BACKGROUND & AIMS: :Reproductive productivity depend on a complex set of characteristics. The number of piglets at birth (Total number born, Litter size, TNB) and the number of alive piglets at birth (Total number born alive, NBA) are the main indicators of the reproductive productivity of sows in pig breeding. Great hopes are pinned on GWAS (Genome-Wide Association Studies) to solve the problems associated with studying the genetic architecture of reproductive traits of pigs. This paper provides an overview of international studies on SNP (Single nucleotide polymorphism) associated with TNB and NBA in pigs presented in PigQTLdb as "Genome map association". Currently on the base of Genome map association results 306 SNPs associated with TNB (218 SNPs) and NBA (88 SNPs) have been identified and presented in the Pig QTLdb database. The results are based on research of pigs such as Large White, Yorkshire, Landrace, Berkshire, Duroc and Erhualian. The presented review shows that most SNPs found in chromosome areas where candidate genes or QTLs (Quantitative trait locus) have been identified. Further research in the given direction will allow to obtain new data that will become an impulse for creating breakthrough breeding technologies and increase the production efficiency in pig farming.

背景与目标： ：生殖生产力取决于一系列复杂的特征。出生时的仔猪数量（出生总数，产仔数，TNB）和出生时的活仔猪数量（活产总数，NBA）是猪繁殖中母猪繁殖力的主要指标。 GWAS（全基因组关联研究）寄予了巨大的希望，以解决与研究猪的生殖性状的遗传结构有关的问题。本文概述了与猪TNB和NBA相关的SNP（单核苷酸多态性）的国际研究，该研究在PigQTLdb中以“基因组图谱关联”的形式呈现。当前，基于基因组图谱关联结果，已识别出与TNB相关的306个SNP（218个SNP）和NBA相关的88个SNP（88个SNP），并将其显示在Pig QTLdb数据库中。该结果基于对大型白猪，约克郡，长白，伯克希尔，杜洛克和二化hua等猪的研究。提出的综述显示，在已鉴定候选基因或QTL（定量性状基因座）的染色体区域中发现了大多数SNP。在给定方向上的进一步研究将允许获得新数据，这些新数据将成为推动突破性育种技术和提高养猪生产效率的动力。

BACKGROUND & AIMS: :CYP1A1 gene belongs to the cytochrome P450 family and is known better as smokers' gene due to its hyperactivation as a consequence of long term smoking. The expression of CYP1A1 induces polycyclic aromatic hydrocarbon production in the lungs, which when over expressed, is known to cause smoking related diseases, such as cardiovascular pathologies, cancer, and diabetes. Single nucleotide polymorphisms (SNPs) are the simplest form of genetic variations that occur at a higher frequency, and are denoted as synonymous and non-synonymous SNPs on the basis of their effects on the amino acids. This study adopts a systematic in silico approach to predict the deleterious SNPs that are associated with disease conditions. It is inferred that four SNPs are highly deleterious, among which the SNP with rs17861094 is commonly predicted to be harmful by all tools. Hydrophobic (isoleucine) to hydrophilic (serine) amino acid variation was observed in the candidate gene. Hence, this investigation aims to characterize a candidate gene from 159 SNPs of CYP1A1.

背景与目标： ：CYP1A1基因属于细胞色素P450家族，由于长期吸烟而过度激活，因此被称为吸烟者基因。 CYP1A1的表达诱导肺中多环芳烃的产生，而该表达过高时，已知会引起与吸烟有关的疾病，例如心血管疾病，癌症和糖尿病。单核苷酸多态性（SNP）是发生频率较高的最简单的遗传变异形式，根据其对氨基酸的影响，被称为同义和非同义SNP。这项研究采用系统的计算机模拟方法来预测与疾病状况相关的有害SNP。可以推断，四个SNP具有很高的有害性，其中rs17861094的SNP通常被所有工具认为是有害的。在候选基因中观察到疏水性（异亮氨酸）至亲水性（丝氨酸）氨基酸变化。因此，本研究旨在从CYP1A1的159个SNP中鉴定候选基因。

BACKGROUND & AIMS: :Prediction of physical appearance based on genetic analysis is a very attractive prospect for forensic investigations. Recent studies have proved that there is a significant association between some genetic variants of the melanocortin 1 receptor (MC1R) gene and red hair color. The present study focuses on the potential forensic applicability of variation within this pigment-related gene. Sequencing of the complete MC1R gene was performed on a group of red-haired individuals and controls with different pigmentation. A major role in determination of red hair color is played by two MC1R variants--C451T and C478T. The optimized minisequencing assay for genotyping of the above positions and three other important red hair-related MC1R polymorphisms, C252A, G425A, and G880C was successfully applied to analyze typical forensic specimens. Determination of a homozygous or heterozygous combination can be a good predictor of both red hair color and fair skin of a subject.

背景与目标： ：基于遗传分析的外观预测是法医研究的一个非常诱人的前景。最近的研究证明，黑皮质素1受体（MC1R）基因的某些遗传变异与红头发之间存在显着关联。本研究的重点是该色素相关基因内变异的潜在法证适用性。对一组红发个体和具有不同色素沉着的对照组进行完整的MC1R基因测序。 MC1R的两个变体-C451T和C478T在确定红头发的颜色中起主要作用。用于上述位置和其他三个重要的与红发相关的MC1R多态性C252A，G425A和G880C的基因分型的优化小序列测定法已成功用于分析典型的法医标本。纯合或杂合组合的测定可以是受试者的红头发颜色和白皙皮肤的良好预测指标。

BACKGROUND & AIMS: :High gene flow is considered the norm for most marine organisms and is expected to limit their ability to adapt to local environments. Few studies have directly compared the patterns of differentiation at neutral and selected gene loci in marine organisms. We analysed a transcriptome-derived panel of 281 SNPs in Atlantic herring (Clupea harengus), a highly migratory small pelagic fish, for elucidating neutral and selected genetic variation among populations and to identify candidate genes for environmental adaptation. We analysed 607 individuals from 18 spawning locations in the northeast Atlantic, including two temperature clines (5-12 °C) and two salinity clines (5-35‰). By combining genome scan and landscape genetic analyses, four genetically distinct groups of herring were identified: Baltic Sea, Baltic-North Sea transition area, North Sea/British Isles and North Atlantic; notably, samples exhibited divergent clustering patterns for neutral and selected loci. We found statistically strong evidence for divergent selection at 16 outlier loci on a global scale, and significant correlations with temperature and salinity at nine loci. On regional scales, we identified two outlier loci with parallel patterns across temperature clines and five loci associated with temperature in the North Sea/North Atlantic. Likewise, we found seven replicated outliers, of which five were significantly associated with low salinity across both salinity clines. Our results reveal a complex pattern of varying spatial genetic variation among outlier loci, likely reflecting adaptations to local environments. In addition to disclosing the fine scale of local adaptation in a highly vagile species, our data emphasize the need to preserve functionally important biodiversity.

背景与目标： 高基因流动被认为是大多数海洋生物的常态，预计会限制它们适应当地环境的能力。很少有研究直接比较海洋生物中性基因位点和选定基因位点的分化模式。我们分析了转录组的281个SNP的转录组，该杂交组是高度迁移的小型中上层鱼类大西洋鲱鱼（Clupea harengus），用于阐明种群之间的中性和选择性遗传变异，并确定环境适应性候选基因。我们分析了来自东北大西洋18个产卵地点的607个人，包括两个温度线（5-12°C）和两个盐度线（5-35‰）。通过基因组扫描和景观遗传分析相结合，确定了四个遗传上不同的鲱鱼群：波罗的海，波罗的海-北海过渡区，北海/不列颠群岛和北大西洋；值得注意的是，对于中性和选定位点，样品表现出不同的聚类模式。我们发现统计上有力的证据表明，在全球范围内有16个离群位点存在差异选择，并且与9个位点的温度和盐度有显着相关性。在区域尺度上，我们确定了两个跨温度谱线具有平行模式的异常基因座，以及五个与北海/北大西洋的温度相关联的基因座。同样，我们发现了七个重复的离群值，其中五个与两个盐度谱系的低盐度显着相关。我们的结果揭示了异常基因座之间空间遗传变异的复杂模式，可能反映了对当地环境的适应。除了揭示高度易变物种的局部适应的精细规模外，我们的数据还强调了必须保护功能上重要的生物多样性。

BACKGROUND & AIMS: :While the melanocortin receptors (MCRs) are known to be involved in numerous biological pathways, the potential roles of the MC5R have not been clearly elucidated in humans. Agouti-related protein (AgRP), an MC3R/MC4R antagonist and MC4R inverse agonist, contains an exposed β-hairpin loop composed of six residues (Arg-Phe-Phe-Asn-Ala-Phe) that is imperative for binding and function. Within this active loop of AgRP, four human missense polymorphisms were deposited into the NIH Variation Viewer database. These polymorphisms, Arg111Cys, Arg111His, Phe112Tyr, and Ala115Val (AgRP full-length numbering), were incorporated into the peptide macrocycles c[Pro1-Arg2-Phe3-Phe4-Xaa5-Ala6-Phe7-dPro8], where Xaa was Dap5 or Asn5, to explore the functional effects of these naturally occurring substitutions in a simplified AgRP scaffold. All peptides lowered potency at least 10-fold in a cAMP accumulation assay compared to the parent sequences at the MC4Rs. Compounds MDE 6-82-3c, ZMK 2-82, MDE 6-82-1c, ZMK 2-85, and ZMK 2-112 are also the first AgRP-based chemotypes that antagonize the MC5R.

背景与目标： ：虽然已知黑皮质素受体（MCR）参与许多生物学途径，但尚未明确阐明MC5R在人类中的潜在作用。刺痛相关蛋白（AgRP）是一种MC3R / MC4R拮抗剂和MC4R反向激动剂，包含一个暴露的β-发夹环，该环由六个残基（Arg-Phe-Phe-Asn-Ala-Phe）组成，这些残基对于结合和功能必不可少。在这个活跃的AgRP循环中，四个人类错义多态性被存入NIH Variation Viewer数据库。这些多态性Arg111Cys，Arg111His，Phe112Tyr和Ala115Val（AgRP全长编号）被整合到肽大环c [Pro1-Arg2-Phe3-Phe4-Xaa5-Ala6-Phe7-dPro8]中，其中Xaa是Dap5或Asn5。 ，以探索在简化的AgRP支架中这些天然取代基的功能效果。与MC4Rs的亲本序列相比，所有肽在cAMP累积分析中的效价降低至少10倍。化合物MDE 6-82-3c，ZMK 2-82，MDE 6-82-1c，ZMK 2-85和ZMK 2-112也是拮抗MC5R的首批基于AgRP的化学型。

BACKGROUND & AIMS: :Diffuse gliomas are the most common malignant primary brain tumors and remain incurable. A better knowledge of the tumor etiology is required. Specific single nucleotides polymorphisms (SNPs) rs4977756 (CDKN2A/B), rs6010620 (RTEL1), rs498872 (PHLDB1), rs2736100 (TERT), and rs4295627 (CCDC26) have been associated with glioma susceptibility and are potential risk biomarkers. This study aimed to analyze five SNPs associated with glioma susceptibility, in the Portuguese population. SNPs were genotyped using the Sequenom MassARRAY platform in 127 gliomas and 180 controls. Unconditional logistic regression models were used to calculate odds ratio (OR) and 95% confidence intervals. The false-positive report probability was also assessed. The associations between polymorphisms and survival were evaluated using the log-rank test. It was found that the AG and GG genotypes of the rs4977756 (CDKN2A/B) were associated with an increased risk of gliomas (OR 1.85 and OR 2.38) and glioblastomas (OR 2.77 and OR 3.94). The GA genotype of the rs6010620 (RTEL1) was associated with a decreased risk of glioblastomas (OR 0.45). We also observed that the GA genotype of the rs498872 (PHLDB1) was associated with an increased risk of gliomas (OR 2.92) and glioblastomas (OR 2.39). No significant risk associations were found for the rs2736100 (TERT) and rs4295627 (CCDC26). In addition, the genotype AA of the rs498872 (PHLDB1) was associated with poor overall survival of gliomas patients (AA vs. GA, p = 0.037). The rs6010620 (RTEL1), rs4977756 (CDKN2A/B), and rs498872 (PHLDB1) are associated with glioma risk in the Portuguese population and these data may contribute to understanding gliomas etiology.

背景与目标： ：弥漫性神经胶质瘤是最常见的恶性原发性脑肿瘤，仍然无法治愈。需要对肿瘤病因有更好的了解。特定的单核苷酸多态性（SNP）rs4977756（CDKN2A / B），rs6010620（RTEL1），rs498872（PHLDB1），rs2736100（TERT）和rs4295627（CCDC26）已与神经胶质瘤易感性相关联，并且是潜在的危险生物标志物。这项研究旨在分析葡萄牙人群中与神经胶质瘤易感性相关的五个SNP。使用Sequenom MassARRAY平台在127个神经胶质瘤和180个对照中对SNP进行基因分型。使用无条件逻辑回归模型来计算比值比（OR）和95％置信区间。还评估了假阳性报告的可能性。使用对数秩检验评估多态性与生存之间的关联。发现rs4977756（CDKN2A / B）的AG和GG基因型与胶质瘤（OR 1.85和OR 2.38）和胶质母细胞瘤（OR 2.77和OR 3.94）的风险增加相关。 rs6010620（RTEL1）的GA基因型与胶质母细胞瘤的风险降低相关（OR 0.45）。我们还观察到，rs498872（PHLDB1）的GA基因型与胶质瘤（OR 2.92）和胶质母细胞瘤（OR 2.39）的风险增加相关。没有发现rs2736100（TERT）和rs4295627（CCDC26）有明显的风险关联。此外，rs498872（PHLDB1）的基因型AA与胶质瘤患者的整体生存期差有关（AA vs. GA，p = 0.037）。 rs6010620（RTEL1），rs4977756（CDKN2A / B）和rs498872（PHLDB1）与葡萄牙人群的神经胶质瘤风险相关，这些数据可能有助于了解神经胶质瘤的病因。

BACKGROUND & AIMS: :The present study was undertaken to genotype four single nucleotide polymorphisms, which were previously found to be associated with schizophrenia, in 77 patients with schizophrenia and 52 control subjects in order to assess their genotypic association with plasma IL-2 levels. Kruskal-Wallis analysis revealed an association between rs4811528 and plasma IL-2 levels in the patient group (χ(2)=7.60, df=2, p=0.022) but not in the control group; binary logistic regression also confirmed the association of rs4811528 with altered IL-2 secretion (χ(2)=8.191, df=3, p=0.042) after adjustment for age and sex. TGM2 may be involved in dysfunction of the immune system in schizophrenia.

背景与目标： ：本研究旨在对77位精神分裂症患者和52位对照受试者的四个单核苷酸多态性进行基因分型，这些基因先前被发现与精神分裂症有关，以评估其与血浆IL-2水平的基因型关联。 Kruskal-Wallis分析显示患者组中rs4811528与血浆IL-2水平之间存在关联（χ（2）= 7.60，df = 2，p = 0.022），而在对照组中则没有。二元逻辑回归还证实，在调整了年龄和性别之后，rs4811528与IL-2分泌改变有关（χ（2）= 8.191，df = 3，p = 0.042）。 TGM2可能与精神分裂症的免疫系统功能异常有关。

BACKGROUND & AIMS: :SNPmasker is a comprehensive web interface for masking large eukaryotic genomes. The program is designed to mask SNPs from recent dbSNP database and to mask the repeats with two alternative programs. In addition to the SNP masking, we also offer population-specific substitution of SNP alleles in genomic sequence according to SNP frequencies in HapMap Phase II data. The input to SNPmasker can be defined in chromosomal coordinates or inserted as a sequence. The sequences masked by our web server are most useful as a preliminary step for different primer and probe design tasks. The service is available at http://bioinfo.ebc.ee/snpmasker/ and is free for all users.

背景与目标： ：SNPmasker是用于掩盖大型真核生物基因组的综合Web界面。该程序旨在从最近的dbSNP数据库中屏蔽SNP，并使用两个替代程序来屏蔽重复。除了掩盖SNP，我们还根据HapMap II期数据中的SNP频率提供基因组序列中SNP等位基因的群体特异性替代。 SNPmasker的输入可以在染色体坐标中定义或作为序列插入。我们的网络服务器掩盖的序列对于不同引物和探针设计任务的预备步骤最为有用。该服务可从http://bioinfo.ebc.ee/snpmasker/获得，并且对所有用户免费。

BACKGROUND & AIMS: BACKGROUND:Single Nucleotide Polymorphisms (SNPs) are the most common type of polymorphisms found in the human genome. Effective genetic association studies require the identification of sets of tag SNPs that capture as much haplotype information as possible. Tag SNP selection is analogous to the problem of data compression in information theory. According to Shannon's framework, the optimal tag set maximizes the entropy of the tag SNPs subject to constraints on the number of SNPs. This approach requires an appropriate probabilistic model. Compared to simple measures of Linkage Disequilibrium (LD), a good model of haplotype sequences can more accurately account for LD structure. It also provides a machinery for the prediction of tagged SNPs and thereby to assess the performances of tag sets through their ability to predict larger SNP sets. RESULTS:Here, we compute the description code-lengths of SNP data for an array of models and we develop tag SNP selection methods based on these models and the strategy of entropy maximization. Using data sets from the HapMap and ENCODE projects, we show that the hidden Markov model introduced by Li and Stephens outperforms the other models in several aspects: description code-length of SNP data, information content of tag sets, and prediction of tagged SNPs. This is the first use of this model in the context of tag SNP selection. CONCLUSION:Our study provides strong evidence that the tag sets selected by our best method, based on Li and Stephens model, outperform those chosen by several existing methods. The results also suggest that information content evaluated with a good model is more sensitive for assessing the quality of a tagging set than the correct prediction rate of tagged SNPs. Besides, we show that haplotype phase uncertainty has an almost negligible impact on the ability of good tag sets to predict tagged SNPs. This justifies the selection of tag SNPs on the basis of haplotype informativeness, although genotyping studies do not directly assess haplotypes. A software that implements our approach is available.

背景与目标： 背景：单核苷酸多态性（SNPs）是人类基因组中最常见的多态性类型。有效的遗传关联研究需要识别可捕获尽可能多单倍型信息的标签SNP集。标签SNP选择类似于信息论中的数据压缩问题。根据Shannon的框架，最佳标签集会受到SNP数量的限制，从而使标签SNP的熵最大化。这种方法需要适当的概率模型。与简单的连锁不平衡（LD）相比，单倍型序列的良好模型可以更准确地说明LD结构。它还提供了一种机制，用于预测标记的SNP，从而通过其预测更大的SNP集的能力来评估标记集的性能。
结果：在这里，我们计算了一系列模型的SNP数据的描述代码长度，并基于这些模型和熵最大化策略开发了标签SNP选择方法。使用HapMap和ENCODE项目中的数据集，我们显示出Li和Stephens引入的隐马尔可夫模型在以下几个方面优于其他模型：SNP数据的描述代码长度，标签集的信息内容以及标签SNP的预测。这是在标签SNP选择的背景下首次使用此模型。
结论：我们的研究提供了有力的证据，表明我们基于Li和Stephens模型的最佳方法选择的标签集优于通过几种现有方法选择的标签集。结果还表明，与正确标记的SNP预测率相比，使用良好模型评估的信息内容对于评估标记集的质量更为敏感。此外，我们表明，单倍型相位不确定性对良好标签集预测标签SNP的能力影响几乎可以忽略。尽管基因分型研究并未直接评估单倍型，但这证明了根据单倍型信息性选择标签SNP的合理性。提供了实现我们方法的软件。

BACKGROUND & AIMS: OBJECTIVES:Tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) participate in the establishment of inflammatory lesions in periodontitis. High production of these cytokines may relate to the severity of periodontitis. There have already been several studies examining the association between periodontitis and single nucleotide polymorphisms (SNPs) that affect cytokine productivity. Recently, new SNPs of TNF-alpha, -1031, -863 and -857, variants of which are observed in a relatively large proportion in Japanese, have been identified. The variant alleles of these SNPs have been suggested to be related to high TNF-alpha production. For a better understanding of the genetic factors associated with the severity of periodontitis, further analysis including these newly identified SNPs is essential. In addition, previous reports on TNF-alpha or IL-1beta SNPs associated with periodontitis were mainly for Caucasian populations. Therefore, the aim of this study is to examine the association between severe periodontitis in Japanese and the following SNPs: five in the TNF-alpha gene promoter (-1031, -863, -857, -308, -238) and three in the IL-1beta gene (-511, -31, +3953). MATERIAL AND METHODS:A total of 128 Japanese individuals were enrolled in this study. They were 64 patients with severe adult periodontitis and 64 healthy subjects. TNF-alpha and IL-1beta SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism for all subjects. TNF-alpha and IL-1beta production from LPS-stimulated monocytes/macrophages was also measured for 15 healthy male subjects. RESULTS:TNF-alpha production in TNF-alpha-1031/-863 (linkage disequilibrated) or -857 SNP variant allele carriers tended to be elevated, and the frequency of subjects who carried at least one variant allele in TNF-alpha-1031, -863 or -857 SNPs among severe periodontitis patients was significantly higher than in healthy subjects. CONCLUSION:Since the frequency of subjects who carried at least one variant allele in TNF-alpha-1031, -863 or -857 SNPs was higher in periodontitis patients than in healthy subjects, TNF-alpha-1031, -863 and -857 SNPs appear to be associated with severe adult periodontitis in Japanese populations.

背景与目标： 目的：肿瘤坏死因子-α（TNF-alpha）和白细胞介素-1β（IL-1beta）参与牙周炎炎症性病变的建立。这些细胞因子的高产量可能与牙周炎的严重程度有关。已经有几项研究研究了牙周炎与影响细胞因子生产率的单核苷酸多态性（SNP）之间的关联。最近，已经确定了TNF-α的新的SNP，-1031，-863和-857，其变体在日本人中观察到的比例较大。这些SNP的变异等位基因已被认为与高TNF-α产生有关。为了更好地了解与牙周炎严重程度相关的遗传因素，进一步分析包括这些新发现的SNP至关重要。此外，先前有关与牙周炎相关的TNF-α或IL-1beta SNP的报道主要针对高加索人群。因此，本研究的目的是检查日语中的严重牙周炎与以下SNP之间的关联：TNF-alpha基因启动子中有五个（-1031，-863，-857，-308，-238）和三个SNP之间。 IL-1beta基因（-511，-31，3953）。
材料与方法：本研究共纳入128名日本人。他们是64位患有严重成人牙周炎的患者和64位健康受试者。通过聚合酶链反应-限制性片段长度多态性对所有受试者进行TNF-α和IL-1beta SNP基因分型。还测量了15名健康男性受试者从LPS刺激的单核细胞/巨噬细胞中产生的TNF-α和IL-1beta。
结果：TNF-alpha-1031 / -863（连锁失衡）或-857 SNP变异等位基因携带者中的TNF-α产生趋于升高，并且在TNF-alpha-1031中携带至少一个变异等位基因的受试者的频率，严重牙周炎患者中的-863或-857 SNP显着高于健康受试者。
结论：由于牙周炎患者中携带至少一种等位基因在TNF-alpha-1031，-863或-857 SNP中的频率高于健康受试者，因此出现TNF-alpha-1031，-863和-857 SNP的频率更高在日本人群中与严重的成人牙周炎有关。

BACKGROUND & AIMS: :A sustained virological response is not achieved by a significant proportion of chronic hepatitis C patients treated with interferon-based regimens. Due to the associated side effects and high costs, therapy response markers have been thoroughly sought. Two Single Nucleotide Polymorphisms (SNPs), rs12979860 and rs8099917, which are located upstream from the IL28B gene, have been remarkably described to have a strong association with treatment efficacy. The aim of this study was to develop a straightforward method for genotyping such polymorphisms. A Polymerase Chain Reaction (PCR) followed by enzymatic restriction of amplicons was established for SNPs genotyping. Online computation resources were employed for retrieving reference sequences, such as the selection of oligonucleotides and restriction enzymes. Two pairs of primers were designed and validated for the amplification of segments encompassing rs12979860 (694bp) and rs8099917 (496bp) with common thermocycling parameters. The endonucleases Hpy166II and BsrDI were selected and used for allelic discrimination related to rs12979860 (C/T) and rs8099917 (T/G), respectively. The expected electropherotypes were confirmed for all possible genotypes in 75 blood samples. In addition, the results were validated by sequencing. The method constitutes a simple and reliable assay, which may be readily available for genotyping of rs12979860 and rs8099917 in laboratories that support hepatitis C treatment centers.

背景与目标： ：相当大比例的以干扰素为基础的慢性丙型肝炎患者无法获得持续的病毒学应答。由于相关的副作用和高昂的费用，已经彻底寻求了治疗反应的标志物。明显描述了位于IL28B基因上游的两个单核苷酸多态性（SNP）rs12979860和rs8099917，与治疗效果密切相关。这项研究的目的是开发一种用于对此类多态性进行基因分型的直接方法。建立了SNPs基因分型的聚合酶链式反应（PCR），然后进行酶促扩增子限制。在线计算资源被用于检索参考序列，例如寡核苷酸和限制酶的选择。设计并验证了两对引物，用于扩增具有常见热循环参数的rs12979860（694bp）和rs8099917（496bp）片段。选择核酸内切酶Hpy166II和BsrDI，分别用于与rs12979860（C / T）和rs8099917（T / G）相关的等位基因识别。确认了75种血液样本中所有可能的基因型的预期电表型。另外，通过测序验证了结果。该方法构成了一种简单而可靠的测定方法，可以很容易地在支持丙型肝炎治疗中心的实验室中对rs12979860和rs8099917进行基因分型。

BACKGROUND & AIMS: :beta-Defensins are cationic antimicrobial peptides expressed in epithelia. They exhibit antibacterial, antifungal, and antiviral properties. Defensins are a component of the innate immune response, and it has been proposed that they have a protective role in the oral cavity. Previous studies have shown that human beta-defensin 1 (hBD-1) is constitutively expressed in oral epithelial cells but that expression varies between individuals. We tested the hypothesis that genetic variations in defensin peptide expression may be associated with opportunistic infections. This may be critical in the immunocompromised patient population, in which innate immune responses may have a relatively more important role. Oral Candida carriage status and the presence of six single-nucleotide polymorphisms (SNPs) in the DEFB1 gene encoding hBD-1 were evaluated in type I diabetic patients (n = 43) and nondiabetic controls (n = 50). Genomic DNA was obtained from buccal swabs. Portions of the DEFB1 gene were amplified, and each SNP was analyzed by a TaqMan assay, standardized with control DNA of known genotype. Candida carriage status was determined from unstimulated saliva on CHROMagar plating medium. A low level of Candida carriage was defined as < or = 350 CFU/ml. A high level of Candida carriage was seen in 44% of the diabetic subjects but only in 28% of the nondiabetic controls (P < 0.05). C. albicans predominated; however, diabetic subjects, especially those with high levels of carriage, showed an increased proportion of Candida glabrata and C. tropicalis. There was a strong association between an SNP in the 5' untranslated region (C-->G at position -44) and Candida carriage in both groups. Among individuals in the diabetic population who had the SNP allele 2 (G), 58% had low CFU, while 6% had high CFU. The C-->G SNP at position -44 is associated with low levels of Candida carriage. The resultant odd ratios are statistically significant for a protective effect (odd ratios, 25 for diabetic subjects and 8.5 for nondiabetic subjects). These results indicate that genetic variations in the DEFB1 gene encoding hBD-1 may have a major role in mediating and/or contributing to susceptibility to oral infection.

背景与目标： β-防御素是在上皮细胞中表达的阳离子抗菌肽。它们具有抗菌，抗真菌和抗病毒特性。防御素是先天性免疫反应的组成部分，有人提出它们在口腔中具有保护作用。先前的研究表明，人β-防御素1（hBD-1）在口腔上皮细胞中组成性表达，但该表达因人而异。我们测试了防御素肽表达的遗传变异可能与机会性感染有关的假说。这在免疫受损的患者人群中可能是至关重要的，其中先天免疫应答可能具有相对更重要的作用。在I型糖尿病患者（n = 43）和非糖尿病对照（n = 50）中评估了口服念珠菌的运输状态以及在编码hBD-1的DEFB1基因中六个单核苷酸多态性（SNP）的存在。从颊拭子获得基因组DNA。扩增DEFB1基因的部分，并且通过TaqMan测定法分析每个SNP，所述TaqMan测定法用已知基因型的对照DNA标准化。从CHROMagar平板培养基上未刺激的唾液中确定念珠菌的运输状态。低水平的假丝酵母运输被定义为<或= 350 CFU / ml。在44％的糖尿病受试者中发现了高水平的念珠菌运输，但在28％的非糖尿病对照组中仅见（P <0.05）。白色念珠菌占主导地位;但是，糖尿病患者，尤其是携带量高的糖尿病患者，其光滑念珠菌和热带念珠菌的比例有所增加。两组中5'非翻译区的SNP（C-> G在-44位）和念珠菌运输之间有很强的联系。在具有SNP等位基因2（G）的糖尿病人群中，58％的CFU较低，而6％的CFU较高。 -44位的C-> G SNP与低水平的假丝酵母运输有关。所得的奇数比在保护作用方面具有统计学意义（奇数比，糖尿病患者为25，非糖尿病患者为8.5）。这些结果表明，编码hBD-1的DEFB1基因的遗传变异可能在介导和/或促进口腔感染的易感性中起主要作用。

BACKGROUND & AIMS: AIMS:We introduce a family-based confidence set inference (CSI) method that can be used in preliminary genome-wide association studies to obtain confidence sets of SNPs that contribute a specific percentage to the additive genetic variance of quantitative traits. METHODS:Developed in the framework of generalized linear mixed models, the method utilizes data from outbred families of arbitrary size and structure. Through our own simulation study and analysis of the Genetics Analysis Workshop 16 simulated data, we study the properties of our method and compare its performance to that of the family association method described by Chen and Abecasis [Am J Hum Genet 2007;81:913-926]. We also analyze the Framingham Heart Study data to identify SNPs regulating high-density lipoprotein levels. RESULTS:The simulation studies demonstrated that CSI yields confidence sets with correct coverage and that it can outperform the method introduced by Chen and Abecasis [Am J Hum Genet 2007;81:913-926]. Furthermore, we identified five SNPs that potentially regulate high-density lipoprotein levels: rs9989419, rs11586238, rs1754415, rs9355648, and rs9356560. CONCLUSION:The CSI method provides confidence sets of SNPs that contribute to the genetic variance of quantitative traits and is a competitive alternative to currently used family association methods. The approach is particularly useful in genome-wide association studies as it significantly reduces the number of SNPs investigated in follow-up studies.

背景与目标： 目的：我们引入一种基于家庭的置信度集推断（CSI）方法，该方法可用于初步的全基因组关联研究，以获取对定量性状的加性遗传方差贡献特定百分比的SNP的置信度集。
方法：该方法是在广义线性混合模型的框架内开发的，利用了任意大小和结构的远交系的数据。通过我们自己的模拟研究和对Genetics Analysis Workshop 16个模拟数据的分析，我们研究了该方法的属性，并将其性能与Chen和Abecasis [Am J Hum Genet 2007; 81：913- 926]。我们还分析了Framingham心脏研究数据，以确定可调节高密度脂蛋白水平的SNP。
结果：仿真研究表明，CSI可以产生具有正确覆盖率的置信集，并且可以胜过Chen和Abecasis所介绍的方法[Am J Hum Genet 2007; 81：913-926]。此外，我们确定了五个可能调节高密度脂蛋白水平的SNP：rs9989419，rs11586238，rs1754415，rs9355648和rs9356560。
结论：CSI方法提供了SNP的置信度集，这些集有助于定量性状的遗传变异，并且是当前使用的家庭关联方法的竞争性替代方法。该方法在全基因组关联研究中特别有用，因为它大大减少了后续研究中研究的SNP数量。

BACKGROUND & AIMS: BACKGROUND:The study of genetic variation will promote our understanding of the differential predisposition to common diseases and variation in drug responses of individuals and ethnic populations. Such genetic variation is intrinsically structured into blocks of haplotypes in populations. Therefore, a comprehensive haplotype map based on the most abundant form of genetic variation, single nucleotide polymorphisms, will be useful. At the present time, however, our knowledge of the similarities and differences of haplotype structure among different ancestral populations is still inadequate. METHODS:To determine whether common underlying haplotype patterns existed across ethnic populations, we analyzed data derived from African and European Americans for twenty-two genes spanning a total of 516 kb and the HapMap ENCODE data across 500 kb on chromosome 2p16.3 from three major world populations. RESULTS AND CONCLUSIONS:We observed that strong pairwise linkage disequilibrium (LD) between SNPs selected from populations having African ancestry was highly conserved across other non-African populations. Common haplotypes described by these LD-selected SNPs demonstrated a simple evolutionary structure with up to three major frameworks, which were likely ancestral backgrounds upon which more recent mutations have been superimposed. Also, haplotype block boundaries defined in populations having African ancestry revealed completely concordant recombinant haplotypes across all populations, providing a consistent definition of block structure. Finally, a large fraction of regulatory polymorphisms described in the literature appeared to tag these conserved haplotype frameworks, strongly suggesting their significance for disease association and pharmacogenetic studies.

背景与目标： 背景：遗传变异的研究将促进我们对常见疾病的不同易感性以及个体和种族的药物反应变异的了解。这样的遗传变异本质上被构造成种群中单倍型的块。因此，基于遗传变异的最丰富形式，即单核苷酸多态性的综合单倍型图将很有用。然而，目前，我们对不同祖先群体单倍型结构的异同的认识仍然不足。
方法：为确定族群之间是否存在常见的潜在单倍型模式，我们分析了来自非洲和欧洲裔的22个基因的数据，这些基因跨度共516 kb，而HapMap ENCODE数据涉及3个主要染色体2p16.3上的500 kb世界人口。
结果与结论：我们观察到，从具有非洲血统的人群中选出的SNP之间的强烈成对连锁不平衡（LD）在其他非非洲人群中都得到了高度保守。这些由LD选择的SNP描述的常见单倍型显示出具有多达三个主要框架的简单进化结构，这可能是祖先的背景，在这些背景上已叠加了更多的近期突变。同样，在具有非洲血统的种群中定义的单倍型块边界揭示了所有种群中完全一致的重组单倍型，从而提供了一致的块状结构定义。最后，文献中描述的大部分调控多态性似乎标记了这些保守的单倍型框架，强烈暗示了它们对疾病关联和药物遗传学研究的重要性。

BACKGROUND & AIMS: :A major challenge in translating findings from genome-wide association studies (GWAS) to biological mechanisms is pinpointing functional variants because only a very small percentage of variants associated with a given trait actually impact the trait. We used an extensive epigenetics, transcriptomics, and genetics analysis of the TBX15/WARS2 neighbourhood to prioritize this region's best-candidate causal variants for the genetic risk of osteoporosis (estimated bone density, eBMD) and obesity (waist-hip ratio or waist circumference adjusted for body mass index). TBX15 encodes a transcription factor that is important in bone development and adipose biology. Manual curation of 692 GWAS-derived variants gave eight strong candidates for causal SNPs that modulate TBX15 transcription in subcutaneous adipose tissue (SAT) or osteoblasts, which highly and specifically express this gene. None of these SNPs were prioritized by Bayesian fine-mapping. The eight regulatory causal SNPs were in enhancer or promoter chromatin seen preferentially in SAT or osteoblasts at TBX15 intron-1 or upstream. They overlap strongly predicted, allele-specific transcription factor binding sites. Our analysis suggests that these SNPs act independently of two missense SNPs in TBX15. Remarkably, five of the regulatory SNPs were associated with eBMD and obesity and had the same trait-increasing allele for both. We found that WARS2 obesity-related SNPs can be ascribed to high linkage disequilibrium with TBX15 intron-1 SNPs. Our findings from GWAS index, proxy, and imputed SNPs suggest that a few SNPs, including three in a 0.7-kb cluster, act as causal regulatory variants to fine-tune TBX15 expression and, thereby, affect both obesity and osteoporosis risk.

背景与目标： ：将全基因组关联研究（GWAS）的发现转化为生物学机制的主要挑战是精确定位功能性变异，因为与给定性状相关的变异中只有很小一部分实际上会影响该性状。我们对TBX15 / WARS2邻域进行了广泛的表观遗传学，转录组学和遗传学分析，以优先考虑该地区的最佳候选因果变异，以评估骨质疏松症（估计的骨密度，eBMD）和肥胖症（腰围比或腰围或腰围调整）的遗传风险用于体重指数）。 TBX15编码在骨骼发育和脂肪生物学中很重要的转录因子。手动管理692个GWAS衍生的变体为因果SNP提供了八种强力候选物，这些SNP调节皮下脂肪组织（SAT）或成骨细胞中TBX15的转录，后者高度且特异性地表达了该基因。这些SNP都没有通过贝叶斯精细映射确定优先级。八个调节性因果SNP位于增强子或启动子染色质中，优先出现在TBX15 intron-1或上游的SAT或成骨细胞中。它们与强烈预测的等位基因特异性转录因子结合位点重叠。我们的分析表明，这些SNP在TBX15中独立于两个错义SNP起作用。值得注意的是，五个调节性SNP与eBMD和肥胖症相关，并且具有相同的特征增加等位基因。我们发现，与WARS2肥胖相关的SNP可以归因于与TBX15 intron-1 SNP的高度连锁不平衡。我们从GWAS指数，代理和推定SNP中获得的发现表明，一些SNP，包括一个0.7-kb簇中的三个，可作为因果调节变异体，以微调TBX15的表达，从而影响肥胖症和骨质疏松症的风险。