应用遗传连锁分析法对伴传导功能障碍的扩张型心肌病家系致病基因的定位

Genetic linkage analysis in localizing a gene of autosomal dominant familial dilated cardiomyopathy with conduction defect

目的:对一个常染色体显性遗传扩张型心肌病(familial dilated cardiomyopathy,FDCM)家系进行基因定位.方法: 收集FDCM 家系, 对该家系成员进行详细心血管内科检查确诊为扩张型心肌病,且伴发有传导功能障碍;采集外周血3～5 mL,并抽提基因组DNA;选取与该表型相关的已定位区间CMD1A(1q21.2-q21.3),CMD1H(2q14-q22), CMD1E(3p22-p25)和CMD1F(6q22-23)内的共计18个微卫星DNA标记,在该家系中进行排除性定位分析;最后,进行全基因组扫描及连锁分析.结果:①已定位区间的18个微卫星DNA标记位点的LOD值均<-2,证实该家系与已知DCM位点不连锁;②全基因组扫描及两点连锁分析结果显示,该家系致病基因位点与遗传标记D3S1614(3q26)连锁, 在θ= 0时得到最大LOD值2.68.结论: 该家系与已知的4个DCM位点均不连锁,其致病基因位于D3S1614(3q26)附近的一个新位点.

Objective To localize the gene of autosomal dominant familial dilated cardiomyopathy with conduction defect. Methods A Chinese family which was diagnosed as dilated cardiomyopathy with conduction defect was studied. Venous blood （3 -5 mL） from some family members was collected, and genomic DNA was extracted from the blood. Then whole genome wide scan was performed after excluding the known markers on the candidate loci （CMD1A, CMD1E, CMD1F, and CMD1H） by two-point linkage analysis. Results No significant evidence for linkage was found in the two point linkage analyses to the known markers in the analyzed family. And the whole genome wide scan showed the maximum LOD score reached 2.68 at marker D3S1614 （at recombination fraction θ = 0）. Conclusion The related gene in this kindred is located on 3q26 other than on CMD1A, CMD1H, CMD1E, and CMD1F.