共查询到18条相似文献,搜索用时 156 毫秒
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精神发育迟滞(旧称智力低下)作为儿科神经科常见的一组疾患,具有高度的遗传和表型异质性,大约25%~50%的精神发育迟滞是由遗传因素引起的,其中X染色体基因/基因组变异占25%~30%,导致X连锁的精神发育迟滞。X连锁的精神发育迟滞患者占所有精神发育迟滞患者的10%~15%以上,约20%~25%的男性精神发育迟滞归因于X连锁的精神发育迟滞。精神发育迟滞男女患病比例为1.3:1,这与男性只有一条X染色体的遗传背景有关。随着新一代基因组检测技术的快速发展和临床应用,尤其是全外显子测序、高深度测序、X染色体深度测序和全基因组芯片杂交,这些大大改善了精神发育迟滞患者的X染色体基因/基因组变异检出。本文综述了致精神发育迟滞的X染色体基因组/基因变异特点、其对男性精神发育迟滞的致病性,以及如何采用新测序技术提高检出率,旨在促进科研人员认识X染色体变异在男性精神发育迟滞的致病性,拓宽精神发育迟滞遗传病因的认识,同时也为遗传咨询和产前诊断提供理论依据。 相似文献
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小麦条锈菌国际鉴别寄主Vilmorin23的抗条锈病基因YrV23微卫星标记 总被引:7,自引:0,他引:7
Vilmorin23是小麦条锈菌国际鉴别寄主和国际上重要抗源材料。采用SSR技术,利用由Vilmorin23为基因供体转育而成的小麦抗条锈近等基因系Taichung29*6/YrV23,选用YrV23所在2B染色体上的55对SSR引物,对Taichung29*6/ YrV23及其轮回亲本Taichung29和抗性基因供体Vilmorin23的基因组DNA进行PCR扩增和聚丙烯酰胺凝胶电泳分析。结果显示,引物Xwmc356在近等基因系与轮回亲本间扩增出特异性DNA片段,经F2代群体150个抗、感单株检测证实,该片段位点与抗条锈病基因YrV23有连锁关系,遗传距离为9.4 cM。Xwmc356可作为抗条锈基因YrV23的SSR标记。
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OPHN1基因编码RhoGTP酶激活蛋白(RhoGAP), 是X连锁的与非特异性精神发育迟滞有关的基因之一。采用PCR-RFLP方法, 对234名陕西秦巴山区正常的汉族儿童以及精神发育迟滞(Mental retardation, MR)患者的OPHN1基因5′非翻译区中的单核苷酸多态位点(Single nucleotide polymorphism, SNP) rs492933的等位基因频率和基因型频率以及是否与非特异精神发育迟滞相关进行分析。结果发现: 这一位点基因频率C为0.826, T为0.174; MR组与对照组之间基因型频率和基因频率没有显著性差异, 边缘组与对照组之间基因型频率和基因频率也没有显著性差异。证明OPHN1基因内SNP rs492933的多态性与秦巴山区汉族儿童精神发育迟滞不存在相关性。 相似文献
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The Mre11-Rad50-Xrs2 complex in Saccharomyces cerevisiae has roles in the intra-S checkpoint, homologous recombination, non-homologous end joining, meiotic recombination, telomere maintenance and the suppression of gross chromosomal rearrangements (GCRs). The discovery of mutations in the genes encoding the human homologues of two MRX subunits that underlie the chromosome fragility syndromes, Ataxia telangiectasia-like disorder and Nijmegen breakage syndrome suggest that the MRX complex also functions in suppression of GCRs in human cells. Previously, we demonstrated that the deletion mutations in each of the MRX genes increased the rate of GCRs up to 1000-fold compared to wild-type rates. However, it has not been clear which molecular function of the MRX complex is important for suppression of GCRs. Here, we present evidence that at least three different activities of the MRX complex are important for suppression of GCRs. These include the nuclease activity of Mre11, an activity related to MRX complex formation and another activity that has a close link with the telomere maintenance function of the MRX complex. An activity related to MRX complex formation is especially important for the suppression of translocation type of GCRs. However, the non-homologous end joining function of MRX complex does not appear to participate in the suppression of GCRs. 相似文献
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X-linked mental retardation (XLMR) affects 1.8 per thousand male births and is usually categorized as "syndromic" (MRXS) or "non-specific" (MRX) forms according to the presence or absence of specific signs in addition to the MR. Up to 60 genes have been implicated in XLMR and certain mutations can alternatively lead to MRXS or MRX. Indeed the extreme phenotypic and allelic heterogeneity of XLMR makes the classification of most genes difficult. Therefore, following identification of new genes, accurate retrospective clinical evaluation of patients and their families is necessary to aid the molecular diagnosis and the classification of this heterogeneous group of disorders. Analyses of the protein products corresponding to XLMR genes show a great diversity of cellular pathways involved in MR. Common mechanisms are beginning to emerge : a first group of proteins belongs to the Rho and Rab GTPase signaling pathways involved in neuronal differentiation and synaptic plasticity and a second group is related to the regulation of gene expression. In this review, we illustrate the complexity of XLMR conditions and present recent data about the FMR1, ARX and Oligophrenin 1 genes. 相似文献
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Mutations in the ZNF41 gene are associated with cognitive deficits: identification of a new candidate for X-linked mental retardation
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Shoichet SA Hoffmann K Menzel C Trautmann U Moser B Hoeltzenbein M Echenne B Partington M Van Bokhoven H Moraine C Fryns JP Chelly J Rott HD Ropers HH Kalscheuer VM 《American journal of human genetics》2003,73(6):1341-1354
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A novel ribosomal S6-kinase (RSK4; RPS6KA6) is commonly deleted in patients with complex X-linked mental retardation 总被引:8,自引:0,他引:8
Yntema HG van den Helm B Kissing J van Duijnhoven G Poppelaars F Chelly J Moraine C Fryns JP Hamel BC Heilbronner H Pander HJ Brunner HG Ropers HH Cremers FP van Bokhoven H 《Genomics》1999,62(3):332-343
Large deletions in Xq21 often are associated with contiguous gene syndromes consisting of X-linked deafness type 3 (DFN3), mental retardation (MRX), and choroideremia (CHM). The identification of deletions associated with classic CHM or DFN3 facilitated the positional cloning of the underlying genes, REP-1 and POU3F4, respectively, and enabled the positioning of the MRX gene in between these genes. Here, we report the cloning and characterization of a novel gene, ribosomal S6-kinase 4 (RSK4; HGMW-approved symbol RPS6KA6), which maps in the MRX critical region. RSK4 is completely deleted in eight patients with the contiguous gene syndrome including MRX, partially deleted in a patient with DFN3 and present in patients with an Xq21 deletion and normal intellectual abilities. RSK4 is most abundantly expressed in brain and kidney. The predicted protein of 746 amino acids shows a high level of homology to three previously isolated members of the human RSK family. RSK2 is involved in Coffin-Lowry syndrome and nonspecific MRX. The localization of RSK4 in the interval that is commonly deleted in mentally retarded males together with the high degree of amino acid identity with RSK2 suggests that RSK4 plays a role in normal neuronal development. Further mutation analyses in males with X-linked mental retardation must prove that RSK4 is indeed a novel MRX gene. 相似文献
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The Saccharomyces cerevisiae Mre11p/Rad50p/Xrs2p (MRX) complex is evolutionarily conserved and functions in DNA repair and at telomeres [1-3]. In vivo, MRX is required for a 5' --> 3' exonuclease activity that mediates DNA recombination at double-strand breaks (DSBs). Paradoxically, abolition of this exonuclease activity in MRX mutants results in shortened telomeric DNA tracts. To further explore the role of MRX at telomeres, we analyzed MRX mutants in a de novo telomere addition assay in yeast cells [4]. We found that the MRX genes were absolutely required for telomerase-mediated addition in this assay. Furthermore, we found that Cdc13p, a single-stranded telomeric DNA binding protein essential for telomere DNA synthesis and protection [5], was unable to bind to the de novo telomeric DNA substrate in cells lacking Rad50p. Based on the results from this model system, we propose that the MRX complex helps to prepare telomeric DNA for the loading of Cdc13p, which then protects the chromosome from further degradation and recruits telomerase and other DNA replication components to synthesize telomeric DNA. 相似文献
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Helger G. Yntema Bellinda van den Helm Johan Kissing Gerard van Duijnhoven Francis Poppelaars Jamel Chelly Claude Moraine Jean-Pierre Fryns Ben C. J. Hamel Helmut Heilbronner Hans-Jürgen Pander Han G. Brunner Hans-Hilger Ropers Frans P. M. Cremers Hans van Bokhoven 《Genomics》1999,62(3):332
Large deletions in Xq21 often are associated with contiguous gene syndromes consisting of X-linked deafness type 3 (DFN3), mental retardation (MRX), and choroideremia (CHM). The identification of deletions associated with classic CHM or DFN3 facilitated the positional cloning of the underlying genes, REP-1 and POU3F4, respectively, and enabled the positioning of the MRX gene in between these genes. Here, we report the cloning and characterization of a novel gene, ribosomal S6-kinase 4 (RSK4; HGMW-approved symbol RPS6KA6), which maps in the MRX critical region. RSK4 is completely deleted in eight patients with the contiguous gene syndrome including MRX, partially deleted in a patient with DFN3 and present in patients with an Xq21 deletion and normal intellectual abilities. RSK4 is most abundantly expressed in brain and kidney. The predicted protein of 746 amino acids shows a high level of homology to three previously isolated members of the human RSK family. RSK2 is involved in Coffin–Lowry syndrome and nonspecific MRX. The localization of RSK4 in the interval that is commonly deleted in mentally retarded males together with the high degree of amino acid identity with RSK2 suggests that RSK4 plays a role in normal neuronal development. Further mutation analyses in males with X-linked mental retardation must prove that RSK4 is indeed a novel MRX gene. 相似文献
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Submicroscopic duplications of the hydroxysteroid dehydrogenase HSD17B10 and the E3 ubiquitin ligase HUWE1 are associated with mental retardation
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Froyen G Corbett M Vandewalle J Jarvela I Lawrence O Meldrum C Bauters M Govaerts K Vandeleur L Van Esch H Chelly J Sanlaville D van Bokhoven H Ropers HH Laumonnier F Ranieri E Schwartz CE Abidi F Tarpey PS Futreal PA Whibley A Raymond FL Stratton MR Fryns JP Scott R Peippo M Sipponen M Partington M Mowat D Field M Hackett A Marynen P Turner G Gécz J 《American journal of human genetics》2008,82(2):432-443
Submicroscopic copy-number imbalances contribute significantly to the genetic etiology of human disease. Here, we report a novel microduplication hot spot at Xp11.22 identified in six unrelated families with predominantly nonsyndromic XLMR. All duplications segregate with the disease, including the large families MRX17 and MRX31. The minimal, commonly duplicated region contains three genes: RIBC1, HSD17B10, and HUWE1. RIBC1 could be excluded on the basis of its absence of expression in the brain and because it escapes X inactivation in females. For the other genes, expression array and quantitative PCR analysis in patient cell lines compared to controls showed a significant upregulation of HSD17B10 and HUWE1 as well as several important genes in their molecular pathways. Loss-of-function mutations of HSD17B10 have previously been associated with progressive neurological disease and XLMR. The E3 ubiquitin ligase HUWE1 has been implicated in TP53-associated regulation of the neuronal cell cycle. Here, we also report segregating sequence changes of highly conserved residues in HUWE1 in three XLMR families; these changes are possibly associated with the phenotype. Our findings demonstrate that an increased gene dosage of HSD17B10, HUWE1, or both contribute to the etiology of XLMR and suggest that point mutations in HUWE1 are associated with this disease too. 相似文献
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Lindsay G. Ball Michelle D. Hanna Amanda D. Lambrecht Bryan A. Mitchell Barry Ziola Jennifer A. Cobb Wei Xiao 《PloS one》2014,9(10)
Yeast DNA postreplication repair (PRR) bypasses replication-blocking lesions to prevent damage-induced cell death. PRR employs two different mechanisms to bypass damaged DNA, namely translesion synthesis (TLS) and error-free PRR, which are regulated via sequential ubiquitination of proliferating cell nuclear antigen (PCNA). We previously demonstrated that error-free PRR utilizes homologous recombination to facilitate template switching. To our surprise, genes encoding the Mre11-Rad50-Xrs2 (MRX) complex, which are also required for homologous recombination, are epistatic to TLS mutations. Further genetic analyses indicated that two other nucleases involved in double-strand end resection, Sae2 and Exo1, are also variably required for efficient lesion bypass. The involvement of the above genes in TLS and/or error-free PRR could be distinguished by the mutagenesis assay and their differential effects on PCNA ubiquitination. Consistent with the observation that the MRX complex is required for both branches of PRR, the MRX complex was found to physically interact with Rad18 in vivo. In light of the distinct and overlapping activities of the above nucleases in the resection of double-strand breaks, we propose that the interplay between distinct single-strand nucleases dictate the preference between TLS and error-free PRR for lesion bypass. 相似文献