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）。ESRD组和对照组中频率最高的三位点单倍型都是A*33：03-B*58：01-DRB1*03：01。实验结果表明,广西汉族ESRD患者HLA-A、B和DRB1高频率的等位基因及单倍型与广西汉族健康人基本相同,其中HLA-A*11：01、A*02：01、B*13：01、DRB1*12：02、DRB1*04：05、DRB1*14：54和DRB1*11：01可能与广西汉族ESRD高发病风险相关;HLA-A*11：02、A*30：01、A*32：01、B*13：02、B*07：02、DRB1*07：01和DRB1*13：02可能与广西汉族ESRD低发病风险相关。     

JAK2基因单倍型46/1对中国人群骨髓增殖性肿瘤易感性的影响

从91例骨髓增殖性肿瘤(MPNs)患者及1 028例健康志愿者(均为中国人)外周血中提取基因组DNA,应用等位基因特异性PCR(ASP)技术,检测作为蛋白质酪氨酸激酶JAK2单倍型46/1标签的rs12343867和rs10974944位点的基因型,并结合临床资料,应用SNPstats软件进行统计学分析.实验结果表明:MPNs患者JAK2单倍型46/1出现的几率明显高于健康志愿者(P0.000 1);MPNs患者的JAK2单倍型46/1更易在JAK2V617F突变阳性MPNs患者(n=70)中出现(P0.000 1);具有JAK2单倍型46/1的中国人群患MPNs的风险增加显著,该结果与测试欧美人群的结果一致.     

Application of the phylogenetic analysis in mitochondrial disease study

Mitochondrial disease currently received an increasing concern. However, the case-control design commonly adopted in this field is vulnerable to genetic background, population stratification and poor data quality. Although the phylogenetic analysis could help solve part of these problems, it has not received adequate attention. This paper is a review of this method as well as its application in mitochondrial disease study.     

Sequence variation of mitochondrial DNA ND5 in captive South China tigers (Panthera tigris amoyensis)

This paper represents the first study of the genetic diversity of captive South China tigers Panthera tigris amoyensis by sequence variation in a fragment of mitochondrial DNA (mtDNA) NADH dehydrogenase subunit 5 (ND5) gene. Two haplotypes (haplotype I and haplotype II) were identified and the captive population had a bias towards haplotype I. This subspecies as a whole demonstrated an extremely low level of genetic diversity with the nucleotide diversity of 0.057±0.021%. The mtDNA ND5 variations detected in the present study could provide significant information to the studbook data of the South China tiger.     

Repeated sampling adds to the genetic diversity of Lepidochelys olivacea (Eschscholtz 1829) olive ridley sea turtle

ABSTRACT

First sampled in the late 1990s, Campamento Tortuguero La Gloria, in Jalisco, Mexico, was resampled for olive ridley sea turtle (Lepidochyles olivacea Eschscholtz) diversity 10 years later. A comparison with all previously reported mitochondrial sequences revealed that these new samples added to the known genetic diversity for this species, and revealed unexpectedly high genetic diversity among turtles nesting on this beach. The results highlight the importance of systematic resampling in known nesting rookeries to verify the genetic diversity of study populations. Three new olive ridley haplotypes are reported, all more closely related to Baja Californian haplotypes than to Australian haplotypes. Significant genetic divergence is reported within populations, within ocean basins (Atlantic, Pacific, Indian and Indo-Pacific), and between ocean basins. Furthermore, this is the first study that integrates satellite tagging data to demonstrate diverse post-nesting migration patterns of turtles with identical haplotypes, and it demonstrates flexibility in post-nesting migratory behaviour for olive ridley sea turtles of the same genetic provenance.     

不同MHC-B单倍型SPF鸡对禽白血病的抗性研究

目的探索不同MHC-B单倍型SPF鸡对禽白血病(Avian leukosis,AL)的抗性差异,为建立AL抗性和易感鸡系提供实验依据。方法选择纯合G1、G5、G6鸡系及杂合G8鸡系雏鸡进行人工感染白血病病毒A亚群(Avian leukosis virus,ALV-A)RAV-1毒株实验,G8系雏鸡(6羽)作为对照。攻毒后对各鸡系的死亡率、病变率、血液中抗体水平以及外周血淋巴细胞的病毒载量等与抗性相关指标进行动态评估与统计学分析,最终确定抗性较强和较弱的鸡系。结果 G5系病变率和死亡率均明显高于其它攻毒鸡系,G1系最低,G6和G8系居中;G1系在攻毒后第5周开始,抗体效价一直高于其它鸡系,而G5系则最低,并且在攻毒后第8周至11周和第15周至18周,G1系的抗体效价显著高于G5系(P0.05);G1系的病毒载量在攻毒后第7周至15周,低于其它鸡系,而G5系自攻毒后第9周至13周,极显著高于G1系(P0.01)。结论 G1系在感染ALV后,死亡率较低,病变轻微,抗体保护力较强,且病毒的增殖较慢,因而其对AL具有较强的抗性,而G5系则相反较为易感。本研究不仅为建立AL抗性较强和较易感的鸡系提供了实验依据,而且对进一步阐明鸡主要组织相容性复合体(Major histocompatablity complex,MHC)多态性与AL抗病性的关系有重要作用。     

A decrease in the estimated frequency of the extended HLA haplotype B18 CF130 DR3 DQw2 is common to non-insulin-dependent diabetes,juvenile rheumatoid arthritis,and Berger's disease

Extended HLA haplotypes frequencies were estimated from the HLA, C2, Bf and C4 phenotypes of 74 patients with non-insulin-dependent diabetes (NIDD), 92 with juvenile rheumatoid arthritis (JRA), 44 with Berger's disease (BD), 83 with insulin-dependent diabetes (IDD), and 140 healthy controls. The extended HLA haplotype B18 CF130 DR3 DQw2, which is common (around 10% phenotype frequency) in healthy Spaniards and in other populations of paleo-North African origin, was found to be significantly less frequent in NIDD, JRA and BD, whereas its frequency was normal in IDD (although DR3 DQw2 haplotypes were increased in the latter disease). These data support the existence of a common HLA-linked pathogeneic mechanism in NIDD, JRA and BD, and point to a genetic difference between IDD and NIDD at the HLA level. This effect is readily detectable in our population because the uncommon BfF1 allele marks that haplotype instead of the more common BfS, which marks B8 CS01 DR3 DQw2 in other Caucasians. Our results support the hypothesis of strong selective pressures operating at the HLA level to preserve extended HLA haplotypes with advantageous gene sets from dilution by crossing-over. Imbalanced incomplete haplotypes may give rise to inappropriate T-cell repertoire selection in the thymus and/or antigen handling in the periphery, and be partly responsible for the pathogenesis of certain HLA-linked diseases (i.e. NIDD, JRA, and BD).     

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.     

The susceptibility gene for familial nasopharyngeal carcinoma is mapped on chromosome 4p11-p14 by haplotype analyses

In our previous study, one candidate susceptibility locus for familial nasopharyngeal carcinoma (NPC) has been defined to a 14.21-cM region on 4p15.1-q12, whereas the distal minimum boundary of this region remained to be further determined in respect that the two markers D4S2996 and D4S428 were uninformative. In the present study, we carried out a haplotype analysis to identify the exact boundary by using the combination of a set of microsatellite markers and single nucleotide polymorphism (SNP) markers in two major NPC families. We defined the exact distal boundary between D4S1577 and D4S3347, and consequently shortened the susceptibifity locus to an 8.29-cM segment on 4pll-p14.