A genome scan for familial combined hyperlipidemia reveals evidence of linkage with a locus on chromosome 11
A genome scan for familial combined hyperlipidemia reveals evidence of linkage with a locus on chromosome 11
复制标题
DOI：
10.1086/302490
复制
发表时间：
1999-08-01
影响因子：
9.8
通讯作者：
Lusis, AJ
中科院分区：
文献类型：
--
作者：
Aouizerat, BE;Allayee, H;Lusis, AJ
家族性混合性高脂血症（FCHL）是一种常见的家族性脂质紊乱，其特征是血浆胆固醇和/或甘油三酯水平升高的可变模式。它存在于10%-20%的早发冠心病患者中。该疾病的遗传病因学，包括涉及的基因数量及其影响的程度，是未知的。使用一个子集的35个荷兰家庭确定为FCHL，我们筛选的基因组，与一组393个遗传标记，染色体区域与基因有助于FCHL。在两阶段研究设计中，通过使用参数连锁方法对结果进行分析。染色体2 p、11 p、16 q和19 q上的4个位点显示出与FCHL连锁的暗示性证据（LOD得分为1.3-2.6）。然后在原始样本和其他荷兰FCHL家族中检查这些区域内的标记。2号染色体上的基因座未能显示连锁的证据，而16号和19号染色体上的基因座只产生了不确定的或暗示性的连锁证据。然而，在本设计的第二阶段，在人类11号染色体短臂上靠近标记D11 S1324的一个位点继续显示与FCHL连锁的证据。该区域不包含任何强候选基因。这些结果为FCHL的候选染色体区域提供了证据，并支持FCHL是复杂和异质性的概念。
Familial combined hyperlipidemia (FCHL) is a common familial lipid disorder characterized by a variable pattern of elevated levels of plasma cholesterol and/or triglycerides. It is present in 10%-20% of patients with premature coronary heart disease. The genetic etiology of the disease, including the number of genes involved and the magnitude of their effects, is unknown. Using a subset of 35 Dutch families ascertained for FCHL, we screened the genome, with a panel of 393 genetic markers, for chromosomal regions linked to genes contributing to FCHL. The results were analyzed by use of parametric-linkage methods in a two-stage study design. Four loci, on chromosomes 2p, 11p, 16q, and 19q, exhibited suggestive evidence for linkage with FCHL (LOD scores of 1.3-2.6). Markers within each of these regions were then examined in the original sample and in additional Dutch families with FCHL. The locus on chromosome 2 failed to show evidence for linkage, and the loci on chromosome 16q and 19q yielded only equivocal or suggestive evidence for linkage. However, one locus, near marker D11S1324 on the short arm of human chromosome 11, continued to show evidence for linkage with FCHL, in the second stage of this design. This region does not contain any strong candidate genes. These results provide evidence for a candidate chromosomal region for FCHL and support the concept that FCHL is complex and heterogeneous.