应用连锁不平衡检验法进行单纯性先天性心脏病易感基因的初步定位

Susceptibility gene location of simple congenital heart defect by transmission disequilibrium test

目的将人类单纯性先天性心脏病（ｃｏｎｇｅｎｉｔａｌｈｅａｒｔｄｅｆｅｃｔ，ＣＨＤ）易感基因初步定位，为进一步对其克隆奠定基础。方法在胚胎心脏发育调控相关基因——ＨＯＸ基因Ａ簇、Ｂ簇所在的染色体区域７ｐ１４－１５、１７ｑ２１内选择３个微卫星ＤＮＡ标记Ｄ７Ｓ１８０８、Ｄ７Ｓ６７３、Ｄ１７Ｓ７９１，应用荧光标记聚合酶链反应技术扩增微卫星片段，对３９个单纯性ＣＨＤ核心家系的１１２名成员进行基因型分析，并进行遗传连锁不平衡检验（ｔｒａｎｓｍｉｓｓｉｏｎｄｉｓｅｑｕｉｌｉｂｒｉｕｍｔｅｓｔ，ＴＤＴ）。结果Ｄ７Ｓ１８０８及Ｄ７Ｓ６７３这两个位点ＴＤＴ检验计算χ２值分别为３１．３（Ｐ＜０．００５）和１１．１２（Ｐ＜０．０５），表明此两位点与ＣＨＤ分别有非常显著和较显著的相关性，而Ｄ１７Ｓ７９１位点ＴＤＴ检验计算χ２值为６．５６（Ｐ＞０．０５），未检出连锁不平衡。结论人类单纯性ＣＨＤ与ＨＯＸＡ簇基因位点有关，ＨＯＸＡ簇基因可能是ＣＨＤ的候选基因，从而将ＣＨＤ易感基因初步定位于ＨＯＸＡ簇基因的染色体区域７ｐ１４－１５。

Objective To locate the susceptibility gene of human simple congenital heart defect(CHD) and provide a sound basis for further gene cloning. Methods Three short tandem repeats(STRs) in regions of chromosome 7p1415, 17q21 where exist Hox gene family's A, B clusters which regulate the embryonic heart development were chosen. Genotypes of 112 members in 39 CHD families were analyzed by amplifying the STR fragments using fluorescencePCR technique. Then transmission disequilibrium test (TDT) was used to test the data of genotypes. Results Statistical 2 values of D7S1808, D7S673 and D17S791 were 31.3(P<0.005), 11.12(P<0.05) and 6.65 (P>0.05) respectively. These suggest that the former two are associated with CHD, while the latter is not. Conculsion Human simple CHD is associated with Hox gene A cluster. Hox A gene may be a candidate CHD's susceptive genes. The location of the CHD's susceptive genes is in chromosome 7p1415.