中国人群中家族性精神分裂症与1号染色体的连锁分析

目的 探讨中国人群中家族性精神分裂症易感基因1号染色体的分子遗传学关系。方法 用基因组扫描的方法，选择了平均分布在1号染色体上的29个标记，对32个家族性精神分裂症家系样本进行易感基因扫描。结果 参数连锁分析结果,在隐性模型下，多点连锁在262.52cM位置得到最大异质性Lod分为1．70；非参数连锁分析结果，262.52cM位置处理到最大的多点非参数连锁分为1.71(P=0.046)首次是149.70cM位置处得到多点非参数连锁分为1.37(P=0.086)，分别对应于标记D1S206，D1S425位点的位置。结论 进一步支持在染色体1q上可能存在家族性精神分裂症的易感基因。     

精神分裂症的遗传学基因研究

精神分裂症的遗传学研究开始于1916年,系谱分析、双生子法和寄养子法等群体遗传学研究提示精神分裂症有明显的遗传背景.近年来,随着分子生物学在精神分裂症遗传研究中的应用和遗传流行病学方法学的进步,人们在精神分裂症的易感基因、相关基因多态性、候选基因等方面进行了大量研究,并取得一些初步成果.有人甚至提出,精神分裂症遗传学研究黄金时代已经到来[1].     

精神分裂症易感基因

精神分裂症是一类遗传倾向性较高的多基因疾病.近年来,随着遗传学和分子生物学为主的多学科研究技术的快速发展,不断有新的易感基因报道;一些重要易感基因的生物学功能及其在该疾病发病机制中的作用研究也取得了一定进展.     

中国人群中精神分裂症与22号染色体的连锁不平衡研究

目的 探讨精神分裂症易感基因与22号染色体的分子遗传学联系,寻找、定位精神分裂症的易感基因。方法 在中国汉族人群中,选择了22号染色体上6个二核苷酸重复标记位点,应用荧光标记半自动基因分型技术,对126个精神分裂症同胞对核心家系进行基因分型和连锁不平衡检验（transmission/disequilibrium test,TDT)。结果 IL8Rβ位点TDT－χ^2值为25．30,P值为0．01,具有统计学意义,显示IL－2Rβ与精神分裂症的易感基因存在连锁不平衡;其他D22S944、D22S264、D22S303、D22S278、CYP2D6五个位点的P值均大于0．05,不存在连锁不平衡。结论 IL2Rβ基因或邻近区域可能存在精神分裂症的易感基因。     

基于数据融合算法的精神分裂症易感基因排序及其信号通路研究

目的利用已有的研究结果,采用数据融合分析方法,对与已知的精神分裂症易感基因有密切关系的候选基因进行统计分析,得出基因排序及其信号通路的结果,以此证明数据融合算法能够有效筛选精神分裂症易感基因。方法根据已知的与精神分裂症相关的基因,利用Endeavour工具,通过数据融合算法将候选基因排序,并用DAVID数据库对基因排序结果进行功能注释和富集分析。结果利用数据融合算法获得的排序较高的基因与已有研究进行比较,证实排名第二的NRG3和排名第三的AKT1与精神分裂症有密切联系。其他排名较高的基因可以作为潜在的疾病易感基因,为精神分裂症的研究提供参考。结论数据融合算法能够准确评价候选基因与精神分裂症的联系,使用该方法能有效地对精神分裂症易感基因进行筛选和判定。     

精神分裂症的影像遗传学方法研究

近年来随着神经影像技术和基因检测技术的发展,影像遗传学的研究有助于理解精神疾病易感基因对脑功能或结构的影响。该研究首先结合精神分裂症的背景,介绍了影像遗传学的研究进展,然后对影像遗传学方法多模态典型相关分析、联合独立成分分析、并行独立成分分析和基于稀疏表示的变量选择方法的基本原理和特点进行了归纳总结,随后阐述了有关精神分裂症的最新研究进展,最后对影像遗传学的未来研究发展进行了展望。     

Graves病遗传学研究进展

Graves病为多基因遗传病 ,是多对易感基因与环境因素共同作用的结果。本文就 Graves病发病的遗传易感性、家族遗传方式、免疫遗传学特点以及今后的研究趋向等作一综述     

Graves病遗传学研究进展

Graves病为多基因遗传病，是多对易感基因与环境因素共同作用的结果。本文就Graves病发病的遗传易感性、家族遗传方式、免疫遗传学特点以及今后的研究趋向等作一综述。     

基于多目标评价方法的乳腺癌易感基因排序及其网络表达研究

目的 利用已有的研究结果和数据,采用多目标评价方法建立乳腺癌易感基因评价模型,对与已知乳腺癌基因关系密切的其它基因进行分析和排序,并给出结果的网络表达模式.方法 通过分析已有的文献,并利用有关的基因数据库和已有文献中的数据,提炼出乳腺癌易感基因的多目标评价体系,构建基于加权和法的乳腺癌易感基因评价模型,并利用Cytoscape软件进行评价结果计算和评价结果的网络模式表达.结果 利用多目标模型所得到的评价结果,与已有的研究结果一致.其中,乳腺癌易感基因TopBP1排名第二,已知乳腺癌候选易感基因HMMR排名第六.结论 文章提出的多目标评价模型能够准确评价被选基因与乳腺癌易感性之间的关系,所提出的评价方法与相关软件结合使用,将成为癌症易感基因研究方面有效的分析方法和途径.     

强直性脊柱炎最新研究进展

澳大利亚布朗(Brown)教授指出,遗传学研究显示,13个非主要组织相容性复合体(MHC)区的易感基因为AS的易感基因。基因学研究显示,IL-23信号通路在一定程度上参与AS发病,人类白细胞抗原(HLA)-B27可通过在ERAR1基因中的     

精神分裂症的分子遗传学研究进展

群体遗传学研究表明,精神分析症具有肯定的遗传倾向。现代分子生物学技术的发展使进一步寻找该病的易感基因成为可能。本文就国际近年来关于精神分裂症遗传研究的一些结果进行综述;⑴该病遗传度约为６０％￣８０％,标准化诊断及症状量表为主要的表型界定工具;⑵基因组扫描及候选基因筛选查为目前主要的研究手段,受累同胞对分析法（ａｆｆｅｃｔｅｄ ｓｉｂ－ｐａｉｒ,ＡＳＰ）及传递不平衡检验（ｔｒａｎｓｍｉｓｓｉｏｎ ｄｉｓｅｑｕｉｌｉｂｒｉｕｍ ｔｅｓｔ,ＴＤＴ）为目前较理想的统计分析方法;⑶目前研究发现具有独立重复的阳性区域主要集中在６ｐ、２２ｑ和８ｐ,候选基因的阳性结果主要涉及５－ＨＴ２Ａ受体、ＤＲＤ３及ＮＴ－３等。进一步研究途径包括：更准确的表型界定、引入可靠的生物学标记、扩大样本量、发展更高效能的统计学方法以及实验室新技术的     

Genetics of affective (mood) disorders

The enormous public health importance of mood disorders, when considered alongside their substantial heritabilities, has stimulated much work, predominantly in bipolar disorder but increasingly in unipolar depression, aimed at identifying susceptibility genes using both positional and functional molecular genetic approaches. Several regions of interest have emerged in linkage studies and, recently, evidence implicating specific genes has been reported; the best supported include BDNF and DAOA but further replications are required and phenotypic relationships and biological mechanisms need investigation. The complexity of psychiatric phenotypes is demonstrated by (a) the evidence accumulating for an overlap in genetic susceptibility across the traditional classification systems that divide disorders into schizophrenia and mood disorders, and (b) evidence suggestive of gene-environment interactions.     

Informative phenotypes for genetic studies of psychiatric disorders.

Despite its initial promise, there has been both progress and some set backs in genetic studies of the major psychiatric disorders of childhood and adulthood. Finding true susceptibility genes may be delayed because the most genetically informative phenotypes are not being used on a regular basis in linkage analysis and association studies. It is highly likely that using alternative phenotypes instead of DSM diagnostic categories will lead more rapid success in the search for these susceptibility genes. The objective of this paper is to describe the different types of informative phenotypes that can be employed in psychiatric genetic studies, to clarify their uses, to identify several methodologic issues the design and conduct of linkage and association studies that use alternative phenotypes and finally to suggest possible solutions to those difficulties. This is a conceptual review with a focus on methodological issues that may arise in psychiatric genetics and examples are taken from the literature on autism, schizophrenia, bipolar disorder, and alcoholism.     

Chasing genes for mood disorders and schizophrenia in genetically isolated populations

Major affective disorders and schizophrenia are among the most common brain diseases worldwide and their predisposition is influenced by a complex interaction of genetic and environmental factors. So far, traditional linkage mapping studies for these complex disorders have not achieved the same success as the positional cloning of genes for Mendelian diseases. The struggle to identify susceptibility genes for complex disorders has stimulated the development of alternative approaches, including studies in genetically isolated populations. Since isolated populations are likely to have both a reduced number of genetic vulnerability factors and environmental background and are therefore considered to be more homogeneous compared to outbred populations, the use of isolated populations in genetic studies is expected to improve the chance of finding susceptibility loci and genes. Here we review the role of isolated populations, based on linkage and association studies, in the identification of susceptibility genes for bipolar disorder and schizophrenia.     

Identifying psychophysiological risk for psychopathology: Examples from substance abuse and schizophrenia research

A problem confronting the search for psychopathology-related genes concerns the difficulty identifying gene carriers. Psychiatric diagnosis provides imperfect identification of affected individuals, and unaffected gene carriers go undetected. Psychophysiological measures may assist molecular genetic investigations by indicating genetic susceptibility for psychopathology, thus increasing the probability of identifying affected and unaffected gene carriers. Research strategies based on these premises are applied to the study of psychoactive substance use disorders and schizophrenia. Data are presented illustrating (1) that individual differences in inhibitory control involving autonomic and antisaccade eye movement measures and the P3 component of the event-related potential may be sensitive to susceptibility for substance use disorders, and (2) that eye tracking variables may identify genetic risk for schizophrenia.     

精神分裂症的分子遗传学研究进展

精神分裂症的流行病学研究提示了遗传因子的作用,但精神分裂症的分子遗传学研究至今尚未发现导致该病的主要的、特异性的基因。连锁（linkage）和关联（association）研究几乎都得出阴性或有争议的结果,这些研究主要涉及某些侯选基因,如多巴胺受体基因和其它脑神经递质基因,目前,有些侯选基因已被排除作为精神分裂症的特异性病因学因素。最近大多数实验结果提示：精神分裂症的遗传易感性极可能是多基因的,其作用效果依赖于生理、心理、环境因素的相互作用。     

Eye tracking dysfunction is a putative phenotypic susceptibility marker of schizophrenia and maps to a locus on chromosome 6p in families with multiple occurrence of the disease

The difficulties in defining the borders of the schizophrenia spectrum is one major source of variance in linkage studies of schizophrenia. The employment of biological markers may prove advantageous. Due to empirical evidence, eye tracking dysfunction (ETD) has been discussed to be the most promising marker for genetic liability to schizophrenia. With respect to the recent progress in genomic scans, which have pointed to the short arm of chromosome 6, we carried out a scan of the 6p21–23 region with 16 microsatellite markers to test for linkage between chromosomal markers and ETD as well as schizophrenia. We tested 5 models of inheritance of ETD and found maximum two-point lod scores of 3.51 for D6S271 and 3.44 for D6S282. By including these markers in a multipoint analysis, a lod score of 4.02 was obtained. In the case of schizophrenia, 7 models were tested; however, with non-significant results. Our findings, together with another recent linkage report, point to the possibility of a second susceptibility locus for schizophrenia which may be located centromeric to the HLA region. Also, the evidence of ETD being a susceptibility marker for schizophrenia receives further support.