Major new genome partnership to catalogue all common copy number variations

Toronto, Boston, Hinxton – An international team will use high-density microarrays and new computer algorithms to improve the detection of variants in the human genome which are implicated in various diseases. The new systems are the foundation of Phase 2 of the Genome Structural Variation Consortium, which was set up in 2004 and seeks to identify structurally variable regions in the human genome.

In 2006, the Genome Structural Variation Consortium, along with other international collaborators, generated a first-generation map of copy number variants (CNVs) covering the human genome. The CNVs that they identified, which in many cases lead to deletion or duplication of genes along chromosomes, tended to encompass large stretches of DNA ranging from thousands to millions of chemical bases of DNA. These changes are part of the normal variability between apparently healthy people, but some may also predispose individuals to disease.

The data also suggested that thousands more CNVs exist, but technological limitations associated with that earlier study precluded the discovery of more CNVs. The new comprehensive map will be critical for studies attempting to identify genes involved in both rare and common diseases.

“Our experiments will generate the highestresolution CNV catalogue of worldwide populations. The initiative will also complement ours, and other efforts to sequence entire genomes,” says Dr Stephen Scherer, senior scientist and director, the Centre for Applied Genomics (TCAG) at the Hospital for Sick Children (SickKids) in Toronto.

In its second phase, this international research collaboration will develop a comprehensive, higher resolution CNV map for the Human Genome – at a level 100-fold finer than the first map. Working with NimbleGen Systems of Madison, Wisconsin, the consortium has designed a novel set of 2.1-million-feature microrrays that will enable genome-wide detection of CNVs with 42 million probes.

The set of microarrays are referred to as whole-genome oligonucleotide tiling arrays because they cover almost all DNA along chromosomes, spaced at intervals of only 50 bases, or letters of DNA code. The international consortium is led by Dr Scherer, Drs Nigel Carter, Matthew Hurles, and Chris Tyler-Smith of the Wellcome Trust Sanger Institute, and Dr Charles Lee from Brigham and Women’s Hospital and Harvard Medical School.

“Copy Number Variation has emerged over the past few years as a novel and productive focus for understanding variation within the human genome as well as other species’ genomes,” noted Dr Christian Burks, president and CEO of the Ontario Genomics Institute. “We are delighted, in conjunction with funding from Genome Canada and Ontario’s Ministry of Research and Innovation, to be supporting this work, and to see Ontario and Canada at the forefront of this area of biomedical research.”