Mapping of developmental dysplasia of the hip to two novel regions at 8q23-q24 and 12p12
Mapping of developmental dysplasia of the hip to two novel regions at 8q23-q24 and 12p12
复制标题
将髋关节发育不良映射到 8q23-q24 和 12p12 的两个新区域
DOI：
10.3892/etm.2020.8513
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发表时间：
2020-04-01
影响因子：
2.7
通讯作者：
Li, Qiwei
中科院分区：
文献类型：
--
作者：
Zhang, Lixin;Xu, Xiaowen;Li, Qiwei
髋关节发育不良（DDH），以前被称为先天性髋关节脱位，是一种常见的致残疾病，其特征是在以后的生活中过早关节炎。遗传因素在DDH的病因学中起关键作用。在本研究中，使用Affymetrix 10K基因芯片对一个中国四代家庭进行全基因组连锁扫描，该家庭包括19名健康成员和5名患者。采用genesspring GT v.2.0软件进行参数和非参数多点联动分析，计算赔率（LOD）评分和非参数联动（NPL）评分的对数。进行参数连锁分析，假设常染色体隐性性状具有全外显率和Affymetrix“亚洲”等位基因频率。在8q23-24染色体上发现了最强烈的连锁证据，其峰值LOD评分为2.658 (theta=0)，覆盖单核苷酸多态性（snp） rs724717至rs720132的2.377 Mb。该区间包括另外9个连续的snp: rs1566071、rs1902121、rs756404、rs702768、rs777813、rs2033995、rs147959、rs2884367和rs1898287。从非参数多点连锁分析中，同一地区的不良贷款得分最高，为2.883 （P=0.0156）。rs1919980、rs763853和rs725124 3个连续标记在12p12染色体上的NPL评分为2.727 (P=0.0156)， LOD评分为2.528 (θ =0)，位居第二。值得注意的是，除了这两个区域外；其他染色体区域未发现明显的连锁（LOD和NPL评分为bb0 2.0）。至少在这个家系中，本研究的证据首次表明，DDH被定位到8q23-q24和12p12两个新的区域。
Developmental dysplasia of the hip (DDH), previously known as congenital hip dislocation, is a frequently disabling condition characterized by premature arthritis later in life. Genetic factors play a key role in the aetiology of DDH. In the present study, a genome-wide linkage scan with the Affymetrix 10K GeneChip was performed on a four-generation Chinese family, which included 19 healthy members and 5 patients. Parametric and non-parametric multipoint linkage analyses were carried out with Genespring GT v.2.0 software, and the logarithm of odds (LOD) score and nonparametric linkage (NPL) score were calculated. Parametric linkage analysis was performed, assuming an autosomal recessive trait with full penetrance and Affymetrix 'Asian' allele frequencies. The strongest evidence for linkage was found on chromosome 8q23-24, with a peak LOD score of 2.658 (theta=0), covering 2.377 Mb from single nucleotide polymorphisms (SNPs) rs724717 to rs720132. This interval included nine additional successive SNPs: rs1566071, rs1902121, rs756404, rs702768, rs777813, rs2033995, rs147959, rs2884367 and rs1898287. The same region also yielded the highest NPL score of 2.883 (P=0.0156) from the non-parametric multipoint linkage analysis. Additionally, the second highest NPL score of 2.727 (P=0.0156) and LOD score of 2.528 (theta=0) were obtained on chromosome 12p12 for three consecutive markers (rs1919980, rs763853 and rs725124). This region overlapped a narrow distance of 0.642 Mb. Notably, in addition to these two regions; no significant linkage was identified for other chromosomal regions (with LOD and NPL scores >2.0). For the first time, at least for this pedigree, the evidence in the present study showed that DDH is mapped to two novel regions at 8q23-q24 and 12p12.