北京和东京人群MYO9B单核苷酸多态性差异比较分析

为探讨中国北京汉族人群(CHB)和日本东京人群(JPT)肌球蛋9B(MYO9B)单核苷酸基因多态性(SNP)、单体域和单体型的差异,我们利用人类基因组单体型图(Hap Map)公布的Ⅲ期MYO9B SNP数据,通过Haploview4.2软件选择合格SNP、标签SNP(tagSNP)、估计最小等位基因频率(minimum allele frequency,MAF)及构建单体域,并比较其差异。然后通过Phase2.1软件构建特殊tagSNP位点单体型并行置换检验以比较两个人群所构建单体型的差异。研究结果表明,从CHB及JPT MYO9B中分别筛选出52个及50个合格SNP,其中49个是一致的。两人群合格SNP MAF频数最高组段及最低组段相同,且整体比较无差别(p=0.07)。于两人群MYO9B各构建7个和5个单体域,其中两个基本相同,一个单体域为CHB独有,其余在两人群分布不同但互有重叠。从两人群MYO9B分别筛选出23个及17个tagSNP,其中17个tagSNP相同,另6个SNP在CHB单独成为tagSNP而不与其他SNP相关联。利用两人群MYO9B特殊tagSNP位点共构建10个频率2%的相同的单体型,累计频率分别为51.37%和51.99%,且两者均以TCTCG和TTTCG单体型为主。两人群MYO9B特殊位点单体型构成基本相同(p=0.765)。综上所述,CHB和JPT的MYO9B SNP及单体域特征以共性为主,与人群的地域和种族属性一致;北京汉族与东京人群特殊SNP位点构建的MYO9B单体型构成及频率无差别。     

尼罗罗非鱼β2m基因SNP位点和单倍型与无乳链球菌抗性的关联分析

β₂-微球蛋白(β₂-microglobulin, β₂m)作为MHCⅠ类分子的亚基, 在鱼类的免疫系统中发挥重要作用。实验采用直接测序法从P₀代尼罗罗非鱼(Oreochromis niloticus)的β₂m基因组序列中筛选到30个SNPs, 其中1个SNP位于5?UTR, 16个SNPs位于外显子区域(15个非同义突变位点, 1个同义突变位点), 9个SNPs位于内含子区域, 4个SNPs位于3?UTR。利用snapshot分型法对F₁代的102尾易感群体和102尾抗病群体进行基因分型, 并通过Popgen32和PIC-CALC软件统计分析尼罗罗非鱼β₂m基因序列的SNPs的H_e、H_o、N_e和PIC等遗传参数, 表明易感群体中7个SNPs属于中度多态水平(0.251代2个群体中的基因型频率和等位基因频率, 分析其与链球菌抗性或易感性状之间的相关性。结果表明: 24个SNPs的基因型和等位基因频率与无乳链球菌(Streptococcus agalactiae)抗性/易感性状显著相关(P<0.05)。通过连锁不平衡分析发现30个SNPs构成4个单倍块和14种单倍型。其中, 4个单倍型与无乳链球菌抗性性状显著相关(P<0.05), 4个单倍型与易感性状显著相关(P<0.05)。标签SNP分析发现, 单倍块2中的4个SNPs和单倍块3中的13个SNPs彼此之间高度连锁(r2>0.9), 这意味着我们在β₂m基因中发现2个htSNPs。研究筛选到的与链球菌抗性/易感性状相关的SNP位点及单倍型具有辅助尼罗罗非鱼抗链球菌病品种选育的潜力。     

人类基因组单体型图初步绘就

由美国、中国、日本等国200多位科学家参加的"国际人类基因组单体型图计划(HapMap)"日前取得阶段成果,科学家于26日公布了第一阶段人类基因组单体型图。科学家说,这份描述人类基因组中最常见差异的图谱,将大大促进疾病和人类进化的研究。人类基因组拥有大约     

滇金丝猴线粒体D-loop 片段SNPs 位点的鉴别及初步分析

本文利用已测序的157 个滇金丝猴控制区(D-loop)片段,通过与参考序列比对,鉴别了线粒体D-loop 片段中的52 个SNP (Single Nucleotide Polymorphisms)位点,定义了30 种滇金丝猴单倍型,排除概率为0. 938。谱系及种群遗传结构分析结果与以前利用D-loop 片段的研究结果相似。同时表明基于粪便样品进行保护遗传学、谱系生物地理学、种群遗传学等研究时,与线粒体标记和微卫星标记相比,SNP 标记可能具有一定的优越性,并建议进一步分析滇金丝猴线粒体D-loop 全序列甚至线粒体全基因组上的SNPs 位点的信息,以促进滇金丝猴保护遗传学等研究的开展。     

结合已有知识体系的酒精中毒相关的SNP单体型及其相关基因挖掘

高通量的单核苷酸多态（single nucleotide polymorphism,SNP）检测技术与已有的知识体系（如KEGG,GO数据库等）为与疾病相关的SNP单体型及相关基因挖掘提供了有力支撑．本研究对高通量SNP基因型数据,采用4种SNP单体型板块（block）识别方法（置信区间、FGT、连锁不平衡的稳定连接以及单体型板块融合技术）,用聚类分析方法验证其效能,通过风险分析方法确定酒精中毒相关的SNP单体型,并基于已有知识体系建立SNP单体型与基因的映射,通过查询NCBISNP与gene数据库定位SNP单体型板块,确定候选基因,最后结合KEGG,Biocarta及GO数据库进行基因功能注释．在对人类22对常染色体的分析中,寻找到可能与酒精中毒相关的159个单体型板块,包含227个SNP单体型,并预测其中102个SNP单体型可能会增加酒精中毒的发病风险．挖掘得到了121个酒精中毒相关基因,并进一步进行可靠的生物学功能注释验证．结果提示：采用聚类效果验证及风险分析的单体型识别机制,基于单体型的疾病相关基因定位并结合已有知识体系的疾病相关基因挖掘策略,不仅能大大缩减SNP数据挖掘的工作量,实现复杂疾病相关基因的精细定位,而且对于多因素复杂疾病发病机制的探索将更有指导意义．     

复杂疾病的遗传易感基因区域的精细定位

以单核苷酸多态性(Single-nucleotide polymorphism, SNP)为遗传标记, 采用全基因组关联研究(Genome-wide association studies, GWAS)的策略, 已经在660多种疾病(或性状)中发现了3800多个遗传易感基因区域。但是, 其中最显著关联的遗传变异或致病性的遗传变异位点及其生物学功能并不完全清楚。这些位点的鉴定有助于阐明复杂疾病的生物学机制, 以及发现新的疾病标记物。后GWAS时代的主要任务之一就是通过精细定位研究找到复杂疾病易感基因区域内最显著关联的易感位点或致病性的易感位点并阐明其生物学功能。针对常见变异, 可通过推断或重测序增加SNP密度, 寻找最显著关联的SNP位点, 并通过功能元件分析、表达数量性状位点(Expression quantitative trait locus, eQTL)分析和单体型分析等方法寻找功能性的SNP位点和易感基因。针对罕见变异, 则可采用重测序、罕见单体型分析、家系分析和负荷检验等方法进行精细定位。文章对这些策略和所面临的问题进行了综述。     

人类的选择

发现：2006年,芝加哥大学的Jonathan Pritchard研究小组采用新公布的HapMap数据去寻找存在于三类人群中,与SNPs高频连锁的基团。他们发现,成百上千的基因组区域可能遭遇了正向选择。     

线粒体单体型与线粒体相关的人类疾病

线粒体是一种拥有自身遗传体系的半自主细胞器,它的遗传物质线粒体DNA(mitochondrial DNA,mt DNA)随着人类的迁移、隔离、进化而形成了广泛的线粒体基因组多态性,同一祖先所具有的一些相同mt DNA SNP位点的集合称为线粒体单体型.不同的线粒体单体型会在一定程度上影响线粒体功能,从而影响整个细胞的生长,并在某些情况下导致一些个体的病变,例如Leber遗传性视神经病变、母系遗传性耳聋、Ⅱ型糖尿病、帕金森以及各种癌症等复杂疾病.本文列举总结了几种线粒体相关疾病及其与线粒体单体型如A、B、D、F、G、H、J、K、M、N、T、U、Y及一些有特点的多态位点如G11778A、A1555G、T3394C、G10398A等的相关性.     

国际人类基因组单体型图计划

人类基因组单体型图(Haplotypemap,以下简称HapMap)计划是与不久前完成的基因组测序计划相当的又一多国参与的重大国际合作项目,也是人类基因组研究领域的第2个重大战略目标。其目的是在通过测序了解了遗传基本信息的基础上,进一步确立世界上主要族群基因组的遗传变异图谱。这一计划的主要     

SNPs及其在水产动物遗传学与育种学研究中的应用

1 SNP简介1.1 SNP的概念单核苷酸多态性(Single nucleotide polymorphism,SNP)指基因组DNA序列中某个特定位点的单个核苷酸发生变异而引起的序列多态性,包括单碱基的转换、颠换、插入及缺失等形式,其中一种等位基因在群体中的频     

Genetic diversity of Toll-like receptor 5 among pig populations

The Toll-like receptor 5 (TLR5) recognizes flagellin of Gram-positive and -negative bacteria and plays an important role in the host defense system. Here, we surveyed single nucleotide polymorphisms (SNPs) in the coding sequence of the porcine TLR5 gene in 83 individuals from five pig breeds, these including Chinese local populations and Western commercial pig breeds. A total of 19 medium polymorphic SNPs (0.25 < PIC < 0.5) were identified, three of which were missense mutations that clustered within the extracellular domain of TLR5. One of the non-synonymous SNPs fell within a 228-amino acid region which has been shown to be important for flagellin recognition. Four SNPs were only found with high frequencies in Oriental pig breeds. The 19 SNPs were found in 30 haplotypes, one of which segregated at high frequency in all samples. Compared with Western pig breeds, Chinese local populations had higher genetic diversity and more haplotypes. Tajima’s test showed no evidence for deviation from neutrality. The data provide useful information for future genetic marker characterization by means of disease association analysis and/or stimulating the mutation carrier with relevant ligands.     

Effects of adiponectin polymorphisms on the risk of advanced age-related macular degeneration

Abstract

Objective: To determine the relationships between variants in adiponectin gene (ADIPOQ) with advanced forms of age-related macular degeneration (AMD) susceptibility.

Methods: A total of 189 advanced AMD patients and 168 controls were recruited. Seven tagging single-nucleotide polymorphisms in ADIPOQ were genotyped by the SNaPshot method.

Results: Alleles or genotypes of rs822396 distributed significantly differently in advanced AMD patients and controls. The minor allele G at rs822396 was associated with an increased risk of advanced AMD in a dominant model. Furthermore, haplotype analysis revealed that haplotypes AGGACCT and TGACCCC were significantly increased the advanced AMD susceptibility, whereas haplotypes AGAACGC, TGAACGT and TGACAGC had protective effects.

Conclusion: ADIPOQ genetic variant rs822396 might affect an individual’s susceptibility to AMD, making it efficient genetic biomarkers for early detection of AMD.     

Y-chromosome haplotype distribution in Han Chinese populations and modern human origin in East Asians

We investigated the distribution of Y-chromosome haplotype using 19 Y-SNPs in Han Chinese populations from 22 provinces of China. Our data indicate distinctive patterns of Y chromosome between southern and northern Han Chinese populations. The southern populations are much more polymorphic than northern populations. The latter has only a subset of the southern haplotypes. This result confirms the genetic difference observed between southern and northern ethnic populations in East Asia. It supports the hypothesis that the first settlement of modern humans of African origin occurred in the southern part of East Asia during the last Ice Age, and a northward migration led to the peopling of northern China.     

The whole mitochondrial genome sequence of the zebra finch (Taeniopygia guttata)

Here we describe the complete nucleotide sequence of the mitochondrial genome (16 583/4 bp) of the zebra finch (Taeniopygia guttata). Primers were designed based on highly conserved regions of an alignment of three passerine complete mitochondrial DNA (mtDNA) sequences. A combination of overlapping long polymerase chain reaction (PCR) purification, followed by fully nested PCR and sequencing was used to determine the complete mtDNA genome. Six birds, from distinct maternal lineages of a pedigreed population were sequenced. Five novel haplotypes were identified. These sequences provide the first data for sequence variation across the whole mitochondrial genome of a passerine bird species.     

Allele-specific PCR can improve the efficiency of experimental resolution of heterozygotes in resequencing studies

Resolution of the two haplotypes present in an individual that is heterozygous at a locus has been a difficult problem for nucleotide sequence-based population genetic studies. Here, we demonstrate a method in which allele-specific polymerase chain reaction (AS-PCR) and computational phasing are combined for relatively high-throughput, efficient resolution of phase in resequencing studies. Using data from multiple loci that were fully experimentally phased, we demonstrate that the popular computational tool PHASE can accurately phase heterozygous individuals with common SNPs (single nucleotide polymorphisms) and/or common haplotypes. However, we also demonstrate that experimental phasing with AS-PCR can efficiently supplement computational phasing, providing a rapid means to phase individuals with rare SNPs or haplotypes and with heterozygous insertion/deletion polymorphisms. By following simple stepwise procedures, AS-PCR can result in much more efficient and accurate experimental phasing of haplotypes than is possible with traditional methods such as cloning.     

Genetic variations at the human growth hormone receptor (GHR) gene locus are associated with idiopathic short stature

GH plays an essential role in the growing child by binding to the growth hormone receptor (GHR) on target cells and regulating multiple growth promoting and metabolic effects. Mutations in the GHR gene coding regions result in GH insensitivity (dwarfism) due to a dysfunctional receptor protein. However, children with idiopathic short stature (ISS) show growth impairment without GH or GHR defects. We hypothesized that decreased expression of the GHR gene may be involved. To test this, we investigated whether common genetic variants (microsatellites, SNPs) in regulatory regions of the GHR gene region were associated with the ISS phenotype. Genotyping of a GT‐repeat microsatellite in the GHR 5′UTR in a Montreal ISS cohort (n = 37 ISS, n = 105 controls) revealed that the incidence of the long/short (L/S) genotype was 3.3× higher in ISS children than controls (P = 0.04, OR = 3.85). In an Italian replication cohort (n = 143 ISS, n = 282 controls), the medium/short (M/S) genotype was 1.9× more frequent in the male ISS than controls (P = 0.017, OR = 2.26). In both ISS cohorts, logistic regression analysis of 27 SNPs showed an association of ISS with rs4292454, while haplotype analysis revealed specific risk haplotypes in the 3′ haploblocks. In contrast, there were no differences in GT genotype frequencies in a cohort of short stature (SS) adults versus controls (CARTaGENE: n = 168 SS, n = 207 controls) and the risk haplotype in the SS cohort was located in the most 5′ haploblock. These data suggest that the variants identified are potentially genetic markers specifically associated with the ISS phenotype.     

秦川牛脂联素基因SNPs检测及其与胴体、肉质性状的相关性

利用PCR-SSCP结合测序技术对405头24月龄秦川牛脂联素基因SNPs位点进行检测, 运用SPSS统计程序中的GLM模型将检测到的SNPs位点与部分胴体及肉质性状的相关性进行了分析。结果检测到AA、AB、BB、CC、CD 5种基因型, 其中AB、BB型个体在脂联素基因第2外显子 64 bp处发现G→C突变, CD型个体第3外显子50 bp处发现C→T的突变, G→C导致谷氨酸(GGA)转化为谷氨酰胺(GCA), C→T导致丝氨酸(TCA)转化为亮氨酸(TTA)。方差分析结果表明: AA型个体的宰前活重、胴体重、眼肌面积显著高于BB型(P<0.05), 而在胴体腿臀围方面, AA型个体极显著高于AB型、BB型个体(P<0.01)。CD型个体的宰前活重、胴体腿臀围、皮下脂肪厚、背膘厚、嫩度都显著优于CC型个体(P<0.05)。脂联素基因该位点可能是影响秦川牛胴体及肉质性状的主效QTL或与之紧密连锁, 可作为秦川牛高档牛肉生产的候选分子标记。     

脂肪分化相关蛋白基因多态性与优质鸡屠宰性状和肌内脂肪含量的相关性研究

对脂肪分化相关蛋白(Adipocyte Differentiation-Related Protein, ADFP)基因的外显子进行SNPs 检测, 探讨其作为鸡脂肪性状候选基因的可能性。实验以四川省畜牧科学研究院和大恒家禽育种有限公司培育的优质肉鸡新品系为素材, 采用PCR-SSCP的方法进行SNPs 检测和基因型的分析。结果找到3个SNPs位点: 4 079位由A→T(位点A)、4 843位由C→T(位点B)和7 070位由A→G(位点C)。单位点基因型对屠宰性状的遗传效应分析表明, 位点A的基因型对腿肌率、腹脂重、腹脂率和肌内脂肪含量有显著性影响(P < 0.05), 位点B的基因型对活重和屠体重均有显著性影响(P < 0.05), 位点C的基因型对胸肌重和肌内脂肪含量有显著性影响(P < 0.05), 对胸肌率有极显著性影响(P < 0.01)。初步推断ADFP基因可能是影响鸡脂肪性状的主效基因或与主效基因连锁, 推测可以利用多态位点A和C对鸡腹脂重、腹脂率和肌内脂肪含量进行标记辅助选择。     

Amounts and patterns of nucleotide variation within and between two Japanese conifers, sugi (Cryptomeria japonica) and hinoki (Chamaecyparis obtusa) (Cupressaceae sensu lato)

Sugi (Cryptomeria japonica) and hinoki (Chamaecyparis obtusa) are the most important timber species in Japan. To quantify and compare the level of nucleotide variation in these species, we investigated their variation at ten nuclear loci. Average values of nucleotide diversity at synonymous sites (π _SYN) found in sugi and hinoki were 0.0038 and 0.0069, respectively. However, although the average value of nucleotide diversity was higher in hinoki than in sugi, their average values of haplotype diversity were similar. Deviations from the standard neutral model were detected at two loci in hinoki using Tajima’s D, Fay and Wu’s H, and Strobeck’s S statistics, which seem to be due to its historical population structure. Levels of divergence between the two species at synonymous sites of the ten genes ranged from 0.121 to 0.566 (0.28 on average). These values positively correlated with their guanine + cytosine contents at third-codon positions of synonymous sites (%GC3s).