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1.
两个常染色体显性遗传寻常性鱼鳞病家系致病基因的定位 总被引:1,自引:0,他引:1
为了对寻常性鱼鳞病的致病基因进行定位, 收集了2个湖南寻常性鱼鳞病家系, 采集外周血, 提取基因组DNA, 采用1号染色体和10号染色体上2个已知寻常性鱼鳞病位点的微卫星标记对这两个家系进行基因分型和连锁分析。结果显示, 寻常性鱼鳞病家系1的致病基因位于D1S498(1q21)附近, 与已知定位区间重叠; 寻常性鱼鳞病家系2的致病基因位点与已知的寻常性鱼鳞病位点不连锁, 可能存在新的致病基因位点。 相似文献
2.
几个水稻品种抽穗期主效基因与微效基因的定位研究 总被引:18,自引:1,他引:17
在构建2张RFLP图谱的基础上,定位分析了控制水稻抽穗期的主效基因和微效基因。在特三矮2号/C.B.群体中定位到2个主效基因和2个微效基因。该2个主基因分别位于第3、8染色体上,累加贡献率约达50%,加性效应值分别为7天和6天,而分别位于第1、12染色体的2个微效基因的贡献率仅分别为8.3%和9.6%,加性效应值仅为3天和4天。在外引2号/C.B.群体中定位了2个连锁于第6染色体的主效基因和1个位于第8染色体的微效基因,该2个主效基因的贡献率分别为35.5%和27.4%,来自外引2号的该2个基因其效应均为明显推迟抽穗,因而可推测它们为感光性基因,微效基因的贡献率仅为8.9%,基因效应值较小。 相似文献
3.
用基因芯片技术研究高(H)、低(L)转移卵巢癌细胞株(HO-8910PM和HO-8910)和正常卵巢上皮(C)基因表达谱差异,筛选与卵巢癌转移相关的基因,并利用生物信息学方法对检测结果进行差异基因在染色体定位和功能分析。结果:高、低转移卵巢癌细胞株比较表达差异2倍以上共有409个基因,其中表达上调(信号比的对数值[SLR]≥1)有271个,表达下调(SLR≤-1)有138个。从表达差异的基因在染色体定位分析,发现除1个基因未知其定位外,其余所有差异表达基因散在分布于各条染色体上,但以1号染色体最多有43个(占10.7%)。其次是6号染色体有39个(占9.6%),第三是2号染色体有29个(占7.1%)。第四是17号染色体有28个(占6.9%)。第五是3号染色体有25个(占6.2%)。第6是5号和11号染色体各有24个(各占5.9%)。而差异表达的基因发生在染色体短臂(q)的有264个(占64.7%),在13,14,15,21和22号仅发现在q都有异常表达。从表达差异基因的分子功能分类看,属于酶和酶调控子基因为最多(104个,占25.4%),其次是信号传导基因(43个,占10.5%)。第3类是核酸结合基因(42个,占10.3%)。第4类是蛋白结合基因(34个,占8.3%)。以上4大类共占基因总数54.5%。还有功能未知的基因有76个,占18.6%。高、低转移卵巢癌细胞株差异表达基因散在分布在各条染色体上,但以1、6、2、17、3、5和11号染色体差异表达基因居多。肿瘤的转移是多基因共同作用的结果。4大类(酶和酶调控子、信号传导、核酸结合和蛋白结合)相关基因异常是我们今后研究卵巢癌转移的重要基因。 相似文献
4.
5.
外源性人TIMP-1基因在转基因小鼠染色体上的整合及定位 总被引:1,自引:0,他引:1
为探讨外源基因人基质金属蛋白酶组织抑制物-1(human tissue inhibitor of metalloproteinase-1, hTIMP-1)基因在转基因小鼠家系染色体上的整合和精确定位,应用Southrn印迹检测外源基因在染色体上整合的位点及拷贝数.结果表明,外源基因是以单拷贝、单位点形式整合;应用荧光原位杂交(fluorescence in situ hybridization, FISH)技术检测F4~F20代转基因小鼠中外源基因的整合.结果证明,该家系转基因小鼠自F4代起是纯合子,外源基因整合在17号染色体E区;反向PCR法(Inverse PCR, IPCR)克隆出约3.8 kb外源基因整合位点处的侧翼序列.分析表明,外源基因整合在17号染色体E1.3区,ALK(anaplastic lymphoma kinase, ALK)基因第23个内含子区域.结果提示,获得的转基因小鼠为纯系,外源基因hTIMP-1已稳定整合在转基因小鼠染色体上,并能遗传给后代. 相似文献
6.
利用标准化的Affymetrix公司生产的U133A基因芯片检测胃癌(T)与切缘正常胃黏膜(C)基因表达谱差异,并利用生物信息学方法对检测结果进行差异基因在染色体定位和功能分析。结果表明:胃癌与正常胃黏膜比较差异8倍以上共有270个基因,其中表达上调[信号比的对数值(SLR)≥3]有157个,表达下调(SLR≤-3)有113个。从表达差异的基因在染色体定位分析,发现除4个基因未知其定位外,其余所有差异表达基因散在分布和各条染色体上,但以1号染色体为最多,有26个(占9.8%),其次是11和19号染色体上分别有24个(各占9.1%)。而差异表达的基因发生在染色体短臂(q)上有173个(占65%)。从表达差异的基因功能分类看,属于酶和酶调控子基因最多(67个,24.8占%),其次是信号传导基因(43个,占15.9%),第3类是核酸结合基因(17个,占6.3%),第4类是转运子基因(15个,占5.5%),第5类是蛋白结合基因(12个,占4.4%),还有功能未知的基因有50个,占18.5%。以上5大类共占基因总数56.9%。胃癌差异表达基因散在分布在各条染色体上,但以1、11、19号染色体差异表达基因居多。这5大类(酶和酶调控子、信号传导、核酸结合、转运子、蛋白结合)相关基因异常是今后研究胃癌的重要基因。 相似文献
7.
凉山半细毛羊1号染色体微卫星遗传连锁图谱的构建 总被引:1,自引:1,他引:0
实验选择绵羊1号条染色体上的9个微卫星标记,采用父系半同胞家系群体(共387个个体)构建凉山半细毛羊1号染色体遗传连锁图。建立的资源参考家系通过20个微卫星标记进行了系谱确证。试验结果表明,9个标记的等位基因数变化范围为5~15个,杂合度在0.202~0.831之间,平均杂合度为0.617,各标记的平均多态信息含量PIC=0.604。构建的凉山半细毛羊1号条染色体遗传连锁图总长度311.0 cM,与美国肉畜中心(USDA)和国际绵羊作图中心(IMF)构建的绵羊1号条染色遗传连锁图结果基本一致。可用于下一步的QTL定位研究。 相似文献
8.
常染色体显性遗传小眼球病与12个微卫星多态标志的初步连锁分析 总被引:1,自引:0,他引:1
本文报道了一个常染色体显性遗传小眼球的大家系,初步排除了此家系致病基因在目前已知位点(CHX10、MITF、RX、MCOP、NNO1、NNO2)的可能,并探讨了与11号染色体上的微卫星DNA标志的连锁关系。采用聚合酶链(PCR)扩增微卫星DNA片段,扩增产物进行聚丙烯酰胺凝胶电泳,用银染显示结果;用MLINK连锁分析软件计算LOD值。结果显示,本家系小眼球致病基因与6个已知位点及11号染色体上的微卫星DNA标志之间不存在连锁,提示此家系的致病位点目前尚未被定位。 相似文献
9.
应用荧光原位杂交检测EB病毒BNLF—1基因在转基因小鼠子代染色体上 … 总被引:2,自引:0,他引:2
应用荧光原位杂交技术研究了EB病毒潜伏膜蛋白基因(BNLF-1)在转基因小鼠子二代染色体上的整合及其定位。结果在两只子二代转基因小鼠中,分别观察80个和60个分裂相,出现杂交信号的核型分别为27和18个,检出率为33.8%和30%。转基因分别整合在14号染色体和10号染色体上。提示转基因BNLF-1已稳定整合到转基因小鼠的染色体上,并通过生殖细胞遗传给子代;推测转基因原代鼠的转基因整合可能是随机的 相似文献
10.
常染色体显性遗传小眼球病与12个微卫星多态标志的初步连锁分析 总被引:1,自引:0,他引:1
本文报道了一个常染色体显性遗传小眼球的大家系,初步排除了此家系致病基因在目前已知位点(CHXl0、MITF、RX、MCOP、NN01、NN02)的可能,并探讨了与11号染色体上的微卫星DNA标志的连锁关系。采用聚合酶链(PCR)扩增微卫星DNA片段,扩增产物进行聚丙烯酰胺凝胶电泳,用银染显示结果;用MLINK连锁分析软件计算LOD值。结果显示,本家系小眼球致病基因与6个已知位点及ll号染色体上的微卫星DNA标志之间不存在连锁,提示此家系的致病位点目前尚未被定位。 相似文献
11.
Multiple osteochondromas (MO; also referred to as hereditary multiple exostoses [HME] in the literature) is an autosomal dominant disorder characterized by benign, cartilage-capped bone tumors that grow from the metaphyses of long bones. Two genes are associated with this disease: EXT1 on 8q24.11-q24.13 and EXT2 on 11p12-p11. Mutations in EXT1 and EXT2 are found in 54-96% of patients with MO and are generally more frequent in EXT1 than in EXT2. We previously studied 43 Japanese families with MO using single-strand conformation polymorphism analysis for EXT1 and EXT2, and reported 23 families (54%) with mutations and 20 families (46%) with no mutations in these genes. Among the families with mutations, 17 families (40%) had mutations in EXT1, and 6 families (14%) had mutations in EXT2. Here we examined the same 43 Japanese families using denaturing high-performance liquid chromatography as an alternative technique. We detected five mutations, three of which are novel, in seven families in addition to the previously described mutations. In summary, we detected mutations in EXT1 or EXT2 in 30 (70%) out of 43 families. Our result suggests the presence of other gene(s) responsible for MO, at least in Japanese patients. 相似文献
12.
Hereditary multiple exostoses (EXT) is a genetically heterogeneous bone disorder caused by genes segregating on human chromosomes
8, 11, and 19 and designated EXT1, EXT2 and EXT3, respectively. Recently, the EXT1 gene has been isolated and partially characterized
and appears to encode a tumor suppressor gene. We have identified six mutations in the human EXT1 gene from six unrelated
multiple exostoses families segregating for the EXT gene on chromosome 8. One of the mutations we detected is the same 1-bp
deletion in exon 6 that was previously reported in two independent EXT families. The other five mutations, in exons 1, 6,
9, and the splice junction at the 3′ end of exon 2, are novel. In each case, the mutation is likely to result in a truncated
or nonfunctional EXT1 protein. These results corroborate and extend the previous report of mutations in this gene in two EXT
families, and provide additional support for the EXT1 gene as the cause of hereditary multiple exostoses in families showing
linkage to chromosome 8.
Received: 2 August 1996 / Revised: 18 November 1996 相似文献
13.
Refinement of the Multiple Exostoses Locus (EXT2) to a 3-cM Interval on Chromosome 11 总被引:5,自引:2,他引:3
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Wim Wuyts Sarvan Ramlakhan Wim Van Hul Jacqueline T. Hecht Ans M. W. van den Ouweland Wendy H. Raskind Floris C. Hofstede Edwin Reyniers Dan E. Wells Bert de Vries Ernest U. Conrad April Hill Dmitry Zalatayev Jean Weissenbach Michael J. Wagner Egbert Bakker Dicky J. J. Halley Patrick J. Willems 《American journal of human genetics》1995,57(2):382-387
Hereditary multiple exostoses (EXT) is an autosomal dominant skeletal disorder characterized by the formation of multiple exostoses on the long bones. EXT is genetically heterogeneous, with at least three loci involved: one (EXT1) in the Langer-Giedion region on 8q23-q24, a second (EXT2) in the pericentromeric region of chromosome 11, and a third (EXT3) on chromosome 19p. In this study, linkage analysis in seven extended EXT families, all linked to the EXT2 locus, refined the localization of the EXT2 gene to a 3-cM region flanked by D11S1355 and D11S1361/D11S554. This implies that the EXT2 gene is located at the short arm of chromosome 11, in band 11p11-p12. The refined localization of EXT2 excludes a number of putative candidate genes located in the pericentromeric region of chromosome 11 and facilitates the process of isolating the EXT2 gene. 相似文献
14.
An extension of the admixture test for the study of genetic heterogeneity in hereditary multiple exostoses 总被引:13,自引:0,他引:13
Laurence Legeai-Mallet Patricia Margaritte-Jeannin Mohamed Lemdani M. Le Merrer Henry Plauchu Pierre Maroteaux A. Munnich Françoise Clerget-Darpoux 《Human genetics》1997,99(3):298-302
Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by the presence of multiple cartilage-capped
exostoses in the juxta-epiphyseal regions of the long bones. EXT is heterogeneous with at least three different locations
currently having been identified on chromosomes 8, 11 and 19. We have tested a series of 29 EXT families for possible linkage
to the three disease loci and estimated the probability of linkage of the disease to each locus in our series, by using an
extension of the admixture test, which makes modelling of heterogeneous monogenic disease feasible. The maximum likelihood
was obtained for proportions of 44%, 28% and 28% of families being linked to chromosome 8, 11 and 19, respectively. The a
posteriori probability of linkage of the disease to EXT1, EXT2 and EXT3 was greater than 80% for 8/29, 5/29 and 3/29 families,
respectively, and did not give evidence of a fourth locus for the disease. The present approach can be generalized to the
investigation of genetic heterogeneity in other monogenic diseases, as it simultaneously estimates the location of each disease
gene and the proportion of families linked to each locus.
Received: 28 May 1996 / Revised: 7 October 1996 相似文献
15.
W Wuyts W Van Hul K De Boulle J Hendrickx E Bakker F Vanhoenacker F Mollica H J Lüdecke B S Sayli U E Pazzaglia G Mortier B Hamel E U Conrad M Matsushita W H Raskind P J Willems 《American journal of human genetics》1998,62(2):346-354
Hereditary multiple exostoses (EXT; MIM 133700) is an autosomal dominant bone disorder characterized by the presence of multiple benign cartilage-capped tumors (exostoses). Besides suffering complications caused by the pressure of these exostoses on the surrounding tissues, EXT patients are at an increased risk for malignant chondrosarcoma, which may develop from an exostosis. EXT is genetically heterogeneous, and three loci have been identified so far: EXT1, on chromosome 8q23-q24; EXT2, on 11p11-p12; and EXT3, on the short arm of chromosome 19. The EXT1 and EXT2 genes were cloned recently, and they were shown to be homologous. We have now analyzed the EXT1 and EXT2 genes, in 26 EXT families originating from nine countries, to identify the underlying disease-causing mutation. Of the 26 families, 10 families had an EXT1 mutation, and 10 had an EXT2 mutation. Twelve of these mutations have never been described before. In addition, we have reviewed all EXT1 and EXT2 mutations reported so far, to determine the nature, frequency, and distribution of mutations that cause EXT. From this analysis, we conclude that mutations in either the EXT1 or the EXT2 gene are responsible for the majority of EXT cases. Most of the mutations in EXT1 and EXT2 cause premature termination of the EXT proteins, whereas missense mutations are rare. The development is thus mainly due to loss of function of the EXT genes, consistent with the hypothesis that the EXT genes have a tumor- suppressor function. 相似文献
16.
Mutation screening of the EXT1 and EXT2 genes in patients with hereditary multiple exostoses. 总被引:4,自引:0,他引:4
C Philippe D E Porter M E Emerton D E Wells A H Simpson A P Monaco 《American journal of human genetics》1997,61(3):520-528
Hereditary multiple exostoses (HME), the most frequent of all skeletal dysplasias, is an autosomal dominant disorder characterized by the presence of multiple exostoses localized mainly at the end of long bones. HME is genetically heterogeneous, with at least three loci, on 8q24.1 (EXT1), 11p11-p13 (EXT2), and 19p (EXT3). Both the EXT1 and EXT2 genes have been cloned recently and define a new family of potential tumor suppressor genes. This is the first study in which mutation screening has been performed for both the EXT1 and EXT2 genes prior to any linkage analysis. We have screened 17 probands with the HME phenotype, for alterations in all translated exons and flanking intronic sequences, in the EXT1 and EXT2 genes, by conformation-sensitive gel electrophoresis. We found the disease-causing mutation in 12 families (70%), 7 (41%) of which have EXT1 mutations and 5 (29%) EXT2 mutations. Together with the previously described 1-bp deletion in exon 6, which is present in 2 of our families, we report five new mutations in EXT1. Two are missense mutations in exon 2 (G339D and R340C), and the other three alterations (a nonsense mutation, a frameshift, and a splicing mutation) are likely to result in truncated nonfunctional proteins. Four new mutations are described in EXT2. A missense mutation (D227N) was found in 2 different families; the other three alterations (two nonsense mutations and one frameshift mutation) lead directly or indirectly to premature stop codons. The missense mutations in EXT1 and EXT2 may pinpoint crucial domains in both proteins and therefore give clues for the understanding of the pathophysiology of this skeletal disorder. 相似文献
17.
April Cook Wendy Raskind Susan Halloran Blanton Richard M. Pauli Ronald G. Gregg Claire A. Francomano Eric Puffenberger Ernest U. Conrad Gregory Schmale Gerard Schellenberg Ellen Wijsman Jacqueline T. Hecht Dan Wells Michael J. Wagner 《American journal of human genetics》1993,53(1):71-79
We have carried out a linkage analysis on 11 families segregating gene(s) for hereditary multiple exostoses (EXT). Four highly informative, short tandem-repeat (STR) markers that have been physically mapped to an interval surrounding the Langer-Giedion chromosomal region (8q24.11-q24.13) were used in a multipoint linkage analysis. Significant evidence for linkage of EXT with genetic heterogeneity was found. A model of heterogeneity with linkage of the disease gene to the STR markers in 70% of the families (with a 95% confidence interval of 26%–96%) produced a maximum LOD score of 8.11, with the most likely position of EXT between D8S85 and D8S199. Thus there are at least two genes that are capable of causing hereditary multiple exostoses, one in the Langer-Giedion region and one at another, unlinked location. 相似文献
18.
Hereditary multiple exostoses (EXT): mutational studies of familial EXT1 cases and EXT-associated malignancies. 总被引:5,自引:1,他引:4
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J T Hecht D Hogue Y Wang S H Blanton M Wagner L C Strong W Raskind M F Hansen D Wells 《American journal of human genetics》1997,60(1):80-86
Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by the formation of cartilage-capped prominences that develop from the growth centers of the long bones. EXT is genetically heterogeneous, with three loci, currently identified on chromosomes 8q24.1, 11p13, and 19q. The EXT1 gene, located on chromosome 8q24.1, has been cloned and is encoded by a 3.4-kb cDNA. Five mutations in the EXT1 gene have been identified--four germ-line mutations, including two unrelated families with the same mutation, and one somatic mutation in a patient with chondrosarcoma. Four of the mutations identified resulted in frameshifts and premature termination codons, while the fifth mutation resulted in a substitution of leucine for arginine. Loss of heterozygosity (LOH) analysis of chondrosarcomas and chondroblastomas revealed multiple LOH events at loci on chromosomes 3q, 8q, 10q, and 19q. One sporadic chondrosarcoma demonstrated LOH for EXT1 and EXT3, while a second underwent LOH for EXT2 and chromosome 10. A third chondrosarcoma underwent LOH for EXT1 and chromosome 3q. These results agree with previous findings that mutations at EXT1 and multiple genetic events that include LOH at other loci may be required for the development of chondrosarcoma. 相似文献
19.
L. Xu J. Xia H. Jiang J. Zhou H. Li D. Wang Q. Pan Z. Long C. Fan H.-X. Deng 《Human genetics》1999,105(1-2):45-50
Hereditary multiple exostoses (EXT; MIM 133700) is an autosomal dominant bone disorder. It is genetically heterogeneous with
at least three chromosomal loci: EXT1 on 8q24.1, EXT2 on 11p11, and EXT3 on 19p. EXT1 and EXT2, the two genes responsible for EXT1 and EXT2, respectively, have been cloned. Recently, three other members of the EXT gene
family, named the EXT-like genes (EXTL: EXTL1, EXTL2, and EXTL3), have been isolated. EXT1, EXT2, and the three EXTLs are homologous with one another. We have identified the intron-exon boundaries of EXTL1 and EXTL3 and analyzed EXT1, EXT2, EXTL1, and EXTL3, in 36 Chinese families with EXT, to identify underlying disease-related mutations in the Chinese population. Of the 36 families,
five and 12 family groups have mutations in EXT1 and EXT2, respectively. No disease-related mutation has been found in either EXTL1 or EXTL2, although one polymorphism has been detected in EXTL1. Of the 15 different mutations (three families share a common mutation in EXT2), 12 are novel. Most of the mutations are either frameshift or nonsense mutations (12/15). These mutations lead directly
or indirectly to premature stop codons, and the mutations generate truncated proteins. This finding is consistent with the
hypothesis that the development of EXT is mainly attributable to loss of gene function. Missense mutations are rare in our
families, but these mutations may reflect some functionally crucial regions of these proteins. EXT1 is the most frequent single cause of EXT in the Caucasian population in Europe and North America. It accounts for about 40%
of cases of EXT. Our study of 36 EXT Chinese families has found that EXT1 seems much less common in the Chinese population, although the frequency of the EXT2 mutation is similar in the Caucasian and Chinese populations. Our findings suggest a possibly different genetic spectrum
of this disease in different populations.
Electronic Publication 相似文献
20.
Hereditary multiple exostosis and chondrosarcoma: linkage to chromosome II and loss of heterozygosity for EXT-linked markers on chromosomes II and 8. 总被引:5,自引:3,他引:2
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J T Hecht D Hogue L C Strong M F Hansen S H Blanton M Wagner 《American journal of human genetics》1995,56(5):1125-1131
Hereditary multiple exostosis (EXT) is an autosomal dominant disorder characterized by bony exostoses at the ends of the long bones. Linkage studies have recently suggested that there are three chromosomal locations for EXT genes, 8q24.1 (EXT1), the pericentric region of 11 (EXT2), and 19p (EXT3). As part of a larger study to determine the frequencies of the three EXT types in the United States, we have ascertained a large multigenerational family with EXT and one family member with a chondrosarcoma. This family demonstrated linkage of the disease to chromosome 11 markers. The constitutional and tumor DNAs from the affected family member were compared using short-tandem-repeat markers from chromosomes 8, 11, and 19. Loss of heterozygosity (LOH) in the tumor was observed for chromosome 8 and 11 markers, but chromosome 19 markers were intact. An apparent deletion of the marker D11S903 was observed in constitutional DNA from all affected individuals and in the tumor sample. These results indicate that the EXT2 gene maps to the region containing marker D11S903, which is flanked by markers D11S1355 and D11S1361. Additional constitutional and chondrosarcoma DNA pairs from six unrelated individuals, two of whom had EXT, were similarly analyzed. One tumor from an individual with EXT demonstrated LOH for chromosome 8 markers, and a person with a sporadic chondrosarcoma was found to have tumor-specific LOH and a homozygous deletion of chromosome 11 markers. These findings suggest that EXT genes may be tumor-suppressor genes and that the initiation of tumor development may follow a multistep model. 相似文献