Characterization of the major susceptibility region for psoriasis at chromosome 6p21.3
Characterization of the major susceptibility region for psoriasis at chromosome 6p21.3
复制标题
DOI：
10.1046/j.1523-1747.1999.00710.x
复制
发表时间：
1999-09-01
影响因子：
6.5
通讯作者：
Trembath, RC
中科院分区：
文献类型：
--
作者：
Balendran, N;Clough, RL;Trembath, RC
牛皮癣是一种常见的炎症性皮肤病，由遗传和环境因素引起。最近的全基因组连锁分析已经确定了一个基因座编码银屑病的易感性，并将该基因放置在染色体6p21.3上标记D 6S 426和D 6S 276之间的12 cM间隔。这是一个广泛的区域，包括人类主要组织相容性复合体。我们试图通过对118个受影响的同胞对、其父母和其他受影响的家庭成员进行基因分型，利用连锁、单倍型和连锁不平衡信息，更精确地定位易感基因。共有14个高度多态性的标记进行基因分型，结合匿名位点与I类基因HLA-B和-C分布在一个遗传间隔约14厘米，包括整个主要组织相容性复合体。通过在主要组织相容性复合体中应用高密度定位，我们确定了银屑病患者中最常见的遗传同源区域。使用传递不平衡检验，我们发现了连锁和等位基因关联的重要证据，跨越由标记tn 62（p = 1.0 x 10（-7））、HLA-B（p = 4.0 x 10（-7））和HLA-C（p = 2.7 x 10（-9））定义的区间，该区域包含在285 kb基因组DNA片段内。因此，这些研究有助于细化银屑病易感基因的定位，并将关键区域靠近HLA-C。
Psoriasis is a common inflammatory skin condition caused by genetic and environmental factors. Recent genome-wide linkage analyses have identified a locus encoding susceptibility to psoriasis and placed this gene in the 12 cM interval between markers D6S426 and D6S276 on chromosome 6p21.3. This is a broad region and encompasses the human major histocompatibility complex. We have sought to localize the susceptibility gene more precisely by exploiting the linkage, haplotype, and linkage disequilibrium information available through genotyping 118 affected sib pairs, their parents and other affected family members. A total of 14 highly polymorphic markers were genotyped, combining anonymous loci with the class I genes HLA-B and -C distributed across a genetic interval of approximately 14 cM including the entire major histocompatibility complex. Through the application of higher density mapping within the major histocompatibility complex, we identified those regions most commonly shared identical by descent in patients with psoriasis. Using the transmission-disequilibrium test, we found significant evidence of linkage and allelic association across an interval defined by the markers tn62 (p = 1.0 x 10(-7)), HLA-B (p = 4.0 x 10(-7)), and HLA-C (p = 2.7 x 10(-9)), a region encompassed within a 285 kb genomic DNA fragment. Hence these studies contribute to the refinement of the localization of a major psoriasis susceptibility gene and place the critical region near to HLA-C.