广东汉族人群TLR9基因单核苷酸多态性及其单倍型(英文)

采用PCR扩增和直接测序法对191例健康且无血缘关系的广东汉族人群筛查了TLR9全基因序列,包括调控区、5′非翻译区、第1,2外显子、内含子及3′非翻译区上所有的单核苷酸多态性(SNP)位点.共检出五个SNP位点,分别为调控区的-1 486 T/C和-1 421 C/T、内含子区的+1174 A/G、第2外显子的+1 387 T/C和+2848 G/A,其中-1421 C/T和+1 387 T/C为首次发现的新位点.连锁不平衡分析表明-486 T/C,1174 A/G以及2848 G/A之间存在紧密连锁,并且涵盖了整个基因区域,形成了一个单倍域.在此基础上运用Hhase软件构建了TLR9基因的单倍型,共得到七种单倍型并模拟了它们可能的分布频率.进一步的中性检验表明TLR9基因在广东汉族人群中符合中性进化模式.     

HLA高分辨等位基因多态性及单倍体与广西汉族终末期肾病易感性的相关性分析

为研究广西汉族终末期肾病(End Stage Renal Disease, ESRD)与人类白细胞抗原(Human Leukocyte Antigen, HLA)等位基因及单倍体的关联性,本研究采用聚合酶链反应-序列特异性寡核苷酸(Polymerase Chain Reaction-Sequence Specific Oligonucleotides, PCR-SSO)技术对广西汉族578例终末期肾病患者(ESRD组)进行HLA-A、B和DRB1基因分型,HLA等位基因频率用直接计数法来计算,采用Arlequin 3.5.2.2软件计算单倍型频率,并与1 644例广西汉族健康造血干细胞捐献者(对照组)比较。结果显示,ESRD组HLA-A*11:01、A*02:01、B*13:01、DRB1*12:02、DRB1*04:05、DRB1*14:54和DRB1*11:01的基因频率大于对照组(P<0.05),HLA-A*11:02、A*30:01、A*32:01、B*13:02、B*07:02、DRB1*07:01和DRB1*13:02的基因频率小于对照组(P<0.05)。ESR...     

川渝黔地区山羊起源于A和B两母系遗传谱系

本研究旨在从DNA水平揭示四川、重庆和贵州地区山羊的母系起源和群体遗传特征.通过对川渝黔地区13个山羊品种(类群)共152个体或序列mtDNA D-loop高变区HVI片段(481 bp)变异的分析,结合13个山羊参考序列(分属于A、B、C、D、F和G单倍群)构建系统进化树和单倍型网络分析以及不同单倍群群体扩张分析,结果表明:152只山羊mtDNA DloopHVI序列被类聚为A和B两个单倍群,其中单倍群B又分化为B1和B2两亚单倍群.从2种单倍群的地理分布特征可以发现,北川白山羊和阿坝藏山羊全部属于单倍群A,而其他山羊品种中单倍群A和B具有不同的分布频率.归并于A和B两个谱系的山羊并没有历经种群扩张.结果提示,川渝黔地区山羊可能起源于A和B两母系遗传谱系,而谱系B虽然分化为B1和B2两支系,但均未历经种群扩张.     

白细胞分化抗原基因多态性与缺血性脑卒中发生与发展的关系

目的探讨白细胞分化抗原基因多态性与缺血性脑卒中发生与发展的关系.方法选取缺血性脑卒中患者404例为观察组,同期体检的同年龄段健康人群398名为对照组.采集空腹外周静脉血,单碱基延伸PCR技术对白细胞分化抗原40基因rs1535045 C/T,rs3765459 C/T,rs4810485 C/T,rsl3040307G/A位点多态性进行分型.结果白细胞分化抗原40基因各位点分布情况显示:rs1535045 C/T位点中CC,CT,TT基因型之间差异具有统计学意义(P0.01); rs3765459 C/T,rs4810485 C/T,rsl3040307 G/A位点各基因型之间差异无统计学意义(P0.05).rs1535045 C/T位点等位基因频率在观察组与对照组间差异具有统计学意义(P0.01);携带T突变型等位基因的缺血性脑卒中发生风险较携带C野生型等位基因明显增加,是携带C野生型的1.846倍.rs3765459 C/T,rs4810485 C/T,rsl3040307 G/A位点等位基因频率在观察组与对照组间差异无统计学意义(P0.05).联合基因型分析显示:观察组携带TCCA,TCCG基因单倍型的比例明显高于对照组,携带CCCG基因单倍型的比例明显低于对照组,差异具有统计学意义(P0.05);携带TCCA,TCCG基因单倍型明显增加缺血性脑卒中的发生风险,携带CCCG基因单倍型明显降低缺血性脑卒中的发生风险.结论白细胞分化抗原40基因rs1535045 C/T位点及TCCA,TCCG,CCCG单倍型与缺血性脑卒中的发生与发展可能存在相关性,其中携带T突变型等位基因可能为缺血性脑卒中的遗传易感基因.     

家系数据紧密连锁位点的单体型频率估计

在对单体型进行重构或进行连锁不平衡分析时,往往首先要估计单体型频率.针对家系数据,提出了紧密连锁位点的单体型频率估计方法.利用子代信息减少亲代单体型的不确定性,构建家系数据的似然函数,把家系中的个体潜在的单体型看成缺失数据,采用EM迭代算法,给出了家系数据单体型频率的极大似然估计.其结果表明,家系数据紧密连锁位点的单体型频率估计可通过简单的递归迭代进行,后一步的单体型的频率估计即为前一步的加权单体型频率.     

CD14基因多态性与强直性脊柱炎的关联性研究

目的探讨CD14基因rs2569190位点的单核苷酸多态性与强直性脊柱炎易感性的关系.方法采用PCRRFLP方法对240例AS患者进行CD14基因多态性检测,并与140名健康对照者进行对比.结果 rs2569190位点基因型频率两组间差异具有统计学意义(χ~2=6.778,υ=2,P0.05);强直性脊柱炎组携带突变体A基因的频率高于对照组,差异具有统计学意义(χ~2=3.876,υ=1,P0.05).结论 CD14基因rs2569190位点单核苷酸多态性与强直性脊柱炎易感性存在关联,携带CD14突变体A基因者患AS风险较大.     

中国人群β珠蛋白基因簇RFLP连锁不平衡及其在产前诊断中的意义

根据中国人群β珠蛋白基因簇上八个RFLP所构成的单倍型的分布频率,应用群体遗传学方法和统计学方法,分析了各种组合的RFLP之间的连锁不平衡情况,发现中国人群β~A和β~T珠蛋白基因簇上RFLP都存在不均一的连锁不平衡,把整个β蛋白基因簇分成5′—基因簇和3′—基因簇两部分。根据连锁不平衡对遗传标记的诊断意义的影响规律,结合可诊断率的研究结果,我们认为,在产前诊断β地中海贫血时,选择3′—基因簇的RFLP较选择5′—基因簇内的RFLP为佳,但在排除基因重组的情况下,则同时选择两个基因簇的RFLP可大大提高可以进行准确产前诊断的β地中海贫血家庭。     

强直性脊柱炎患者中IL-23 R基因rs7517847多态性分析

目的研究IL-23R基因rs7517847位点的单核苷酸多态性与强直性脊柱炎易感性的关系.方法采用PCRRFLP方法对100例强直性脊柱炎患者进行IL-23R基因多态性检测,并与35例健康者对照分析.结果 rs7517847位点各基因型频率和等位基因频率在AS组与对照组之间的分布差异均具有统计学意义(P0.05);并在假设遗传方式下,rs7517847位点的纯合突变GG基因型与(TG+TT)基因型比较,其频率分布差异在AS组与对照组之间也具有统计学意义(P0.05).结论 IL-23R基因rs7517847位点的多态性与吉林地区人群AS易感性有关;携带G等位基因且为GG基因型的个体患AS的危险性增大,这可能是患AS的易感因素之一.     

基于单体型重构的传递不平衡检验

传递不平衡检验是基于家系检测疾病位点与标记位点之间连锁与连锁不平衡的经典分析方法。论文针对紧密连锁位点,提出了单体型的传递不平衡检验方法,并把此方法用于分析IgA肾病的两紧密连锁位点的基因定位数据。首先在估计核心家系的单体型频率的基础上,重构单体型的传递/未传递的交叉分类表格,然后通过检验此表格的对称性与边缘齐性进行传递不平衡检验,同时,自编Excel宏命令VBA程序,用于家系数据单体型频率估计与重构。此方法充分利用所有家系信息,并能处理缺失数据。C2093T-C2081T的单体型多态性与IgA肾病关联。此方法推广了已有单体型传递不平衡检验。     

陶家寨墓地M5号墓主线粒体DNA片段分析

以青海省西宁市陶家寨墓地M5号墓中的14个个体的牙齿样本为研究对象进行线粒体DNA研究.考古学研究表明该墓葬年代为东汉-魏晋时期(距今2000 a左右),并可能为家族墓地.通过对该墓地的14个个体的高可变一区(HVRⅠ),高可变二区(HVRⅡ)测序及扩增片段长度多态性(APLP)分型,共检出8个单倍型,分属于A,B,D,Flc,Z和M,6个单倍型类群.与周边地区的古代人群相比较,实验样本与同一地区距今约4000 a前的喇家古人群在遗传结构上具有一定的连续性.而与现代人群比较发现,实验样本与羌族人群有较近的亲缘关系.     

Essential requirement for major histocompatibility complex recognition in T-cell tolerance induction

The induction of T-cell responses involves the recognition of extrinsic antigen in association with antigens of the major histocompatibility complex (MHC), in mice and man, with different T cells recognizing antigen in association with either class I (H-2K/D, HLA-A, B, C) or class II (Ia, HLA-D/DR) MHC antigens. However, the requirement of MHC recognition in the induction of immunological tolerance remains ill defined. With human T helper clones recognizing synthetic peptides of influenza haemagglutinin (HA-1), we have investigated the nature of antigen-induced stimulation, and antigen-induced antigen-specific unresponsiveness, immunological tolerance. Tolerance is not due to cell death, as the cells remain responsive to interleukin-2 and is associated with the loss of T3 antigen from the cell surface. Using monoclonal antibodies to the non-polymorphic regions of human class II antigens to inhibit the induction of T-cell tolerance we report here that induction of tolerance requires the recognition of MHC antigens.     

Responses to the H-2Kba mutant involve recognition of syngeneic Ia molecules

Conventional antigens appear to be recognized by T lymphocytes only when associated with major histocompatibility complex (MHC) antigens. Using antigen-specific proliferation as a model for helper T lymphocytes, it has been demonstrated that Ly1+T cells recognize antigen presented in association with syngeneic Ia molecules. In contrast to responses to conventional antigens, however, a large number of studies have suggested that the stimulation of alloreactive Ly1+T cells, and helper T cells specific for allogeneic cytotoxic T lymphocyte (CTL) responses, involve the direct recognition of Ia alloantigens. For the generation of optimal allogeneic CTL activity it has been proposed that Ly1+T cells recognize allo-Ia antigens directly and provide help to pre-CTLs that respond to allo-H-2K and/or D determinants. Thus, the B6.C.H-2bm1 mutant (bm1, formerly referred to as Hz1), which is believed to consist of a substitution of two amino acids in the H-2Kb antigen, has presented a paradox, for it can stimulate strong mixed lymphocyte culture (MLC), graft versus host and CTL responses by T cells of H-2b haplotype mice in the apparent absence of any alloantigenic differences in the I region. We now present evidence that the stimulation of proliferative and helper T cells by the mutant B6.C.H-2bm1 results from the H-2Kba antigen being recognized in the context of syngeneic Ia determinants. Thus responses to both conventional antigens and allogeneic MHC gene products may proceed via the recognition of antigen in the context of self Ia molecules.     

Molecular genetic basis of the histo-blood group ABO system

The histo-blood group ABO, the major human alloantigen system, involves three carbohydrate antigens (ABH). A, B and AB individuals express glycosyltransferase activities converting the H antigen into A or B antigens, whereas O(H) individuals lack such activity. Here we present a molecular basis for the ABO genotypes. The A and B genes differ in a few single-base substitutions, changing four amino-acid residues that may cause differences in A and B transferase specificity. A critical single-base deletion was found in the O gene, which results in an entirely different, inactive protein incapable of modifying the H antigen.     

Structure of the human class I histocompatibility antigen, HLA-A2

The class I histocompatibility antigen from human cell membranes has two structural motifs: the membrane-proximal end of the glycoprotein contains two domains with immunoglobulin-folds that are paired in a novel manner, and the region distal from the membrane is a platform of eight antiparallel beta-strands topped by alpha-helices. A large groove between the alpha-helices provides a binding site for processed foreign antigens. An unknown 'antigen' is found in this site in crystals of purified HLA-A2.     

胸腺素的临床应用

本文阐述胸腺素的生物学功能和临床应用动态.已知诸如类风湿性关节炎和强直性脊柱炎等风湿性疾病的发病机制与机体免疫功能异常密切相关,而胸腺素对免疫功能有调节平衡的作用;结合作者用胸腺素治疗风湿性疾病的临床体会,胸腺素可能是对强直性脊柱炎和类风湿性关节炎等一些风湿性疾病有致缓解作用的一种药物.有必要对其临床应用价直和机制作更深入的研究.     

云南怒族八种红细胞血型抗原调查分析

目的 :了解云南怒族ABO、Rh、MN、P、GPC、GPA、KeLL、Wrb血型系统抗原分布情况 ,为解决临床输血及人类学、遗传学、分子生物学提供理论依据。方法 :在怒族自然村采用随机抽样调查128人 ,进行血清学检测定型的方法。结果 :云南怒族ABO血型系统中表现型A>O>B>AB ;基因频率r>p>q。Rh血型系统中Rh( -D)阴性率占4 69 % ,d基因频率为0 2165 ,分布较高于我国各民族(除新疆维吾尔族外) ,该民族表现型CCDee居多 ,占31 25% ,其分布特征为CCDee>CcDee>CcDE>ccDE>ccdee>ccDee。MN血型系统中表现型M>MN>N ;基因频率m>n,该系统中的Mur抗原阳性率特别高为22 65%(29/128) ,与上海汉族阳性率为0 66%(6/900)相比 ,怒族Mur抗原分布明显高于汉族Mur抗原。P血型系统中基因频率P2(0 7552)>P1(0 2448) ;GPC、GPA、KeLL、Wrb血型皆为阳性。结论 :不同民族的血型抗原存在一定的差异性 ,怒族的血型分布有自己的特点。     

蒙西医结合治疗强直性脊柱炎的临床观察

目的:探讨蒙西医结合治疗强直性脊柱炎的疗效.方法:对28例强直性脊柱炎采用蒙药阿魏二十五味散、珍宝丸、嘎日迪五味丸治疗的同时服用西药柳氮磺吡啶(SASP)和甲氨碟呤(MTX).结果:28例中临床缓解12例(42.8%),显效12例(42.8%),有效3例(10.7%),无效1例(3.6%).总有效率96.3%.结论:蒙西药物相结合治疗强直性脊柱炎能起到标本兼治的作用,不易复发,疗效显著.     

Peripheral deletion of self-reactive B cells

B LYMPHOCYTES are key participants in the immune response because of their specificity, their ability to take up and present antigens to T cells, and their capacity to differentiate into antibody-secreting cells. To limit reactivity to self antigens, autospecific B cells can be functionally inactivated or deleted. Developing B cells that react with membrane antigens expressed in the bone marrow are deleted from the peripheral lymphocyte pool. It is important to ascertain the fate of B cells that recognize membrane autoantigens expressed exclusively on peripheral tissues because B cells in the peripheral lymphoid organs are phenotypically and functionally distinct from bone-marrow B cells. Here we show that in immunoglobulin-transgenic mice, B cells specific for major histocompatibility complex class I antigen can be deleted if they encounter membrane-bound antigen at a post-bone-marrow stage of development. This deletion may be necessary to prevent organ-specific autoimmunity.     

Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA

The extreme polymorphism in the human leukocyte antigen (HLA) class I region of the human genome is suggested to provide an advantage in pathogen defence mediated by CD8+ T cells. HLA class I molecules present pathogen-derived peptides on the surface of infected cells for recognition by CD8+ T cells. However, the relative contributions of HLA-A and -B alleles have not been evaluated. We performed a comprehensive analysis of the class I restricted CD8+ T-cell responses against human immunodeficiency virus (HIV-1), immune control of which is dependent upon virus-specific CD8+ T-cell activity. In 375 HIV-1-infected study subjects from southern Africa, a significantly greater number of CD8+ T-cell responses are HLA-B-restricted, compared to HLA-A (2.5-fold; P = 0.0033). Here we show that variation in viral set-point, in absolute CD4 count and, by inference, in rate of disease progression in the cohort, is strongly associated with particular HLA-B but not HLA-A allele expression (P < 0.0001 and P = 0.91, respectively). Moreover, substantially greater selection pressure is imposed on HIV-1 by HLA-B alleles than by HLA-A (4.4-fold, P = 0.0003). These data indicate that the principal focus of HIV-specific activity is at the HLA-B locus. Furthermore, HLA-B gene frequencies in the population are those likely to be most influenced by HIV disease, consistent with the observation that B alleles evolve more rapidly than A alleles. The dominant involvement of HLA-B in influencing HIV disease outcome is of specific relevance to the direction of HIV research and to vaccine design.