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Microarray Technology and Applications in the Arena of Genome-Wide Association

¹ The Center for Applied Genomics and Division of Human Genetics, the Abramson Research Center of the Joseph Stokes Jr. Research Institute, The Children’s Hospital of Philadelphia; ² Department of Pediatrics, The University of Pennsylvania School of Medicine, Philadelphia, PA.

Address correspondence to the authors at: Struan F.A. Grant, Center for Applied Genomics, 1216F Abramson Research Center, 3615 Civic Center Blvd., Philadelphia, PA 19104-4318. Fax 267-426-0363; e-mail grants{at}chop.edu; or Hakon Hakonarson, Center for Applied Genomics, 1216E Abramson Research Center, 3615 Civic Center Blvd., Philadelphia, PA 19104-4318. Fax 267-426-0363; e-mail hakonarson{at}chop.edu

Background: There is a revolution occurring in single nucleotide polymorphism (SNP) genotyping technology, with high-throughput methods now allowing large numbers of SNPs (10⁵–10⁶) to be genotyped in large cohort studies. This has enabled large-scale genome-wide association (GWA) studies in complex diseases, such as diabetes, asthma, and inflammatory bowel disease, to be undertaken for the first time.

Content: The GWA approach serves the critical need for a comprehensive and unbiased strategy to identify causal genes related to complex disease, and is rapidly replacing the more traditional candidate gene studies and microsatellite-based linkage mapping approaches that have dominated gene discovery attempts for common diseases. As a consequence of employing array-based technologies, over the last 3 years dramatic discoveries of key variants involved in multiple complex diseases and related traits have been reported in the top scientific literature and, most importantly, have been largely replicated by independent investigator groups. As a consequence, several novel genes have been identified, most notably in the metabolic, cardiovascular, autoimmune, and oncology disease areas, that are clearly rooted in the biology of these disorders. These discoveries have opened up new avenues for investigators to address novel molecular pathways that were not previously linked to or thought of in relation with these diseases.

Summary: This review provides a synopsis of recent advances and what we may expect to still emerge from this field.

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