assembled by the two human genome projects.
The genomes represent mosaics of different individuals, and as such should harbour differences reflecting normal human variation. Although some differences may be due to computational or experimental error, the authors show that a great deal of bona fide variation can be extracted from such a comparison. In particular, 220 variable regions were confirmed, consisting of small insertions and deletions, as well as larger copy number variants and inverted pieces of DNA. More than 1.5 million single-base-pair changes were also confirmed.
The authors conclude that whole-genome assembly comparison is the most sensitive way to identify all types of genetic variation, and could constitute a cost-effective approach if whole-genome sequencing on a wide scale becomes economically feasible.
Matt Hurles (The Wellcome Trust Sanger Institute, Cambridge, UK)
Don Powell (Press and PR, The Wellcome Trust Sanger Institute, Cambridge, UK)
Stephen Scherer (The Hospital for Sick Children, Toronto, Canada)
Huntington F. Willard (Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA) N&V author
(C) Nature press release.
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