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关键词： 羊水染色体核型   高龄孕妇   细胞遗传学   产前诊断   遗传咨询  

摘要： 目的:分析高龄孕妇细胞遗传学产前诊断结果和遗传咨询。方法:采用回顾性方法分析,选取本院自2017年9月至2019年12月收治的60例高龄孕妇作为研究对象,进行羊膜腔穿刺行染色体核型分析,统计一次性穿刺成功率、并发症及其胎儿异常染色体核型检出率情况。结果:60例高龄孕妇均接受羊膜腔穿刺,一次性穿刺成功的有59例,穿刺成功率为98.33%;60例高龄孕妇进行羊膜穿刺后,均未发生妊娠并发症;羊水染色体检查共检查出异常染色体核型8例,异常检出率为13.33%。其中常染色体数目异常4例,常染色体结构异常2例,性染色体数目异常1例,性染色体结构异常1例。结论:孕期羊水染色体核型分析是孕妇产前诊断遗传性疾病的有效方法,尤其是对高龄孕妇检查分析,可发现两性畸形、先天智力低下等情况、排除潜在的缺陷胎儿,可为遗传咨询提供参考借鉴。

关键词： 骨骼发育不良   基因检测   分子诊断  

摘要： 骨骼发育不良(skeletal dysplasia,SD)是一类影响骨骼发育的遗传性疾病,临床表型复杂多样。探索和明确SD的致病基因和分子机制,可帮助临床医师鉴别诊断疾病的类型和病因,也是研究和改进治疗方案、开展遗传咨询和产前诊断的基础。随着全外显子测序等新一代测序技术的发展,SD的分子遗传学研究取得了较多突破性的进展。近年来,关于成骨不全、综合征性脊柱侧凸和先天性肢端畸形等SD的研究发现了许多新的致病突变并探索了导致疾病的具体分子机制,本文就此做一综述。

关键词： 东南大学   生物个体   遗传学   生命本质   变异规律   百年历史   表达模式   基因结构  

摘要： 遗传学是一个古老而发展迅速的基础学科,基于细胞或生物个体的基因结构、功能及其表达模式的研究,解析生物遗传性状的传递和变异规律。遗传学理论与技术已经渗透到生物学及其相关的学科领域,成为理解生命本质最重要的基础学科。我国遗传学研究从初始到如今的蓬勃发展已有百年历史。江苏省遗传学学会也历经了几十年的峥嵘岁月。在纪念江苏省遗传学会成立40周年之际,回顾我国遗传学的发展历程,看到了东南大学遗传学发展的历史身影。

关键词： 孕中期   羊水遗传学检验   高危产妇   胎儿染色体异常   效应风险   应用价值  

摘要： 目的分析孕中期羊水遗传学检验对高危产妇胎儿染色体异常类型与效应风险的应用价值。方法以2017年4月至2019年5月196例南阳市第一人民医院收治的孕中期高危产妇为对象,均接受羊水遗传学检验(超声指导下行羊膜腔穿刺取羊水进行细胞培养开展核型分析),比较不同核型染色体异常发生及分布情况,对比不同年龄高危产妇的胎儿染色体异常发生及分布情况,记录随访所得妊娠结果。结果196例孕中期高危产妇中检出胎儿染色体异常率为4.59%,其中染色体数目异常占比最高(55.56%),其次是性染色体数目异常占比(22.22%),多态与倒位占比(均为11.11%)。9例孕中期胎儿染色体异常,其核型主要可分为5类,依次是21-三体、18-三体、47,XXX、多态性、倒立性。35~37岁、38~40岁、>40岁高危产妇胎儿染色体异常发生率,差异存在统计学意义(P<0.05);9例孕中期胎儿染色体异常高危产妇中,人工引产数量最多(6例),其次是完成生产2例(均存在不同程度智力低下),自然流产1例。结论对于孕中期高危产妇胎儿染色体异常疾病类型采取羊水遗传学检验具有高诊断价值,可明显降低染色体异常疾病发生风险。

关键词： 表观遗传学调控   生精功能障碍   不育   动物模型   小鼠  

摘要： 目的:探讨表观遗传学调控对生精功能障碍性不育C57BL/6J雄性小鼠动物模型的作用及影响。方法:60只C57BL/6J雄性小鼠随机均分为对照组和模型组。应用附睾靶向多肽(CSA)结合吲哚青绿包载游离纳米粒(ICG-NPs)联合白消安和二甲基亚砜构建生精功能障碍性不育动物模型。在附睾中检测精子DNA碎片指数(DFI)、精子顶体完整率和自发顶体反应率,FISH检测ERp29基因的扩增,Real time-PCR和Western印迹定量ERp29、PTEN、TSC2 mRNA和蛋白差异,ChIP-Seq分析ERp29、PTEN、TSC2基因差异,甲基化DNA免疫共沉淀测序(MeDIP-Seq)。结果:与对照组相比,干预后模型组的精子DFI[(30.15±2.87)%vs(15.67±1.33)%,P<0.05]和精子顶体完整率[(47.16±3.45)%vs(65.33±7.14)%,P<0.05]有显著差异;精子自发顶体反应率无显著差异[(11.48±2.27)%vs(11.52±2.31)%,P>0.05]。FISH证实5-AZA-DC干预前模型组ERp29基因无扩增,干预后ERp29基因明显扩增,对照组无影响。5-AZA-DC干预后模型组DNMT1 mRNA(9.33±1.15 vs 7.01±1.14,P<0.05)和蛋白(15.66±1.45 vs 12.33±1.27,P<0.05)显著下调,模型组ERp29(3.04±1.13 vs 6.54±1.18,P<0.05)、PTEN(3.25±1.01 vs 5.85±1.04,P<0.05)、TSC2(4.27±1.16 vs 6.98±1.13,P<0.05)mRNA和(4.37±1.02 vs 6.95±1.03,P<0.05)、(3.54±1.01 vs 5.17±1.02,P<0.05)、(3.83±1.12 vs 6.98±1.13,P<0.05)蛋白显著上调,对照组无显著差异(P>0.05)。ChIP-Seq筛选出附睾组织中差异显著基因高表达为18个,低表达为25个。5-AZA-DC干预后,模型组的25个低表达基因均有不同程度的上调,其中ERp29、PTEN和TSC2基因上调最显著。高表达的18个基因均有不同程度下调,对照组差异无统计学意义(P>0.05)。MeDIP-Seq结果显示5-AZA-DC干预后模型组附睾组织中ERp29、PTEN和TSC2启动子区域甲基化水平差异显著,有统计学意义(P<0.05),对照组差异无统计学意义(P>0.05)。结论:稳定高效的动物模型为生精功能障碍性不育诊疗提供了重要的实验研究依据。ERp29是影响不育的重要基因,可作为男性不育治疗的表观遗传学调控潜在靶点。

关键词： 川崎病   儿童   遗传学  

摘要： 川崎病作为一种儿童急性自限性系统血管炎,作为自身免疫性疾病。近年来,川崎病发病率呈增长趋势,同时已经取代风湿热发展为儿童获得性心脏病的常见诱因。该疾病的发生原因及机制尚未完全明确,川崎病的发生与地域、种族密切相关,该病具有的易感性与遗传多基因位点有关,可能是多个信号通路共同作用,遗传在川崎病发生发展阶段发挥重要作用。现就川崎病发病的遗传学研究展开综述。

关键词： inflammation   autoimmune hepatitis   autoimmunity   genetics   drug-induced liver injury  

摘要： Drug-induced liver injury (DILI) is a challenging clinical event in medicine, particularly because of its ability to present with a variety of phenotypes including that of autoimmune hepatitis or other immune mediated liver injuries. Limited diagnostic and therapeutic tools are available, mostly because its pathogenesis has remained poorly understood for decades. The recent scientific and technological advancements in genomics and immunology are paving the way for a better understanding of the molecular aspects of DILI. This review provides an updated overview of the genetic predisposition and immunological mechanisms behind the pathogenesis of DILI and presents the state-of-the-art experimental models to study DILI at the pre-clinical level.

关键词： HLA   KIR   immunogenetics   whole-genome sequencing   imputation   clinical sequencing  

摘要： Immunogenetic variation in humans is important in research, clinical diagnosis and increasingly a target for therapeutic intervention. Two highly polymorphic loci play critical roles, namely the human leukocyte antigen (HLA) system, which is the human version of the major histocompatibility complex (MHC), and the Killer-cell immunoglobulin-like receptors (KIR) that are relevant for responses of natural killer (NK) and some subsets of T cells. Their accurate classification has typically required the use of dedicated biological specimens and a combination of in vitro and in silico efforts. Increased availability of next generation sequencing data has led to the development of ancillary computational solutions. Here, we report an evaluation of recently published algorithms to computationally infer complex immunogenetic variation in the form of HLA alleles and KIR haplotypes from whole-genome or whole-exome sequencing data. For both HLA allele and KIR gene typing, we identified tools that yielded >97% overall accuracy for four-digit HLA types, and >99% overall accuracy for KIR gene presence, suggesting the readiness of in silico solutions for use in clinical and high-throughput research settings.

ISBN: (数字)9781119818113 ISBN: (纸本)9781789450163

摘要： In the age of genomics, oncogenetics is a growing discipline. It is defined as the identification and management of families where there is a suspected hereditary risk of cancer. This relatively new discipline is part of a modern medicine that aims to be both preventive and predictive. Constitutional Oncogenetics gives precise descriptions of the main syndromes that cause a predisposition for cancer. The first part examines the most common syndromes in the majority of the world, including the heightened hereditary risk of breast and ovarian cancer and Lynch syndrome. The second part introduces less common infracentesimal syndromes, such as Bloom syndrome and Fanconi syndrome. This book is intended for oncogenetic practitioners and other specialists, as well as medical students.

摘要： Spinoza's magnum opus, the, is written in a very peculiar, "geometrical" style, one that builds metaphysical and ethical doctrines out of mathematical, deductive proofs. These proofs rely on a series of definitions, axioms, propositions, and demonstrations. Nowhere in the does Spinoza explain his fundamental definitions and axioms, nor does he proffer a defense of his manner of presentation. I claim that by a thorough and systematic investigation of his earliest writings we can peel back the mystery of this geometrical garb and grasp why Spinoza presents his philosophy with formal, mathematical structure. I argue for the view that his methodology is more extensive and diverse than the geometrical presentation of the with which he is most closely associated. This essay pays special attention to Spinoza's earliest unpublished works with particular emphasis paid to. Therein, Spinoza provides his only extant attempt at explicitly and systematically developing his method. By focusing on the genetic development of key epistemological concepts in this text, the origins of Spinoza's system comes into stark relief. I argue that the can function like a prolegomena for the. Though there are important doctrinal disagreements between the texts, the when conceived as a proper propaedeutic to the can make the experience of the latter more powerful and comprehensible, filling in gaps in meaning left open by the geometrical presentation. One route for accomplishing this task requires a sustained conceptual analysis of, Spinoza's term for intuitive knowledge, the greatest form of knowledge in his epistemology. I offer a developmental account of intuitive knowledge and explore a unique interpretation of its nature that elucidates and organizes the creative momentum of Spinoza's method from the to the and beyond.