Researchers at the University of Chicago and The Wellcome Trust Sanger Institute have determined that small deletions in the human genome occur in a much greater number than previously assumed, as reported recently in the advance online publication of Nature Genetics.
Researchers mined publicly available data gathered for the International HapMap Project, which mapped the common patterns of DNA variation between humans with the goal of determining the genetic variants that influence how people differ in their risk of disease or their response to drugs.
Looking closely at SNPs, or single base changes in DNA, the researchers extrapolated synonymous regions of genomic deletions, from 0.3 to 1,200 Kb in size.
These deletions were then validated by NimbleGen System’s high-resolution comparative genomic hybridization (CGH) arrays.
"Using ultra-high resolution custom array CGH has not only allowed us to verify the presence of many deletions in a single experiment, but also to define precisely the breakpoints of those deletions and uncover additional unexpected copy number changes in flanking sequences," said Matthew Hurles, author on the paper and researcher at The Wellcome Trust Sanger Institute.
This paper, "A high-resolution survey of deletion polymorphism in the human genome," has important implications for how researchers will be interpreting HapMap data and structuring association studies in clinical cohorts.
Jonathan Pritchard, corresponding author on the paper and assistant professor in the Department of Human Genetics at the University of Chicago, said, "This paper shows that deletion polymorphisms are surprisingly widespread in the human genome, in many cases knocking out coding regions."
The authors also concluded that the prevalence of deletion polymorphisms within genes may be an important contributor to complex disease risk.
The revelation of widespread genomic variability in DNA copy number illustrates another level of complexity in the human genome.