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 stature（IS...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 casecontrol 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 highthroughput Illumina GoldenGate?Assay were analyzed by statistical software.Results Both individual tagSNPs and haplotypes showed an association with ISS in the Han Chinese population（P <0.05）.For each single test,both allele and genotype were tested.By allele frequency analysis,six positive SNP sites （rsNo.l,rsNo.2,rsNo.3,rsNo.4,rsNo.5,and rsNo.6）of 3 genes（JAK2,IGF-1 R,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-1 R 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 casecontrol 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 highthroughput Illumina GoldenGate?Assay were analyzed by statistical software.Results Both individual tagSNPs and haplotypes showed an association with ISS in the Han Chinese population（P <0.05）.For each single test,both allele and genotype were tested.By allele frequency analysis,six positive SNP sites （rsNo.l,rsNo.2,rsNo.3,rsNo.4,rsNo.5,and rsNo.6）of 3 genes（JAK2,IGF-1 R,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-1 R 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.
