单纯性马蹄内翻足易感基因位点筛查

Susceptibility gene location of idiopathic congenital talipes equinovarus

目的将人类单纯性马蹄内翻足(ICTEV)易感基因初步定位,为进一步对其克隆提供基础依据。方法选取与肢体发育、关节翻转及与软骨发育相关的基因作为候选基因,在基因内或其附近选取微卫星标记,应用PCR-短串联重复序列(STR)方法扩增微卫星片段,对84个ICTEV核心家系的252名成员进行基因型分析,并进行遗传连锁不平衡检验(TDT)。结果IX型胶原COL9A1基因(6q12-13区域)内及其附近的2个位点-D6S348及509-8B2经TDT检验表明,此2个位点与ICTEV有相关性(分别χ2=42.15,χ2=31.18,P<0.05);其他位点经TDT检验,不存在连锁不平衡(均P>0.05)。结论COL9A1基因可能是ICTEV的候选基因,从而将ICTEV易感基因初步定位于COL9A1基因所在的染色体区域6q12-13。

Objective To locate the susceptibility gene of human idiopathic congenital talipes equinovarus（ICTEV） for further cloning of the gene.Methods A number of candidate genes were proposed as potential susceptibility loci for ICTEV.The genes were predominantly related with limb development,joint turnover and encode structural proteins of the extracellular matrix.Each candidate gene was targeted using one or more intragenic or closely linked microsatellite marker.Genotypes of 252 members in 84 ICTEV families were analyzed with PCR-STR technique.Then transmission disequilibrium test（TDT） was used to test the data of genotypes.Results The analysis revealed that two loci within or closely linked microsatellite marker of IX collagen gene COL9A1（6q12-13） were associated with ICTEV,with a χ^2 value of 42.15 and 31.18（P〈0.05）.Conclusion COL9A1 gene may be a candidate susceptive gene of ICTEV.The location of ICTEV＇s susceptive genes is in chromosome 6q12-13.