| 1. Progress of studies on genetic susceptibility and susceptible genes of nasopharyngeal carcinomaBenefited form the launching and progress of Human Genome Project (HGP), the past two decades have witnessed an explosion in the identification, largely by positional cloning, of genes associated with Mendelian diseases. The roughly 1,200 genes that have been characterized, have clarified our understanding of the molecular basis of human genetic disease. Because of their large social and economic value, location susceptible genes of poly genie inheritance disorders and analysis their genetic susceptibility become a more and more important and difficult research field. At the present time, some complex disease genes have been cloned, but for many multifactorial inheritance disorders, especially which have complicated inheritance model, including nasopharyngeal carcinoma (NPC), their susceptibility gene or genes are still unknown.Epidemiological investigation shows that NPC has remarkable geographical and racial differentiations. It occurs with high frequency in South China and South-East Asia. In areas with high incidence, NPC clusters in families. These observations have suggested theexistence of genetic susceptibility in at least a proportion of NPC patients, and the susceptible gene or genes may play influence the pathogenesis of NPC.At present, there are two ways to study the gene or genes pause of NPC, phenotypic cloning strategy and positional cloning strategy. Phenotypic cloning strategy means to search NPC associated genes by compare difference of NPC and normal tissues. Our laboratory has performed a genome-wide scan of microsatellite allelic imbalance (AI) and comparative genomic hybridization (CGH), finding that the AI of chromosome regions 3p, 9p, and 6q are common in NPC and may be the early event of NPC, there are some key genes of NPC located in these regions. Some similar studies performed by other labs also obtain the same result. Using this strategy, our lab have cloned many NPC associated genes, functional analysis have proved that these genes may play important role in start and progress of NPC, but it is necessary to prove whether them influence the genetic susceptibility of NPC.Positional cloning strategy can locate NPC susceptible genes on certain chromosome regions by perform a serial of genetic analysis using large numbers of NPC genetic resource, and then clone them. A group of researchers leaded by professor Yi-xin Zeng reported a results of a genome-wide search carried out in families at high riskof NPC from Guangdong Province, China. Their findings provide evidence of a major susceptibility locus for NPC on chromosome 4p15.1 - 4q12 in a subset of families. Because there is genetic heterogeneity among different NPC families, we dose not know whether this result is still true in other people, it is necessary to perform parallel test in other ethnic group.2. The purpose of this paperAs reasons of above-mentioned, a family-based linkage analysis strategy was used to look forward to locate susceptible genes of familial NPC of Hunan province. We have collected 18 NPC families in Hunan province, and selected a serial of microsatellite loci in high frequency allele imbalance chromosome region 3p, 9p, 6q, and 4p15.1 -4ql2, which linked with Guangdong familial NPC in Yi-xin Zeng's paper, genotyped these loci in NPC families and then performed linkage analysis. On the other hand, a case - control - based association analysis strategy was used for confirm the relationship between NPC associated genes and NPC genetic susceptibility. We selected three genes, NGX6, UBAP1, NOR1, which cloned by our lab and have functional evidence on NPC progress, and a suppressor gene, CDKN2A, which located in chromosome 9p21 NPC deletion region, search some single nucleotide polymorphisms (SNP) in these genes,genotyped these SNP loci in case and control subjects and performed association analysis.3. Linkge analysis of short arm of chromosome 3 and NPC10 loci, D3S129...
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