Y染色体单倍型在中国汉族人群中的多态性分布与中国人群的起源及迁移

观察了由19个单核苷酸多态位点（SNP）组成的Y染色体单倍型在全国22个省市汉族人群中的分布。结果表明，中国南北人群的Y染色体单倍型组成有较大差异，南方人群的多态性明显高于北方人群，而后者中的单倍型仅含前者的一部分，其中单倍型H7，H10和H12仅出现在南方群体，这一观察结果与中国南北少数民族人群间差异相符，提示现代人类自南方进入中国，随后由南向北逐渐迁移，同时对携带南北人群共同的单倍型个体在3个Y染色体微卫星标记位点进行了基因组分型，据此估算了现代人类进入中国的时间大致在18000#approx#60000a前。

单核苷酸多态性的研究技术

在对人类基因组单核苷酸多态性(SNP)的概念做简要说明的基础上,系统地介绍14种检测分析SNP的技术和方法的原理、操作要点及其优缺点。

Evolution of the DRD2 gene haplotype and its association with alcoholism in Mexican Americans

The human D2 dopamine receptor gene (DRD2) plays a central role in the neuromodulation of appetitive behaviors and is implicated in having a possible role in susceptibility to alcoholism. We genotyped an SNP in DRD2 Exon 8 in 251 nonalcoholic, unrelated, healthy controls and 200 alcoholic Mexican Americans. The DRD2 haplotypes were analyzed using the Exon 8 genotype in combination with five other SNP genotypes, which were obtained from our previous study. The ancestral origins of the DRD2 polymorphisms have been determined by sequencing the homologous region in other higher primates. Twenty DRD2 haplotypes, defined as H1 to H20 based on their frequency from high to low, were obtained in this major minority population. The ancestral haplotype "I-132-G-C-G-A1" and two one-step mutation haplotypes were absent in our study population. The haplotype H1, "I-B1-T-C-A-A1", with the highest frequency in the population, is a three-step mutation from the ancestral form. The first five or eight major haplotypes make up 87% or 95% of the entire population, respectively. The prevalence of the haplotype H1+ (H1/H1 and H1/Hn genotypes) is significantly higher in alcoholics and alcoholic subgroups, including early onset drinkers and benders, than in their respective control groups. The Promoter -141C allele is in linkage disequilibrium (LD) with five other loci in the nonalcoholic group, but not in the alcoholic group. All of the other five loci are in LD in both the alcoholic and control groups. The DRD2 TaqI B allele is in complete LD with the allele located in intron 6. Five SNPs, Promoter -141C, TaqI B (or Intron 6), Exon 7, Exon 8, and TaqI A, are sufficient to define the DRD2 haplotypes in Mexican Americans. Our data indicate that the DRD2 haplotypes are associated with alcoholism in Mexican Americans. (c) 2005 Elsevier Inc. All rights reserved.

Identification of genes differentially expressed in wild type and Purkinje cell degeneration mice

Purkinje cell degeneration (pcd) mice are characterized by death of virtually all cerebellar Purkinje cells by postnatal day 30. In this study, we used DNA microarray analysis to investigate differences in gene expression between the brains of wild type and pcd mice on postnatal day 20, before the appearance of clear-cut phenotypic abnormalities. We identified 300 differentially expressed genes, most of which were involved in metabolic and physiological processes. Among the differentially expressed genes were several calcium binding proteins including calbindin -28k, paravalbumin, matrix gamma-carboxygluta mate protein and synaptotagamins 1 and 13, suggesting the involvement of abnormal Ca2+ signaling in the pcd phenotype.

Evidence for Positive Selection on the Osteogenin (BMP3) Gene in Human Populations

Background: Human skeletal system has evolved rapidly since the dispersal of modern humans from Africa, potentially driven by selection and adaptation. Osteogenin (BMP3) plays an important role in skeletal development and bone osteogenesis as an antagonist of the osteogenic bone morphogenetic proteins, and negatively regulates bone mineral density. Methodology/Principal Findings: Here, we resequenced the BMP3 gene from individuals in four geographically separated modern human populations. Features supportive of positive selection in the BMP3 gene were found including the presence of an excess of nonsynonymous mutations in modern humans, and a significantly lower genetic diversity that deviates from neutrality. The prevalent haplotypes of the first exon region in Europeans demonstrated features of long-range haplotype homogeneity. In contrast with findings in European, the derived allele SNP Arg192Gln shows higher extended haplotype homozygosity in East Asian. The worldwide allele frequency distribution of SNP shows not only a high-derived allele frequency in Asians, but also in Americans, which is suggestive of functional adaptation. Conclusions/Significance: In conclusion, we provide evidence for recent positive selection operating upon a crucial gene in skeletal development, which may provide new insight into the evolution of the skeletal system and bone development.

Prion protein gene (PRNP) polymorphisms in native Chinese cattle

Le polymorphisme au sein de quatre regions du gene codant pour la proteine prion bovine (PRNP) confere la susceptibilite a l'encephalopathie bovine spongiforme (BSE). Ceux-ci comprennent un polymorphisme d'insertion/deletion (indel) de 23 pb dans le promoteur, un indel de 12 pb dans l'intron 1, un octapeptide repete ou un indel de 24 pb au sein du cadre de lecture, et un polymorphisme mononucleotidique (SNP) dans la region codante. Dans ce travail, les auteurs ont examine la frequence des genotypes, des alleles et des haplotypes pour ces indel au sein de 349 bovins d'origine chinoise, de meme que la sequence nucleotidique de ce gene chez 50 de ces animaux. Leurs resultats montrent que l'allele ayant la deletion de 12 pb et l'haplotype combinant la deletion de 23 pb et la deletion de 12 pb, lesquels ont ete suggeres comme etant importants pour la susceptibilite a la BSE, sont rares au sein des bovins du sud de la Chine. Une difference significative a ete observee entre les bovins affectes par la BSE et les bovins chinois sains pour ce qui est de l'indel de 12 pb. Au total, 14 SNP ont ete observes dans la region codante du gene PRNP chez les bovins chinois. Trois de ces SNP etaient associes a des changements d'acides amines (K3T, P54S et S154N). La substitution E211K qui a ete rapportee recemment chez un cas atypique de la BSE chez un bovin americain n'a pas ete detectee dans ce travail.

The Genomes of Oryza sativa: A history of duplications

We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped superscaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000 - 40,000. Only 2% - 3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism ( SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family.

鸭催乳素基因外显子4单核苷酸多态性与就巢性状的相关分析

研究采用PCR-SSCP技术研究番鸭不同就巢群体(就巢1月群、就巢2月群、就巢3月群)、番鸭非就巢群和白改鸭5个群体250个个体PRL基因第4外显子多态性与就巢性状之间的相关性.结果表明,在外显子4编码区内发现2个SNP位点,分别位于该基因的3 777 bp (T/C)和3 785 bp(A/C)处.基因型与就巢性状指标相关分析的结果表明,番鸭非就巢群体与各就巢群体间差异极显著(P<0.01),同时番鸭与白改鸭差异显著(P<0.05),推测PRL基因与就巢性有一定的相关.

鸭催乳素基因外显子4单核苷酸多态性与就巢性状的相关分析

研究采用PCR-SSCP技术研究番鸭不同就巢群体(就巢1月群、就巢2月群、就巢3月群)、番鸭非就巢群和白改鸭5个群体250个个体PRL基因第4外显子多态性与就巢性状之间的相关性.结果表明,在外显子4编码区内发现2个SNP位点,分别位于该基因的3 777 bp(T/C)和3 785 bp(MG)处.基因型与就巢性状指标相关分析的结果表明,番鸭非就巢群体与各就巢群体间差异极显著(P<0.01),同时番鸭与白改鸭差异显著(P<0.05),推测PRL基因与就巢性有一定的相关.

鸭催乳素基因外显子5多态性与就巢性状的关联分析

下载PDF阅读器将番鸭不同就巢群体(就巢1月群、就巢2月群、就巢3月群)、番鸭非就巢群和白改鸭群体作为试验材料,采用PCR-SSCP技术研究番鸭不同就巢群体、番鸭非就巢群和白改鸭5个群体250个个体催乳素(PRL)基因第5外显子多态性及其与就巢性状之间的相关性.结果表明:外显子5片段编码区发现3个SNP位点,位于5 871 bp(G/A)、5 926 bp(A/G)和6 029 bp(C/T)处,其中5 871 bp(G/A)与5 926 bp(A/G)处氨基酸序列均改变,分别为I→V和R→K.统计多态片段的基因型频率和基因频率,并对5个试验鸭群间基因频率作差异进行显著性分析,番鸭非就巢群体与各就巢群体间差异显著(P<0.05),同时番鸭与白改鸭差异极显著(P<0.01).

Identification and association of the single nucleotide polymorphisms in calpain3 (CAPN3) gene with carcass traits in chickens

Background: The aim of this study is to screen single nucleotide polymorphisms (SNP) of chicken Calpain3 (CAPN3) gene and to analyze the potential association between CAPN3 gene polymorphisms and carcass traits in chickens. We screened CAPN3 single nucleo

SNPNB: analyzing neighboring-nucleotide biases on single nucleotide polymorphisms (SNPs)

SNPNB is a user-friendly and platform-independent application for analyzing Single Nucleotide Polymorphism NeighBoring sequence context and nucleotide bias patterns, and subsequently evaluating the effective SNP size for the bias patterns observed from the whole data. It was implemented by Java and Perl. SNPNB can efficiently handle genome-wide or chromosome-wide SNP data analysis in a PC or a workstation. It provides visualizations of the bias patterns for SNPs or each type of SNPs.

Accelerating Bayesian hierarchical clustering of time series data with a randomised algorithm.

We live in an era of abundant data. This has necessitated the development of new and innovative statistical algorithms to get the most from experimental data. For example, faster algorithms make practical the analysis of larger genomic data sets, allowing us to extend the utility of cutting-edge statistical methods. We present a randomised algorithm that accelerates the clustering of time series data using the Bayesian Hierarchical Clustering (BHC) statistical method. BHC is a general method for clustering any discretely sampled time series data. In this paper we focus on a particular application to microarray gene expression data. We define and analyse the randomised algorithm, before presenting results on both synthetic and real biological data sets. We show that the randomised algorithm leads to substantial gains in speed with minimal loss in clustering quality. The randomised time series BHC algorithm is available as part of the R package BHC, which is available for download from Bioconductor (version 2.10 and above) via http://bioconductor.org/packages/2.10/bioc/html/BHC.html. We have also made available a set of R scripts which can be used to reproduce the analyses carried out in this paper. These are available from the following URL. https://sites.google.com/site/randomisedbhc/.

Combined effects of polyfluorinated and perfluorinated compounds on primary cultured hepatocytes from rare minnow (Gobiocypris rarus) using toxicogenomic analysis

Polyfluorinated and perfluorinated compounds (PFCs) are used in numerous commercial products and have been ubiquitously detected in the environment as well as in the blood of humans and wildlife. To assess the combined effects caused by PFCs in mixtures, gene expression profiles were generated using a custom cDNA microarray to detect changes in primary cultured hepatocytes of rare minnows exposed to six individual PFCs (perfluorooctanoic acid, perfluorononanoic acid, perfluorodecanoic acid, perfluorododecanoic acid, perfluorooctane sulfonate, and 8:2 fluorotelomer alcohol) and four formulations of the PFCs mixtures. Mixtures as well as individual compounds consistently regulated a particular gene set, which suggests that these conserved genes may play a central role in the toxicity mediated by PFCs. Specifically, a number of genes regulated by the mixtures were identified in this study, which were not affected by exposure to any single component. These genes are implicated in multiple biological functions and processes, including fatty acid metabolism and transport, xenobiotic metabolism, immune responses, and oxidative stress. More than 80% of the altered genes in the PFOA- and PFOS-dominant mixture groups were of the same gene set, while the gene expression profiles from single PFOA and PFOS exposures were not as similar. This work contributes to the development of toxicogenomic approaches in combined toxicity assessment and allows for comprehensive insights into the combined action of PFCs mixtures in multiple environmental matrices. (C) 2009 Elsevier B.V. All rights reserved.

Transcriptome of embryonic and neonatal mouse cortex by high-throughput RNA sequencing

Brain structure and function experience dramatic changes from embryonic to postnatal development. Microarray analyses have detected differential gene expression at different stages and in disease models, but gene expression information during early brain development is limited. We have generated >27 million reads to identify mRNAs from the mouse cortex for>16,000 genes at either embryonic day 18 (E18) or postnatal day 7 (P7), a period of significant synapto-genesis for neural circuit formation. In addition, we devised strategies to detect alternative splice forms and uncovered more splice variants. We observed differential expression of 3,758 genes between the 2 stages, many with known functions or predicted to be important for neural development. Neurogenesis-related genes, such as those encoding Sox4, Sox11, and zinc-finger proteins, were more highly expressed at E18 than at P7. In contrast, the genes encoding synaptic proteins such as synaptotagmin, complexin 2, and syntaxin were up-regulated from E18 to P7. We also found that several neurological disorder-related genes were highly expressed at E18. Our transcriptome analysis may serve as a blueprint for gene expression pattern and provide functional clues of previously unknown genes and disease-related genes during early brain development.