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Genomic control for association studies   总被引:96,自引:0,他引:96  
Devlin B  Roeder K 《Biometrics》1999,55(4):997-1004
A dense set of single nucleotide polymorphisms (SNP) covering the genome and an efficient method to assess SNP genotypes are expected to be available in the near future. An outstanding question is how to use these technologies efficiently to identify genes affecting liability to complex disorders. To achieve this goal, we propose a statistical method that has several optimal properties: It can be used with case control data and yet, like family-based designs, controls for population heterogeneity; it is insensitive to the usual violations of model assumptions, such as cases failing to be strictly independent; and, by using Bayesian outlier methods, it circumvents the need for Bonferroni correction for multiple tests, leading to better performance in many settings while still constraining risk for false positives. The performance of our genomic control method is quite good for plausible effects of liability genes, which bodes well for future genetic analyses of complex disorders.  相似文献
The CD133 antigen, identified as a hematopoietic stem cell marker, appears in various human embryonic epithelia including the neural tube, gut, and kidney. We herein investigated whether CD133(+) cells isolated from human hepatocellular carcinoma cell lines possess cancer stem/progenitor cell-like properties. Among the three cell lines studied, the CD133 antigen was found to be expressed only on the surface of Huh-7 cells. CD133(+) cells from Huh-7 performed a higher in vitro proliferative potential and lower mRNA expressions of mature hepatocyte markers, glutamine synthetase and cytochrome P450 3A4, than CD133(-) population of Huh-7 cells. When either CD133(+) or CD133(-) cells were subcutaneously injected into SCID mice, CD133(+) cells formed tumors, whereas CD133(-) cells induced either a very small number of tumors or none at all. Taken together, the identification of CD133(+) cells could thus be a potentially powerful tool to investigate the tumorigenic process in the hepatoma system and to also develop effective therapies targeted against hepatocellular carcinoma.  相似文献
不同品种猪肌肉生长抑制素基因单核苷酸多态性分析   总被引:38,自引:2,他引:36  
用PCR-RFLPs和PCR-SSCP分析方法,对"双肌臀”大白猪、大白猪、长白猪、杜洛克、汉普夏、皮特兰、二花脸、东北民猪、湖北白猪和部分杂交猪等不同品种猪肌肉生长抑制素基因3'编码区、5'调控区及内含子1区3个单核苷酸多态性位点(SNPs)进行了分析.结果表明,3'编码区的SNP发生的频率较低,在274头猪中未检出突变纯合体.对5'调控区的SNP,引进猪种(大白猪、长白猪、杜洛克、汉普夏和皮特兰)及其杂交猪以等位基因T为主,二花脸和湖北白猪则以等位基因A为主,均偏离Hardy-Weinberg平衡状态(P<0.01).东北民猪的3种基因型近乎相等,处于Hardy-Weinberg衡状态.对内含子1区的SNP,大白猪及其与长白猪的杂交猪等位基因G占优势,二花脸和湖北白猪则以等位基因A为主,均偏离Hardy-Weinberg平衡状态(P<0.01);东北民猪和大二猪的等位基因G和A近乎相等,处于Hardy-Weinberg平衡状态."双肌臀”大白猪在5'调控区和内含子1区这两个位点的A等位基因稍高于普通大白猪.5'调控区和内含子1区SNPs所产生的等位基因表现出连锁遗传现象.  相似文献
以基因表达谱芯片对人正常肝及肝癌组织基因表达的差异性进行了研究比较。奖4096条人cDNA用点样仪点在特制玻片上制备成表达谱芯片;利用肝和肝癌组织的mRNA通过逆转录方法,将Cy3和Cy52种荧光分别标记到两种组织的cDNA上,制备成cDNA探针,并与表达谱芯片进行杂交及扫描,重复4次实验,通过计算机数据处理判定基因是否在上述2种组织中有表达差异,筛选出差异表达的基因共903条。基因芯片技术可同时  相似文献
罗怀容  施鹏  张亚平 《遗传》2001,23(5):471-476
本文在对人类基因组单核苷酸多态性(SNP)的概念做简要说明的基础上,系统地介绍14种检测分析SNP的技术和方法的原理、操作要点及其优缺点。 Abstract:Based on summarizing the single nucleotide polymorphisms (SNP) of human genome,14 methods for detection were reviewed in detail,including the principle,operational point,the advantages and the disadvantages of each method.  相似文献
With the global pandemic of hepatitis B and C infections, the incidence of Hepatocellular carcinoma (HCC) is rapidly increasing world wide. We identified glypican-3 (GPC3), a novel oncofetal gene over-expressed specifically in human HCC, as based on data of cDNA microarrays. As GPC3 is a GPI-anchored membrane protein and could be secreted, we attempted to detect secreted GPC3 protein in sera from HCC patients using Western blotting and ELISA. GPC3 protein was positive in sera of 40.0% (16/40) of HCC patients, and negative in sera from subjects with liver cirrhosis (LC) (0/13), chronic hepatitis (CH) (0/34), and healthy donors (0/60). All subjects were Japanese. Although 12 of 40 HCC patients were negative for both alpha-fetoprotein (AFP) and PIVKA-II well known tumor markers of HCC, four of these were GPC3-positive in the sera. We also observed vanishing GPC3 protein in the sera of three patients after the surgical treatment for HCC. On the other hand, immunohistochemical analysis revealed that HCC expressed GPC3 protein in all 14 HCC patients tested. In conclusion, GPC3, as defined in this study was shown to be a useful tumor marker for cancer-diagnosis for large numbers of patients with HCC.  相似文献
新一代分子标记--SNPs及其应用   总被引:29,自引:0,他引:29       下载免费PDF全文
邹喻苹  葛颂 《生物多样性》2003,11(5):370-382
单核苷酸多态性(SNPs)是广泛存在于基因组中的一类DNA序列变异,其频率为1%或更高。它是由单个碱基的转换或颠换引起的点突变,稳定而可靠,并通常以二等位基因的形式出现。采用生物芯片和DNA微阵列技术来检测SNP,便于对基因组进行大幅度和高通量分析。因此,作为新一代分子标记,SNP在生物学诸多领域具有广阔应用前景。本文简要叙述SNPs技术的发展历史、研究动态以及相关的理论,介绍了与SNPs相关的基本术语、概念及其特点,列举了发现与检测SNPs主要技术的原理和方法,同时还根据一些具体实例介绍了SNPs在模式动、植物遗传图谱构建、品种鉴定、物种起源与亲缘关系、连锁不平衡与关联分析及其在群体遗传结构及其变化机制研究中的应用。最后展望了SNPs在群体遗传、分子育种和生物进化等研究领域中的应用前景。  相似文献
Proteome analysis of hepatocellular carcinoma   总被引:26,自引:0,他引:26  
Development of hepatocellular carcinoma (HCC) is a complex process involving multiple changes in gene expression and usually occurs in the presence of liver cirrhosis. In this research, we observed proteome alterations of three tissue types isolated from livers of HCC patients: normal, cirrhotic, and tumorous tissue. Proteome alterations were observed using two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Comparing the tissue types with each other, a significant change in expression level was found in 21 proteins. Of these proteins, sarcosine dehydrogenase, liver carboxylesterase, peptidyl-prolyl isomerase A, and lamin B1 are considered novel HCC marker candidates. In particular, lamin B1 may be considered as a marker for cirrhosis, because its expression level changes considerably in cirrhotic tissue compared with normal tissue. The proteins revealed in this experiment can be used in the future for studies pertaining to hepatocarcinogenesis, or as diagnostic markers and therapeutic targets for HCC.  相似文献
A rice semidwarfing gene, sd-1, known as the "green revolution gene," was isolated by positional cloning and revealed to encode gibberellin 20-oxidase, the key enzyme in the gibberellin biosynthesis pathway. Analysis of 3477 segregants using several PCR-based marker technologies, including cleaved amplified polymorphic sequence, derived-CAPS, and single nucleotide polymorphisms revealed 1 ORF in a 6-kb candidate interval. Normal-type rice cultivars have an identical sequence in this region, consisting of 3 exons (558, 318, and 291 bp) and 2 introns (105 and 1471 bp). Dee-Geo-Woo-Gen-type sd-1 mutants have a 383-bp deletion from the genome (278-bp deletion from the expressed sequence), from the middle of exon 1 to upstream of exon 2, including a 105-bp intron, resulting in a frame-shift that produces a termination codon after the deletion site. The radiation-induced sd-1 mutant Calrose 76 has a 1-bp substitution in exon 2, causing an amino acid substitution (Leu [CTC] to Phe [TTC]). Expression analysis suggests the existence of at least one more locus of gibberellin 20-oxidase which may prevent severe dwarfism from developing in sd-1 mutants.  相似文献
基于生物信息学的SNP候选位点搜寻方法   总被引:22,自引:3,他引:19  
陈炜  张戈  张思仲 《遗传》2001,23(2):153-156
单核苷酸多态性(Single Nucleotide Polymorphism,SNP)是人类基因组中最常见的遗传多态,在遗传学研究的很多方面具有重要的作用。它的搜寻正受到广泛关注。近年来,国际上出现了一种基于生物信息学的发掘SNP新方法,本对方法的两种策略及其各自所存在的问题作一介绍。  相似文献
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