Affymetrix 500K Array Used to Generate First Copy Number Variation Map of the Human Genome

Affymetrix Inc. has announced that scientists working on the International Genome Structural Variation Consortium’s Copy Number Variation Project have used the 500K Array to help generate the comprehensive copy number variation (CNV) map of the human genome.

The team discovered hundreds of CNVs that will enable researchers to perform more powerful association studies on diseases such as cancer, Parkinson’s and Alzheimer’s.

The results of this study have been published in the November 23, 2006 issue of Nature1 along with a supporting paper in Genome Research2.

The study is the first publication to demonstrate the performance of whole-genome single nucleotide polymorphism (SNP) arrays in detecting CNVs in the general population.

The Affymetrix 500K Array can genotype more than 500,000 SNPs and it offers the industry’s highest-resolution view of CNVs in the human genome.

Researchers in the study discovered that CNVs are much more prevalent than previously thought. CNV regions were found to comprise about 360 megabases, or around 12 percent of the human genome.

CNVs can consist of deletions, duplications or multi-site variants in DNA segments, ranging from a few kilobases to megabases in length.

They are particularly important in genetic research because they can be associated with specific diseases, such as an increased susceptibility to cancer, Parkinson’s and Alzheimer’s, as well as to conditions like HIV-1 infection and glomerulonephritis.

Certain CNVs also appear to influence drug metabolism and increase sensitivity to particular chemical carcinogens, which will also help to decipher the complex ways in which an individual’s genes and the environment impact disease.

“Our results suggest that sub-microscopic structural variants along chromosomes are more widespread than previously thought and that researchers should study both SNPs and CNVs when undertaking disease research,” said Stephen Scherer, Ph.D., senior scientist in Genetics & Genome Biology at The Hospital for Sick Children, director of The Center for Applied Genomics and one of the lead researchers in the study.

“Our new approach will be useful in understanding the role of copy number alteration in disease pathology. This information should lead to the development of diagnostic tests with sub-microscopic resolution that can detect not only mutations in cancer but other genetic variations associated with common diseases,” said Hiroyuki Aburatani, M.D., Ph.D., professor at the University of Tokyo and one of the lead researchers.

“This study illustrates that in addition to generating genotypes for over 500,000 SNPs, the Affymetrix 500K Array enables researchers to detect more CNVs than any other available platform. It's important to note that the combination of high-density markers and robust analysis methods have allowed us to identify CNVs and delineate the boundaries at a high resolution, which helps in establishing the link between CNVs and disease pathology,” said Keith Jones, Ph.D., vice president of molecular genetics at Affymetrix and another of the lead researchers.

Researchers in the Nature study constructed the CNV map of the human genome by analyzing samples from 270 people of European, Asian or African descent, who were originally included in the International HapMap Project.

The DNA from these individuals was scanned using the Affymetrix 500K Array and a BAC array platform developed by the Wellcome Trust Sanger Institute.

Using this combination of techniques on these samples, the researchers discovered 1,447 CNV regions containing hundreds of genes, disease loci, functional elements and segmental duplications.

The other researchers working on the International Genome Structural Variation Consortium’s Copy Number Variation Project were Nigel Carter and Matthew Hurles of the Wellcome Trust Sanger Institute and Charles Lee at the Department of Pathology at Brigham and Women’s Hospital.