Findings published today in Science will accelerate the search for genes involved in human disease. The report provides a first genome-wide view of how the unique composition of genetic variation within each of us leads to unique patterns of gene activity.
By defining those genetic variants with a biological effect, the results will help prioritise regions of the genome that are investigated for association with disease. This is an important step to understanding links between genes and disease for individuals, and across populations.
The Human Genome Project gave us the instruction manual for building a human. The HapMap and Copy Number Variation (CNV) Projects developed indices of where to find differences in the manuals of different people. One of the challenges for research into variation and disease is that most variants have no consequence for our wellbeing.
The new study gives a global view of the consequences of those differences for gene activity. The work shows that activity of more than 1000 genes is affected by sequence variation and is the first map of human populations that identifies the most important fraction of DNA variation, that which directly affects gene activity.
The research was led by scientists from the Wellcome Trust Sanger Institute, together with colleagues from the University of Cambridge, Hospital for Sick Children/University of Toronto and Harvard Medical School/Brigham and Women's Hospital.
Using the HapMap series of cell samples from four populations, they measured the activity of more than 14,000 genes in cells grown in culture. The cell samples provide a snapshot of genetic activity in one cell type. The activity of each gene was then correlated with genetic variation nearby, as defined by the HapMap, an index of single-base changes (single nucleotide polymorphisms, or SNPs) and the new index of copy number variants (CNVs).