Mapping The Locus For Congenital Preauricular Fistula And A Study Of The Candidate Gene To Schizophrenia

The thesis contains two main pieces of work. In the first one, wemapped the locus for Congenital Preauricular Fistula using linkageanalysis based on a large family. In another piece of work, we studiedthe linkage and assciation between the SNP in G72/G30 genes andschizophrenia in the Han Chinese population using atransmission/disequilibrium test. Congenital Preauricular Fistula (MIM 128700) is a common auricularabnormality, the incidence of which is around 1%. The formation of CPFis closely associated with embryological development of the auricle,which is developed from the first and second branchial arches. In thiswork, we have first mapped the locus for CPF onto chromosome 8q11.1-q13.3using a family composed of 7 affected and 11 normal subjects. The LOD scorewith two-point linkage analysis is 2.40 shown by markers D8S285 andD8S1113 at recombination fractionθ=0.00. The results from another threemarkers (D8S1110, D8S260 and D8S1136) in the same region further supportthe linkage. The haplotype analysis for this family confined the locuswithin an interval of approximately 26.7 cM flanked by markers D8S532 andD8S279. Studies have shown a strong positive association betweenschizophrenia and G72/G30 genes, demonstrated by both individual markers 2先天性耳前瘘管基因定位及精神分裂症候选基因分析and haplotypes. A further functional study also supports the role of G72in the etiology of schizophrenia. In this study, we have replicated theseresults of transmission/disequilibrium test and haplotype analysis in theHan Chinese population, showing P values of 0.0018 and 0.00007 forindividual markers and haplotypes, respectively. Hence, our data supportsthe hypothesis that G72/G30 genes are important candidate genes forexplaining schizophrenia in the Han Chinese population.