中国汉族瘢痕疙瘩家系易感基因位点的定位分析研究

Location study for the susceptible locus for keloid in Chinese pedigree of Han nationality

目的定位中国汉族瘢痕疙瘩家系的易感基因位点。方法采集2个4代发病的中国汉族瘢痕疙瘩大家系51例成员的外周静脉血样,提取基因组DNA;假定Fas基因为该家系致病基因的候选基因位点,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有关的已知基因相邻的微卫星标记D10S1687、D10S1765、D10S1735和D10S1562,对这些微卫星位点进行PCR扩增,产物片断基因分型,再进行连锁分析。结果在重组率θ=0～0.5时,这些微卫星标记的两点LOD值绝大部分都小于1,排除连锁关系存在。结论研究发现中国汉族瘢痕疙瘩家系易感基因位点不在染色体10q23.31区域。

Objective To locate the susceptible locus for a candidate leloid gene in two Chinese pedigrees of Han nationality. Methods Two Chinese keloid pedigrees with affected family members over four generations were investigated and confirmed. Venous blood samples from 51 members in the two family were collected and genomic DNA was extracted. The Fas gene was assumed to be a possible pathogenic gene for this disease. Four markers, D10S1687, D10S1765, D10S1735 and D10S1562 which are next to the known genes relating with apoptosis in the 10 Mbp region around the 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 linkage analyses were performed. Results Among the 4 selected markers, the two point LOD scores were less than 1 at θ= 0- 0.5, and they were excluded as the linkage to the disease locus. Conclusion After linkage analyses, this study provided genetic evidence that keloid susceptibility loci in these 2 Chinese keloid pedigrees were not on chromosome 10q23.31, demonstrating locus heterogeneity in familial keloid formation.