Abecasis G R, Noguchi E, Heinzmann A, Traherne J A, Bhattacharyya S, Leaves N I, Anderson G G, Zhang Y, Lench N J, Carey A, Cardon L R, Moffatt M F, Cookson W O
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, England OX3 7BN.
Am J Hum Genet. 2001 Jan;68(1):191-197. doi: 10.1086/316944. Epub 2000 Nov 13.
The positional cloning of genes underlying common complex diseases relies on the identification of linkage disequilibrium (LD) between genetic markers and disease. We have examined 127 polymorphisms in three genomic regions in a sample of 575 chromosomes from unrelated individuals of British ancestry. To establish phase, 800 individuals were genotyped in 160 families. The fine structure of LD was found to be highly irregular. Forty-five percent of the variation in disequilibrium measures could be explained by physical distance. Additional factors, such as allele frequency, type of polymorphism, and genomic location, explained <5% of the variation. Nevertheless, disequilibrium was occasionally detectable at 500 kb and was present for over one-half of marker pairs separated by <50 kb. Although these findings are encouraging for the prospects of a genomewide LD map, they suggest caution in interpreting localization due to allelic association.
常见复杂疾病相关基因的定位克隆依赖于遗传标记与疾病之间连锁不平衡(LD)的识别。我们在来自英国血统无关个体的575条染色体样本中,检测了三个基因组区域中的127个多态性。为了确定相位,对160个家庭中的800名个体进行了基因分型。发现LD的精细结构非常不规则。不平衡测量中45%的变异可以用物理距离来解释。其他因素,如等位基因频率、多态性类型和基因组位置,解释的变异不到5%。然而,在500 kb处偶尔可检测到不平衡,并且在相隔小于50 kb的标记对中,超过一半存在不平衡。尽管这些发现对于全基因组LD图谱的前景令人鼓舞,但它们表明在因等位基因关联而进行定位解释时需谨慎。