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981.
Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants 总被引:2,自引:0,他引:2
Wellcome Trust Case Control Consortium;Australo-Anglo-American Spondylitis Consortium 《Nature genetics》2007,39(11):1329-1337
We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases. 相似文献
982.
RNA polymerase is poised for activation across the genome 总被引:2,自引:0,他引:2
Muse GW Gilchrist DA Nechaev S Shah R Parker JS Grissom SF Zeitlinger J Adelman K 《Nature genetics》2007,39(12):1507-1511
983.
984.
985.
Houlden H Johnson J Gardner-Thorpe C Lashley T Hernandez D Worth P Singleton AB Hilton DA Holton J Revesz T Davis MB Giunti P Giunti P Wood NW 《Nature genetics》2007,39(12):1434-1436
The microtubule-associated protein tau (encoded by MAPT) and several tau kinases have been implicated in neurodegeneration, but only MAPT has a proven role in disease. We identified mutations in the gene encoding tau tubulin kinase 2 (TTBK2) as the cause of spinocerebellar ataxia type 11. Affected brain tissue showed substantial cerebellar degeneration and tau deposition. These data suggest that TTBK2 is important in the tau cascade and in spinocerebellar degeneration. 相似文献
986.
Saenz HL Engel P Stoeckli MC Lanz C Raddatz G Vayssier-Taussat M Birtles R Schuster SC Dehio C 《Nature genetics》2007,39(12):1469-1476
The bacterial genus Bartonella comprises 21 pathogens causing characteristic intraerythrocytic infections. Bartonella bacilliformis is a severe pathogen representing an ancestral lineage, whereas the other species are benign pathogens that evolved by radial speciation. Here, we have used comparative and functional genomics to infer pathogenicity genes specific to the radiating lineage, and we suggest that these genes may have facilitated adaptation to the host environment. We determined the complete genome sequence of Bartonella tribocorum by shotgun sequencing and functionally identified 97 pathogenicity genes by signature-tagged mutagenesis. Eighty-one pathogenicity genes belong to the core genome (1,097 genes) of the radiating lineage inferred from genome comparison of B. tribocorum, Bartonella henselae and Bartonella quintana. Sixty-six pathogenicity genes are present in B. bacilliformis, and one has been lost by deletion. The 14 pathogenicity genes specific for the radiating lineage encode two laterally acquired type IV secretion systems, suggesting that these systems have a role in host adaptability. 相似文献
987.
MacArthur DG Seto JT Raftery JM Quinlan KG Huttley GA Hook JW Lemckert FA Kee AJ Edwards MR Berman Y Hardeman EC Gunning PW Easteal S Yang N North KN 《Nature genetics》2007,39(10):1261-1265
More than a billion humans worldwide are predicted to be completely deficient in the fast skeletal muscle fiber protein alpha-actinin-3 owing to homozygosity for a premature stop codon polymorphism, R577X, in the ACTN3 gene. The R577X polymorphism is associated with elite athlete status and human muscle performance, suggesting that alpha-actinin-3 deficiency influences the function of fast muscle fibers. Here we show that loss of alpha-actinin-3 expression in a knockout mouse model results in a shift in muscle metabolism toward the more efficient aerobic pathway and an increase in intrinsic endurance performance. In addition, we demonstrate that the genomic region surrounding the 577X null allele shows low levels of genetic variation and recombination in individuals of European and East Asian descent, consistent with strong, recent positive selection. We propose that the 577X allele has been positively selected in some human populations owing to its effect on skeletal muscle metabolism. 相似文献
988.
Peutz-Jeghers syndrome (PJS, OMIM 175200) is an unusual inherited intestinal polyposis syndrome associated with distinct peri-oral
blue/black freckling [1–9]. Variable penetrance and clinical heterogeneity make it difficult to determine the exact frequency
of PJS [4]. PJS is a cancer predisposition syndrome. Affected individuals are at high risk for intestinal and extra-intestinal
cancers. In 1997, linkage studies mapped PJS to chromosome 19p [10, 11], and subsequently a serine/threonine kinase gene defect
(LKB1) was noted in a majority of PJS cases [12, 13]. A phenotypically similar syndrome has been produced in an LKB1 mouse
knockout model [14–18]. Several PJS kindred without LKB1 mutations have been described, suggesting other PJS loci [19–22].
The management of PJS is complex and evolving. New endoscopic technologies may improve management of intestinal polyposis.
Identification of specific genetic mutations and their targets will more accurately assess the clinical course, and help gage
the magnitude of cancer risk for affected individuals.
Received 20 February 2006; received after revision 5 May 2006; accepted 15 June 2006 相似文献
989.
Site- and state-specific lysine methylation of histones is catalyzed by a family of proteins that contain the evolutionarily
conserved SET domain and plays a fundamental role in epigenetic regulation of gene activation and silencing in all eukaryotes.
The recently determined three-dimensional structures of the SET domains from chromosomal proteins reveal that the core SET
domain structure contains a two-domain architecture, consisting of a conserved anti-parallel β-barrel and a structurally variable
insert that surround a unusual knot-like structure that comprises the enzyme active site. These structures of the SET domains,
either in the free state or when bound to cofactor S-adenosyl-L-homocysteine and/or histone peptide, mimicking an enzyme/cofactor/substrate complex, further yield the structural insights
into the molecular basis of the substrate specificity, methylation multiplicity and the catalytic mechanism of histone lysine
methylation.
Received 10 June 2006; accepted 22 August 2006 相似文献
990.
The macromolecular peptide-loading complex in MHC class I-dependent antigen presentation 总被引:5,自引:1,他引:4
A challenging task for the adaptive immune system of vertebrates is to identify and eliminate intracellular antigens. Therefore
a highly specialized antigen presentation machinery has evolved to display fragments of newly synthesized proteins to effector
cells of the immune system at the cell surface. After proteasomal degradation of unwanted proteins or defective ribosome products,
resulting peptides are translocated into the endoplasmic reticulum by the transporter associated with antigen processing and
loaded onto major histocompatibility complex (MHC) class I molecules. Peptide-MHC I complexes are transported via the secretory
pathway to the cell surface where they are then inspected by cytotoxic T lymphocytes, which can trigger an immune response.
This review summarizes the current view of the intracellular machinery of antigen processing and of viral immune escape mechanisms
to circumvent destruction by the host.
Received 4 October 2005; received after revision 19 November 2005; accepted 24 November 2005 相似文献