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摘要： The objective of this study was to evaluate the genetics of functional teat number in swine. Piglet survival is of great importance for swine producers throughout the world due to its relationship with animal well-being and farm profitability. Availability and accessibility of functional teats on a sow is essential for enhancing piglet livability. Teat traits including total teat number (TT), functional teat number (FT), and non-functional teat number (NFT), were observed and recorded on 3,099 Landrace × Large White F1 sows. Variance components were estimated using AIREMLF90. Models included parity, farm, individual scorer, and phase of production as fixed effects. Means for TT, FT and NFT at farrowing were 14.93, 13.90 and 1.03, respectively, and 14.43, 13.02 and 1.15, respectively, at weaning. For farrowing, weaning and combined datasets, TT means were greater (P<0.01) than FT means. Heritability estimates for TT, FT and NFT ranged from 0.18 to 0.37, 0.16 to 0.28, and 0.14 to 0.18, respectively. Total teat number and functional teat number had positive genetic correlation estimates across farrowing and weaning datasets ranging from 0.68 to 0.77. Functional mammary glands had genetic correlation estimates of 0.72 and -0.57 with FT and NFT, respectively. At farrowing the genetic correlation estimate between NW and FT was positive (0.50), whereas the genetic correlation estimate between NW and NFT was negative (-0.38). An increase of one functional teat increased number of piglets weaned by 0.27. Sufficient genetic variation for total teat number and functional teat number was observed signifying that genetic improvement for these traits is possible. Results suggest that by focusing selection on functional teat number an increase in nonfunctional teat number can be avoided. Therefore, utilizing functional teat number in the breeding goal should improve general teat quality and sow performance. By increasing the number of functional teats on a sow, producers can incre

关键词： genome-wide association studies   rare variant analysis   cardiometabolic traits  

摘要： Diet and lifestyle have changed dramatically in the last few decades, leading to an increase in prevalence of obesity, defined as a body mass index >30Kg/m2, dyslipidaemias (defined as abnormal lipid profiles) and type 2 diabetes (T2D). Together, these cardiometabolic traits and diseases, have contributed to the increased burden of cardiovascular disease, the leading cause of death in Western societies. Complex traits and diseases, such as cardiometabolic traits, arise as a result of the interaction between an individual's predisposing genetic makeup and a permissive environment. Since 2007, genome-wide association studies (GWAS) have been successfully applied to complex traits leading to the discovery of thousands of trait-associated variants. Nonetheless, much is still to be understood regarding the genetic architecture of these traits, as well as their underlying biology. This thesis aims to further explore the genetic architecture of cardiometabolic traits by using complementary approaches with greater genetic and phenotype resolution, ranging from studying clinically ascertained extreme phenotypes, deep molecular profiling, or sequence level data. In chapter 2, I investigated the genetic architecture of healthy human thinness (N=1,471) and contrasted it to that of severe early onset childhood obesity (N=1,456). I demonstrated that healthy human thinness, like severe obesity, is a heritable trait, with a polygenic component. I identified a novel BMI-associated locus at PKHD1, and found evidence of association at several loci that had only been discovered using large cohorts with >40,000 individuals demonstrating the power gains in studying clinical extreme phenotypes. In chapter 3, I coupled high-resolution nuclear magnetic resonance (NMR) measurements in healthy blood donors, with next-generation sequencing to establish the role of rare coding variation in circulating metabolic biomarker biology. In gene-based analysis, I identified ACSL1, MYCN, FBXO36 and B4GA

关键词： Biology   Genetics   Mathematics  

摘要： Advances in sequencing and genotyping technologies have enabled data collection at unprecedented scales. This data deluge has driven demand for new, scalable methods and has allowed genomic approaches to be used to answer a broader set of questions. In this dissertation I analyze probabilistic models arising in population genetics, and I develop statistical techniques for extracting information from sequencing and genotyping data. I begin by analyzing Ʌ and Ξ coalescents, which arise as models of the genealogy of a sample from a population with large variance in the number of offspring per individual, such as marine species with sweepstakes-like reproduction or viruses undergoing continuous, strong selection. In particular, I show how to compute the expected value of a common summary statistic--the site frequency spectrum--under such models, and prove theorems about the identifiability of the model from the observed frequency spectrum. Such results suggest that it may be possible to learn about the underlying biological processes from observed site frequency spectra. I then present a method to find segments of Neanderthal ancestry in present-day humans, and use that method to learn about selective pressures on Neanderthal ancestry. I find that the observed patterns of Neanderthal ancestry are consistent with simple negative selection, as opposed to hybrid incompatibilities. Lastly, I develop a fast method to infer fine-scale recombination rates and apply it to 26 diverse human populations, elucidating the evolutionary dynamics and molecular modifiers of local recombination rates.

关键词： 红水河   巴马拟缨鱼   群体形态学   雌雄鉴别   遗传多样性   D-loop区  

摘要： 巴马拟缨鱼(Pseudocrossocheilus bamaensis)隶属于鲤形目(Cyprinformes)鲤科(Cyprinidae)野鲮亚科(Labeoninae)拟缨鱼属(Pseudocrossocheilus),主要分布在我国珠江水系红水河,常见于广西区内的天峨、巴马、大化和都安等地,在贵州的平塘和罗甸也偶有分布,是一种小型土著名优经济鱼类。随着人们消费水平的提高,巴马拟缨鱼市场需求量越来越大。在尚未完全实现其规模化人工繁育的情况下,近年来的酷渔滥捕已造成了该物种自然资源的严重退化,急需对其种质资源进行系统调查与评估。本研究采用形态学和遗传学研究方法,详细比较了该物种不同地理群体以及3龄雌雄样本的形态差异,对影响3龄雌雄样本体质量的关键形态指标进行了科学评估,并通过线粒体D-loop区分析了不同地理群体遗传多样性和遗传结构,结合相关资料推测和解析了其当前地理分布格局的形成机制,旨在为巴马拟缨鱼种质资源保护和合理开发利用提供理论依据。1、巴马拟缨鱼群体形态差异分析本研究结合传统形态学和框架形态学对8个地理群体的巴马拟缨鱼样本进行了多元统计分析。主成分分析共提取了9个主成分(PCA1～PCA9),其中前3个主成分贡献率较高,主要反映了鱼体头部、尾部及背腹部的形态变化。PCA1和PCA2散点图显示,部分地理群体已能明显区分,各群体在PCA1轴上的差异较在PCA2轴上的差异更为显著;经逐步判别分析筛选出的18项标准化性状参数对各地理群体判别准确率在89.06～97.67%之间,综合判别准确率为92.83%,能对各群体进行较好区分;聚类分析结果显示,各地理群体大体可聚集为3支,其中东兰、大化、天峨和合山4个群体先聚为第一分支,接着与第二分支中的平塘、罗甸和巴马3个群体聚类,最后才与第三分支中的都安群体聚到一起;差异系数计算结果表明,除巴马群体外,其它各群体在标准化性状参数上均体现出亚种分化情况,但群体间形态分化方向不具有一致性,且相邻群体间亦不存在形态上的亚种分化,因此判断巴马拟缨鱼不存在亚种。此外,从主成分散点图和聚类分析结果中均发现各群体间形态距离与地理分布远近不具有明显一致性,推测可能与巴马拟缨鱼在形态上对局域环境变化较为敏感而产生了趋异演化有关。2、巴马拟缨鱼雌雄形态差异分析及可量性状和体质量关系探讨本研究以3龄巴马拟缨鱼雌雄个体为研究对象,进行了以多元统计分析为基础的传统形态学和框架形态学比较。主成分散点图显示雌雄间形态差异主要体现在鱼体腹部特征(PCA2)上;经逐步判别分析建立的3龄巴马拟缨鱼性别判别方程对2龄、3龄、4龄及4龄以上雌雄样本进行较好区分;通过统计3龄雌雄样本各生长性状参数发现巴马拟缨鱼雌性体型明显大于雄性,并推测可能与其野外成熟的雄性个体较少导致生殖耗能较多,以及雌性的生育力选择进化等因素有关。探讨3龄巴马拟缨鱼雌雄个体的14项可量性状和体质量关系发现,影响雄性体质量的关键性状参数为全长、体厚和体高,雌性的为全长、体厚、体高、躯干长和尾柄高,影响雌雄体质量的关键性状参数有所不同,建议在后续良种选育过程中按性别对其进行分类选择。3、巴马拟缨鱼群体遗传学研究基于巴马拟缨鱼线粒体D-loop区全长(942 bp)对8个地理群体进行遗传学分析,共检测出23个单倍型,群体单倍型多样性(h)为0.672,核苷酸多样性(π)为0.0012,整体遗传多样性水平偏低。各群体中遗传多样性水平较高的有天峨(h=0.870,π=0.0022)、罗甸(h=0.705,π=0.0009)和大化(h=0.660,π=0.0005),较低的为东兰(h=0.239,π=0.0001)、平塘(h=0.123,π=0.0001)和巴马(h=0.213,π=0.0000)。此外,巴马拟缨鱼群体间遗传分化指数(Fst)在-0.02596～0.94204之间,遗传距离变化范围为0.0000～0.0037,平均核苷酸差异数(K)范围为0.393～5.182,由这3项遗传学参数以及群体间基因流(N)、确切P检验和单倍型系统发育树均可做出推论:即巴马拟缨鱼按地理分布可划分为两大支系,红水河上游的平塘、罗甸和天峨3个地理群体为一支,中下游的东兰、巴马、大化、都安和合山5个地理群体为另一支系。两支系间以及上游的平塘群体和罗甸、天峨2群体间均存在较大遗传分化,下游的5个地理群体间遗传分化较小。将2个支系进行分子方差分析(AMOVA)发现,巴马拟缨鱼群体间遗传分化主要来源于水系中的不同地理区间以及地理区间内的各群体间。单倍型网络图表现出明显的与地理分布相对应的谱系结构,根据网络图推断出该物种的祖先单倍型为HAP1和HAP2,结合各群体核苷酸多样性(π)推测出其祖先发源地可能为广西壮族自治区的天峨县。Tajima’s D和Fu’s Fs中性检验结果则提示巴

ISBN: (数字)9780128139400 ISBN: (纸本)9780128139394

摘要： Pharmacoepigenetics provides a comprehensive volume on the role of epigenetics and epigenomics in drug discovery and development, providing a detailed, but accessible, view of the field, from basic principles, to applications in disease therapeutics. Leading international researchers from across academia, clinical settings and the pharmaceutical industry discuss the influence of epigenetics and epigenomics in human pathology, epigenetic biomarkers for disease prediction, diagnosis, and treatment, current epigenetic drugs, and the application of epigenetic procedures in drug development. Throughout the book, chapter authors offer a balanced and objective discussion of the future of pharmacoepigenetics and its crucial contribution to the growth of precision and personalized medicine.

关键词： Environmental health   Public health  

摘要： The alteration of gene expression mediated by epigenetic modifications has been proposed as a mechanism by which chemical and biological factors during gestation and childhood may influence health and adult disease onset. Changes in DNA methylation, the most commonly assessed epigenetic mechanism, have been linked to numerous exposures including diet, metals, and chemicals, such as phthalates. The majority of individuals, including pregnant women and children, have detectable levels of metabolites of phthalates, which are used in consumer products to increase flexibility of plastics and as solvents. Phthalate exposure during early life has been associated with poor birth and developmental health outcomes, which may be mediated by epigenetics. Increasing evidence in human and animal models has shown an association between exposure to phthalates and DNA methylation levels. However, there is limited research on the relationship between pregnancy phthalate exposure and imprinted gene methylation. Imprinted genes exhibit expression of one parental allele and many are involved in early growth and development. Progress in the field of metabolomics has allowed for the assessment of thousands of metabolites in biological specimens. Metabolomic levels in humans have been associated with age and obesity; however, research of the effect of metabolites, especially the diverse classes of lipid metabolites, on DNA methylation is sparse. Animal studies have identified associations between maternal fatty acid dietary supplementation and offspring DNA methylation. The relationship between maternal lipid metabolites and DNA methylation of newborns has only been examined thus far in 40 mother-child dyads from a predominantly Caucasian study population. Environmental exposures, in addition to their role in epigenetic regulation, have been shown to impact human health, such as obesity status. Despite advances in the identification of additional risk factors of obesity, the influence of m

关键词： 银屑病   主要组织相容性复合体   家族史   易感基因   遗传度  

摘要： 研究背景银屑病是由免疫、遗传、感染等多因素参与的炎症性皮肤病,部分患者有明显的家族遗传倾向。目前银屑病的遗传学发病机制尚不完全清楚,随着遗传学研究方法的不断发展,通过连锁分析,全基因组关联分析,二代测序等方法,已发现80余个疾病的易感基因,解释了银屑病的部分遗传机制。人类白细胞抗原(human leukocyte antigen,HLA)系统是人体已知的最复杂、最多态性的系统,它包含一个编码人类主要组织相容性复合体(major histocompatibility complex,MHC)蛋白的基因大家族。这些基因位于染色体6p21上,主要分为I、II和III三类。MHC区域的基因具有高度多态性、单倍型遗传和广泛连锁不平衡的特点,已成为遗传学家研究的热点之一。HLA与许多人体疾病有关,如癌症、自身免疫性疾病和传染病等。近年来,越来越多的证据表明HLA与银屑病,特别是HLA I类基因有显著相关性,HLA-C*06:02在多个人种及银屑病的不同亚型中被证实是最强的疾病易感基因。尽管关于HLA区域与银屑病遗传研究已开展很多,但是尚无关于家族史亚型遗传变异特点的相关研究。目的(1)对HLA区域进行深度测序,分别寻找银屑病有家族史和无家族史人群各自的遗传变异位点。(2)比较HLA区域作用于有家族史和无家族史人群的遗传度的不同。(3)进一步寻找有无家族史亚型之间的差异位点,作为鉴别两个亚型的遗传标记。方法(1)利用Illumina测序平台对8,350例中国汉族人群寻常型银屑病患者及9,906例健康对照进行HLA区域深度测序,整理基因分型数据。(2)将患者人群按照有无家族史这一特点分为有家族史人群和无家族史人群。运用Plink软件分别对有家族史对对照组,无家族史对对照组进行亚型分析。对两组基因分型数据进行质控,校正年龄、性别、地域等因素后进行逐步回归分析,按照Bonferroni校正的P值标准,寻找两个亚型各自的显著性风险位点。(3)使用GCTA软件分别计算有家族史和无家族史组别的遗传度,比较HLA区域作用于两组遗传力度的不同。(4)运用Plink软件对有无家族史直接对比进行分析,寻找两者的差异位点作为遗传鉴别标记。结果对HLA区域的测序数据进行初步整理,包括等位基因,氨基酸,单核苷酸多态性(single nucleotide polymorphism,SNP),结果共有26,775个变异位点,按照Bonferroni校正的标准,显著性意义的P值取值为0.05/26,775=1.87×10-6。在有家族史患者对健康对照组,发现的最显著位点为HLA-C*06:02(P=1.00×10-352,OR=12.49,95%CI=11.07-14.09)。基于HLA-C*06:02我们进行逐步条件回归分析过程,分别发现多个显著性位点,分别为等位基因HLAC*07:04(P=6.87×10-13,OR=3.56,95%CI=2.51-5.03),C2基因内rs28732166(P=4.62×10-15,OR=2.21,95%CI=1.81-2.70),HLA-DPB2基因内rs9394133(P=2.97×10-9,OR=1.31,95%CI=1.20-1.43),HLA-A基因9号氨基酸,HLA-A amino acid 9(P=6.00×10-7,OR=0.77,95%CI=0.70-0.86),共计5个与有家族史亚型相关的独立信号。在无有家族史患者与健康对照组,最显著的位点为HLA-C*06:02(P=1.00×10-687,OR=13.20,95%CI=12.20-14.27),逐步回归分析分别发现HLA-C*07:04(P=1.40×10-33,OR=4.05,95%CI=3.23-5.08),HLA-B基因67号氨基酸,HLA-B amino acid 67(P=1.13×10-45,OR=2.07,95%CI=1.87-2.29),HLA-B基因32号氨基酸,HLA-B amino acid 32(P=4.71×10-20,OR=0.70,95%CI=0.64-0.75),基因GABBR1(P=1.42×10-19,OR=1.70,95%CI=1.52-1.91),基因C6orf10内rs3129917(P=6.57×10-16,OR=1.47,95%CI=1.34-1.62)和HLA-DPB2内rs9394133(P=1.23×10-12,OR=1.23,95%CI=1.16-1.30),共计7个与无家族史亚型相关的独立信号。运用GCTA计算遗传度,结果为有家族史亚型12.1%,95%置信区间9.7-14.5%,标准误0.012;无家族史亚型的遗传度15.8%,95%置信区间13.8-17.8%,标准误0.010。根据结果得出HLA区域

关键词： 突触传递   短时程可塑性   光遗传刺激  

摘要： 近年来，视紫红质通道蛋白2（Channelrhodposin-2，ChR2）作为光敏通道蛋白已被广泛地用于神经环路的功能研究。然而在光遗传学刺激下，额外的钙离子会通过ChR2和/或电压敏感的钙离子通道(voltage-gated calcium channel，VGCC)，进入细胞。这些额外的钙离子是否影响递质释放及突触短时程可塑性，至今尚未被系统地研究过。以Calyx of Held突触为研究对象，定量地观测了电刺激和光遗传刺激所引发的递质释放。在低光剂量照射条件下，最小阈上光刺激被发现显著改变突触传递及突触短时程可塑性。随着刺激光剂量增加，突触可塑性所受的影响更为显著，主要表现为非生理性的短时程突触抑制的增强。进一步的实验发现，以轴突照射代替突触终末光照刺激则可消除上述光遗传刺激对突触传递及突触短时程可塑性的非生理性影响。综上所述，发现，光遗传刺激所引入的额外的钙离子组分，显著改变了囊泡动员(priming)和囊泡释放概率，进而影响了突触传递的可靠性。由此提请就光遗传学方法在突触传递研究中的局限性和适用性开展深入的研究。

关键词： 方茎白粉藤   基因组大小   染色体数目   重复序列   长末端重复  

摘要： 方茎白粉藤(Cissus quadrangularis L.)属于葡萄科(Vitaceae)白粉藤属,是多年生藤本植物,茎多肉,广泛分布于非洲和南亚等干旱和半干旱地区。过去方茎白粉藤的植株或根茎一直作为药物被广泛用于人类和动物的疾病治疗。近年其整株或部分组织的提取物也被用于医疗和保健。同时该植物的茎也是生产天然纤维的潜在原材料。虽然该植物在分布区被广泛利用,但是对于它的细胞遗传学相关研究却鲜见报道。本研究以方茎白粉藤为主要研究材料,确定了其基因组大小和染色体数目,并利用二代测序(NGS)数据和生物信息学分析初步揭示了其基因组重复序列的特征。获得的主要结果如下;1.利用流式细胞仪评估了方茎白粉藤的基因组大小。以萝卜作为标准参照物,绘制荧光直方图(CV值小于5)。依据萝卜基因组大小和峰值读数,估算方茎白粉藤基因组大小约为2C=1.410 pg。与白粉属目前已经报道了基因组大小的其他成员相比,方茎白粉藤的基因组增加了一倍,推测可能与其进化过程中的加倍事件有关。2.以根尖为材料,采用荧光显微镜结合DAPI染色法对方茎白粉藤的染色体进行计数。由于其染色体较小,仅观察到两对染色体上的着丝粒。计数结果表明方茎白粉藤的染色体数目为2n=48。考虑到白粉藤属植物已报道的染色体基数(n=11或n=12)和其他成员已鉴定的染色体数目,加之可识别着丝粒的两对大染色体,我们推测方茎白粉藤为四倍体。3.使用改良后CTAB法从方茎白粉藤新鲜叶中提取了 DNA。通过低通量基因组测序和生物信息学分析初步揭示了方茎白粉藤的基因组组成。发现方茎白粉藤基因组由大约52%的重复序列和48%的非重复序列组成。对重复元件的注释表明长末端重复序列(LTR-反转录转座子)是其主要组分,约占重复元件的40%。对LTR的注释表明其主要由两个LTR超家族:Copia和Gypsy组成。基因组重复序列比较分析表明方茎白粉藤与其起源关系较近的葡萄属欧亚种葡萄(Vitis vinifera)之间差异显著,推测这种差异可能是由长期分化过程中的多倍化或全基因组复制等事件导致的。

摘要： 本刊1978 年创刊,由中华人民共和国国家卫生健康委员会主管,中华医学会与哈尔滨医科大学共同主办,是公开发行的国家级学术期刊.总编为傅松滨教授.国内统一连续出版物号为 CN 23-1536/R,ISSN 1673-4386. 2008 年起本刊被中国科技论文统计源期刊(中国科技核心期刊)收录.本刊为中华医学会国际医学系列杂志之一,系公开发行的专业学术期刊. 《国际遗传学杂志》主要报道国内外遗传学与医学遗传学领域的研究成果与技术创新,主要报道形式为论著、综述、技术与方法、教学园地、研究快报、讲座和会议介绍等,适于生命科学与遗传学相关领域科研人员、教师、临床医师和研究生参考阅读.投稿需登录网站( http:/ /cmaes. medline. org. cn)进行注册投稿.