Locus Mapping And Mutation Detecting For Blepharophimosis Ptosis Epicanthus Inversus Syndrome(BPES) And A Study Of The Candidate Gene To Schizophrenia

The thesis contains two main pieces of work. In the first one, we mapped the locus for Blepharophimosis ptosis epicanthus inversus syndrome(BPES) using linkage analysis based on a large family and detected a T insertion mutation. In another piece of work, we studied the linkage disquilibrium between the SNP in RGS4 gene and schizophrenia in the Han Chinese population using a case-control test. Blepharophimosis ptosis epicanthus inversus syndrome(BPES) (MIM 110100) is a common ophthalmic disorder, the incidence of which is around 0.1%. BPES is caused by entire or part dysfunction of upper-eyelid lifting muscle or Muller smooth muscle. In this work, we have first mapped the locus for BPES onto chromosome 3q23 using a family composed of 18 affected and 13 normal subjects in Han Chinese. The LOD score with two-point linkage analysis is 5.12 shown by markers D3S1541 at recombination fractionθ=0.00. The results from another four markers (D3S3617,D3S3684 and D3S1292) in the same region furthermore support the linkage. The precise analysis for this family confined the locus within the FOXL2 gene. We sequenced the gene and dected a T insertion mutation. Studies have shown a strong positive association between schizophrenia and RGS4 gene, demonstrated by both individual markers and haplotypes. A further functional study also supports the role of RGS4 in the etiology of schizophrenia. In this study, we have replicated these results of case-control test and haplotype analysis in the Han Chinese population, showing P values of 0.0001 and 0.00001 for individual markers...