一汉族瘢痕疙瘩家系的易感基因定位分析研究

目的采用连锁分析方法探讨瘢痕疙瘩(keloid)家系的疾病易感基因与15q22.31-q23及18q21.1区域的连锁关系。方法1个中国东北地区5代keloid家系,采集家系中32名成员的外周血标本提取DNA,选择位于15q22.31-q23及18q21.1区域7个微卫星标记,应用聚合酶链式反应(PCR)得到扩增产物片断,测定PCR产物片段大小,得到每个样本的基因型,运用连锁分析软件Linkage5.11的MLINK程序计算每个标记的LOD值,根据两点间LOD值判断连锁关系。结果D15S108、D15S216、D15S534、D18S363、D18S846五个位点的两点LOD值在重组率为0时均小于-2,可以排除连锁关系,而D18S460、D18S467两位点在重组率θ为0.05和0.10时的两点LOD值均大于1,D18S460在θ=0时大于2,提示此家系keloid易感基因与这两个位点存在一定连锁关系。结论此汉族keloid家系的易感基因可能位于染色体18q21.1区域内,初步确定SMAD2和PIAS2基因为可能的易感基因。

Preliminary linkage analysis and mapping of keloid susceptibility locus in a Chinese pedigree

OBJECTIVE: To investigate the linkage between the susceptibility locus to keloid and two loci, 15q22.31-q23 and 18q21.1, the authors performed linkage analysis of a pedigree. METHODS: A five-generation Han Chinese family of keloid was investigated and confirmed. Venous blood samples of 32 members in this family were collected for PCR and genetic analysis. Seven microsatellite markers spanning the critical regions on chromosomes 15q22.31-q23 and 18q21.1 were genotyped, and the DNA extracted from each sample was amplified for these markers. The PCR products of them were scanned at ABI PRISM 310 Genetic Analyzer, the eligible genotyping data were used for linkage analysis. The two-point LOD scores were calculated by MLINK program of Linkage5.11. RESULTS: Among the 7 markers, the two-point LOD scores of 5 ones (D15S108, D15S216, D15S534, D18S363, D18S846) were less than -2 at theta = 0, they were excluded the linkage to the disease locus; but the scores of other two (D18S460, D18S467) were either more than 1 at theta = 0.05 & 0.10 and D18S460 was 2.201, which showed linkage to the disease locus in some extent. Conclusions This study firstly reported and provided some evidence that keloid susceptibility locus of Chinese family maybe on chromosome 18q21.1, SMAD and PIAS2 may be the possible genes.