人类基因组国际单体型图计划(The International Haplotype Map Project,HapMap)旨在构建全基因组范围的常见遗传变异数据库,为复杂性疾病、人类进化和其它遗传学研究提供基础数据。此研究基于HapMap计划第Ⅰ期数据,通过群体基因组学策...人类基因组国际单体型图计划(The International Haplotype Map Project,HapMap)旨在构建全基因组范围的常见遗传变异数据库,为复杂性疾病、人类进化和其它遗传学研究提供基础数据。此研究基于HapMap计划第Ⅰ期数据,通过群体基因组学策略对亚、欧、非人群中的正选择信号进行扫描。在基因组范围建立了一个包含多层次信息(基因、窗口、大型区域)的正选择图谱。研究表明:人类基因组中存在一定程度的正选择,正选择的"候选窗口"占总筛查窗口的～5%;基因组中的正选择信号集中于某些特定的染色体区域;确定了62个可能受到强正选择的大型区域,以及区域内相应的88个受到强正选择的"候选基因"。研究还发现人群特异的选择在人群的分化过程中发挥了重要的作用。此研究将为后续的人类进化和自然选择研究提供新的线索。展开更多
Objective To investigate relationships of polymorphisms in six genes （ GHR, IGF-1, IGF-1R, IGFBP-3, JAK2, and STAT5b） in the growth hormone （GH）/insulin-like growth factor-1 （IGF-1） axis with idiopathic short st...Objective To investigate relationships of polymorphisms in six genes （ GHR, IGF-1, IGF-1R, IGFBP-3, JAK2, and STAT5b） in the growth hormone （GH）/insulin-like growth factor-1 （IGF-1） axis with idiopathic short stature （ISS） in the Chinese Han population. Methods A case- control study was carried out on a cohort of 198 ISS patients and 306 healthy controls. A total of 106 tagging single nucleotide polymorphisms （tagSNPs） from the six genes were selected from the HapMap （haplotype map of the human genome ） Han Chinese in the Beijing subset. Results of genotyping conducted by high- throughput lllumina GoldenGateTM Assay were analyzed by statistical software. Results Both individual tagSNPs and haplotypes showed an association with 1SS in the Han Chinese population （ P 〈 O. 05 ）. For each single test, both allele and genotype were tested. By allele frequency analysis, six positive SNP sites （ rsNo. 1, rsNo. 2, rsNo. 3, rsNo. 4, rsNo. 5, and rsNo. 6） of 3 genes （ JAK2, 1GF-1R, and GHR） were found having associations with ISS. By genotype frequency analysis, there were significant differences between the patient and control groups in the following SNP sites： 4 sites in JAK2 gene （ rsNo. 1, rsNo. 2, rsNo. 3, and rsNo. 4） and 1 site in GHR gene （ rsNo. 6）. The risk which affected ISS was found related to the JAK2 gene in 4 sites （ increase in rsNo. 1 and decrease in rsNo. 2, rsNo. 3, and rsNo. 4 ） and to the GHR gene in 1 site （decrease in rsNo. 6）. They were four haplotypes in gene of IGF-1R as ＂TGC＂, ＂CGCT＂, ＂TA＂, and ＂ CA＂, one haplotype in IGFBP-3 as ＂TA＂, and one haplotype in JAK2 as ＂CTG＂, which revealed high significance for risks of affecting ISS. At last, multivariate logistic regression analysis of specific site rsNo. 6 of the GHR gene revealed that the serum IGF-1 was related to genotypes AA and AC, with genotype CC as the reference （ P =0. 015）. Conclusion Genetic variances in six genes within the GH/IGF-1 axis may be important etiological factors for ISS in the Chinese Han population.展开更多
文摘人类基因组国际单体型图计划(The International Haplotype Map Project,HapMap)旨在构建全基因组范围的常见遗传变异数据库,为复杂性疾病、人类进化和其它遗传学研究提供基础数据。此研究基于HapMap计划第Ⅰ期数据,通过群体基因组学策略对亚、欧、非人群中的正选择信号进行扫描。在基因组范围建立了一个包含多层次信息(基因、窗口、大型区域)的正选择图谱。研究表明:人类基因组中存在一定程度的正选择,正选择的"候选窗口"占总筛查窗口的～5%;基因组中的正选择信号集中于某些特定的染色体区域;确定了62个可能受到强正选择的大型区域,以及区域内相应的88个受到强正选择的"候选基因"。研究还发现人群特异的选择在人群的分化过程中发挥了重要的作用。此研究将为后续的人类进化和自然选择研究提供新的线索。
基金Supported by National Natural Science Foundation of China(30771029)
文摘Objective To investigate relationships of polymorphisms in six genes （ GHR, IGF-1, IGF-1R, IGFBP-3, JAK2, and STAT5b） in the growth hormone （GH）/insulin-like growth factor-1 （IGF-1） axis with idiopathic short stature （ISS） in the Chinese Han population. Methods A case- control study was carried out on a cohort of 198 ISS patients and 306 healthy controls. A total of 106 tagging single nucleotide polymorphisms （tagSNPs） from the six genes were selected from the HapMap （haplotype map of the human genome ） Han Chinese in the Beijing subset. Results of genotyping conducted by high- throughput lllumina GoldenGateTM Assay were analyzed by statistical software. Results Both individual tagSNPs and haplotypes showed an association with 1SS in the Han Chinese population （ P 〈 O. 05 ）. For each single test, both allele and genotype were tested. By allele frequency analysis, six positive SNP sites （ rsNo. 1, rsNo. 2, rsNo. 3, rsNo. 4, rsNo. 5, and rsNo. 6） of 3 genes （ JAK2, 1GF-1R, and GHR） were found having associations with ISS. By genotype frequency analysis, there were significant differences between the patient and control groups in the following SNP sites： 4 sites in JAK2 gene （ rsNo. 1, rsNo. 2, rsNo. 3, and rsNo. 4） and 1 site in GHR gene （ rsNo. 6）. The risk which affected ISS was found related to the JAK2 gene in 4 sites （ increase in rsNo. 1 and decrease in rsNo. 2, rsNo. 3, and rsNo. 4 ） and to the GHR gene in 1 site （decrease in rsNo. 6）. They were four haplotypes in gene of IGF-1R as ＂TGC＂, ＂CGCT＂, ＂TA＂, and ＂ CA＂, one haplotype in IGFBP-3 as ＂TA＂, and one haplotype in JAK2 as ＂CTG＂, which revealed high significance for risks of affecting ISS. At last, multivariate logistic regression analysis of specific site rsNo. 6 of the GHR gene revealed that the serum IGF-1 was related to genotypes AA and AC, with genotype CC as the reference （ P =0. 015）. Conclusion Genetic variances in six genes within the GH/IGF-1 axis may be important etiological factors for ISS in the Chinese Han population.
