排序方式: 共有80条查询结果,搜索用时 15 毫秒
61.
Iliana A. Chatzispyrou Sergio Guerrero-Castillo Ntsiki M. Held Jos P.N. Ruiter Simone W. Denis Lodewijk IJlst Ronald J. Wanders Michel van Weeghel Sacha Ferdinandusse Frédéric M. Vaz Ulrich Brandt Riekelt H. Houtkooper 《生物化学与生物物理学报:疾病的分子基础》2018,1864(11):3650-3658
Barth syndrome (BTHS) is a rare X-linked disorder that is characterized by cardiac and skeletal myopathy, neutropenia and growth abnormalities. The disease is caused by mutations in the tafazzin (TAZ) gene encoding an enzyme involved in the acyl chain remodeling of the mitochondrial phospholipid cardiolipin (CL). Biochemically, this leads to decreased levels of mature CL and accumulation of the intermediate monolysocardiolipin (MLCL). At a cellular level, this causes mitochondrial fragmentation and reduced stability of the respiratory chain supercomplexes. However, the exact mechanism through which tafazzin deficiency leads to disease development remains unclear. We therefore aimed to elucidate the pathways affected in BTHS cells by employing proteomic and metabolic profiling assays. Complexome profiling of patient skin fibroblasts revealed significant effects for about 200 different mitochondrial proteins. Prominently, we found a specific destabilization of higher order oxidative phosphorylation (OXPHOS) supercomplexes, as well as changes in complexes involved in cristae organization and CL trafficking. Moreover, the key metabolic complexes 2-oxoglutarate dehydrogenase (OGDH) and branched-chain ketoacid dehydrogenase (BCKD) were profoundly destabilized in BTHS patient samples. Surprisingly, metabolic flux distribution assays using stable isotope tracer-based metabolomics did not show reduced flux through the TCA cycle. Overall, insights from analyzing the impact of TAZ mutations on the mitochondrial complexome provided a better understanding of the resulting functional and structural consequences and thus the pathological mechanisms leading to Barth syndrome. 相似文献
62.
X-linked immunodeficiency with hyperimmunoglobulinemia M appears to be linked to the DXS42 restriction fragment length polymorphism locus 总被引:1,自引:1,他引:0
E. J. B. M. Mensink A. Thompson L. A. Sandkuyl M. E. M. Kraakman J. D. L. Schot T. Espanol R. K. B. Schuurman 《Human genetics》1987,76(1):96-99
Summary The gene involved in X-linked immunodeficiency with hyperimmunoglobulinemia M (XHM) was localized by the use of nine restriction fragment length polymorphic (RFLP) markers covering the entire X chromosome. Multipoint linkage analysis of RFLP data obtained in a three generation XHM pedigree indicates the Xq24-q27 area around the DXS42 RFLP locus as the most likely localization of the XHM locus. 相似文献
63.
Bart Janssen Julian Sampson Mieke van der Est Wout Deelen Senno Verhoef Ian Daniels Arjenne Hesseling Phillip Brook-Carter Mark Nellist Dick Lindhout Lodewijk Sandkuijl Dicky Halley 《Human genetics》1994,94(4):437-440
Tuberous sclerosis (TSC) is a heterogeneous trait. Since 1990, linkage studies have yielded putative TSC loci on chromosomes 9, 11, 12 and 16. Our current analysis, performed on 14 Dutch and British families, reveals only evidence for loci on chromosome 9q34 (TSC1) and chromosome 16p13 (TSC2). We have found no indication for a third locus for TSC, linked or unlinked to either of these chromosomal regions. The majority of our families shows linkage to chromosome 9. We have refined the candidate region for TSC1 to a region of approximately 5 cM between ABL and ABO. 相似文献
64.
A leucine-to-proline mutation in the insulin receptor in a family with insulin resistance. 总被引:5,自引:0,他引:5
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M P Klinkhamer N A Groen G C van der Zon D Lindhout L A Sandkuyl H M Krans W M?ller J A Maassen 《The EMBO journal》1989,8(9):2503-2507
We have determined the primary structure of a mutant insulin receptor of a leprechaun patient born from a consanguineous marriage. A characteristic feature of leprechaunism is an extreme resistance to insulin. In this patient the insulin resistance seems to result from an observed lack of insulin binding to intact cells. Solubilization of cells in non-ionic detergents leads to the appearance of insulin receptors which can bind insulin. However, the insulin-stimulated autophosphorylation of the receptor's beta subunit is markedly reduced. Cloning and sequencing of cDNA derived from insulin receptor mRNA of this patient revealed a leucine-to-proline mutation at position 233 in the alpha subunit. By means of DNA amplification we found that the patient is homozygous for this mutation and that the parents and two grandparents from the consanguineous line are heterozygous. The heterozygous individuals all show decreased insulin binding to cultured fibroblasts. In addition, they are mildly insulin resistant in vivo. These observations show a linkage between the leucine-to-proline mutation and the observed insulin resistance in this family. We therefore conclude that the mutation in the homozygous form is responsible for the extreme insulin resistance in the leprechaun patient. The mutation for the first time characterizes a region in the insulin receptor which seems to be involved in transmitting the insulin binding signal to the tyrosine kinase domain. 相似文献
65.
Yosef Shiloh Gilad Litvak Yael Ziv Thomas Lehner Lodewijk Sandkuyl Minka Hildesheimer Vered Buchris Frans P. M. Cremers Paul Szabo Bradley N. White Jeanette J. A. Holden Jurg Ott 《American journal of human genetics》1990,47(1):20-27
X-linked albinism-deafness syndrome (ADFN) was described in one Israeli Jewish family and is characterized by congenital nerve deafness and piebaldness. The ADFN mutation probably affects the migration of neural crest-derived precursors of the melanocytes. As a first step toward identifying the ADFN gene, a linkage study was performed to localize the disease locus on the X chromosome. The family was found to be informative for 11 of 107 RFLPs along the X, and two-point analysis showed four of them--factor 9 (F9), DXS91, DXS37, and DNF1--to have definite or suggestive linkage with ADFN. Multipoint linkage analysis indicated two possible orders within this cluster of loci, neither of which was preferable. In both orders F9 was the most distal, and the best estimate for the location of ADFN was between F9 and the next proximal marker (8.6 cM from F9 [Z = 8.1] or 8.3 cM from F9 [Z = 7.9]). These results suggest that the ADFN is at Xq26.3-q27.1. Disagreement between our data and previous localization of DXS91 at Xq11-q13 was resolved by hybridization of the probe pXG-17, which detects the DXS91 locus, to a panel of somatic cell hybrids containing different portions of the X chromosome. This experiment showed that this locus is definitely at Xq24-q26. Together with the linkage data, our results place DXS91 at Xq26 and underscore the importance of using more than one mapping method for the localization of molecular probes. 相似文献
66.
Joep P. M. Derikx Dick A. van Waardenburg Geertje Thuijls Henri?tte M. Willigers Marianne Koenraads Annemarie A. van Bijnen Erik Heineman Martijn Poeze Ton Ambergen André van Ooij Lodewijk W. van Rhijn Wim A. Buurman 《PloS one》2008,3(12)
Background
Gut barrier loss has been implicated as a critical event in the occurrence of postoperative complications. We aimed to study the development of gut barrier loss in patients undergoing major non-abdominal surgery.Methodology/Principal Findings
Twenty consecutive children undergoing spinal fusion surgery were included. This kind of surgery is characterized by long operation time, significant blood loss, prolonged systemic hypotension, without directly leading to compromise of the intestines by intestinal manipulation or use of extracorporeal circulation. Blood was collected preoperatively, every two hours during surgery and 2, 4, 15 and 24 hours postoperatively. Gut mucosal barrier was assessed by plasma markers for enterocyte damage (I-FABP, I-BABP) and urinary presence of tight junction protein claudin-3. Intestinal mucosal perfusion was measured by gastric tonometry (PrCO2, Pr-aCO2-gap). Plasma concentration of I-FABP, I-BABP and urinary expression of claudin-3 increased rapidly and significantly after the onset of surgery in most children. Postoperatively, all markers decreased promptly towards baseline values together with normalisation of MAP. Plasma levels of I-FABP, I-BABP were significantly negatively correlated with MAP at ½ hour before blood sampling (−0.726 (p<0.001), −0.483 (P<0.001), respectively). Furthermore, circulating I-FABP correlated with gastric mucosal PrCO2, Pr-aCO2-gap measured at the same time points (0.553 (p = 0.040), 0.585 (p = 0.028), respectively).Conclusions/Significance
This study shows the development of gut barrier loss in children undergoing major non-abdominal surgery, which is related to preceding hypotension and mesenterial hypoperfusion. These data shed new light on the potential role of peroperative circulatory perturbation and intestinal barrier loss. 相似文献67.
68.
Renault MA Jalvy S Potier M Belloc I Genot E Dekker LV Desgranges C Gadeau AP 《The Journal of biological chemistry》2005,280(4):2708-2713
69.
The current development of densely spaced collections of single nucleotide polymorphisms (SNPs) will lead to genomewide association studies for a wide range of diseases in many different populations. Determinations of the appropriate number of SNPs to genotype involve a balancing of power and cost. Several variables are important in these determinations. We show that there are different combinations of sample size and marker density that can be expected to achieve the same power. Within certain bounds, investigators can choose between designs with more subjects and fewer markers or those with more markers and fewer subjects. Which designs are more cost-effective depends on the cost of phenotyping versus the cost of genotyping. We show that, under the assumption of a set cost for genotyping, one can calculate a "threshold cost" for phenotyping; when phenotyping costs per subject are less than this threshold, designs with more subjects will be more cost-effective than designs with more markers. This framework for determining a cost-effective study will aid in the planning of studies, especially if there are choices to be made with respect to phenotyping methods or study populations. 相似文献
70.
Genomewide linkage disequilibrium mapping of severe bipolar disorder in a population isolate
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Ophoff RA Escamilla MA Service SK Spesny M Meshi DB Poon W Molina J Fournier E Gallegos A Mathews C Neylan T Batki SL Roche E Ramirez M Silva S De Mille MC Dong P Leon PE Reus VI Sandkuijl LA Freimer NB 《American journal of human genetics》2002,71(3):565-574
Genomewide association studies may offer the best promise for genetic mapping of complex traits. Such studies in outbred populations require very densely spaced single-nucleotide polymorphisms. In recently founded population isolates, however, extensive linkage disequilibrium (LD) may make these studies feasible with currently available sets of short tandem repeat markers, spaced at intervals as large as a few centimorgans. We report the results of a genomewide association study of severe bipolar disorder (BP-I), using patients from the isolated population of the central valley of Costa Rica. We observed LD with BP-I on several chromosomes; the most striking results were in proximal 8p, a region that has previously shown linkage to schizophrenia. This region could be important for severe psychiatric disorders, rather than for a specific phenotype. 相似文献