昆虫性比失调因子及其作用机理

性比失调因子是一类自私的遗传因子 ,在多种昆虫种类中广泛存在。本文综述了性比失调因子导致宿主昆虫性比失调的多种作用机理 ,以及与性比失调因子相关的昆虫性别决定机制的进化。     

情感性障碍遗传因素与遗传方式的研究A

本文对205例情感性障碍患者的遗传因素与遗传方式作了研究．分析了先证者的家族遗传史,各级亲属的患病率及环境因素的作用,认为遗传因素在悄感性障碍的病因中具有重要的意义．同时,通过统计分析,指出情感性障碍的遗传方式为多基因遗传,其加权午均遗传率为78.99%.     

利用转基因技术进行植物遗传改良

生物技术的发展为植物遗传改良开辟了一条新途径。论述了转基因技术在植物遗传改良中的应用及其与传统育种方法的关系。     

遗传资源获取和利益分享与知识产权保护

随着人类对遗传资源开发利用程度的加剧、物种资源不断减少以及国际交流合作的日益频繁,遗传资源获取和利益分享中的知识产权问题日益受到国际社会的关注。为了保护和持续利用遗传资源,本文根据《生物多样性公约》第15条的规定,以及国际社会在遗传资源获取和利益分享方面的做法,分析了我国遗传资源保护和利用以及知识产权保护的现状,提出建立和完善保护遗传资源知识产权的专利制度,遗传资源的管理制度以及遗传资源保护和利用的市场化机制等管理措施,最后,对中国和阿根廷NIDERA公司在大豆遗传资源交换,合作研究和利益分享的案例进行了分析。     

近视与遗传

近视在生理上表现为屈光不正。亚洲人群的近视发生率与几十年前相比迅速增加,而我国较发达的城市中多数人口已经或正在成为近视。近年来的研究已经报道了6种近视相关基因。从中国现代化进程和近视人口的迅速增长角度看,这种远远打破遗传平衡的变化已经不能用简单的基因突变或者孟德尔遗传来解释。城乡差别和受教育程度的比较可见,近视的成因受环境和基因两个方面的影响。近视直接关系国家发展和民族的健康,应当是全社会共同关注的一个重要课题。     

利用微卫星遗传标记对恒河猴进行遗传同质性分群的探索

目的探索建立利用微卫星遗传标记对中国恒河猴免疫遗传学同质性分群的方法。方法根据已报道的中国恒河猴和印度恒河猴微卫星标记和与MHC基因高度连锁的微卫星遗传标记,对52只恒河猴进行了微卫星检测和遗传同质性分群。结果依据判断标准,可以将检测的恒河猴分为印度恒河猴,中国恒河猴和无法判定来源的恒河猴3个地理类别,并根据MHC附近的微卫星遗传标记将其分为若干MHC基因相同的同质性群体。结论此方法的建立将有利于恒河猴参与的实验分组,也为恒河猴繁殖管理提供了参考。     

利用线粒体COI基因揭示中国乌骨鸡遗传多样性和群体遗传结构

全面了解中国乌骨鸡的遗传背景有利于保护和开发利用其种质资源。本研究测定了中国12个乌骨鸡品种线粒体细胞色素c氧化酶亚基I (cytochrome c oxidase subunit I, COI)基因, 比较分析其遗传多样性和群体遗传结构。255份乌骨鸡样品共检测到22个变异位点, 占分析位点的3.17%; 核苷酸多样性为0.00142-0.00339, 单倍型多样性为0.380-0.757, 其中略阳乌鸡核苷酸多样性最高, 德化黑鸡最低。检测到7个氨基酸变异位点, 来自6个品种共11个个体。定义了24种单倍型, 其中单倍型H1和H3为12个乌骨鸡品种共享, 出现频率分别为115次和64次; 盐津乌骨鸡单倍型数最多, 广西乌鸡最少。中性检验与错配分析显示实验种群未经历显著的群体扩张事件。分子变异分析显示81.06%的变异来自群体内; 品种间遗传距离为0.002-0.004, 品种间遗传分化系数F_st值为-0.035至0.594, 雪峰乌骨鸡与其他种群间的遗传分化程度最高。邻接树显示, 乌骨鸡未能独立形成分支, 不能从家鸡和红原鸡中有效区分开来。中国乌骨鸡中介网络图将24个单倍型分为3条进化主支, 呈现出一定的品种特异性, 由无量山乌骨鸡、云南盐津乌骨鸡和雪峰乌骨鸡组成单倍型H8、H9、H11、H12游离于这3条进化主支之外。增加其他家鸡和红原鸡COI基因的中介网络图主体结构与中国乌骨鸡的相同。结果表明中国乌骨鸡品种遗传多样性较低, 但品种间遗传分化显著, 可能是从当地家鸡中选育而来, 需要加强种质资源的保护。     

多基因联合揭示海南鲌的遗传结构与遗传多样性

海南鲌(Culter recurviceps)是我国华南地区重要经济鱼类, 由于受到近些年水利开发、过度捕捞、环境污染等诸多因素的影响, 其资源量快速下降, 亟需得到更多的关注和保护。为保护和合理开发海南鲌种质资源, 本研究采集了华南地区23个地理群体207尾海南鲌样本, 测定了2个线粒体基因(Cytb和ND2)并从Barcode of Life Data System数据库获得相对应线粒体COI基因, 结合多种分析方法(系统发育分析、分化时间估算、单倍型网状图、群体遗传分析和Mantel检验)对海南鲌的遗传结构和遗传多样性展开研究。系统发育分析和单倍型网状图表明华南地区海南鲌群体被分成3个谱系(I、II和III), 其中谱系I和III由珠江的群体组成, 谱系II由海南岛的群体组成。分化时间估算发现3个谱系之间的分化时间介于0.028-0.251 Ma之间, 表明华南地区更新世气候变化可能是造成海南鲌谱系分化的重要原因。群体遗传分析发现海南鲌群体之间存在极显著的遗传分化(F_ST = 0.511, P < 0.001), 并且符合距离隔离模式(R = 0.348, P = 0.0010)。群体动态历史分析表明, 海南鲌群体可能在0.010-0.025 Ma经历了群体扩张, 表明更新世的气候波动也影响了海南鲌的群体大小和分布。综上所述, 海南鲌群体由3个谱系组成, 更新世气候变化是导致3个谱系分化和影响海南鲌群体动态历史的重要因素。此外, 海南鲌群体之间的遗传分化也可能受到了空间距离的影响。     

云贵高原银星竹鼠的遗传多样性与遗传结构研究

作为一类营地下生活的啮齿动物,银星竹鼠Rhizomys pruinosus具有较高的食用价值和药用价值,已成为我国南方地区特种经济动物养殖业的重点发展物种。以核内重组蛋白激活基因1(RAG1)的基因片段为分子标记,采用分子生物学方法,本研究对来自12个采样点的173个银星竹鼠个体进行群体遗传分析,探讨该物种群体遗传多样性和遗传结构。序列多态性分析结果显示,银星竹鼠RAG1基因部分序列848 bp,共检测出多态性位点18个,其中单突变位点3个,简约信息位点15个。遗传多样性分析表明,173份样本共统计出RAG1基因单倍型11个,单倍型多样性为0.712±0.025,核苷酸多样性为0.002 64±0.003 71,显著低于其他啮齿动物。最大似然法、邻接法和贝叶斯法构建的系统发育树显示,银星竹鼠群体分化为3个分支,其谱系地理格局出现明显分化。同时,分子变异分析结果证实,银星竹鼠种群间的遗传变异极显著高于种群内的,说明该物种存在显著的遗传结构和遗传分化水平。上述研究结果综合表明,银星竹鼠群体的遗传多样性水平较低,遗传分化结构较为显著,这可能与该物种的地下生活方式、扩散能力弱、山脉河流阻隔作用、地质气候事件等因素有关。本研究结果将为云贵高原地区物种多样性、生物多样性保护提供科学的参考依据。     

Association between circadian genes,bipolar disorders and chronotypes

Abnormalities in circadian rhythms play an important role in the pathogenesis of bipolar disorders (BD). Previous genetic studies have reported discrepant results regarding associations between circadian genes and susceptibility to BD. Furthermore, plausible behavioral consequences of at-risk variants remain unclear since there is a paucity of correlates with phenotypic biomarkers such as chronotypes. Here, we combined association studies with a genotype/phenotype correlation in order to determine which circadian genes variants may be associated with the circadian phenotypes observed in patients with BD. First, we compared the allele frequencies of 353 single nucleotide polymorphisms spanning 21 circadian genes in two independent samples of patients with BD and controls. The meta-analysis combining both samples showed a significant association between rs774045 in TIMELESS (OR?=?1.49 95%CI[1.18–1.88]; p?=?0.0008) and rs782931 in RORA (OR?=?1.31 95%CI[1.12–1.54]; p?=?0.0006) and BD. Then we used a “reverse phenotyping approach” to look for association between these two polymorphisms and circadian phenotypes in a subsample of patients and controls. We found that rs774045 was associated with eveningness (p?=?0.04) and languid circadian type (p?=?0.01), whereas rs782931 was associated with rigid circadian type (p?=?0.01). Altogether, these findings suggest that these variants in the TIMELESS and RORA genes may confer susceptibility to BD and impact on circadian phenotypes in carriers who thus had lower ability to properly adapt to external cues.     

Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders

Online Mendelian Inheritance in Man (OMIM™) is a comprehensive, authoritative and timely knowledgebase of human genes and genetic disorders compiled to support research and education in human genomics and the practice of clinical genetics. Started by Dr Victor A. McKusick as the definitive reference Mendelian Inheritance in Man, OMIM (www.ncbi.nlm.nih.gov/omim) is now distributed electronically by the National Center for Biotechnology Information (NCBI), where it is integrated with the Entrez suite of databases. Derived from the biomedical literature, OMIM is written and edited at Johns Hopkins University with input from scientists and physicians around the world. Each OMIM entry has a full-text summary of a genetically determined phenotype and/or gene and has numerous links to other genetic databases such as DNA and protein sequence, PubMed references, general and locus-specific mutation databases, approved gene nomenclature, and the highly detailed mapviewer, as well as patient support groups and many others. OMIM is an easy and straightforward portal to the burgeoning information in human genetics.     

Targeted sequencing and integrative analysis of 3,195 Chinese patients with neurodevelopmental disorders prioritized 26 novel candidate genes

Neurodevelopmental disorders(NDDs) are a set of complex disorders characterized by diverse and cooccurring clinical symptoms. The genetic contribution in patients with NDDs remains largely unknown.Here, we sequence 519 NDD-related genes in 3,195 Chinese probands with neurodevelopmental phenotypes and identify 2,522 putative functional mutations consisting of 137 de novo mutations(DNMs) in 86 genes and 2,385 rare inherited mutations(RIMs) with 22 X-linked hemizygotes in 13 genes, 2 homozygous mutations in 2 genes and 23 compound heterozygous mutations in 10 genes. Furthermore, the DNMs of16,807 probands with NDDs are retrieved from public datasets and combine in an integrated analysis with the mutation data of our Chinese NDD probands by taking 3,582 in-house controls of Chinese origin as background. We prioritize 26 novel candidate genes. Notably, six of these genes d ITSN1, UBR3, CADM1,RYR3, FLNA, and PLXNA3 d preferably contribute to autism spectrum disorders(ASDs), as demonstrated by high co-expression and/or interaction with ASD genes confirmed via rescue experiments in a mouse model. Importantly, these genes are differentially expressed in the ASD cortex in a significant manner and involved in ASD-associated networks. Together, our study expands the genetic spectrum of Chinese NDDs,further facilitating both basic and translational research.     

Role of base excision repair DNA glycosylases in hereditary and infectious human diseases

DNA glycosylases are enzymes that initiate base excision repair, which removes damaged bases from cell DNA. Recent data demonstrate that some genetic variants of two human DNA glycosylases, MUTYH and OGG1, are associated with an increased risk of cancer. In addition, various DNA glycosylases are involved in protection from some neurodegenerative diseases, immune disorders, and virus infections. On the other hand, DNA glycosylases of pathogenic microorganisms help them to evade the host defense mechanisms. Thus, DNA glycosylases are considered to be both potential therapeutic agents and drug targets.     

联合应用RNA-seq和ATAC-seq寻找FOXQ1转录因子的下游靶基因

结直肠癌(Colorectal cancer, CRC)是一种全球高发的恶性肿瘤,发病原因复杂且预后较差。近年来发现叉头框Q1(Forkhead box Q1,FOXQ1)基因作为一类核转录因子在结直肠癌中高表达,可控制下游基因转录活性。本实验拟探究CRC细胞中FOXQ1的转录调控功能并寻找其下游基因。方法:(1)构建低表达FOXQ1基因的稳定转染CRC细胞株;(2)应用RNA-seq检测FOXQ1敲低前后表达量显著差异的基因;(3)应用转座酶可接近性核染色质区域测序分析(Assay for Transposase-Accessible Chromatin using sequencing, ATAC-seq)检测FOXQ1敲低前后细胞染色质易接近性的变化;(4)进一步对FOXQ1敲低前后的RNA-seq和ATAC-seq数据进行一系列生物信息学分析,寻找CRC中FOXQ1转录调控的潜在下游基因。结果:应用RNA-seq筛选出了敲低FOXQ1后表达显著差异的基因EI24、TLR2、SMAD3,通过联合分析两细胞系的测序结果,发现FOXQ1基因敲低后,在DLD1和SW480两个细胞系中染色质易接近性均增强且表达量均上调的基因有61个,染色质易接近性均减弱且表达量均下调的基因有70个,且EI24、TLR2、SMAD3基因均位于重叠分析结果中,其中TLR2、SMAD3基因的染色质区域有明显变化,而EI24基因的染色质区域变化不明显。通过代谢通路分析找到了EI24、TLR2、SMAD3基因所富集的代谢通路。其中SMAD3、TLR2基因在炎症性肠病(Inflammatory bowel disease, IBD)通路中显著富集。EI24基因在p53信号通路(p53 signaling pathway)通路中显著富集。结论:基于染色质易接近性的变化和转录水平的研究发现:敲低FOXQ1基因对CRC细胞系中染色质的开放情况有较大的影响,且影响FOXQ1转录调控的下游基因的表达。找到了FOXQ1敲低后在SW480、DLD1中均发生变化的基因,为丰富FOXQ1转录因子的下游调控网络提供了研究基础。     

Genomic imprinting and human hereditary disorders

Modern data are reviewed that concern hereditary disorders caused by abnormal expression of imprinted genes rather than mutations and structural aberrations. As an example, the molecular organization of the critical chromosomal region 15(q11.2–q13) and the possible pathogenetic mechanisms are described in detail for Prader-Willi and Angelman syndromes.     

Measurement of biological information with applications from genes to landscapes

Biological diversity is quantified for reasons ranging from primer design, to bioprospecting, and community ecology. As a common index for all levels, we suggest Shannon's (S)H, already used in information theory and biodiversity of ecological communities. Since Lewontin's first use of this index to describe human genetic variation, it has been used for variation of viruses, splice-junctions, and informativeness of pedigrees. However, until now there has been no theory to predict expected values of this index under given genetic and demographic conditions. We present a new null theory for (S)H at the genetic level, and show that this index has advantages including (i) independence of measures at each hierarchical level of organization; (ii) robust estimation of genetic exchange over a wide range of conditions; (iii) ability to incorporate information on population size; and (iv) explicit relationship to standard statistical tests. Utilization of this index in conjunction with other existing indices offers powerful insights into genetic processes. Our genetic theory is also extendible to the ecological community level, and thus can aid the comparison and integration of diversity at the genetic and community levels, including the need for measures of community diversity that incorporate the genetic differentiation between species.     

高通量测序技术在遗传性耳聋研究中的应用及研究进展

耳聋是一种常见的严重出生缺陷,阐明遗传性耳聋的致病机理不仅能够在临床上辅助诊断,为遗传咨询及耳聋预防提供依据,而且能促进人们更深入地了解耳聋的致病机制,开发新的治疗方法。随着基因组研究技术不断创新,以全基因组测序、全外显子组测序、目标区域测序为代表的高通量测序技术在遗传性耳聋研究中已得到广泛应用。本文总结了近5年全外显子组测序和目标区域测序在遗传性耳聋致病基因研究及临床分子诊断中应用及研究进展,希望能够有助于我国临床耳聋基因诊断技术的发展及诊断水平的提升。     

Magnesium homeostasis: Mechanisms and inherited disorders

Mechanisms of magnesium homeostasis intensively studied over the last 10–15 years by means of pathophysiological and molecular genetic approaches have been considered. Impairments of magnesium homeostasis causes the development of magnesium-deficient states, which have been found in many common diseases (diabetes mellitus, cardiovascular diseases, chronic fatigue syndrome, alcoholism, psychiatric and neurologic diseases, etc.), stress condition, effects of some environmental factors as well as therapy with some drugs. Special attention is paid to familial hypomagnesemias caused by genetic defects of magnesium transport systems. The review considers clinical and biochemical characteristics of twelve familial disorders including mechanisms of their development. Deeper understanding of mechanisms of regulation of magnesium homeostasis will results in the development of new approaches in diagnostics, prophylaxis and treatment of magnesium-deficient conditions.