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Genetic Research Into A Schizophrenia-associated Gene On Chromosome 13q32

Posted on:2005-07-01Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y HuFull Text:PDF
GTID:1104360125450076Subject:Radiation Medicine
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The Human Genome Project (HGP), a marvelous science approach to human biology, is attempting to elucidate the structure and constituent of human genome, and to decipher the sequence of DNA. These achievements facilitate the human being to understand themselves well and unravel the mystery of human life. The human genome is the whole set of DNA arrayed in 24 distinct chromosomes, which consists of 3.2 billions of base pairs (bp). The genomic DNA is 99.9% identical to that of other humans and 0.1% is variable. One of the fruits of the Human Genome Project is the discovery of millions of DNA sequence variants in the human genome. The use of these genetic markers has been playing an increasing part in genetics studies. Most variation of the human genome is attributable to single nucleotide polymorphisms (SNPs), which contributes to the differences between individuals in physical appearances, susceptibility to a disease and response to medication with drugs. SNPs have been widely used. A dense set of SNP markers opens up the possibility of studying the genetic basis of complex disease. In recent years, SNPs have been used as new DNA markers to replace microsatellites in mapping of disease-related genes in humans. There is no doubt that SNPs will play a key role in identifying and cloning of disease-related genes, investigating the mechanism of the genome-environment interaction and gene-gene interaction.Schizophrenia is a serious mental disorder with a lifetime prevalence rate of 1% in the general population worldwide. It was characterized by the abnormal mental functions and disturbed behaviors, which characteristically appear as a series of clinical features, such as positive and negative symptoms, and disturbances in basic cognitive functions. Because the illness causes heavy economical and social burdens to families and societies, it is very important to establish a procedure of treating and preventing schizophrenia. While the cause for schizophrenia remains unknown, several lines of evidence from family, twin and adoption suggest that genetic factors are likely to play an essential role in the developing of schizophrenia and influence susceptibility to schizophrenia. Epidemiological data have demonstrated that schizophrenia is not a simple Mendelian disease but looks like a complex disease involving several genes with each susceptiblity gene having only a modest individual effect. The completion of the HGP has provided a good opportunity for mapping all the genes involved in human diseases, including schizophrenia. Basically, there are two steps for mapping a disease-related gene in the human genome, the linkage-based genome-wide scan and the regional mapping with linkage disequilibrium (LD) analysis. Genome-wide scan has suggested that the following chromosomal regions may contain several genes contributing to schizophrenia, including 1q21-22, 5q31-33, 6p21-24, 6q25-26, 8p21-22, 10p11-15, 13q14-33 and 22q11-13. To validate these initial findings, the present study has been focused on identifying the candidate susceptibility genes on the 13q32 region using a family-based LD and case-control analysis and was designed to construct a SNP-based LD map.The family trio consists of healthy fathers, healthy mothers and affected offspring with schizophrenia. The SNP-based LD map was constructed between the GPC6 gene and the LOC122330 by looking through the known genes and SNPs of each gene on the 13q32 region using bioinformatics methods. 7 SNPs were chosen in this region spanning 13139.8kb including rs2892679 present in the GPC6 locus, rs2282135 in the EST LOC160889, rs2761072,rs626716 and rs624066 in the KPNB3 locus, rs1886089 in the STK24 locus, as well as rs942358 in the EST LOC122330.SNPs were genotyped using PCR-based RFLP analysis. Genotyping data were put into the SPSS database. The Hardy-Weinberg (H-W) equilibrium was tested for genotype frequency distributions of SNPs using the goodness of fit test. The LD between paired SNPs was estimated with the EH plus (version 1.11) and UNPHASED programs. The...
Keywords/Search Tags:chizophrenia, single nucleotide polymorphism, linkage disequilibrium, susceptibility, 13q32
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