Analytical Studies Of The Genetics Of Asthma Susceptibility Gene Cloning, And Two Single-gene Genetic Diseases

Asthma has become the most common chronic childhood disease in developed nations, affecting more than 155 million individuals. Both, gene–gene as well as gene–environment interactions contribute to its overall phenotype. The development of asthma appears to be determined by the interaction between host susceptibility (genetics) and a variety of environmental exposures. Numerous genetic studies have mapped an asthma susceptibility genes to a region on chromosome 5q31-q33 in several populations. This region contains a cluster of proinflammatory cytokines important in immune regulation including the genes encoding the T helper 2-type cytokines (the interleukin genes IL3, IL4, IL5, IL9, and IL13),Two members of this cluster, IL4 and IL13, have been both genetically and functionally implicated in the pathogenesis of asthma. The increasing knowledge of the human genome and the large number of SNPs that are becoming available as well as improved technology for genotyping make large scale association studies possible. In an effort to discover additional polymorphisms in genes whose variants have been implicated in asthma, we scrutinized the genetic polymorphisms in IL13, IL4, IL4R,IL3, IL9, CD14, IL5, IL12B genes to evaluate it as potent candidate genes for asthma host genetic study. We performed extensive screening of these genes by direct sequencing to detect polymorphisms and statistical analysis to examine the genetic effects on asthma.Here, we present thirty genetic polymorphisms found in these genes and the results of an association study in Chinese population. Our genetic association analysis of polymorphisms revealed that six polymorphisms in IL4R gene, three of which resulted in an amino-acid change, showed significant association with the risk of asthma (P=0.0002). In Chinese population, these six polymorphisms segregated in strong linkage disequilibrium. This information about the genetic association of important genes with asthma might provide valuable insights into strategies for the pathogenesis of asthma.Osteopetrosis is an inherited skeletal condition characterized by increased bone radiodensity. There are three clinical groups: infantile-malignant autosomal recessive, fatal within the first few years of life; intermediate autosomal recessive, appears during the first decade of life but does not follow a malignant course; and autosomal dominant, with full-life expectancy but many orthopaedic problems.Here, we identified and analysed a four-generation family affected with ADO type II. We used linkage analysis strategy to map the disease locus and found a linkage between markers on 16q13 and the ADO type II phenotype. According to previous reports, Benichou used a whole genome scan strategy to map the disease locus on the same region 16q13-22. Following the assignment of the gene causing ADO type II to chromosome 16p13.3, Wim Van Hul report seven different mutations in the gene encoding the CICN7 chloride channel in all 12 ADO type II families analysed. For excluding the possibility that the mutation segregating in this family was in the CICN7 gene we have directly sequence the CICN7 gene in two affected members of this family, no mutation were identified. These results suggested there is other gene located on this region responsible for this disorder in this family.Keloid formation is a common scarring disorder that can occur with an autosomal dominant inheritance pattern but incomplete clinical penetrance and variable expression.in some families. A.lexander performed a genome-wide linkage search for genes predisposing to keloid formation in two large families, and identified keloid susceptibility loci on chromosomes 2q23 and 7p11.This is a only report of gene locus for familial keloid formation so far.We have collected one family with a high occurrence of keloids, excluded these two keloids susceptibility loci on chromosomes 2q23 and 7p11 by linkage analysis and haplotype analysis. Based on the high occurrence of keloid in the African -American population and the observed variation in severity of keloid formation, it is likely that additional loci for keloids exist in Chinese population. Despite detailed histological and biochemical analyses of keloid tissue and keloid fibroblasts in culture, the causes for keloid formation remain unknown. Identifying these genes will lead to a better understanding of the biological mechanisms that regulate scarring.