Linkage Analysis Of Susceptible Gene In Yunnan Pedigrees With Congenital Dislocation Of The Hip

Objective: To investigate genetic linkage between the phenotype of congenital dislocation of the hip(CDH) and genes located in chromosome 22,7,X,and attempt initially process of the genome-wide scan for searching disease-susceptibility loci.Methods: According to epidemiological data ,we studied 4 kindred with CDH in yunna ,which include 65 persons in 5 generations .the affected status of 17 individuals had been established on the basis of their clinical and radiological presentation of the disorder. 44 blood specimens were collected from those members who could be followed trail ,and their nucleus DNA wsa extracted from peripheral leukocytes as phenol method .35 Tetnuc or Trinuc repeatmicrosatellite markers exploited by CHLC were chosen .8 markers distributed on chromosome 22,and 10 markers distributed on 7chromosome with an average interval of 10 cM and 17 distributed on X chromosome .Genimic DNA were amplified by PCR technique. The PCR products were subjected to vertical electrophoresis in PAGE gel with continous buffer system, followed by siliver staining.graphic analysis system was used to define each alleles. Parametric linkage analysi using maximum likelihood estimation were computed by the LINKAGE package for various recombination fraction valus, with a disease gene grequency of 0.02.Result: 35 STR loci are showen to provide good discrimination power by highly polymorphism and heterozygosity. Gnotype datd were obtainedand conformed to Mendel law.Linkage analysis with those markers gave minus two-point LOD score values(Z<1),which the markers in 22and 7 chromosome indicated that there no linkage between the markers and CDH gene in those pedigrees.But , The maximum LOD score of 2.184339 was obtained with genetic marker Dxs8091 with no recombination. So we selected 7 markers which around Dxs8091 with an average interval of 3 cM. Wo did the same expriment.The result was that the lod score was less than 1,which indicated there was no linkage between the markers and CDH gene in those pedigrees.Conclusion:CDH susceptibility genes are not likely located on chromosome 22,7 X.The approach to geno-wide scan using highly density STR markers would play an important role in map the gene responsible for CDH.