中国汉族一瘢痕疙瘩家系易感基因的定位研究

目的定位中国汉族瘢痕疙瘩家系的易感基因。方法采集1个5代发病的中国汉族瘢痕疙瘩大家系32名成员的外周静脉血样,提取基因组DNA;设定Fas基因为导致该家系发病的一个候选基因,选取位于10q23.31上Fas基因周围共约10Mbp范围内与细胞凋亡障碍或肿瘤发生有关的所有已知基因相邻的微卫星标记D10S1687、D10S1765、D10S1735和D10S1562共4个,对这些微卫星位点进行PCR扩增,产物片断基因分型和连锁分析。结果连锁分析发现微卫星标记D10S1765LODZMAX为1.74,D10S1735LODZMAX为1.51,支持连锁;D10S1562LODZMAX为0.59,不排除连锁;在θ=0.0～0.10时,D10S1687标记的所有LOD值都小于-2,排除连锁。结论我们的研究首次发现了该中国汉族瘢痕疙瘩家系的易感基因可能位于10q23.31上D10S1765与D10S1735两位点间约1Mbp区域的遗传学证据。

Location of predisposing gene for one Han Chinese keloid pedigree

OBJECTIVE: To locate the locus of predisposing gene for Han Chinese keloid pedigree. METHODS: One large Chinese keloid pedigree with affected family members in five generations was investigated and confirmed. Venous blood samples from 32 members in this family were collected and extracted genomic DNA. Fas gene was assumed as one of the candidate genes resulting in keloids in this pedigree. Four markers, D10S1687, D10S1765, D10S1735 and D10S1562 next to the all known genes relating with apoptosis or tumorigenesis in the 10 Mbp region around Fas gene on chromosomes 10q23.31 were selected as microsatellite markers. Subsequently, these markers were amplified by PCR, and all PCR products were genotyped and the linkage analyses were performed. RESULTS: After linkage analyses, D10S1765LOD(ZMAX) was 1.74, D10S1735LOD(ZMAX) was 1.51. These findings supported the linkage. D10S1562LOD(ZMAX) was 0.59, which did not exclude the linkage. All LODs for D10S1562 were less than - 2, at 0 = 0.0 - 0.10, which excluded the linkage. CONCLUSIONS: This study provides the first genetic evidence that the predisposing gene for this Han Chinese keloid pedigree may be mapped to the region about 1 Mbp on chromosomes 10q23.31, between marker D10S1765 and D10S1735.