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关键词： Mendelian randomization   biomarkers   cardiovascular disease   chronic inflammation   genetics   lipid-lowering medication   metabolic syndrome   metabolomics   molecular epidemiology   non-alcoholic fatty liver   type 2 diabetes   Mendeliaaninen satunnaistaminen   biomarkkerit   ei-alkoholiperäinen rasvamaksa   genetiikka   krooninen tulehdus   lipidilääkkeet   metabolinen oireyhtymä   metabolomiikka   molekyyliepidemiologia   sydän- ja verisuonitaudit   tyypin 2 diabetes   GWAS   PCSK9  

摘要： Metabolic syndrome is a constellation of metabolic abnormalities predisposing to cardiovascular diseases (CVD), type 2 diabetes, and increased mortality. Due to the high prevalence and severe co-morbidities, metabolic syndrome constitutes a major burden for both public health and the global economy. Improved understanding of the detailed molecular mechanisms could provide novel strategies for the treatment and preferably prevention of the metabolic syndrome-related health issues. Recent advancements in ‘omics’ technologies have facilitated the development of novel tools to examine the links between genetic variation and human health. The new techniques allow determination of millions of genotypes or quantification of hundreds of metabolic measures from a single blood sample. In this thesis, genomics and metabolomics approaches are coupled to improve our understanding of the metabolic syndrome-related health issues. More precisely, my projects evaluate the metabolic effects of two lipid-lowering therapies and non-alcoholic fatty liver, as well as assess genetic determinants of chronic inflammation. The present results indicate generally consistent metabolic effects of statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) genetic inhibition. The subtle discrepancies observed could potentially contribute to differences in the efficacy to lower CVD risk between statins and PCSK9 inhibitors. The dissimilar metabolic effects of the four genetic variants that increase the risk of non-alcoholic fatty liver disease (NAFLD) highlight the heterogeneity of the molecular mechanisms involved in NAFLD pathogenesis. The results further suggest that fatty liver by itself might not promote unfavourable metabolic aberrations associated with fatty liver on a population level. The newly identified loci associating with inflammatory phenotypes elucidate the genetic mechanisms contributing to the inflammatory load. In particular, the present results suggest the important r

关键词： population genetics   evolutionary genomics   molecular evolution   adaptation   speciation   phylogenetics   programming   bioinformatics   R   population genetics   evolutionary genomics   molecular evolution   adaptation   speciation   phylogenetics   programming   bioinformatics   R  

ISBN: (数字)9780191868993 ISBN: (纸本)9780198830917

摘要： Evolutionary genetics is the study of how genetic variation leads to evolutionary change. With the recent explosion in the availability of whole genome sequence data, vast quantities of genetic data are being generated at an ever-increasing pace with the result that programming has become an essential tool for researchers. Most importantly, a thorough understanding of evolutionary principles is essential for making sense of this genetic data. This up-to-date textbook covers all the major components of modern evolutionary genetics, carefully explaining fundamental processes such as mutation, natural selection, genetic drift, and speciation, together with their consequences. In addition to the text, study questions are provided to motivate the reader to think and reflect on the concepts in each chapter. Practical experience is essential when it comes to developing an understanding of how to use genetic data to analyze and address interesting questions in the life sciences and how to interpret results in meaningful ways. Throughout the book, a series of online, computer-based tutorials serves as an introduction to programming and analysis of evolutionary genetic data centered on the R programming language, which stands out as an ideal all-purpose platform to handle and analyze such data. The book and its online materials take full advantage of the authors’ own experience in working in a post-genomic revolution world, and introduce readers to the plethora of molecular and analytical methods that have only recently become available.

关键词： Prevalence   optometrists   glaucoma   South India   LVPEI-GLEAMS  

摘要： Purpose: To report the prevalence of primary glaucoma as identified by study optometrists of the L. V. Prasad Eye Institute - Glaucoma Epidemiology and Molecular Genetics Study (LVPEI-GLEAMS). Methods: Two study optometrists and a total number of 3833 individuals participated in the LVPEI-GLEAMS. All subjects underwent a complete medical history and comprehensive eye examination including slit lamp photography, imaging of anterior and posterior segment, frequency doubling technology and standard automated perimetry including gonioscopy with a Sussman 4 mirror goniolens, post dilated evaluation of the optic disc and fundus was done with a 90 D lens by the study optometrist. A diagnosis of primary open angle glaucoma (POAG), primary angle closure suspect (PACS), primary angle closure (PAC), primary angle closure glaucoma (PACG), normal tension glaucoma (NTG), glaucoma/disc suspect or no glaucoma was made based on the clinical examination. Results: Estimated prevalence of OAG (POAG and NTG) was 1.07% (0.74-1.39), PACS 2.03% (1.58-2.48), PAC 1.77% (1.35-2.19), PACG 0.21% (0.06-0.35) as identified by the study optometrists on site. Conclusions: Prevalence of all the categories of primary glaucoma, as reported by the study optometrists of LVPEI-GLEAMS was comparable to previous findings of other regions in South India.

关键词： 伦理学   遗传学   CCR5基因   基因编辑   抗艾滋病   社会公众   外科学   双胞胎  

摘要： 2018年11月26日,南方科技大学贺建奎副教授公开发布消息,称1对名为露露和娜娜的基因编辑婴儿于11月在中国诞生。这对双胞胎的CCR5基因经过修改,使她们出生后即能天然抵抗艾滋病。该消息一经发布引起国内外科学界和社会公众的关注和震惊。2018年12月20日,国际著名期刊Science公布了2018年度国际上3大恶劣科学事件,贺建奎副教授以妊娠为目的的基因编辑事件入选其中。

关键词： SNP-array   新生儿   畸形遗传学   诊断价值  

摘要： 目的评价全基因组SNP-array在新生儿畸形遗传学诊断中的价值。方法收集2013年7月-2017年7月嘉兴市妇幼保健院及安庆市第一人民医院新生儿科发现有畸形的450例新生儿的外周血,使用SNP-array对外周血的全基因组DNA拷贝数变异(CNV)进行检测,然后采用Affymetrix 750K芯片分析样本情况,并进行核型检查,验证芯片异常结果。结果 450例样本中,行SNP-array检测均获得成功,检测成功率为100. 00%。各系统异常CNV检出率的比较中,中枢神经系统、胎儿水肿综合征、羊水过多、淋巴水囊瘤、心血管异常CNV检出率最高,其次为颜面部异常、肌肉骨骼系统、NT增厚和多发畸形,消化系统异常、软指标异常、胎儿肿瘤的检出率最低,均未出现变异。经核型检测可得,三倍体、非整倍体共36例,异常检出率为8. 00%。除了良性CNV,具有临床意义的变异经高分辨率染色体微阵列分析(CMA)检出86例,异常检出率为19. 11%。36例为染色体数目异常,异常检出率为8. 00%,包括6例三倍体和30例非整倍体,符合核型结果;通过正常核型检测,芯片提示存在CNV的有58例(12. 89%),其中临床意义明确的致病性CNV有44例,异常检出率为9. 78%,临床意义暂未明确的有14例,异常检出率为3. 11%。结论全基因组SNP-array技术对新生儿畸形遗传学诊断具有准确性好、分辨率高等特点,引入SNP-array平台进行产前诊断对发现更多未知的综合征型疾病具有积极的意义,为临床遗传病咨询和诊断提供依据,值得在临床推广应用。

关键词： 贫血,再生障碍性   自身免疫   全血细胞减少   突变  

摘要： 获得性再生障碍性贫血发病的主要环节是抗原介导的细胞毒性T细胞功能亢进。其发病机制涉及辅助性T细胞(Th)1/Th2、Th17/调节性T细胞、髓系树突状细胞/淋系树突状细胞失衡,自然杀伤细胞数量及功能异常。记忆T细胞、骨髓间充质干细胞及血细胞端粒相关蛋白等也可能参与其中。近年有关获得性再生障碍性贫血遗传学异常研究增多,包括细胞遗传学异常、体细胞突变等。有些报道的"克隆性再生障碍性贫血"应诊断为"意义未明的克隆性血细胞减少症"。

关键词： 肥厚型心肌病   基因突变   儿童  

摘要： 肥厚型心肌病(hypertrophic cardiomyopathy,HCM)是儿童及青壮年心脏性猝死的重要原因之一,成人HCM的发病率为1/500,主要为编码肌小节相关蛋白突变,最常见的为MYH7和MYBPC3,儿童HCM发病率尚不明确,病因更加复杂,临床表现呈高度异质性,并存在多种非肌小节病变,包括代谢贮积疾病、RASopathies、神经退行性疾病、线粒体疾病等,超过40个基因与儿童HCM相关,最常见的遗传方式为常染色体显性遗传,其他还有常染色体隐性遗传、X连锁显性及隐性遗传、线粒体遗传。

关键词： 军团菌   水环境   系统发育学  

摘要： 目的检测喷泉水中的1株军团菌并进行分子生物学鉴定和系统发育分析。方法采集潍坊市一处人工喷泉水水样,用细菌基因组试剂盒提取水样中的总细菌基因组DNA,使用针对军团菌属16S rRNA基因片段的特异性引物PCR扩增军团菌属16S rRNA基因片段并测序,与从GenBank获得的另外41株军团菌的16S rRNA的基因序列进行对比分析,采用PAUP*4.0b10软件对16S rRNA基因片段序列数据矩阵进行最大简约法分析并绘制基因进化树。结果PCR扩增喷泉水提取物中军团菌属特异性16S rRNA基因片段,片段碱基数654 bp。测序分析该菌株(命名为WF-B)的16S rRNA基因序列与Legionella beliardensis 16S rRNA基因序列的遗传距离较近,相似度达99.8%,在构建的最大简约进化树中该菌与***以自检值97%聚类为一枝。结论该喷泉水中检出的军团菌WF-B与***的亲缘关系较近,相关部门应加强监管力度,降低其感染风险。