陕西渭南地区汉族人群17个Y-STR基因座多态性及遗传关系分析

调查陕西渭南地区汉族群体17个Y-STR基因座的多态性,探讨其群体遗传学及法医学应用价值。应用Y-fi ler荧光标记复合扩增系统,对413名陕西渭南地区汉族无关男性个体17个Y-STR基因座进行复合扩增,用ABI3130遗传分析仪进行基因分型,计算各基因座的群体遗传学参数,并结合已经发表的其他10个群体相应基因座的单倍型资料,分析各群体间的遗传距离。413名陕西渭南汉族个体共检出405种单倍型,其中397种单倍型仅出现1次,单倍型多样性达0.9999,基因多样性(GD)为0.4130(DYS391)~0.9734(DYS385a/b),累计GD值为0.9999。遗传距离分析提示,陕西渭南汉族与辽宁满族的遗传距离最小(0.00110),与青海藏族的遗传距离最大(0.22333)。结果表明,17个Y-STR基因座在陕西渭南汉族群体中具有丰富的遗传多态性和较高的非父排除能力,在法医学和人类群体遗传学研究中具有重要价值。     

Identification of quantitative trait nucleotides that regulate cancer growth: a simulation approach

A general growth model derived from basic cellular properties can be used to describe the dynamic process of cancer growth with mathematical equations. It has been recognized that cancer growth is under genetic control, with a multitude of interacting genes each segregating in a Mendelian fashion and displaying environmental sensitivity. In this article, we integrate the mathematical aspects of the pervasive growth model into a statistical framework for the identification of quantitative trait nucleotides that underlie cancer growth. This integrative framework is constructed with a single nucleotide polymorphism-based haplotype blocking analysis. Simulation studies have been performed to demonstrate the usefulness of the model. The proposed model provides a generic platform model for testing and detecting specific DNA sequence variants that regulates the timing of cancer emergence, growth and differentiation.     

Genetic variation in heat shock protein 60 gene and coronary heart disease in China: tagging-SNP haplotype analysis in a case-control study

Background High levels of circulating heat shock protein 60 (Hsp60) and antibody to human Hsp60 have been associated with greater risk of coronary heart disease (CHD) in several studies, but associations between polymorphisms of the hsp60 gene and CHD risk have not been investigated. Methods By resequencing DNA from 30 unrelated Han Chinese and using HapMap Phase I Chinese data of hsp60 gene, we selected four tagging single nucleotide polymorphisms (tagSNPs) named rs2340690, rs788016, rs2305560, and rs2565163, and determined their frequencies in 1,003 Chinese CHD patients and 1,003 age- and sex-frequency-matched controls. Furthermore, we used PHASE 2.0 software to reconstruct haplotypes and logistic regression to control for potential confounders in multivariate analyses. Results We found 13 SNPs in hsp60 gene (including four novel SNPs) in Han Chinese subjects. Our results showed no significant differences in four selected SNPs in patients with CHD and controls after adjusting for other conventional risk factors and stratifying by age, sex, smoking status, past history of hypertension and DM; however, our results showed that subjects with the GCTC haplotype had about twofold higher risk of CHD than those with the GTTC haplotype (OR = 1.91, 95%CI: 1.26–2.89, P = 0.002). Conclusions Our results suggest that the GCTC haplotype in the hsp60 gene is significantly associated with higher CHD risk in a Chinese population. The first two authors contributed equally to this paper.     

Retrospective analysis of haplotype-based case control studies under a flexible model for gene environment association

Genetic epidemiologic studies often involve investigation of the association of a disease with a genomic region in terms of the underlying haplotypes, that is the combination of alleles at multiple loci along homologous chromosomes. In this article, we consider the problem of estimating haplotype-environment interactions from case-control studies when some of the environmental exposures themselves may be influenced by genetic susceptibility. We specify the distribution of the diplotypes (haplotype pair) given environmental exposures for the underlying population based on a novel semiparametric model that allows haplotypes to be potentially related with environmental exposures, while allowing the marginal distribution of the diplotypes to maintain certain population genetics constraints such as Hardy-Weinberg equilibrium. The marginal distribution of the environmental exposures is allowed to remain completely nonparametric. We develop a semiparametric estimating equation methodology and related asymptotic theory for estimation of the disease odds ratios associated with the haplotypes, environmental exposures, and their interactions, parameters that characterize haplotype-environment associations and the marginal haplotype frequencies. The problem of phase ambiguity of genotype data is handled using a suitable expectation-maximization algorithm. We study the finite-sample performance of the proposed methodology using simulated data. An application of the methodology is illustrated using a case-control study of colorectal adenoma, designed to investigate how the smoking-related risk of colorectal adenoma can be modified by "NAT2," a smoking-metabolism gene that may potentially influence susceptibility to smoking itself.     

Variable responses of formyl peptide receptor haplotypes toward bacterial peptides

The chemoattractant neutrophil formyl peptide receptor (FPR) binds bacterial and mitochondrial N-formylated peptides, which allows the neutrophils to find the bacterial source and/or site of tissue damage. Certain inflammatory disorders may be due in part to an impaired innate immune system that does not respond to acute bacterial damage in a timely fashion. Because the human FPR is encoded by a large number of different haplotypes arising from ten single-nucleotide polymorphisms, we examined the possibility that some of these haplotypes are functionally distinct. We analyzed the response of three common FPR haplotypes to peptides from Escherichia coli, Mycobacterium avium ssp. paratuberculosis, and human mitochondria. All three haplotypes responded similarly to the E. coli and mitochondrial peptides, whereas one required a higher concentration of the M. avium peptide fMFEDAVAWF for receptor downregulation, receptor signaling, and chemotaxis. This raises the possibility of additional bacterial species differences in functional responses among FPR variants and establishes a precedent with potentially important implications for our innate immune response against bacterial infections. We also investigated whether certain FPR haplotypes are associated with rheumatoid arthritis (RA) by sequencing FPR1 from 148 Caucasian individuals. The results suggested that FPR haplotypes do not significantly contribute toward RA. George J. Saari, Deceased.     

Decreased calcium pump expression in human erythrocytes is connected to a minor haplotype in the ATP2B4 gene

Plasma membrane Ca²⁺-ATPases are key calcium exporter proteins in most tissues, and PMCA4b is the main calcium transporter in the human red blood cells (RBCs). In order to assess the expression level of PMCA4b, we have developed a flow cytometry and specific antibody binding method to quantitatively detect this protein in the erythrocyte membrane. Interestingly, we found several healthy volunteers showing significantly reduced expression of RBC-PMCA4b. Western blot analysis of isolated RBC membranes confirmed this observation, and indicated that there are no compensatory alterations in other PMCA isoforms. In addition, reduced PMCA4b levels correlated with a lower calcium extrusion capacity in these erythrocytes. When exploring the potential genetic background of the reduced PMCA4b levels, we found no missense mutations in the ATP2B4 coding regions, while a formerly unrecognized minor haplotype in the predicted second promoter region closely correlated with lower erythrocyte PMCA4b protein levels. In recent GWA studies, SNPs in this ATP2B4 haplotype have been linked to reduced mean corpuscular hemoglobin concentrations (MCHC), and to protection against malaria infection. Our data suggest that an altered regulation of gene expression is responsible for the reduced RBC-PMCA4b levels that is probably linked to the development of human disease-related phenotypes.     

Behaviourally and genetically distinct populations of an invasive ant provide insight into invasion history and impacts on a tropical ant community

Populations of invasive species often exhibit a high degree of spatial and temporal variability in abundance and hence their effects on resident communities. Here, we examine behavioural, genetic and environmental factors that influence variation in populations of the yellow crazy ant, Anoplolepis gracilipes, on the remote Nukunonu Atoll of Tokelau, Pacific Ocean. Behavioural assays revealed high levels of aggression between two groups of yellow crazy ants from different islands, and genetic analysis confirmed the presence of two distinct populations with unique mitochondrial (mt)DNA haplotypes, designated A and D. The two populations likely resulted from two separate invasion events. The populations exhibited significant differences in abundance of A. gracilipes, with a mean sevenfold difference in relative abundance between the two main haplotypes. The higher density haplotype D population coexisted with 50% fewer other ant species and altered ant community composition. Vegetation composition was also significantly different on islands harbouring the two populations. The results suggest genetic differences could play a role in the spatial and temporal variation in the effect of the yellow crazy ant on a small oceanic atoll. We could not differentiate between genetic effects and effects of vegetation. However, our results indicate that spatial variability in behaviour and impacts within populations of invasive species could be in part due to genetic differences, and play a substantial role in influencing the outcome of biological invasions.     

陇东黄土高原石鸡的分子系统地理结构

本文运用聚合链式反应和直接测序的方法测定陇东黄土高原 8个石鸡 (Alectorischukar)地理种群 78个样本的mtDNA控制区 4 91bp ,建立其分子系统地理结构。 78个样本共发现 2 4个变异位点 ,2 5种单倍型。 8个地理种群共享单倍型C1 ,6个种群共享单倍型C2 ,种群间有一定的基因交流。 8个地理种群的 2 5种单倍型在NJ树中相互混杂 ,没有形成独立的地理结构 ,但聚成两个分支。单倍型网络图显示 2 5种单倍型聚成两个星状的集群 ,分别以单倍型C1和C2为中心。这两个群间的遗传差异显著。陇东黄土高原石鸡的系统地理结构属于“系统发生连续 ,具有部分空间隔离”的地理格局。这种地理格局是更新世冰川、泥石流和人类活动共同作用的结果