Inflammatory bowel disease （IBD） includes two similar yet distinct conditions called ulcerative colitis （UC） and Crohn＇s disease （CD）. These diseases affect the digestive system and cause the inflammation of in...Inflammatory bowel disease （IBD） includes two similar yet distinct conditions called ulcerative colitis （UC） and Crohn＇s disease （CD）. These diseases affect the digestive system and cause the inflammation of intestinal tissue, form sores and bleed easily. Most children with IBD are diagnosed in late childhood and adolescence. However, both UC and CD have been reported as early as in infancy. Most information pertaining to the epidemiology of IBD is based upon adult studies. Symptoms include abdominal pain, cramping, fatigue and diarrhea. Genetic factors play a significant role in determining IBD susceptibility. Epidemiological data support a genetic contribution to the pathogenesis of IBD. Recently, numerous new genes have been identified as being involved in the genetic susceptibility to IBD： TNF- 308A, CARD15 （NOD2）, MIF-173, N-acetyltransferase 2 （NAT2）, NKG2D （natural killer cell 2D）, STAT6 （signal transducer and activator of transcription 6）, CTLA-4 （cytotoxic T lymphocyte antigen-4）, MICA-MICB （major histocompatibility complex A and B）, HLA-DRB1, HLA class-Ⅱ, IL-18, IL-4, MICA-A5, CD14, TI R4, Fas-670, p53 and NF-kB. The characterization of these novel genes has the potential to identify therapeutic agents and aid clinical assessment of phenotype and prognosis in patients with IBD （UC and CD）.展开更多
在过去的5年中,全基因组关联研究(Genome-wide association study,GWAS)方法已被证明是研究复杂疾病和性状遗传易感变异的一种有效手段。目前,各国科学家在多种复杂疾病和性状中开展了大量的GWAS,对肿瘤、糖尿病、心脏病、神经精神疾病...在过去的5年中,全基因组关联研究(Genome-wide association study,GWAS)方法已被证明是研究复杂疾病和性状遗传易感变异的一种有效手段。目前,各国科学家在多种复杂疾病和性状中开展了大量的GWAS,对肿瘤、糖尿病、心脏病、神经精神疾病、自身免疫及免疫相关疾病等复杂疾病以及一些常见性状(如身高、体重、血脂、色素等)的遗传易感基因研究取得了重大成果。截止到2010年9月11日,运用GWAS开展了对近200种复杂疾病/性状的研究,发现了3000多个疾病相关的遗传变异。文章就GWAS的发展及其在复杂疾病/性状中的应用做一综述。展开更多
Background The influences of genomic background are confirmed in more diseases. Immunologic tolerance after intrauterine infection of hepatitis B virus is considered to occur in T cells. Cytokines work effectively in ...Background The influences of genomic background are confirmed in more diseases. Immunologic tolerance after intrauterine infection of hepatitis B virus is considered to occur in T cells. Cytokines work effectively in eliminating virus by immune system after hepatitis B virus infection. To explore the relationship between cytokines （tumor necrosis factor-α, interferon-γ, interleukin-4 and interleukin-10）, which expressed abnormal quantity in the peripheral blood to intrauterine hepatitis B virus infectious children, gene single nucleotide polymorphism （SNP） and susceptibility to hepatitis B virus intrauterine infection. Methods This is a cross sectional study of molecular clinical epidemiology. The subjects in this study were selected from outpatients of hepatitis B vaccine follow-up special clinics of our hospital in the period. According to intrant criteria, the high risk children of hepatitis B virus （HBV） intrauterine infection were divided into immune failure group （group Ⅰ） ; and immune effective group （group Ⅱ） and non high risk children belonged to the control group. Four gene SNP sites of TNF-α -238, IFN-γ ＋874, IL-4 -590 and IL-10 -1082 were determined by real-time quantitative fluorescent polymerase chain reaction （PCR）. Results The significant differences of TNF-α- 238 A allele frequency were found between group Ⅰand group Ⅱ（X^2 =6. 797, P 〈 0.05 ） and between group Ⅰ and the control group （ X^2 = 9. 513, P 〈 0.05 ）. No evident differences of TNF-α- 238 A were found between group Ⅱand control group （ X^2 = 0. 047, P 〉 0. 05 ） ; the significant differences of IFN-γ ＋ 874 A allele frequency were found between group Ⅰand group Ⅱ（ X^2 = 7. 238, P〈0. 05）, and between group Ⅰand the control group （X^2 =5. 199,P 〈0. 05）. No evident differences were found between groupⅡ and the control group （ X^2 =0. 602 ,P 〉0. 05 ） ; the significant differences of IL-4 -590 C/T allele frequency were not found between groupⅠand group 展开更多
银屑病是一种常见的免疫异常性增殖性皮肤病。临床特征为皮肤表面履盖大量厚实的鳞屑性斑片。虽然已有大量家族性研究资料表明银屑病的发病存在着遗传因素,但是该病的遗传模式至今尚不清楚。大量研究表明:复杂性疾病的遗传学研究除了MH...银屑病是一种常见的免疫异常性增殖性皮肤病。临床特征为皮肤表面履盖大量厚实的鳞屑性斑片。虽然已有大量家族性研究资料表明银屑病的发病存在着遗传因素,但是该病的遗传模式至今尚不清楚。大量研究表明:复杂性疾病的遗传学研究除了MHC的一些位点的相关结果比较恒定外,绝大多数的研究结果变异较大。全基因组关联分析(genome-wide association study,GWAS)是一种对全基因组范围内的常见遗传变异(单核苷酸多态性和拷贝数变异)进行总体关联分析的方法,在全基因组范围内进行整体研究,能够一次性对疾病进行轮廓性概览,适用于包括银屑病在内的复杂疾病的研究。运用全基因组关联分析对银屑病进行的三个研究,刊登在今年2月的《自然-遗传学》杂志,结果发现了几个银屑病的遗传学易感位点,提示在免疫学和其它领域的几个信号通路可能参与了该病的发病机制。无论是以往的关联研究还是现在的全基因组关联分析研究,均提示银屑病与涉及人类免疫性疾病的免疫反应的MHC位点(如HLA-Cw6和其他MHC变异位点)紧密相关。还有两个与银屑病高度相关的与炎症反应密切关联的非MHC基因(IL-12B和IL23R),也在银屑病的发病机制中起着重要作用。最近运用抗IL-12p40的生物制剂有效治疗银屑病的临床试验,进一步证实了IL-12/23在银屑病病理生理过程中关键作用。在中国人群中进行了银屑病易感基因的GWAS研究发现:位于1q21上的晚期角质化包膜(late cornified envelope,LCE)基因簇中LCE3A和LCE3D的区域异常与银屑病显著性相关。与此同时,国际上另一个研究小组对西班牙、荷兰、意大利和美国人群中进行的银屑病易感基因的GWAS研究发现,LCE基因簇中LCE3B和LCE3C区域的缺失与银屑病显著性相关。这些相互独立的研究有力地证实LCE基因参与银屑病的发病。到目前为止,虽然已经有了一展开更多
2005年至今,全基因组关联研究(Genome-wide association study,GWAS)发现了大量复杂疾病/性状相关变异。近来,科学家们关注的焦点又集中在了如何利用GWAS数据进行深入分析,期待发现更多复杂疾病/性状的易感基因。一些新的策略和方法已...2005年至今,全基因组关联研究(Genome-wide association study,GWAS)发现了大量复杂疾病/性状相关变异。近来,科学家们关注的焦点又集中在了如何利用GWAS数据进行深入分析,期待发现更多复杂疾病/性状的易感基因。一些新的策略和方法已经被尝试应用到复杂疾病/性状GWAS的后续研究中,例如深入分析GWAS数据;鉴定新的复杂疾病/性状易感基因/位点;国际合作和Meta分析;易感区域精细定位及测序;多种疾病共同易感基因研究;以及基因型填补,基于通路的关联分析,基因-基因、基因-环境交互作用和上位研究等。这些策略和方法的应用弥补了经典GWAS的一些不足之处,进一步推动了人类对复杂疾病/性状遗传机制的认识。文章对上述研究的策略、方法以及所面临的问题和挑战进行了综述,为读者描绘了GWAS后期工作的一个简要框架。展开更多
目的:现有研究显示,原发性痛风和高尿酸血症是一类多基因遗传性疾病,是遗传因素和环境因素共同作用的结果。但目前对痛风和高尿酸血症的遗传易感性研究尚不完善,还不能预测哪些人群易患痛风和高尿酸血症。全基因组关联分析(Genome-wide ...目的:现有研究显示,原发性痛风和高尿酸血症是一类多基因遗传性疾病,是遗传因素和环境因素共同作用的结果。但目前对痛风和高尿酸血症的遗传易感性研究尚不完善,还不能预测哪些人群易患痛风和高尿酸血症。全基因组关联分析(Genome-wide association study,GWAS)是近年来发展起来的用于识别、鉴定复杂性疾病致病易感基因的手段,通过对病人和正常对照人群的筛查,结合计算机技术和统计分析手段,可从整个基因组变异来识别、鉴定微效基因及其与相关疾病的相互作用。笔者对近几年发现的尿酸相关基因进行总结分类,为进一步认识痛风和高尿酸血症的分子机制提供依据,为进一步深入研究痛风和高尿酸血症的病因提供有益参考。展开更多
目前宁波地区沙门氏菌对常用抗生素的耐受情况及主要毒力基因携带率的系统检测尚未见报道。本研究选取2006—2013年间宁波地区分离获得的121株沙门氏菌(共27个血清型),对其进行耐药谱检测,相关耐药基因及毒力基因筛查。结果显示:对12种...目前宁波地区沙门氏菌对常用抗生素的耐受情况及主要毒力基因携带率的系统检测尚未见报道。本研究选取2006—2013年间宁波地区分离获得的121株沙门氏菌(共27个血清型),对其进行耐药谱检测,相关耐药基因及毒力基因筛查。结果显示:对12种常见抗生素的耐药率依次是:氨苄西林19.8%,四环素13.2%,强力霉素12.4%,复方新诺明11.6%,氯霉素8.7%,链霉素6.6%,妥布霉素3.3%,头孢曲松2.5%,环丙沙星0.8%,诺氟沙星0%,庆大霉素0%,阿米卡星0%。耐药基因携带率:blaTEM100%,blaPSE29.2%,blaCMY-24.2%,blaCTX8.3%,blaSHV0%,tet A 100%,tet B 100%,tet G 70.8%,tet C 20.8%,sul I 100%,sul II 100%,sul III 80%。毒力基因avr A、ssa Q、gip A、sod C1、mgt C的携带率均达100%,sop E 96.9%,ssi D 93.8%,spo B 93.8%,spv C 21.9%。上述结果表明:宁波地区沙门氏菌耐药情况比较严重,耐药基因与毒力基因携带率较高。本研究为宁波地区沙门氏菌疫情的防控提供数据支持。展开更多
基金Supported by The Science Foundation of Health Bureau of Shaanxi Province,China,No.04D26
文摘Inflammatory bowel disease （IBD） includes two similar yet distinct conditions called ulcerative colitis （UC） and Crohn＇s disease （CD）. These diseases affect the digestive system and cause the inflammation of intestinal tissue, form sores and bleed easily. Most children with IBD are diagnosed in late childhood and adolescence. However, both UC and CD have been reported as early as in infancy. Most information pertaining to the epidemiology of IBD is based upon adult studies. Symptoms include abdominal pain, cramping, fatigue and diarrhea. Genetic factors play a significant role in determining IBD susceptibility. Epidemiological data support a genetic contribution to the pathogenesis of IBD. Recently, numerous new genes have been identified as being involved in the genetic susceptibility to IBD： TNF- 308A, CARD15 （NOD2）, MIF-173, N-acetyltransferase 2 （NAT2）, NKG2D （natural killer cell 2D）, STAT6 （signal transducer and activator of transcription 6）, CTLA-4 （cytotoxic T lymphocyte antigen-4）, MICA-MICB （major histocompatibility complex A and B）, HLA-DRB1, HLA class-Ⅱ, IL-18, IL-4, MICA-A5, CD14, TI R4, Fas-670, p53 and NF-kB. The characterization of these novel genes has the potential to identify therapeutic agents and aid clinical assessment of phenotype and prognosis in patients with IBD （UC and CD）.
文摘在过去的5年中,全基因组关联研究(Genome-wide association study,GWAS)方法已被证明是研究复杂疾病和性状遗传易感变异的一种有效手段。目前,各国科学家在多种复杂疾病和性状中开展了大量的GWAS,对肿瘤、糖尿病、心脏病、神经精神疾病、自身免疫及免疫相关疾病等复杂疾病以及一些常见性状(如身高、体重、血脂、色素等)的遗传易感基因研究取得了重大成果。截止到2010年9月11日,运用GWAS开展了对近200种复杂疾病/性状的研究,发现了3000多个疾病相关的遗传变异。文章就GWAS的发展及其在复杂疾病/性状中的应用做一综述。
文摘Background The influences of genomic background are confirmed in more diseases. Immunologic tolerance after intrauterine infection of hepatitis B virus is considered to occur in T cells. Cytokines work effectively in eliminating virus by immune system after hepatitis B virus infection. To explore the relationship between cytokines （tumor necrosis factor-α, interferon-γ, interleukin-4 and interleukin-10）, which expressed abnormal quantity in the peripheral blood to intrauterine hepatitis B virus infectious children, gene single nucleotide polymorphism （SNP） and susceptibility to hepatitis B virus intrauterine infection. Methods This is a cross sectional study of molecular clinical epidemiology. The subjects in this study were selected from outpatients of hepatitis B vaccine follow-up special clinics of our hospital in the period. According to intrant criteria, the high risk children of hepatitis B virus （HBV） intrauterine infection were divided into immune failure group （group Ⅰ） ; and immune effective group （group Ⅱ） and non high risk children belonged to the control group. Four gene SNP sites of TNF-α -238, IFN-γ ＋874, IL-4 -590 and IL-10 -1082 were determined by real-time quantitative fluorescent polymerase chain reaction （PCR）. Results The significant differences of TNF-α- 238 A allele frequency were found between group Ⅰand group Ⅱ（X^2 =6. 797, P 〈 0.05 ） and between group Ⅰ and the control group （ X^2 = 9. 513, P 〈 0.05 ）. No evident differences of TNF-α- 238 A were found between group Ⅱand control group （ X^2 = 0. 047, P 〉 0. 05 ） ; the significant differences of IFN-γ ＋ 874 A allele frequency were found between group Ⅰand group Ⅱ（ X^2 = 7. 238, P〈0. 05）, and between group Ⅰand the control group （X^2 =5. 199,P 〈0. 05）. No evident differences were found between groupⅡ and the control group （ X^2 =0. 602 ,P 〉0. 05 ） ; the significant differences of IL-4 -590 C/T allele frequency were not found between groupⅠand group
文摘银屑病是一种常见的免疫异常性增殖性皮肤病。临床特征为皮肤表面履盖大量厚实的鳞屑性斑片。虽然已有大量家族性研究资料表明银屑病的发病存在着遗传因素,但是该病的遗传模式至今尚不清楚。大量研究表明:复杂性疾病的遗传学研究除了MHC的一些位点的相关结果比较恒定外,绝大多数的研究结果变异较大。全基因组关联分析(genome-wide association study,GWAS)是一种对全基因组范围内的常见遗传变异(单核苷酸多态性和拷贝数变异)进行总体关联分析的方法,在全基因组范围内进行整体研究,能够一次性对疾病进行轮廓性概览,适用于包括银屑病在内的复杂疾病的研究。运用全基因组关联分析对银屑病进行的三个研究,刊登在今年2月的《自然-遗传学》杂志,结果发现了几个银屑病的遗传学易感位点,提示在免疫学和其它领域的几个信号通路可能参与了该病的发病机制。无论是以往的关联研究还是现在的全基因组关联分析研究,均提示银屑病与涉及人类免疫性疾病的免疫反应的MHC位点(如HLA-Cw6和其他MHC变异位点)紧密相关。还有两个与银屑病高度相关的与炎症反应密切关联的非MHC基因(IL-12B和IL23R),也在银屑病的发病机制中起着重要作用。最近运用抗IL-12p40的生物制剂有效治疗银屑病的临床试验,进一步证实了IL-12/23在银屑病病理生理过程中关键作用。在中国人群中进行了银屑病易感基因的GWAS研究发现:位于1q21上的晚期角质化包膜(late cornified envelope,LCE)基因簇中LCE3A和LCE3D的区域异常与银屑病显著性相关。与此同时,国际上另一个研究小组对西班牙、荷兰、意大利和美国人群中进行的银屑病易感基因的GWAS研究发现,LCE基因簇中LCE3B和LCE3C区域的缺失与银屑病显著性相关。这些相互独立的研究有力地证实LCE基因参与银屑病的发病。到目前为止,虽然已经有了一
文摘2005年至今,全基因组关联研究(Genome-wide association study,GWAS)发现了大量复杂疾病/性状相关变异。近来,科学家们关注的焦点又集中在了如何利用GWAS数据进行深入分析,期待发现更多复杂疾病/性状的易感基因。一些新的策略和方法已经被尝试应用到复杂疾病/性状GWAS的后续研究中,例如深入分析GWAS数据;鉴定新的复杂疾病/性状易感基因/位点;国际合作和Meta分析;易感区域精细定位及测序;多种疾病共同易感基因研究;以及基因型填补,基于通路的关联分析,基因-基因、基因-环境交互作用和上位研究等。这些策略和方法的应用弥补了经典GWAS的一些不足之处,进一步推动了人类对复杂疾病/性状遗传机制的认识。文章对上述研究的策略、方法以及所面临的问题和挑战进行了综述,为读者描绘了GWAS后期工作的一个简要框架。
文摘目的:现有研究显示,原发性痛风和高尿酸血症是一类多基因遗传性疾病,是遗传因素和环境因素共同作用的结果。但目前对痛风和高尿酸血症的遗传易感性研究尚不完善,还不能预测哪些人群易患痛风和高尿酸血症。全基因组关联分析(Genome-wide association study,GWAS)是近年来发展起来的用于识别、鉴定复杂性疾病致病易感基因的手段,通过对病人和正常对照人群的筛查,结合计算机技术和统计分析手段,可从整个基因组变异来识别、鉴定微效基因及其与相关疾病的相互作用。笔者对近几年发现的尿酸相关基因进行总结分类,为进一步认识痛风和高尿酸血症的分子机制提供依据,为进一步深入研究痛风和高尿酸血症的病因提供有益参考。
文摘目前宁波地区沙门氏菌对常用抗生素的耐受情况及主要毒力基因携带率的系统检测尚未见报道。本研究选取2006—2013年间宁波地区分离获得的121株沙门氏菌(共27个血清型),对其进行耐药谱检测,相关耐药基因及毒力基因筛查。结果显示:对12种常见抗生素的耐药率依次是:氨苄西林19.8%,四环素13.2%,强力霉素12.4%,复方新诺明11.6%,氯霉素8.7%,链霉素6.6%,妥布霉素3.3%,头孢曲松2.5%,环丙沙星0.8%,诺氟沙星0%,庆大霉素0%,阿米卡星0%。耐药基因携带率:blaTEM100%,blaPSE29.2%,blaCMY-24.2%,blaCTX8.3%,blaSHV0%,tet A 100%,tet B 100%,tet G 70.8%,tet C 20.8%,sul I 100%,sul II 100%,sul III 80%。毒力基因avr A、ssa Q、gip A、sod C1、mgt C的携带率均达100%,sop E 96.9%,ssi D 93.8%,spo B 93.8%,spv C 21.9%。上述结果表明:宁波地区沙门氏菌耐药情况比较严重,耐药基因与毒力基因携带率较高。本研究为宁波地区沙门氏菌疫情的防控提供数据支持。
