Musunuru Kiran, Kathiresan Sekar
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.
Circ Cardiovasc Genet. 2008 Oct;1(1):66-71. doi: 10.1161/CIRCGENETICS.108.813675.
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. 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. 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. 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. We review the following: (1) the concept of linkage disequilibrium orallelic association, (2) the HapMap project, and (3) several examples of the utility of HapMap data in genetic mapping for cardiovascular disease phenotypes.
生物医学科学的一个关键目标是了解个体对疾病易感性存在差异的原因。家族病史是大多数心血管疾病形式已确定的风险因素之一，部分原因是遗传的DNA序列变异在疾病易感性中起因果作用。因此，在过去十年中，对这些变异的寻找工作不断加强。一类DNA序列变异表现为单核苷酸变化（单核苷酸多态性，即SNPs），每个SNP通常有两种变异形式或等位基因。SNPs散布在人类基因组的23对染色体中，据估计大约存在1100万个常见多态性（即频率>1%的那些）。沿着一条染色体的SNP等位基因组合被称为单倍型。国际单倍型图谱计划旨在创建一个全基因组范围的常见SNPs公共数据库，从而能够对大多数常见SNPs在人类疾病中的潜在作用进行系统研究。我们将回顾以下内容：（1）连锁不平衡或等位基因关联的概念，（2）单倍型图谱计划，以及（3）单倍型图谱数据在心血管疾病表型基因定位中的几个应用实例。
