云南地方性先天性髋关节脱位遗传病子标记研究

Objective: To investigate genetic linkage between the phenotype of congenital dislocation of the hip(CDH) and genes located in chromosome 7、21、22、X, and attempt initially process of the genome-wide scan for searching disease-susceptibility loci.Methods: According to epidemiological data, 3 kindreds with CDH in yunnan, include 61 persons in 5 generations was studied. The affected status of 14 individuals had been established on the basis of their clinical and radiological presentation of the disorder. 61 blood specimens were collected from those members who could be followed trail, and their nucleus DNA was extracted from peripheral leukocytes as Phenol method. 45 Tetnuc or Trinuc repeat microsatellite markers exploited by CHLC were chosen. Markers are distributed on chromosome 7、21、22、X with an average interval of 10 cM and Xq26-28 of chromosome X. Genomic DNA were amplified by PCR technique. The PCR products were subjected to vertical electrophoresis in PAGE gel with continuous buffer system, followed by silver staining. Graphic analysis system was used to define each alleles. Parametric linkage analysis using maximum likelihood estimation were computed by the LINKAGE package for various recombination fraction values, with a disease gene frequency of 0.02..Result: 45 STR loci are shown to provide good discrimination power by highly polymorphism and heterozygosity. Genotype data were obtained and conformed to Mendel low. Linkage analysis with those markers gave minus two-point LOD score values(Z<1), indicated that there is no linkage between the markers and CDH gene in those pedigrees.Conclusion: CDH is not the result of a mutation of the COL1A2 gene, which coding for typeⅠcollagen, and CDH susceptibility genes are not likely located on chromosome 7、21、22、X. The approach to genome-wide scan using highly density STR markers would play an important role in map the gene responsible for CDH.

在以调查获取30个云南陆良县CDH遗传病家族图谱基础上，应用遗传病家系软件分析其可能囊糯嘌裕ü旧錑带精细分析及STR 和RAPD法精细连锁分析，初步确定遗传性CDH喙鼗蛟谌旧迳峡赡艽嬖诘奈恢茫⒀罢姨匾煨源祝云诿魅稢DH的遗传方式并进行分子标记，为进一步明确CDH的病因，克隆该致病基因作准备。