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关键词： 鼻咽癌   遗传学   单核苷酸多态性   基因易感性  

摘要： 目的:EB病毒(Epstein-Barr virus,EBV)与鼻咽癌(Nasopharyngeal carcinoma,NPC)的发生发展密切相关,EB病毒潜伏膜蛋白LMP1(latent membrane protein 1,LMP1)由EBV基因编码,其介导的NF-κB与JNK信号转导通路在NPC发病过程中起着重要的作用。本研究旨在探索NF-κB与JNK信号转导通路相关基因TNF受体关联因子2(TNF receptorassociated factor 2,TRAF2)、TNF受体关联因子3(TNF receptor-associated factor 3,TRAF3)、核因子κB抑制剂α(nuclear factor of kappa light chain gene enhancer in B cells inhibitor,alpha;NFKBIA)、CHUK(conserved helixloop-helix ubiquitous kinase)及丝裂原激活蛋白激酶激酶4(mitogenactivated protein kinase kinase 4,MAP2K4)基因中的单核苷酸多态性(single nucleotide polymorphism,SNP)与中国汉族人群NPC发病遗传易感性的相关性,以发现有效的NPC相关的分子遗传标记物,为NPC高危人群的筛查及预防提供新的思路。方法:本研究纳入了2017年1月至2018年9月初诊于四川省肿瘤医院的350例经病理活检确诊为NPC的患者。另外搜集2018年7月至9月在四川省人民医院体检的580例正常人作为对照组。通过数据库KEGG(Kyoto Encyclopedia of Genes and Genomes)、NCBI(The National Center for Biotechnology Information)在NF-κB与JNK信号转导通路中基于功能学研究结果寻找与NPC发病相关的基因,运用数据库人类孟德尔遗传在线(Online Mendelian Inheritance in Man,OMIM)进一步明确目的基因功能与NPC发病的关联后,在Ensemble、db SNP、1000 Genomes Project及Ex AC(The Exome Aggregation Consortium)数据库中根据以下标准筛选候选SNP位点:(1)中国汉族人群(Chinese Han in Beijing,China,HCB)或东亚人群(East Asian,EAS)最小等位基因频率(Minor Allele Frequency,MAF)大于等于10%;(2)SNP位于3’或5’端(untranslated region,UTR)、编码区域(非同义SNP)或启动子区域;(3)SNP间基因连锁不平衡(r2<0.8)。在候选基因TRAF2、TRAF3、CHUK、NFKBIA及MAP2K4中,选取了TRAF2(rs7852970、rs3739942、rs5901110)、TRAF3(rs1131877、rs1051750、rs10133111、rs11160707)、MAP2K4(rs4792219)、CHUK(rs2230804)、NFKBIA(rs8904、rs2233406、rs2233409、rs145753299、rs2233407、rs17103265),共15个SNP覆盖共149个基因连锁不平衡(linkage disequilibrium,LD)r2≥0.8的SNP。提取患者及正常人对照组外周血液样本中白细胞的全基因组DNA并测定DNA浓度,确保提取DNA浓度高于20ng/μL、260/280介于1.7至2.0之间。将合格DNA样本进行琼脂糖凝胶电泳,进一步确定DNA样本的质量。应用质谱分析技术(Mass ARRAY)对候选SNP点进行基因分型,并随机抽查5%样本使用Sanger测序验证分型结果。使用Haploview检验Hardy-Weinberg平衡(HWE)、计算对照组中基因型频率、HCB的MAF值以及绘制LD图。应用Plink1.03软件对分型结果进行分析,比较SNP位点在病例组和对照组中的等位基因频率,并计算亚组间优势比(odds ratio,OR)、P值以及95%可信区间(95%confidence interval,95%CI)。设定P<0.05为具有统计学意义。结果:TRAF2(rs7852970)、TRAF3(rs1051750、rs11160707)及NFKBIA(rs145753299)位点分型失败。使用LD r2>0.8的rs17250694代替TRAF2(rs7852970),rs2075771代替TRAF3(rs105175

关键词： Landscape Genetics   ResistanceGA   Functional Connectivity   Biology   Terrestrial and Aquatic Ecology  

摘要： Populations that experience low levels of gene flow commonly display increased levels of inbreeding, lower genetic diversity, and reduced adaptive potential. Landscape genetics allows for spatial and genetic information to be analyzed simultaneously to better understand how the landscape influences gene flow. The eastern massasauga rattlesnake (Sistrurus catenatus) is a federally threatened viper found in wetlands throughout the Great Lakes region. Many remaining populations are small and isolated due primarily to habitat loss. Atypical from a range-wide perspective, eastern massasaugas on Bois Blanc Island (BBI), Michigan live in a relatively undisturbed landscape with a potential for high connectivity across the 88 km2 island. We used landscape genetics to examine the influence of landscape features on gene flow across BBI to determine if eastern massasaugas have detectable gene flow across a well-connected landscape with high abundance. We genotyped 102 snakes at 15 microsatellite loci and measured pairwise genetic distances using the proportion of shared alleles (Dps). We created resistance surfaces for land cover, roads, distance from roads, and compound topographic index. The R package ResistanceGA was used to optimize resistance surfaces and calculate pairwise effective resistance among individuals. We calculated an average observed heterozygosity of 0.574 and found no well-defined genetic structuring among our samples. Significant isolation by distance (IBD) was detected as well as positive spatial autocorrelation at distances less than 1 km. Our landscape genetic analysis identified the distance from roads surface to be our most supported model. In addition, either distance from roads or roads were included in the top three models suggesting the strong influence roads play in structuring patterns of gene flow of eastern massasaugas despite the low number of gravel roads and traffic volume on BBI. Our results suggest that roads act as barriers, reducing conn

关键词： 脑肿瘤   神经外科疾病   肿瘤病因   致病因素   物理因素   身体反应   脑部肿瘤   颅内肿瘤   化学因素   遗传学   癌基因   症状   学习   学界   头晕   头痛   视力   病毒  

摘要： 脑肿瘤也就是颅内肿瘤,是最为常见的神经外科疾病.目前仍没有确切的脑肿瘤病因,医学界认为致病因素可能为遗传学因素、癌基因因素、物理因素、化学因素和致瘤病毒.大多数的人都认为脑部肿瘤一旦患上之后,便会出现相应的巨大身体反应,不仅会直接影响到日常生活,还会对工作和学习产生影响,但事实并不是如此.一部分脑肿瘤在来的时候悄无声息,并且早期并没有异常情况和明显症状,而进入中期后会出现头痛、头晕和视力变差等情况.这些细节都不可轻视,很有可能就隐含着重大问题.

关键词： Analyses of large multi-omics datasets help describe genetics of type 2 diabetes   type 2 diabetes   epigenome   transcriptome   eQTL   genome   Thesis  

摘要： Type 2 diabetes (T2D) is a complex disease that affects an estimated 415 million people worldwide. Genome wide association studies (GWAS) have identified >240 genetic signals that encode predisposition to this disease and related traits. However, the underlying biological mechanisms driving this predisposition are largely unknown, which is a serious impediment in designing precision therapeutic strategies. The focus of my research is to untangle the genetic complexity of T2D to better understand the biological mechanisms of how disease predisposition is encoded in our DNA. Specifically, I aim to understand how T2D genetic risk variants modulate gene expression in orchestrating disease mechanisms. I utilize high throughput molecular profiling data in human pancreatic islets and other diverse tissues along with human and rodent cell line model systems and employ computational and experimental approaches to map functional signatures of genetic variants associated with T2D. First, I compared gene regulatory annotations defined using diverse epigenomic data across 4 cell types to compare their cell specificities and genetics of gene expression regulation. I observed that genetic variants in genomic regions with more cell type-specific enhancer chromatin have lower effects on gene expression than variants in genomic regions with more ubiquitous promoter chromatin. However, genetic variants in cell type-specific enhancer regions have higher effects in chromatin accessibility than those in less cell type-specific promoter regions. Second, I integrated GWAS data with various -omics data in islets to nominate biological mechanisms. I observed that T2D risk variants confluently disrupt DNA binding motifs of the transcription factor (TF) regulatory factor X (RFX) in accessible regions. Third, I describe large scale expression quantitative trait locus (eQTL) mapping efforts along with integration of epigenomic data to describe molecular regulatory mechanisms. Utilizing such larg

关键词： 大麦   附加系   荧光原位杂交   分子标记   条锈病   转录组  

摘要： 大麦(Hordeum vulgare L.)分为野生大麦(*** ***)和栽培大麦(*** ***),因为具有早熟、耐瘠、适应性强、抗条锈病等优良性状,所以种植范围非常广泛。随着小麦种植过程中遗传背景变得狭窄、多样性的降低,所以从小麦近源或者远源物种中挖掘新的优异基因成为主要育种手段。因此大麦属物种的优良基因,成为了拓宽小麦遗传基础的重要基因来源。但是获得大麦和小麦杂交稳定遗传的后代比较困难,所以成功鉴定出小麦-大麦杂交稳定后代,并获得农艺性状良好的新材料受到持续关注。本研究利用普通小麦中国春(CS)和栽培大麦经过多次杂交、回交和自交后,得到了一批含有大麦染色体的附加系。本研究运用荧光原位杂交(FISH)技术建立了大麦亲本材料的染色体核型,进一步结合分子标记技术对这批小麦-大麦附加系进行了精准鉴定,同时对稳定材料进行了农艺性状的统计,进一步对农艺性状良好的材料开展了转录组测序和分析,具体结果如下:(1)通过对亲本大麦材料进行荧光原位杂交鉴定分析,发现探针Oligo-(GAA)可以区分大麦的每条染色体区,但是杂交信号不够分散,进一步实验筛选到两个在大麦染色体上分布相对广泛的探针组合:Oligo-(GAA)(红)和Oligo-(TAG)(绿),Oligo-HVT01(红)和Oligo-(ACT)(绿)。并且通过两套以色列大麦对两个探针组合进行了准确性验证,结果显示这两套探针可以对大麦染色体进行精确鉴定。(2)利用探针Oligo-pSc119.2和Oligo-pTa535,再结合探针Oligo-(GAA)对小大麦杂交后代进行鉴定,鉴定出了一批只含有大麦单一形式染色体的二体附加系(1HS、2H、2HS、2HL、3H、3H、3HL、4H、4HL、5H、5HS、5HL、6H、6HS、6HL、7H、7Hα短),其中2H、2HS、2HL、6H附加系能够稳定传递。对稳定传递的材料进行核型分析,发现附加系中的小麦染色体发了变异。用CINAU二同源引物对2H附加系稳定材料进行筛选,其中43对引物定位于大麦2HL上,17对引物定位于大麦2HS。(3)对附加系材料进行了农艺性状调查,发现2H、2HL附加系具有良好的条锈病抗性,但是2HS附加系对条锈病高感,进而推测条锈病抗性基因来自于2HL染色体上。(4)大麦染色体2H导入小麦背景中,对小麦背景的基因表达产生了影响,其中最显著的是,在2A染色体上大量基因发生差异表达,对2A染色体上下调的基因和2H染色体的上调基因基因功能富集,发现功能主要集中在蛋白代谢、细胞内大分子代谢等,而且2H染色体的导入对小麦2A染色体上功能缺失有一定的弥补作用。综上,本研究鉴定出了一批小麦-大麦染色体的附加系材料,以及定位于大麦染色体上的分子标记,并且对部分材料的差异表达基因进行了比较分析,可以为小麦背景中转入的大麦优异基因鉴定与育种利用提供基础。

关键词： 案例式教学   医学遗传学   模式特点   问题与对策  

摘要： 在新课程教育体系改革下,传统教育教学模式在很大程度上不仅难以达到教育部门提出的新的教学要求,与此同时对学生的成长和发展也造成了极为不利的影响,为此近年来教研工作者加快了对现代化教育教学模式的探索和实践,案例式教学由此应运而生,故此本文主要以医学遗传学专科教学为例,在阐述案例教学法特点和作用的基础上,对其应用问题和优化策略进行了全面探析,以此为学生可持续发展目标的实现奠定良好基础.

摘要： Understanding the evolution and underlying genetic mechanism of morphological adaptations has been an ongoing aim of evolutionary biology. Morphological evolution can occur as a species-specific adaptation and function in reproductive isolation. Despite investigation into the traits themselves, the genetic basis of interspecific morphological traits is poorly understood outside of domesticated plants and vertebrates. In my dissertation work, I combine high-throughput genotyping techniques and differential expression/allele-specific expression analyses to investigate the genetics of morphological evolution in the sister-species Bombyx mandarina and Bombyx mori. My work provides new insights on the genetic architecture of two morphological trait differences between B. mori and B. mandarina, caudal horn length and wing pigmentation. My work also illustrates the utility of combining high-throughput genotyping techniques for genetic mapping and gene expression analysis to hone in on a small number of candidate genes underlying phenotypic trait evolution.

关键词： 表观遗传   DNA甲基化   组蛋白修饰   microRNA   年龄相关性白内障  

摘要： 表观遗传是指遗传改变的基因组结构修改而基因组DNA序列不改变,其遗传机制主要包括DNA甲基化,组蛋白修饰和microRNA。老化、饮食、炎症、药物、氧化应激以及季节性和昼夜节律性生活方式的改变可能对表观遗传产生深远的影响,并引发疾病的易感性。随着世界人口老龄化的发展,年龄相关性白内障(Age-related cataract, ARC)致盲所占比例越来越大,但是目前没有疗效突出的药物来治疗本病,手术治疗存在诸多并发症。近年来越来越多的人开始从表观遗传的角度来研究本病,得到了眼科医师的广泛关注。

关键词： 精准医疗思维融入医学遗传学教学中的价值评价  

摘要： 社会方方面面技术的发展使得人们对疾病的认知程度也在不断加深,人们对医学的要求也在不断增高,这就出现了精准医学.医学遗传学是将基础和临床连接在一起的学科,也是与精准医疗理念联系最为密切的学科之一.将精准医疗思维应用于临床中可显著提升治疗效果,应用价值高;将精准医疗思维应用于医学教学活动中,通过优化教学内容、改进教学方法以培养病患的思维创新能力,培养更加适应新时期发展医护需求的新型精准医疗人才.

摘要： (以下按姓氏汉语拼音排序)总 编 辑 傅松滨副总编辑 白 静 褚嘉祐 贺 林 金 力 王明荣顾 问 黄百渠 黄天华 黄尚志 薛开先 曾溢滔编辑委员 (含总编辑、副总编辑)白 静 陈洁君 陈义汉 陈子江 褚嘉祐 丁彦青 范 明 方伟岗