Trans-ethnic fine mapping of a quantitative trait locus for circulating angiotensin I-converting enzyme (ACE)
Trans-ethnic fine mapping of a quantitative trait locus for circulating angiotensin I-converting enzyme (ACE)
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DOI：
10.1093/hmg/10.10.1077
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发表时间：
2001-05-01
影响因子：
3.5
通讯作者：
Cardon, LR
中科院分区：
文献类型：
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作者：
McKenzie, CA;Abecasis, GR;Cardon, LR
循环血管紧张素I转换酶（ACE）水平受ACE基因的主要数量性状位点（QTL）的影响。系统发育和测量的单倍型分析表明，ACE连锁的QTL位于一个假定的祖先断点的下游，该断点位于6435位附近。然而，在该基因的3'部分标记之间的强烈连锁不平衡阻碍了在高加索受试者中进一步解析该QTL。我们研究了10 ACE基因多态性在非洲裔加勒比家庭在牙买加招募。方差分量分析显示，强有力的证据的联系和协会循环ACE水平。当连锁结果与一组英国白人家庭的结果进行对比时，没有证据表明样本之间存在异质性。然而，在两个数据集中，标记物和循环ACE水平之间的等位基因关联模式显著不同。在英国家系中，有3个标记[G2215 A、Alu插入/缺失和G2350 A]与ACE连锁QTL完全不平衡，在牙买加家系中，只有标记G2350 A与ACE连锁QTL表现出强烈但不完全的不平衡。此外，我们的研究结果表明，方差分量的方法结合结构化的，来自不同种族的家庭之间的定量比较可能是一个有用的策略，以帮助确定哪些，如果有的话，在一个小的基因组区域的变异直接影响数量性状。
Circulating angiotensin I-converting enzyme (ACE) levels are influenced by a major quantitative trait locus (QTL) that maps to the ACE gene. Phylogenetic and measured haplotype analyses have suggested that the ACE-linked QTL lies downstream of a putative ancestral breakpoint located near to position 6435, However, strong linkage disequilibrium between markers in the 3' portion of the gene has prevented further resolution of the QTL in Caucasian subjects. We have examined 10 ACE gene polymorphisms in Afro-Caribbean families recruited in Jamaica. Variance components analyses showed strong evidence of linkage and association to circulating ACE levels. When the linkage results were contrasted with those from a set of British Caucasian families, there was no evidence for heterogeneity between the samples. However, patterns of allelic association between the markers and circulating ACE levels differed significantly in the two data sets. In the British families, three markers [G2215A, Alu insertion/deletion and G2350A] were in complete disequilibrium with the ACE-linked QTL, In the Jamaican families, only marker G2350A showed strong but incomplete disequilibrium with the ACE-linked QTL, These results suggest that additional unobserved polymorphisms have an effect on circulating ACE levels in Jamaican families. Furthermore, our results show that a variance components approach combined with structured, quantitative comparisons between families from different ethnic groups may be a useful strategy for helping to determine which, if any, variants in a small genomic region directly influence a quantitative trait.