I. The Human On The 21st Chromosome Known Gene Sequence Polymorphism And Primate Gene Sequences Ii Of Using Snp-sensitive Genes And The Study Of Hbv Strains To Find Disease Genes For Complex Diseases, Environmental Factors

Single-Nucleotide Polymorphisms (SNPs) are the most abundant form of genetic variations. In this study, we tried to construct a SNP and haplotype database of Chinese population in chromosome 21; compare the sequence between human and primates; look for genes associated with complex disease or environmental fact and analysis the hepatitis B virus (HBV) by polymorphisms. Sequence variations of the coding and regulatory regions of 127 known genes in chromosome 21 were analyzed in samples, include DNAs of 31 individual Chinese, 4 pooled DNAs from Southern Chinese, Northern Chinese, Caucasian and Black populations as well as DNA samples from chimpanzee, gorilla, orangutan and macaque. We identified 1192 SNPs in 711,283 bp in our sampled Chinese individuals. For inter-species sequence comparison, we identified 3003 nucleotide differences between Human and Chimpanzee over a total of 399,264 base pairs. The difference of coding, promoter and coding boundary regions were 0.51%, 0.88% and 0.85% respectively. These data provided interesting first glimpse into the pattern of SNPs across the chromosome 21 and allele frequency differences among different populations and suggested that the ethnic population should be considered in the selection of SNPs for complex diseases study. And in the human-Chimpanzee comparison, the variations appearing only in human genes might lead to the functional evolution and attribute to the humanness phenotype through changing structure and/or dosage of the proteins expressed.SNPs were identified on promoter and coding region of 24 blood pressure candidate genes in 48 samples, which chosen from the two ends of blood pressure distribution in an isolated population. Based on 124,421bp, 286 SNPs were identified and 21 of them showed great allele difference between low and high blood pressure groups. These SNPs were genotyped in more samples and the result indicated that the SNPs in promoter regions of gene catalase (CAT) and growth health 1 (GH1) showed association with essential hypertension. 156benzene-poisoning (BP) patients and 152 workers occupationally exposed to benzene in South China were used for detecting SNPs on the promoter and coding regions of cytochrome P450 2E1 (CYP2E1), NAD(P)H:quinone oxidoreductase I (NQO1), and myeloperoxidase (MPO), and genotypes of glutathione-s-transferase M1 and T1(GSTM1, GSTT1). Our results suggested that the combined effect of polymorphisms in NQO1, CYP2E1, and GSTT1 genes and lifestyle might contribute to BP. By detection and analysis variations on S and C open reading frame (ORF) of hepatitis B virus (HBV) from Tibet, we found that the genotype of HBV in Tibet were C/D hybrid and C, serotype were ayw2 and adw, and two variations in C ORF might have association with vaccination failure in Tibet.