Genetic Variation in the Epidermal Transglutaminase Genes Is Not Associated with Atopic Dermatitis

Background

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder where epidermal barrier dysfunction is a major factor in the pathogenesis. The identification of AD susceptibility genes related to barrier dysfunction is therefore of importance. The epidermal transglutaminases (TGM1, TGM3 and TGM5) encodes essential cross-linking enzymes in the epidermis.

Objective

To determine whether genetic variability in the epidermal transglutaminases contributes to AD susceptibility.

Methods

Forty-seven single nucleotide polymorphisms (SNPs) in the TGM1, TGM3 and TGM5 gene region were tested for genetic association with AD, independently and in relation to FLG genotype, using a pedigree disequilibrium test (PDT) in a Swedish material consisting of 1753 individuals from 539 families. In addition, a German case-control material, consisting of 533 AD cases and 1996 controls, was used for in silico analysis of the epidermal TGM regions. Gene expression of the TGM1, TGM3 and TGM5 gene was investigated by relative quantification with Real Time PCR (qRT-PCR). Immunohistochemical (IHC) analysis was performed to detect TG1, TG3 and TG5 protein expression in the skin of patients and healthy controls.

Results

PDT analysis identified a significant association between the TGM1 SNP rs941505 and AD with allergen-specific IgE in the Swedish AD family material. However, the association was not replicated in the German case-control material. No significant association was detected for analyzed SNPs in relation to FLG genotype. TG1, TG3 and TG5 protein expression was detected in AD skin and a significantly increased TGM3 mRNA expression was observed in lesional skin by qRT-PCR.

Conclusion

Although TGM1 and TGM3 may be differentially expressed in AD skin, the results from the genetic analysis suggest that genetic variation in the epidermal transglutaminases is not an important factor in AD susceptibility.     

Genetic Variation in TLR Genes in Ugandan and South African Populations and Comparison with HapMap Data

Genetic epidemiological studies of complex diseases often rely on data from the International HapMap Consortium for identification of single nucleotide polymorphisms (SNPs), particularly those that tag haplotypes. However, little is known about the relevance of the African populations used to collect HapMap data for study populations conducted elsewhere in Africa. Toll-like receptor (TLR) genes play a key role in susceptibility to various infectious diseases, including tuberculosis. We conducted full-exon sequencing in samples obtained from Uganda (n = 48) and South Africa (n = 48), in four genes in the TLR pathway: TLR2, TLR4, TLR6, and TIRAP. We identified one novel TIRAP SNP (with minor allele frequency [MAF] 3.2%) and a novel TLR6 SNP (MAF 8%) in the Ugandan population, and a TLR6 SNP that is unique to the South African population (MAF 14%). These SNPs were also not present in the 1000 Genomes data. Genotype and haplotype frequencies and linkage disequilibrium patterns in Uganda and South Africa were similar to African populations in the HapMap datasets. Multidimensional scaling analysis of polymorphisms in all four genes suggested broad overlap of all of the examined African populations. Based on these data, we propose that there is enough similarity among African populations represented in the HapMap database to justify initial SNP selection for genetic epidemiological studies in Uganda and South Africa. We also discovered three novel polymorphisms that appear to be population-specific and would only be detected by sequencing efforts.     

Genetic Variation in Circadian Rhythm Genes CLOCK and ARNTL as Risk Factor for Male Infertility

Background

The circadian system has a major role in maintaining homeostasis and proper body functions including reproductive capacity. The aim of this study was to examine whether there is an association between genetic variability in the primary clock genes CLOCK and ARNTL and male infertility in humans.

Methodology/Principal Findings

We performed a case-control study, where we searched for an association between polymorphisms of CLOCK and ARNTL genes and male infertility in 961 Slovenian and Serbian Caucasian men. The study group consisted of 517 patients with idiopathic infertility and a control group of 444 fertile men. A statistically significant difference was found in genotype distribution between the two groups in the CLOCK gene: rs11932595 (p = 6·10⁻⁵, q = 4·10⁻⁴, OR equaled 1.9 with 95% CI 1.4–2.7), rs6811520 (p = 2·10⁻³, q = 8·10⁻³, OR = 1.7 with 95% CI 1.2–2.2) and rs6850524 (p = 0.01, q = 0.02, OR = 1.4 with 95% CI 1.1–1.9). Further analyses of haplotypes were consistent with genotyping results.

Conclusions/Significance

We provide evidence that genetic variability in the CLOCK gene might be associated with male infertility warranting further confirmation and mechanistic investigations.     

Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk

Background

Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk.

Methods

In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons.

Results

The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10^-4).

Conclusion

These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.     

基于线粒体基因分析蓝孔雀与绿孔雀的遗传差异

种间的遗传差异是物种分类和确定保护管理单元的基础,本研究利用DNA条形码技术对未知样本进行鉴定,通过NCBI进行BLAST得到结果是:与绿孔雀的同源性为96%。近一步通过对蓝孔雀(Pavo cristatus)和绿孔雀(Pavo muticus)线粒体细胞色素C氧化酶Ⅰ(cytochrome coxidaseⅠ,COⅠ)基因及线粒体基因组的比较分析,结果表明两物种间的COⅠ基因在碱基组成、核苷酸多样性等各项指标上均具有明显差异。遗传距离分析结果表明蓝孔雀与绿孔雀种内遗传距离为分别0和0.012,种间遗传距离为0.045,表明种间仍具有明显的遗传差异。通过对两物种线粒体基因组各基因的比较分析,发现ND1基因变异位点所占比例相对较高,考虑作为绿孔雀和蓝孔雀种群遗传学研究的最优分子标记。本研究将为分析孔雀类群间的系统发育及制定绿孔雀的保护措施提供了更多科学依据。     

猪伪狂犬病综合诊断及分离毒株gE和TK基因遗传变异分析

2012年以来,许多使用gE基因缺失活疫苗免疫过的猪场广泛性出现伪狂犬病毒(PRV)感染,gE抗体阳性率不断升高,伪狂犬典型病例不断增加。2018年3月鲁南地区几个种猪场先后发生疑似伪狂犬病疫情,怀孕母猪流产、产死胎和木乃伊胎,仔猪出现神经症状且死亡率高。通过对病死猪及死胚剖检进行初步诊断,取病料进一步进行病理组织学诊断及病毒分离鉴定。结果显示,病死猪均可见病毒性脑炎、肝细胞变性坏死及淋巴组织坏死等病理变化,在病变的神经元、肝细胞、扁桃体隐窝上皮细胞等细胞核内见红染包涵体。对分离到的4株PRV进行了gE和TK基因的序列测定及遗传变异分析发现,4株PRV的gE和TK核苷酸序列的同源性分别为98.8%~99.3%和98.9%~99.6%,与国内流行毒株其核苷酸序列的同源性分别99.1%~99.7%和98.6%~99.8%,与匈牙利和美国等流行毒株核苷酸序列的同源性分别为97.3%~97.8%和98.8%~99.5%,表明4株分离株高度同源,与国内PRV变异株处在同一分支,而与匈牙利和美国等毒株遗传距离较远。传统疫苗对PRV变异毒株不能提供有效保护,给猪场伪狂犬病的防控和净化工作带来了新的挑战。     

Genetic and Epigenetic Variation across Genes Involved in Energy Metabolism and Mitochondria of Chinese Hamster Ovary Cell Lines

The increasingdemandfor biopharmaceutical products drives the search for efficient cell factories that are able to sustainably support rapid growth, high productivity, and product quality. As these depend on energy generation, here the genomic variation in nuclear genes associated with mitochondria and energy metabolism and the mitochondrial genome of 14 cell lines is investigated. The variants called enable reliable tracing of lineages. Unique sequence variations are observed in cell lines adapted to grow in protein‐free media, enriched in signaling pathways or mitogen‐activated protein kinase 3. High‐producing cell lines bear unique mutations in nicotinamide adenine dinucleotide (NADH) dehydrogenase (ND2 and ND4) and in peroxisomal acyl‐CoA synthetase (ACSL4), involved in lipid metabolism. As phenotypes are determined not only by functional mutations, but also by the exquisite regulation of expression patterns, it is not surprising that ≈50% of the genes investigated here are found to be differentially methylated and thus epigenetically controlled, enabling a clear distinction of high producers, and cells adapted to a minimal, glutamine (Gln)‐free medium. Similar pathways are enriched as those identified by genome variation. This strengthens the hypothesis that these phenomena act together to define cell behavior.     

中国2000-2004年鸡传染性支气管炎病毒地方分离株核蛋白基因的遗传变异分析

对2000-2004年从中国9个省市分离到的13株IBV的核蛋白基因片段进行序列测定及分析的结果表明,13株IBV分离株核蛋白基因均含有一个长1230bp的ORF,但存在基因突变现象.与GenBank中的42株参考毒株核蛋白基因序列进行比较和分析,系统进化关系显示55株IBV毒株分属于9个群.第Ⅰ-Ⅲ群主要包括美国、日本、荷兰等国家以及中国的部分IBV分离株和疫苗株.其中本研究中的CK/CH/LHN/00I可能为一株分离的疫苗毒,CK/CH/LSD/03I、CK/CH/LDL/01I可能为重组毒.而中国近十年来分离的IBV毒株主要分布在第Ⅵ-Ⅷ群中,此3群内IBV毒株之间N蛋白推导氨基酸同源性为88.3%～100%,与其他各群之间同源性为62.3%～95.1%.因此,此基因型的IBV毒株可能在中国已有较长时期的存在且发生了较大程度的变异.其中第Ⅵ群中两株韩国分离株与中国IBV分离株具有较近的亲缘关系.以上结果表明,中国大多数IBV分离株在N基因进化关系上较为独立,与国外毒株相比,和韩国毒株进化关系密切.此外,中国IBV毒株基因重组现象更加普遍,尤其是疫苗毒和野毒之间的重组.     

中国2000—2004年鸡传染性支气管炎病毒地方分离株核蛋白基因的遗传变异分析

对2000-2004年从中国9个省市分离到的13株IBV的核蛋白基因片段进行序列测定及分析的结果表明,13株IBV分离株核蛋白基因均含有一个长1230bp的ORF,但存在基因突变现象。与GenBank中的42株参考毒株核蛋白基因序列进行比较和分析,系统进化关系显示55株IBV毒株分属于9个群。第Ⅰ-Ⅲ群主要包括美国、日本、荷兰等国家以及中国的部分IBV分离株和疫苗株。其中本研究中的CK/CH/LHN/00I可能为一株分离的疫苗毒,CK/CH/LSD/03I、CK/CH/LDL/01I可能为重组毒。而中国近十年来分离的IBV毒株主要分布在第Ⅵ-Ⅷ群中,此3群内IBV毒株之间N蛋白推导氨基酸同源性为88.3%～100%,与其他各群之间同源性为62.3%～95.1%。因此,此基因型的IBV毒株可能在中国已有较长时期的存在且发生了较大程度的变异。其中第Ⅵ群中两株韩国分离株与中国IBV分离株具有较近的亲缘关系。以上结果表明,中国大多数IBV分离株在N基因进化关系上较为独立,与国外毒株相比,和韩国毒株进化关系密切。此外,中国IBV毒株基因重组现象更加普遍,尤其是疫苗毒和野毒之间的重组。     

Evolution and Variation of Renin Genes in Mice

Inbred strains of mice carry Ren-1, a gene encoding the thermostable Renin-1 isozyme. Ren-1 is expressed at relatively low levels in mouse submandibular gland and kidney. Some strains also carry Ren-2, a gene encoding the thermolabile Renin-2 isozyme. Ren-2 is expressed at high levels in the mouse submandibular gland and at very low levels, if at all, in the kidney. Ren-1 and Ren-2 are closely linked on mouse chromosome 1, show extensive homology in coding and noncoding regions and provide a model for studying the regulation of gene expression. An investigation of renin genes and enzymatic activity in wild-derived mice identified several restriction site polymorphisms as well as putative variants in renin gene expression and protein structure. The number of renin genes carried by different subpopulations of wild-derived mice is consistent with the occurrence of a gene duplication event prior to the divergence of M. spretus (2.75–5.5 million yr ago). This conclusion is in agreement with a prior estimate based upon comparative sequence analysis of Ren-1 and Ren-2 from inbred laboratory mice.     

Genetic Variation and Atherosclerosis

A family history of atherosclerosis is independently associated with an increased incidence of cardiovascular events. The genetic factors underlying the importance of inheritance in atherosclerosis are starting to be understood. Genetic variation, such as mutations or common polymorphisms has been shown to be involved in modulation of a range of risk factors, such as plasma lipoprotein levels, inflammation and vascular calcification. This review presents examples of present studies of the role of genetic polymorphism in atherosclerosis.     

The Nature of Genetic Variation in Sex and Reproduction-related Genes Among Sibling Species of the Drosophila melanogaster Complex

Much is known about the biology of Drosophila melanogaster. As a model organism, a comprehensive understanding of its development, physiology and reproduction has been acquired. As a result, a broad variety of transferable genetic tools and information has allowed sibling species of the D. melanogaster complex to emerge as an important speciation model system. By comparing D. melanogaster with its close relative, Drosophila simulans, as well as its other sibling species, we are beginning to understand the nature of genetic changes during the early stages of speciation. In general, we find that genes and traits involved in sex and reproduction are more variable. A large assortment of genes and traits that are involved in various aspects of mating and fertility reveal diagnostic differences between these sibling species. Sex and reproduction-related (SRR) genes are, on average, more diverged than genes with no apparent reproductive function. Furthermore, SRR genes appear more permissive at opting in novel function. These results follow a general trend observed in other taxa and demonstrate the preferential involvement of SRR genes in reproductive isolation and species formation.     

Variation in Flagellin Genes and Proteins of Burkholderia cepacia

The majority of isolates of Burkholderia cepacia, an important opportunistic pathogen associated with cystic fibrosis, can be classified into two types on the basis of flagellin protein size. Electron microscopic analysis indicates that the flagella of strains with the larger flagellin type (type I) are wider in diameter. Flagellin genes representative of both types were cloned and sequenced to design oligonucleotide primers for PCR amplification of the central variable domain of B. cepacia flagellin genes. PCR-restriction fragment length polymorphism analysis of amplified B. cepacia flagellin gene products from 16 strains enabled flagellin type classification on the basis of product size and revealed considerable differences in sequence, indicating that the flagellin gene is a useful biomarker for epidemiological and phylogenetic studies of this organism.Burkholderia cepacia (formerly Pseudomonas cepacia; a member of the rRNA group II pseudomonads) has emerged as an increasingly important opportunistic pathogen, particularly in relation to patients suffering from cystic fibrosis (CF) (15). Acquisition of B. cepacia, often occurring after lengthy colonization with Pseudomonas aeruginosa, can lead to the rapid deterioration or death of CF patients, and this organism appears to be transmissible between patients (14). There is considerable evidence that some strains of B. cepacia are more virulent than others and that the outcome of colonization by a particular strain can vary from rapidly fatal septicemia to maintenance of stable respiratory function (16). A number of factors have been implicated in the greater virulence of some strains. These include adhesion to respiratory mucin (31, 32) and the presence of cable pili (33).Motility in B. cepacia is by means of polar flagella. Flagella, each consisting of a flagellin filament, hook, and basal body, have been implicated as invasive virulence factors for a number of bacteria (28), including P. aeruginosa (11). Unlike P. aeruginosa, which appears to sit in microcolonies in the viscid mucus, leading to progressive lung damage with episodes of acute debilitating exacerbation, some strains of B. cepacia cause rapidly fatal pneumonia in CF patients (15), suggesting that they may have the ability to move through the mucus. Because of their location on the outside of bacterial cells, flagellins have been targeted in vaccine design. Brett et al. (4) demonstrated that flagellin-specific antisera were capable of protecting diabetic rats from challenge with strains of Burkholderia pseudomallei (another member of rRNA group II). In a recent study, an O-polysaccharide moiety of B. pseudomallei was covalently linked to the flagellin protein from the same strain. O-polysaccharide–flagellin conjugates elicited a high-level immunoglobulin G response capable of protecting diabetic rats from challenge with a heterologous strain of B. pseudomallei (5).Two distinct flagellin protein molecular mass groups in B. cepacia have been reported by Montie and Stover (23). In this previous study, type I flagellins were reported as having a molecular mass of 31 kDa while the molecular mass of type II flagellins was reported as 44 to 46 kDa. This early study, using a limited number of isolates, suggested that with regard to flagellin, B. cepacia is analogous to another CF pathogen, P. aeruginosa, in which two flagellin antigenic types distinguishable by protein or gene size are found (43). Several representatives of the heterologous a-type and homologous b-type fliC loci of P. aeruginosa (encoding flagellins) have been sequenced (37). In addition, PCR amplification of flagellin genes coupled with restriction fragment length polymorphism (RFLP) analysis can be used as a method for differentiating between clinical isolates of P. aeruginosa (7, 43). In this paper we report the development of a similar approach to the study of populations of B. cepacia and discuss the divergence of a highly variable gene, the flagellin gene (fliC), within populations of B. cepacia.     

Association between Common Germline Genetic Variation in 94 Candidate Genes or Regions and Risks of Invasive Epithelial Ovarian Cancer

Background

Recent studies have identified several single nucleotide polymorphisms (SNPs) in the population that are associated with variations in the risks of many different diseases including cancers such as breast, prostate and colorectal. For ovarian cancer, the known highly penetrant susceptibility genes (BRCA1 and BRCA2) are probably responsible for only 40% of the excess familial ovarian cancer risks, suggesting that other susceptibility genes of lower penetrance exist.

Methods

We have taken a candidate approach to identifying moderate risk susceptibility alleles for ovarian cancer. To date, we have genotyped 340 SNPs from 94 candidate genes or regions, in up to 1,491 invasive epithelial ovarian cancer cases and 3,145 unaffected controls from three different population based studies from the UK, Denmark and USA.

Results

After adjusting for population stratification by genomic control, 18 SNPs (5.3%) were significant at the 5% level, and 5 SNPs (1.5%) were significant at the 1% level. The most significant association was for the SNP rs2107425, located on chromosome 11p15.5, which has previously been identified as a susceptibility allele for breast cancer from a genome wide association study (P-trend = 0.0012). When SNPs/genes were stratified into 7 different pathways or groups of validation SNPs, the breast cancer associated SNPs were the only group of SNPs that were significantly associated with ovarian cancer risk (P-heterogeneity = 0.0003; P-trend = 0.0028; adjusted (for population stratification) P-trend = 0.006). We did not find statistically significant associations when the combined data for all SNPs were analysed using an admixture maximum likelihood (AML) experiment-wise test for association (P-heterogeneity = 0.051; P-trend = 0.068).

Conclusion

These data suggest that a proportion of the SNPs we evaluated were associated with ovarian cancer risk, but that the effect sizes were too small to detect associations with individual SNPs.     

Genetic Variation in Heterogeneous Environments

A model of population structure in heterogeneous environments is described and conditions sufficient for maintaining a polymorphism are derived.

The absolute fitness of any genotype is regarded as a function of location in the niche space and the population density at that location. Two modes of habitat selection are examined: (1) organisms are distributed uniformly over the environment; and (2) each organism selects to occupy that habitat in which it is most fit ("optimal habitant selection").—Sufficient conditions for maintenance of genetic polymorphisms are derived for both models. In populations which do not practice habitat selection heterozygote superiority averaged over the environment is sufficient to guarantee the existence of polymorphisms. Comparable conditions for populations which practice optimal habitat selection are much less restrictive. If the heterozygotes are superior to one homozygote in any one part of the niche and to the other homozygote in any other part of the niche then a polymorphism will be defined.—A positive correlation between genetic and environmental variation follows from the model with habitat selection, but not from the other. The adaptive significance of polymorphisms thus depends on how animals behave.

     

Genetic Variation in Prosimian Species

Scheffrahn et al. (1998a,b) aimed to outline the possible contributions of genetics to conservation biology: the determination of genetic variation of wild groups and its use as a guideline in breeding programs. Unfortunately, the amount of genetic variation within wild groups of nonhuman primates is rarely known. In particular, this observation holds for prosimians. Average heterozygosity is widely considered to be a good indicator of the magnitude of intraspecific variation. We provide some values of average heterozygosity of wild populations of Otolemur garnettii, Eulemur macaco macaco and E. m. flavifrons.     

Behavior and Genetic Variation in Natural Populations

An analysis of allelic variation at genetic loci controllingseveral esterases and hemoglobin, as demonstrated by electrophoresis,indicates that wild populations of the house mouse (Mus musculus)are characterized by fine-scale genetic subdivision, which,through the territorial behavior of family groups (tribes),is achieved even in the absence of physical or ecological barriersto migration. Heterogeneity in allele frequencies among samples from farmsin the same region and from barns on the same farm was demonstrated.Spatial variation in allele frequencies within single barns,involving a clustering of like genotypes, was shown by grid-trapping,thus providing direct evidence of tribal subdivision in continuouslydistributed populations. For two loci, Es-3 and Hbb, an excess of heterozygotes appearedin samples from small populations, while a deficit characterizedsamples from large populations. The evolutionary significance of subdivision and consequentdrift in house mouse populations cannot properly be evaluatedat this time. Although stochastic processes may play the dominantrole in determining, at a given locus, the genotypes of individualsand frequencies of alleles in small populations, geographicpatterns of variation, as studied in Texas, are characterizedby uniformity of allelic frequency in major physiographic orclimatic regions, as would be expected if selection is determiningthe frequencies.     

Genetic Variation in Healthy Oldest-Old

Individuals who live to 85 and beyond without developing major age-related diseases may achieve this, in part, by lacking disease susceptibility factors, or by possessing resistance factors that enhance their ability to avoid disease and prolong lifespan. Healthy aging is a complex phenotype likely to be affected by both genetic and environmental factors. We sequenced 24 candidate healthy aging genes in DNA samples from 47 healthy individuals aged eighty-five years or older (the ‘oldest-old’), to characterize genetic variation that is present in this exceptional group. These healthy seniors were never diagnosed with cancer, cardiovascular disease, pulmonary disease, diabetes, or Alzheimer disease. We re-sequenced all exons, intron-exon boundaries and selected conserved non-coding sequences of candidate genes involved in aging-related processes, including dietary restriction (PPARG, PPARGC1A, SIRT1, SIRT3, UCP2, UCP3), metabolism (IGF1R, APOB, SCD), autophagy (BECN1, FRAP1), stem cell activation (NOTCH1, DLL1), tumor suppression (TP53, CDKN2A, ING1), DNA methylation (TRDMT1, DNMT3A, DNMT3B) Progeria syndromes (LMNA, ZMPSTE24, KL) and stress response (CRYAB, HSPB2). We detected 935 variants, including 848 single nucleotide polymorphisms (SNPs) and 87 insertion or deletions; 41% (385) were not recorded in dbSNP. This study is the first to present a comprehensive analysis of genetic variation in aging-related candidate genes in healthy oldest-old. These variants and especially our novel polymorphisms are valuable resources to test for genetic association in models of disease susceptibility or resistance. In addition, we propose an innovative tagSNP selection strategy that combines variants identified through gene re-sequencing- and HapMap-derived SNPs.     

ABO Genetic Variation in Neanderthals and Denisovans

Variation at the ABO locus was one of the earliest sources of data in the study of human population identity and history, and to this day remains widely genotyped due to its importance in blood and tissue transfusions. Here, we look at ABO blood type variants in our archaic relatives: Neanderthals and Denisovans. Our goal is to understand the genetic landscape of the ABO gene in archaic humans, and how it relates to modern human ABO variation. We found two Neanderthal variants of the O allele in the Siberian Neanderthals (O1 and O2), one of these variants is shared with an European Neanderthal, who is a heterozygote for this O1 variant and a rare cis-AB variant. The Denisovan individual is heterozygous for two variants of the O1 allele, functionally similar to variants found widely in modern humans. Perhaps more surprisingly, the O2 allele variant found in Siberian Neanderthals can be found at low frequencies in modern Europeans and Southeast Asians, and the O1 allele variant found in Siberian and European Neanderthal is also found at very low frequency in modern East Asians. Our genetic distance analyses suggest both alleles survive in modern humans due to inbreeding with Neanderthals. We find that the sequence backgrounds of the surviving Neanderthal-like O alleles in modern humans retain a higher sequence divergence than other surviving Neanderthal genome fragments, supporting a view of balancing selection operating in the Neanderthal ABO alleles by retaining highly diverse haplotypes compared with portions of the genome evolving neutrally.     

人类原发性高血压候选基因的研究进展

原发性高血压是一种遗传与环境因素相互作用所致的多基因遗传性疾病,其相关或易感研究在近年来非常活跃。利用家系或同胞对,采用基因组扫描结合候选基因策略,迄今已筛选出了数十年原发性高血压的可能相关基因,本从与人体血压生理生化代谢相关的几条途径中,选择介绍了与血压调节密切相关的几个候选基因的研究进展。