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Methods in Genetics and Clinical Interpretation

HapMap and Mapping Genes for Cardiovascular Disease

Kiran Musunuru, MD, PhD and Sekar Kathiresan, MD

From the Cardiovascular Research Center and Cardiology Division, and Center for Human Genetic Research, Massachusetts General Hospital, Boston and Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Mass (K.M., S.K.).

Correspondence to Sekar Kathiresan, MD, Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge St, CPZN 5.252, Boston, MA 02114. E-mail skathiresan@partners.org

Key Words: cardiovascular diseases • genes • mapping

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
A key goal of biomedical science is to understand why individuals differ in their susceptibility to disease. Family history is among the established risk factors for most forms of cardiovascular disease, in part because inherited DNA sequence variants play a causal role in disease susceptibility. Consequently, the search for these variants has intensified over the past decade.^1–3 One class of DNA sequence variants takes the form of single nucleotide changes (single nucleotide polymorphisms, or SNPs), usually with two variants or alleles for each SNP.⁴ SNPs are scattered throughout the 23 pairs of chromosomes of the human genome, and roughly 11 million common polymorphisms (ie, those >1% frequency) are estimated to exist.⁵ A combination of SNP alleles along a chromosome is termed a haplotype.

The International Haplotype Map Project was designed to create a public genome-wide database of common SNPs and, consequently, enable systematic studies of most common SNPs for their potential role in human disease.^6–8 We review the following: (1) the concept of linkage disequilibrium or allelic association, (2) the HapMap project, and (3) several examples of the utility of HapMap data in genetic mapping for cardiovascular disease phenotypes.

	Linkage Disequilibrium: Correlation Among SNPs

 
Groups of SNPs across the genome are correlated with each other, a phenomenon known as linkage disequilibrium (LD) or allelic association. To understand how LD arises, one needs to recall that during meiosis, recombination occurs at multiple sites between each pair of chromosomes, thus providing for an extra source of genetic variability to pass on to offspring. This is not a . . . [Full Text of this Article]