排序方式: 共有46条查询结果,搜索用时 15 毫秒
1.
M E MacDonald A Novelletto C Lin D Tagle G Barnes G Bates S Taylor B Allitto M Altherr R Myers 《Nature genetics》1992,1(2):99-103
Analysis of 78 Huntington's disease (HD) chromosomes with multi-allele markers revealed 26 different haplotypes, suggesting a variety of independent HD mutations. The most frequent haplotype, accounting for about one third of disease chromosomes, suggests that the disease gene is between D4S182 and D4S180. However, the paucity of an expected class of chromosomes that can be related to this major haplotype by assuming single crossovers may reflect the operation of other mechanisms in creating haplotype diversity. Some of these mechanisms sustain alternative scenarios that do not require a multiple mutational origin for HD and/or its positioning between D4S182 and D4S180. 相似文献
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Chiang C Jacobsen JC Ernst C Hanscom C Heilbut A Blumenthal I Mills RE Kirby A Lindgren AM Rudiger SR McLaughlan CJ Bawden CS Reid SJ Faull RL Snell RG Hall IM Shen Y Ohsumi TK Borowsky ML Daly MJ Lee C Morton CC MacDonald ME Gusella JF Talkowski ME 《Nature genetics》2012,44(4):390-7, S1
We defined the genetic landscape of balanced chromosomal rearrangements at nucleotide resolution by sequencing 141 breakpoints from cytogenetically interpreted translocations and inversions. We confirm that the recently described phenomenon of 'chromothripsis' (massive chromosomal shattering and reorganization) is not unique to cancer cells but also occurs in the germline, where it can resolve to a relatively balanced state with frequent inversions. We detected a high incidence of complex rearrangements (19.2%) and substantially less reliance on microhomology (31%) than previously observed in benign copy-number variants (CNVs). We compared these results to experimentally generated DNA breakage-repair by sequencing seven transgenic animals, revealing extensive rearrangement of the transgene and host genome with similar complexity to human germline alterations. Inversion was the most common rearrangement, suggesting that a combined mechanism involving template switching and non-homologous repair mediates the formation of balanced complex rearrangements that are viable, stably replicated and transmitted unaltered to subsequent generations. 相似文献
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The mature T-cell antigen receptor repertoire is characterized by lack of reactivity to self-components as well as by preferential reactivity to foreign antigens in the context of polymorphic self-proteins encoded within the major histocompatibility complex. Whereas the former characteristic (referred to as negative selection or tolerance) is associated with intrathymic deletion of T cells expressing T-cell antigen receptor beta-chain variable (V beta) domains, which confer a preferential reactivity to self antigens, the existence of the latter (referred to as positive selection or MHC restriction) has so far only been inferred indirectly from functional studies. We show here that intrathymic deletion of V+beta 6 T cells (reactive with a self-antigen encoded by the Mlsa locus) is controlled by polymorphic MHC class II determinants. Furthermore, in mice lacking expression of Mlsa, the same class II MHC loci control the frequency of occurrence of V+beta 6 cells among mature CD4+ T lymphocytes. These data are direct evidence for positive selection by MHC determinants in the thymus in unmanipulated animals. 相似文献
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A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy 总被引:20,自引:0,他引:20
Zhang K Kniazeva M Han M Li W Yu Z Yang Z Li Y Metzker ML Allikmets R Zack DJ Kakuk LE Lagali PS Wong PW MacDonald IM Sieving PA Figueroa DJ Austin CP Gould RJ Ayyagari R Petrukhin K 《Nature genetics》2001,27(1):89-93
Stargardt-like macular dystrophy (STGD3, MIM 600110) and autosomal dominant macular dystrophy (adMD) are inherited forms of macular degeneration characterized by decreased visual acuity, macular atrophy and extensive fundus flecks. Genetic mapping data suggest that mutations in a single gene may be responsible for both conditions, already known to bear clinical resemblance. Here we limit the minimum genetic region for STGD3 and adMD to a 0.6-cM interval by recombination breakpoint mapping and identify a single 5-bp deletion within the protein-coding region of a new retinal photoreceptor-specific gene, ELOVL4, in all affected members of STGD3 and adMD families. Bioinformatic analysis of ELOVL4 revealed that it has homology to a group of yeast proteins that function in the biosynthesis of very long chain fatty acids. Our results are therefore the first to implicate the biosynthesis of fatty acids in the pathogenesis of inherited macular degeneration. 相似文献
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Wu X Northcott PA Dubuc A Dupuy AJ Shih DJ Witt H Croul S Bouffet E Fults DW Eberhart CG Garzia L Van Meter T Zagzag D Jabado N Schwartzentruber J Majewski J Scheetz TE Pfister SM Korshunov A Li XN Scherer SW Cho YJ Akagi K MacDonald TJ Koster J McCabe MG Sarver AL Collins VP Weiss WA Largaespada DA Collier LS Taylor MD 《Nature》2012,482(7386):529-533
Medulloblastoma, the most common malignant paediatric brain tumour, arises in the cerebellum and disseminates through the cerebrospinal fluid in the leptomeningeal space to coat the brain and spinal cord. Dissemination, a marker of poor prognosis, is found in up to 40% of children at diagnosis and in most children at the time of recurrence. Affected children therefore are treated with radiation to the entire developing brain and spinal cord, followed by high-dose chemotherapy, with the ensuing deleterious effects on the developing nervous system. The mechanisms of dissemination through the cerebrospinal fluid are poorly studied, and medulloblastoma metastases have been assumed to be biologically similar to the primary tumour. Here we show that in both mouse and human medulloblastoma, the metastases from an individual are extremely similar to each other but are divergent from the matched primary tumour. Clonal genetic events in the metastases can be demonstrated in a restricted subclone of the primary tumour, suggesting that only rare cells within the primary tumour have the ability to metastasize. Failure to account for the bicompartmental nature of metastatic medulloblastoma could be a major barrier to the development of effective targeted therapies. 相似文献
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J. Weatherston J. E. Percy L. M. MacDonald 《Cellular and molecular life sciences : CMLS》1976,32(2):178-179
Summary Field studies have shown thatcis-11-tetradecenal is an effective attractant for maleChoristoneura conflictana, a pest of aspen. These studies also indicate thatcis-11-tetradecenal is probably a secondary component in the sex pheromone systems ofChoristoneura rosaceana andChoristoneura fumiferana.Christoneura conflictana (Wlk.),C. rosaceana (Harris) andC. fumiferana (Clemens) (Lepidoptera: Tortricidae: Tortricinae).Contribution No. IPRI 296. 相似文献
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Field studies have shown that cis-11-tetradecenal is an effective attractant for male Choristoneura conflictana, a pest of aspen. These studies also indicate that cis-11-tetradecenal is probably a secondary component in the sex pheromone systems of Choristoneura rosaceana and Choristoneura fumiferana. 相似文献
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G E MacDonald 《Nature》1968,217(5134):1158-1159
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