Type 2 diabetes(T2D) is a common metabolic disorder which is caused by multiple genetic perturbations affecting different biological pathways. Identifying genetic factors modulating the susceptibility of this complex ...Type 2 diabetes(T2D) is a common metabolic disorder which is caused by multiple genetic perturbations affecting different biological pathways. Identifying genetic factors modulating the susceptibility of this complex heterogeneous metabolic phenotype in different ethnic and racial groups remains challenging. Despite recent success, the functional role of the T2D susceptibility variants implicated by genome-wide association studies(GWAS) remains largely unknown. Genetic dissection of transcript abundance or expression quantitative trait(eQTL) analysis unravels the genomic architecture of regulatory variants. Availability of eQTL information from tissues relevant for glucose homeostasis in humans opens a new avenue to prioritize GWASimplicated variants that may be involved in triggering a causal chain of events leading to T2D. In this article, we review the progress made in the field of eQTL research and knowledge gained from those studies in understanding transcription regulatory mechanisms in human subjects. We highlight several novel approaches that can integrate eQTL analysis with multiple layers of biological information to identify ethnic-specific causal variants and gene-environment interactions relevant to T2D pathogenesis. Finally, we discuss how the eQTL analysis mediated search for "missing heritability" may lead us to novel biological and molecular mechanisms involved in susceptibility to T2D.展开更多
The fatty acid desaturase 2(fad2) gene was proven to be a major locus for high oleic acid(C18:1).Brassica napus is an amphidiploid species originating from a spontaneous hybridization of Brassica rapa and Brassica ole...The fatty acid desaturase 2(fad2) gene was proven to be a major locus for high oleic acid(C18:1).Brassica napus is an amphidiploid species originating from a spontaneous hybridization of Brassica rapa and Brassica oleracea.B.napus contains multiple copies in genome for most of the genes,including fad2 genes.The research cloned nine fad2 genes from 3 varieties of B.rapa and 3 varieties of B.oleracea,respectively.Alignment of the nine fad2 sequences from B.rapa and B.oleracea detected 6 single nucleotide polymorphic sites,which resulted in 6 amino-acid substitutions.The nucleotide substitutions at position 743 bp in the fad2-A gene and position 947 bp in the fad2-C gene were used as 3' end of allele-specific primers.In use of the allele-specific primers to amplify fad2 gene,we could identify if the fad2 gene originated from A genome or C genome.Besides,the research found that fad2 genes in C genome are more conserved in evolutionary process than those in A genome.The fad2 expression data reported in this study revealed that fad2-A from B.rapa was not only expressed in siliques same as fad2-C from B.oleracea,but also expressed in a high level in stems.Not even the less,fad2 gene from B.napus was expressed higher in roots and flowers.All these results provided evidences that fad2,though it was expressed differently in B.rapa and B.oleracea,but it was regulated by the same approach in B.napus.展开更多
In order to explore the influence of the polymorphism in the 20intron region of the Sansui duck ATP2A2 gene on the eggshell quality,this study used Primer Premier 5 software to design and synthesize a pair of primers ...In order to explore the influence of the polymorphism in the 20intron region of the Sansui duck ATP2A2 gene on the eggshell quality,this study used Primer Premier 5 software to design and synthesize a pair of primers in the 20 intron region,two-way direct sequencing and sequence alignment to mine SNPs Sites,SPSS 18.0 software was used to analyze the relationship between SNP sites and eggshell quality of Sansui duck.Three SNP sites were found in the 20 intron region of the ATP2A2 gene:g.40874 T>C,g.40920 G>A and g.40990 T=C,all of which were moderately polymorphic,at the site g.40874 T>C and g.40920 G>A both deviated significantly from Hardy-Weinberg equilibrium(P>0.05),position g.40990 T=C accords with Hardy-Weinberg equilibrium(P<0.05),and position g.40874 T>C There is a strong linkage disequilibrium between g.40990 T=C;a total of 4 haplotypes and 9 double types were detected at 3 SNP loci;the results of association analysis showed that g.40874 T>C mutation had a significant effect on eggshell strength and eggshell weight.The eggshell strength of CC genotype was significantly higher than that of TC and TT genotypes(P<0.05),the eggshell weight of CC genotype was significantly higher than that of TC genotype(P<0.05),and 40990 T=C mutation had a significant effect on eggshell strength.The eggshell strength of TC genotype was significantly higher than that of the TT genotype(P<0.05).In summary,the g.40874 T>C and g.40990 T=C found in the 20th intron region of the Sansui duck ATP2A2 gene may be the marker sites that affect the quality of the eggshell.展开更多
基金Supported by National Institutes of Health(NIH/NIDDK),Nos.R01 DK090111 and DK039311
文摘Type 2 diabetes(T2D) is a common metabolic disorder which is caused by multiple genetic perturbations affecting different biological pathways. Identifying genetic factors modulating the susceptibility of this complex heterogeneous metabolic phenotype in different ethnic and racial groups remains challenging. Despite recent success, the functional role of the T2D susceptibility variants implicated by genome-wide association studies(GWAS) remains largely unknown. Genetic dissection of transcript abundance or expression quantitative trait(eQTL) analysis unravels the genomic architecture of regulatory variants. Availability of eQTL information from tissues relevant for glucose homeostasis in humans opens a new avenue to prioritize GWASimplicated variants that may be involved in triggering a causal chain of events leading to T2D. In this article, we review the progress made in the field of eQTL research and knowledge gained from those studies in understanding transcription regulatory mechanisms in human subjects. We highlight several novel approaches that can integrate eQTL analysis with multiple layers of biological information to identify ethnic-specific causal variants and gene-environment interactions relevant to T2D pathogenesis. Finally, we discuss how the eQTL analysis mediated search for "missing heritability" may lead us to novel biological and molecular mechanisms involved in susceptibility to T2D.
基金Supported by the National Natural Science Foundation of China (31301357)the Natural Science Foundation of Jiangsu Province,China (BK20130719)
文摘The fatty acid desaturase 2(fad2) gene was proven to be a major locus for high oleic acid(C18:1).Brassica napus is an amphidiploid species originating from a spontaneous hybridization of Brassica rapa and Brassica oleracea.B.napus contains multiple copies in genome for most of the genes,including fad2 genes.The research cloned nine fad2 genes from 3 varieties of B.rapa and 3 varieties of B.oleracea,respectively.Alignment of the nine fad2 sequences from B.rapa and B.oleracea detected 6 single nucleotide polymorphic sites,which resulted in 6 amino-acid substitutions.The nucleotide substitutions at position 743 bp in the fad2-A gene and position 947 bp in the fad2-C gene were used as 3' end of allele-specific primers.In use of the allele-specific primers to amplify fad2 gene,we could identify if the fad2 gene originated from A genome or C genome.Besides,the research found that fad2 genes in C genome are more conserved in evolutionary process than those in A genome.The fad2 expression data reported in this study revealed that fad2-A from B.rapa was not only expressed in siliques same as fad2-C from B.oleracea,but also expressed in a high level in stems.Not even the less,fad2 gene from B.napus was expressed higher in roots and flowers.All these results provided evidences that fad2,though it was expressed differently in B.rapa and B.oleracea,but it was regulated by the same approach in B.napus.
基金Project supported by the National Natural Science Foundation of China(31760663).
文摘In order to explore the influence of the polymorphism in the 20intron region of the Sansui duck ATP2A2 gene on the eggshell quality,this study used Primer Premier 5 software to design and synthesize a pair of primers in the 20 intron region,two-way direct sequencing and sequence alignment to mine SNPs Sites,SPSS 18.0 software was used to analyze the relationship between SNP sites and eggshell quality of Sansui duck.Three SNP sites were found in the 20 intron region of the ATP2A2 gene:g.40874 T>C,g.40920 G>A and g.40990 T=C,all of which were moderately polymorphic,at the site g.40874 T>C and g.40920 G>A both deviated significantly from Hardy-Weinberg equilibrium(P>0.05),position g.40990 T=C accords with Hardy-Weinberg equilibrium(P<0.05),and position g.40874 T>C There is a strong linkage disequilibrium between g.40990 T=C;a total of 4 haplotypes and 9 double types were detected at 3 SNP loci;the results of association analysis showed that g.40874 T>C mutation had a significant effect on eggshell strength and eggshell weight.The eggshell strength of CC genotype was significantly higher than that of TC and TT genotypes(P<0.05),the eggshell weight of CC genotype was significantly higher than that of TC genotype(P<0.05),and 40990 T=C mutation had a significant effect on eggshell strength.The eggshell strength of TC genotype was significantly higher than that of the TT genotype(P<0.05).In summary,the g.40874 T>C and g.40990 T=C found in the 20th intron region of the Sansui duck ATP2A2 gene may be the marker sites that affect the quality of the eggshell.
文摘目的分析筛查2型糖尿病(T2DM)患者早期大血管病变的易感基因和单核苷酸多态性(single nucleotide polymorphism,SNP)位点。方法利用ILLUMINA人类全基因组SNP芯片(HumanCytoSNP-12 v1.0 DNA Analysis BeadChipKit),对在经多因素干预下仍出现大血管病变的34例T2DM病例及同样条件下未发大血管病变的52例对照进行SNP扫描分型;通过全基因组关联分析,筛选T2DM早期大血管病变的易感基因和遗传标记。结果通过PLINK软件对芯片结果进行全基因组关联分析(genome-wide association study,GWAS),筛选出在病例组和对照组间有显著差异(P<0.01)的SNP位点总计452个,其中处于T2DM大血管病变主要代谢通路相关基因内或者附近的SNP位点37个,通过这些SNP位点锁定T2DM患者大血管病变易感基因30个。结论 T2DM大血管病变受遗传多态性影响,可能与多个基因以及位点相关。
