华人遗传性混合息肉病综合征患者单倍型及遗传连锁分析

目的探讨华人遗传性混合息肉病综合征(HMPS)患者基因单倍型定位与公认Ashkenazi家系(SM96)是否一致。方法从31个家系成员外周血标本中提取基因组DNA,多重PCR扩增4个微卫星标记D15S1010、D15S1007、ACTC和D15S118。采用单倍型和遗传连锁分析方法,验证人染色体15q13区域2.8cM范围内遗传标记是否与致病基因连锁。结果12号家系中该病的单倍型在一个患病个体无标记连锁,同时2号家系未发现该病的单倍型。ACTC标记两点及多点遗传连锁分析最大对数优势记分LODs分别为0.20(θ=0.3)和-5.0。结论单倍型及遗传连锁分析提示,Ashkenazi单倍型与华人HMPS无关,两者存在遗传背景的差异性。

Haplotype and linkage analysis in Chinese hereditary mixed polyposis syndrome

OBJECTIVE: To investigate if hereditary mixed polyposis syndrome (HMPS) locus of two Singapore Chinese HMPS families is identical with the Ashkenazi families. METHODS: Genomic DNA was extracted, mutiplex polymerase chain reaction (PCR) was used to amplify 4 microsatellite markers D15S1010, D15S1007, ACTC and D15S118 in 31 individuals from two families. The HMPS locus cosegretion of the markers on 15q13 over a region of 2.8 cM was confirmed by Haplotype and linkage analysis. RESULTS: The disease of haplotype identified in one pedigree was not co-segreagted with an affected individual while no definitive disease hapoltype could be assigned for the second pedigree. The maximum two-point and muti-point LOD scores at ACTC for the two Chinese families are 0.20 (theta = 0.3) and -5.0 respectively. CONCLUSIONS: Haplotype and linkage analysis indicate that the Ashkenazi haplotypes is not associated with HMPS in Singapore Chinese families, which suggests genetic heterogeneity.