BACKGROUND & AIMS: :Susceptibility to esophageal carcinoma (EC) is influenced by the interaction between genetic and environmental factors. To clarify the etiology of EC, several genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in PCLE1 and RFT2 genes as esophageal squamous cell carcinoma (ESCC) susceptibility loci in Asian populations. This study aimed to determine whether these SNPs also modify the risk of esophageal adenocarcinoma (EAC) and ESCC in western populations of Caucasian ethnicity. A European case-control study including 349 EC patients and 580 controls matched for age, sex, geographical location, and race was carried out. The SNPs rs2274223 in the PCLE1 gene at chromosome 10q23 and rs13042395 in the RFT2 gene at chromosome 20p13 were determined using PCR. Genotype distributions were compared between patients and controls, and odds ratios with 95% confidence intervals were calculated. The total EC group included 86 patients with ESCC and 258 patients with EAC. The distribution of PLCE1 and RFT2 genotypes did not differ between patients with EAC or ESSC, and the controls. In contrast to the modulation of the risk of ESCC in Asians, it is unlikely that the PLCE1 rs2274223 and RFT2 13042395 SNPs play a role in EAC or ESCC susceptibility in Dutch Caucasians.

背景与目标： ：食管癌（EC）的易感性受遗传和环境因素之间相互作用的影响。为了阐明EC的病因，多项全基因组关联研究已将PCLE1和RFT2基因中的单核苷酸多态性（SNP）确定为亚洲人群食管鳞状细胞癌（ESCC）易感基因座。这项研究的目的是确定这些SNP是否也能改变西方白人人群中食道腺癌（EAC）和ESCC的风险。一项欧洲病例对照研究包括349名EC患者和580名年龄，性别，地理位置和种族相匹配的对照。使用PCR确定10q23染色体PCLE1基因中的rs2274223和20p13染色体RFT2基因中的rs13042395。比较患者和对照组之间的基因型分布，并计算具有95％置信区间的比值比。整个EC组包括86例ESCC患者和258例EAC患者。 EAC或ESSC患者与对照组之间PLCE1和RFT2基因型的分布没有差异。与调节亚洲人的ESCC风险相反，PLCE1 rs2274223和RFT2 13042395 SNP不太可能在荷兰高加索人的EAC或ESCC易感性中发挥作用。

BACKGROUND & AIMS: :Infection with Helicobacter pylori (H. pylori) is very common and affecting about 50% of the worldwide population. Several genetic variations have been implicated in determining the clinical susceptibility to this infection. In the current study, we examined the association between C1236T (rs1045642) and C3435T (rs1045642) single nucleotide polymorphisms (SNPs) in the ABCB1 gene and the prevalence of H. pylori infection among Jordanians. A total of 412 subjects (257 H. pylori-positive cases and 155 H. pylori-negative controls) were recruited and participated in the study, and the genotyping of the ABCB1 gene was performed using RFLP-PCR techniques. A significant association was detected between C1236T and H. pylori infection (p < 0.01). The frequency of CT genotype was significantly higher in the positive cases (40.1%) compared to the controls (21.3%). In addition, the C3435T SNP was weakly associated with H. pylori infection (p = 0.077). Haplotype analysis of C1236T and C3435T SNPs showed that the TT haplotype was present in 22.7% of the positive cases compared to 30.7% of the negative controls (p < 0.05, odds ratio = 0.663, 95% CI: (0.483-0.911)). Consequently, the TT haplotype seems to decrease the risk of H. pylori infection. In conclusion, the current results suggest an association between ABCB1 SNPs and H. pylori infection in the Jordanian population.

背景与目标： ：幽门螺杆菌（H. pylori）感染非常普遍，影响全球约50％的人口。在确定对这种感染的临床易感性方面，涉及了几种遗传变异。在当前的研究中，我们检查了ABCB1基因中C1236T（rs1045642）和C3435T（rs1045642）单核苷酸多态性（SNPs）与约旦人中幽门螺杆菌感染的相关性。总共招募了412名受试者（257例幽门螺杆菌阳性病例和155例幽门螺杆菌阴性对照）并参加了研究，并使用RFLP-PCR技术对ABCB1基因进行了基因分型。在C1236T和幽门螺杆菌感染之间检测到显着相关性（p <0.01）。阳性病例（40.1％）的CT基因型频率显着高于对照组（21.3％）。此外，C3435T SNP与幽门螺杆菌感染弱相关（p = 0.077）。 C1236T和C3435T SNP的单倍型分析表明，TT单倍型存在于阳性病例的22.7％，而阴性对照为30.7％（p <0.05，优势比= 0.663，95％CI：（0.483-0.911））。因此，TT单倍型似乎降低了幽门螺杆菌感染的风险。总之，当前结果表明约旦人口中ABCB1 SNP与幽门螺杆菌感染之间存在关联。

BACKGROUND & AIMS: :KIT/KITLG signaling system is crucial for spermatogenesis, which suggests that KIT and KITLG genes may be involved in spermatogenesis impairment and male infertility. To explore the possible association of KIT and KITLG genes with male infertility having spermatogenesis impairment, polymorphism distributions of SNP rs3819392 in KIT gene as well as rs995030 and rs4474514 in KITLG gene were investigated in 372 patients with idiopathic azoospermia or oligospermia and 205 fertile controls. As a result, the significant differences in polymorphism distributions of SNP rs3819392 in KIT gene and rs4474514 in KITLG gene were observed between the patients with oligospermia and controls. The frequencies of allele G (94.2% versus 90.0% p = 0.022) and genotype GG (89.2% versus 82.0% p = 0.042) in patients with oligospermia were significantly higher than those in controls at rs3819392 locus in KIT gene. In addition, the genotype CC of rs4474514 in KITLG (8.2% versus 3.4%, p = 0.034) also significantly increased in oligospermic patients in comparison to controls. These findings indicated that SNP rs3819392 in KIT gene and rs4474514 in KITLG gene may be associated with oligospermia, suggesting that polymorphism of KIT and KITLG genes may play a role in oligospermia.

背景与目标： ：KIT / KITLG信号系统对于精子发生至关重要，这表明KIT和KITLG基因可能与精子发生障碍和男性不育有关。为了探讨KIT和KITLG基因与患有精子发生障碍的男性不育症之间的可能关系，对372例特发性无精症或少精症患者和205名受精对照者，调查了KIT基因中SNP rs3819392以及KITLG基因中rs995030和rs4474514的多态性分布。结果，在少精症患者和对照组之间，观察到了KIT基因中的SNP rs3819392和KITLG基因中的rs4474514的多态性分布的显着差异。在KIT基因的rs3819392位点，少精症患者的等位基因G（94.2％vs. 90.0％p = 20.022）和基因型GG（89.2％vs 82.0％p = 0.042）的频率显着高于对照组。此外，与对照相比，少精症患者中KITLG中rs4474514的基因型CC（8.2％比3.4％，p = 0.034）也显着增加。这些发现表明，KIT基因中的SNP rs3819392和KITLG基因中的rs4474514可能与少精症有关，表明KIT和KITLG基因的多态性可能在少精症中起作用。

BACKGROUND & AIMS: :Peroxisome-proliferator-activated receptor gamma (PPARγ) is a key transcription factor that controls adipocyte differentiation and energy in mammals. Therefore, PPARγ is a potential factor influencing animal growth traits. This study primarily evaluates PPARγ as candidate gene for growth traits of cattle and identifies potential molecular marker for cattle breeding. Per previous studies, PPARγ mRNA was mainly expressed at extremely high levels in adipose tissues as shown by quantitative real-time polymerase chain reaction analysis. Three novel SNPs of the bovine PPARγ gene were identified in 514 individuals from six Chinese cattle breeds: SNP1 (AC_000179.1 g.57386668 C > G) in intron 2 and SNP2 (AC_000179.1 g.57431964 C > T) and SNP3 (AC_000179.1 g.57431994 T > C) in exon 7. The present study also investigated genetic characteristics of these SNP loci in six populations. Association analysis showed that SNP1 and SNP3 loci significantly affect weaning growth traits, especially body weight of Nanyang cattle. These results revealed that SNP1 and SNP3 are potential molecular markers for cattle breeding.

背景与目标： ：过氧化物酶体增殖物激活受体γ（PPARγ）是控制哺乳动物脂肪细胞分化和能量的关键转录因子。因此，PPARγ是影响动物生长性状的潜在因素。这项研究主要评估PPARγ作为牛生长特性的候选基因，并确定牛育种的潜在分子标记。根据先前的研究，如定量实时聚合酶链反应分析所示，PPARγmRNA主要在脂肪组织中高水平表达。在来自六个中国牛品种的514个个体中鉴定出三个牛PPARγ基因的新SNP：内含子2中的SNP1（AC_000179.1 g.57386668 C> G）和SNP2（AC_000179.1 g.57431964 C> T）和SNP3（ AC_000179.1 g.57431994 T> C）外显子7。本研究还调查了这6个种群中这些SNP基因座的遗传特征。关联分析表明，SNP1和SNP3基因座显着影响断奶仔猪的生长性状，尤其是南阳牛的体重。这些结果表明，SNP1和SNP3是牛育种的潜在分子标记。

BACKGROUND & AIMS: BACKGROUND:Net blotch caused by Pyrenophra teres f. teres is a major foliar disease of barley. Infection can result in significant yield losses of susceptible cultivars of up to 40%. Of the two forms of net blotch (P. teres f. teres and P. teres f. maculata), P. teres f. teres (net form of net blotch) is the dominant one in Russia. The goal of the current study was to identify genomic regions associated with seedling resistance to several pathotypes of the net form of net blotch in Siberian spring barley genotypes. For this, a genome-wide association study of a Siberian barley collection, genotyped with 50 K Illumina SNP-chip, was carried out. RESULTS:Seedling resistance of 94 spring barley cultivars and lines to four Pyrenophora teres f. teres isolates (S10.2, K5.1, P3.4.0, and A2.6.0) was investigated. According to the Tekauz rating scale, 25, 21, 14, and 14% of genotypes were highly resistant, and 19, 8, 9, and 16% of genotypes were moderate-resistant to the isolates S10.2, K5.1, P3.4.0, and A2.6.0, respectively. Eleven genotypes (Alag-Erdene, Alan-Bulag, L-259/528, Kedr, Krymchak 55, Omsky golozyorny 2, Omsky 13709, Narymchanin, Pallidum 394, Severny and Viner) were resistant to all studied isolates. Nine additional cultivars (Aley, Barkhatny, Belogorsky, Bezenchuksky 2, Emelya, G-19980, Merit 57, Mestny Primorsky, Slavaynsky) were resistant to 3 of the 4 isolates. The phenotyping and genotyping data were analysed using several statistical models: GLM + Q, GLM + PCA, GLM + PCA + Q, and the MLM + kinship matrix. In total, 40 SNPs in seven genomic regions associated with net blotch resistance were revealed: the region on chromosome 1H between 57.3 and 62.8 cM associated with resistance to 2 isolates (to P3.4.0 at the significant and K5.1 at the suggestive levels), the region on chromosome 6H between 52.6 and 55.4 cM associated with resistance to 3 isolates (to P3.4.0 at the significant and K5.1 and S10.2 at the suggestive levels), three isolate-specific significant regions (P3.4.0-specific regions on chromosome 2H between 71.0 and 74.1 cM and on chromosome 3H between 12.1 and 17.4 cM, and the A2.6.0-specific region on chromosome 3H between 50.9 and 54.8 cM), as well as two additional regions on chromosomes 2H (between 23.2 and 23.8 cM, resistant to S10.2) and 3 (between 135.6 and 137.5 cM resistant to K5.1) with suggestive SNPs, coinciding, however, with known net blotch resistance quantitative trait loci (QTLs) at the same regions. CONCLUSIONS:Seven genomic regions on chromosomes 1H, 2H, 3H, and 6H associated with the resistance to four Pyrenophora teres f. teres isolates were identified in a genome-wide association study of a Siberian spring barley panel. One novel isolate-specific locus on chromosome 3 between 12.1 and 17.4 cM was revealed. Other regions identified in the current study coincided with previously known loci conferring resistance to net blotch. The significant SNPs revealed in the current study can be converted to convenient PCR markers for accelerated breeding of resistant barley cultivars.

背景与目标： 背景：由斑节杆菌引起的网斑病。麦汁是大麦的主要叶面疾病。感染可导致易感品种的产量损失高达40％。在两种形式的网斑病中（P. teres f。teres和P. teres f。maculata），P. teres f。 teres（网状斑点的净形式）在俄罗斯占主导地位。当前研究的目标是确定与幼苗对西伯利亚春大麦基因型净斑点净形态的几种病态抗性相关的基因组区域。为此，对西伯利亚大麦收集品进行了全基因组关联研究，并用50 K Illumina SNP芯片进行了基因分型。
结果：94个春大麦品种和品系对4个夏梨的幼苗的抗性。研究了分离株（S10.2，K5.1，P3.4.0和A2.6.0）。根据Tekauz评分量表，有25％，21％，14％和14％的基因型对分离株S10.2，K5.1，P3有中等抵抗力，有19％，8％，9％和16％的基因型对分离株S10.2，K5.1，P3有中等抵抗力.4.0和A2.6.0。 11种基因型（Alag-Erdene，Alan-Bulag，L-259 / 528，Kedr，Krymchak 55，Omsky golozyorny 2，Omsky 13709，Narymchanin，Pallidum 394，Severny和Viner）均具有抗性。另外9个品种（Aley，Barkhatny，Belogorsky，Bezenchuksky 2，Emelya，G-19980，Merit 57，Mestny Primorsky，Slavaynsky）对4个分离株中的3个有抗性。使用几种统计模型对表型和基因型数据进行了分析：GLM Q，GLM PCA，GLM PCA Q和MLM亲属矩阵。总共揭示了七个与净斑点抗性相关的基因组区域中的40个SNP：1H染色体上介于57.3和62.8 cM之间的区域与对2种分离物的抗性相关（显着性水平为P3.4.0，暗示水平为K5.1）。 ，即6H染色体上介于52.6和55.4 cM之间的区域，与对3个分离株的抵抗力相关（显着水平为P3.4.0，在提示水平为K5.1和S10.2），三个分离株特异性显着区域（P3.4.0- 2H染色体上的特定区域介于71.0和74.1 cM之间，3H染色体上的特定区域位于12.1和17.4 cM之间，3H染色体上的A2.6.0特定区域在50.9和54.8 cM之间），以及2H染色体上的两个附加区域（23.2之间）和23.8？cM，对S10.2有抵抗力； 3（对K5.1有抵抗力的135.6和137.5？cM之间）具有提示性SNP，但与此同时，在相同区域还具有已知的净斑点抗性定量性状基因座（QTL）。
结论：1H，2H，3H和6H染色体上的七个基因组区域与对四个Pyrenophora teres f的抗性有关。在西伯利亚春季大麦研究小组的全基因组关联研究中鉴定了这些分离株。揭示了一种新的分离物特异性位点，位于3号染色体上，介于12.1和17.4 cM之间。在本研究中鉴定出的其他区域与先前已知的赋予对净斑点的抗性的基因座相吻合。当前研究中揭示的重要SNP可以转化为方便的PCR标记，以加快抗性大麦品种的育种。

BACKGROUND & AIMS: :Large scale association studies have identified low penetrance susceptibility alleles that predispose to breast cancer. A locus on chromosome 8q24.21 has been shown to harbour variants that predispose to breast, ovarian, colorectal and prostate cancer. The finding of risk variants clustering at 8q24 suggests that there may be common susceptibility alleles that predispose to more than one epithelial cancer. The aim of this study was firstly to determine whether previously identified breast cancer susceptibility alleles are associated with sporadic breast cancer in the West of Ireland and secondly to ascertain whether there are susceptibility alleles that predispose to all three common epithelial cancers (breast, prostate, colon). We genotyped a panel of 24 SNPs that have recently been shown to predispose to prostate, colorectal or breast cancer in 988 sporadic breast cancer cases and 1,016 controls from the West of Ireland. We then combined our data with publicly available datasets using standard techniques of meta-analysis. The known breast cancer SNPs rs13281615, rs2981582 and rs3803662 were confirmed as associated with breast cancer risk (P (allelic test) = 1.8 x 10(-2), OR = 1.17; P (allelic test) = 2.2 x 10(-3), OR = 1.22; P (allelic test) = 5.1 x 10(-2), OR = 1.15, respectively) in the West of Ireland cohort. For the remaining five breast cancer SNPs that were studied there was no evidence of an association with breast cancer in the West Ireland population (P (allelic test) > 6.5 x 10(-2)). There was also no association between any of the prostate or colorectal susceptibility SNPs, whether at 8q24 or elsewhere, with breast cancer risk. Meta-analysis confirmed that all susceptibility SNPs were site specific, with the exception of rs6983269 which is known to predispose to both colorectal and prostate cancer. This study confirms that susceptibility loci at FGFR2, 8q24 and TNCR9 predispose to sporadic breast cancer in the West of Ireland. It also suggests that low penetrance susceptibility SNPs for breast, prostate and colorectal cancer are distinct. Although 8q24 harbours variants that predispose to all three cancers, the susceptibility loci within the region appear to be specific for the different cancer types with the exception of rs6983269 in colon and prostate cancer.

背景与目标： ：大规模的关联研究已经确定了易患乳腺癌的低渗透敏感性等位基因。已显示染色体8q24.21上的一个基因座具有易患乳腺癌，卵巢癌，结肠直肠癌和前列腺癌的变异体。在8q24聚集的风险变异体的发现表明，可能存在易患一种以上上皮癌的常见易感性等位基因。这项研究的目的是首先确定先前确定的乳腺癌易感性等位基因是否与爱尔兰西部的散发性乳腺癌相关；其次要确定是否存在易感性等位基因易患所有三种常见的上皮癌（乳腺癌，前列腺癌，结肠癌） ）。我们对一组24个SNP进行了基因分型，最近发现它们在988个散发性乳腺癌病例和来自爱尔兰西部的1,016个对照中易患前列腺癌，结肠直肠癌或乳腺癌。然后，我们使用标准的荟萃分析技术将我们的数据与可公开获得的数据集进行合并。已知已知乳腺癌SNP rs13281615，rs2981582和rs3803662与乳腺癌风险相关（P（等位基因检验）= 1.8 x 10（-2），OR = 1.17; P（等位基因检验）= 2.2 x 10（-3） ，在爱尔兰西部的队列中，OR = 1.22； P（等位基因检验）分别为5.1 x 10（-2），OR = 1.15）。对于其余五个研究过的乳腺癌SNP，在西爱尔兰人群中没有证据表明与乳腺癌相关（P（等位基因检验）> 6.5 x 10（-2））。在8q24或其他地方，任何前列腺或大肠易感性SNP与乳腺癌风险之间也没有关联。荟萃分析证实，除易患结直肠癌和前列腺癌的rs6983269外，所有易感性SNP均是位点特异性的。这项研究证实，FGFR2、8q24和TNCR9的易感基因座易导致爱尔兰西部的零星乳腺癌。这也表明针对乳腺癌，前列腺癌和结肠直肠癌的低渗透敏感性SNP是截然不同的。尽管8q24带有易患所有三种癌症的变异体，但该区域内的易感基因座似乎对不同类型的癌症具有特异性，但结肠癌和前列腺癌中的rs6983269除外。

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。