排序方式: 共有18条查询结果,搜索用时 15 毫秒
1.
Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans 总被引:2,自引:0,他引:2
Kathiresan S Melander O Guiducci C Surti A Burtt NP Rieder MJ Cooper GM Roos C Voight BF Havulinna AS Wahlstrand B Hedner T Corella D Tai ES Ordovas JM Berglund G Vartiainen E Jousilahti P Hedblad B Taskinen MR Newton-Cheh C Salomaa V Peltonen L Groop L Altshuler DM Orho-Melander M 《Nature genetics》2008,40(2):189-197
2.
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations 总被引:2,自引:0,他引:2
O'Roak BJ Vives L Girirajan S Karakoc E Krumm N Coe BP Levy R Ko A Lee C Smith JD Turner EH Stanaway IB Vernot B Malig M Baker C Reilly B Akey JM Borenstein E Rieder MJ Nickerson DA Bernier R Shendure J Eichler EE 《Nature》2012,485(7397):246-250
It is well established that autism spectrum disorders (ASD) have a strong genetic component; however, for at least 70% of cases, the underlying genetic cause is unknown. Under the hypothesis that de novo mutations underlie a substantial fraction of the risk for developing ASD in families with no previous history of ASD or related phenotypes--so-called sporadic or simplex families--we sequenced all coding regions of the genome (the exome) for parent-child trios exhibiting sporadic ASD, including 189 new trios and 20 that were previously reported. Additionally, we also sequenced the exomes of 50 unaffected siblings corresponding to these new (n = 31) and previously reported trios (n = 19), for a total of 677 individual exomes from 209 families. Here we show that de novo point mutations are overwhelmingly paternal in origin (4:1 bias) and positively correlated with paternal age, consistent with the modest increased risk for children of older fathers to develop ASD. Moreover, 39% (49 of 126) of the most severe or disruptive de novo mutations map to a highly interconnected β-catenin/chromatin remodelling protein network ranked significantly for autism candidate genes. In proband exomes, recurrent protein-altering mutations were observed in two genes: CHD8 and NTNG1. Mutation screening of six candidate genes in 1,703 ASD probands identified additional de novo, protein-altering mutations in GRIN2B, LAMC3 and SCN1A. Combined with copy number variant (CNV) data, these results indicate extreme locus heterogeneity but also provide a target for future discovery, diagnostics and therapeutics. 相似文献
3.
Reconstruction of gene association network reveals a transmembrane protein required for adipogenesis and targeted by PPARγ 总被引:1,自引:0,他引:1
Juliane G. Bogner-Strauss Andreas Prokesch Fatima Sanchez-Cabo Dietmar Rieder Hubert Hackl Kalina Duszka Anne Krogsdam Barbara Di Camillo Evelyn Walenta Ariane Klatzer Achim Lass Montserrat Pinent Wing-Cheong Wong Frank Eisenhaber Zlatko Trajanoski 《Cellular and molecular life sciences : CMLS》2010,67(23):4049-4064
4.
H. P. Rieder G. Ritzel H. Spiegelberg F. Gnirss 《Cellular and molecular life sciences : CMLS》1960,16(12):561-562
Summary In the serum of acute schizophrenic patients, Taraxein could not be detected by means of immuno-electrophoresis, tanned cell hemagglutination and the latex-particle agglutination test. 相似文献
5.
O'Roak BJ Deriziotis P Lee C Vives L Schwartz JJ Girirajan S Karakoc E Mackenzie AP Ng SB Baker C Rieder MJ Nickerson DA Bernier R Fisher SE Shendure J Eichler EE 《Nature genetics》2011,43(6):585-589
Evidence for the etiology of autism spectrum disorders (ASDs) has consistently pointed to a strong genetic component complicated by substantial locus heterogeneity. We sequenced the exomes of 20 individuals with sporadic ASD (cases) and their parents, reasoning that these families would be enriched for de novo mutations of major effect. We identified 21 de novo mutations, 11 of which were protein altering. Protein-altering mutations were significantly enriched for changes at highly conserved residues. We identified potentially causative de novo events in 4 out of 20 probands, particularly among more severely affected individuals, in FOXP1, GRIN2B, SCN1A and LAMC3. In the FOXP1 mutation carrier, we also observed a rare inherited CNTNAP2 missense variant, and we provide functional support for a multi-hit model for disease risk. Our results show that trio-based exome sequencing is a powerful approach for identifying new candidate genes for ASDs and suggest that de novo mutations may contribute substantially to the genetic etiology of ASDs. 相似文献
6.
Sequence variation in the human angiotensin converting enzyme. 总被引:32,自引:0,他引:32
Angiotensin converting enzyme (encoded by the gene DCP1, also known as ACE) catalyses the conversion of angiotensin I to the physiologically active peptide angiotensin II, which controls fluid-electrolyte balance and systemic blood pressure. Because of its key function in the renin-angiotensin system, many association studies have been performed with DCP1. Nearly all studies have associated the presence (insertion, I) or absence (deletion, D) of a 287-bp Alu repeat element in intron 16 with the levels of circulating enzyme or cardiovascular pathophysiologies. Many epidemiological studies suggest that the DCP1*D allele confers increased susceptibility to cardiovascular disease; however, other reports have found no such association or even a beneficial effect. We present here the complete genomic sequence of DCP1 from 11 individuals, representing the longest contiguous scan (24 kb) for sequence variation in human DNA. We identified 78 varying sites in 22 chromosomes that resolved into 13 distinct haplotypes. Of the variant sites, 17 were in absolute linkage disequilibrium with the commonly typed Alu insertion/deletion polymorphism, producing two distinct and distantly related clades. We also identified a major subdivision in the Alu deletion clade that enables further analysis of the traits associated with this gene. The diversity uncovered in DCP1 is comparable to that described for other regions in the human genome. The highly correlated structure in DCP1 raises important issues for the determination of functional DNA variants within genes and genetic studies in humans based on marker association. 相似文献
7.
Yen AS Gellert R Schröder C Morris RV Bell JF Knudson AT Clark BC Ming DW Crisp JA Arvidson RE Blaney D Brückner J Christensen PR DesMarais DJ de Souza PA Economou TE Ghosh A Hahn BC Herkenhoff KE Haskin LA Hurowitz JA Joliff BL Johnson JR Klingelhöfer G Madsen MB McLennan SM McSween HY Richter L Rieder R Rodionov D Soderblom L Squyres SW Tosca NJ Wang A Wyatt M Zipfel J 《Nature》2005,436(7047):49-54
The mineralogical and elemental compositions of the martian soil are indicators of chemical and physical weathering processes. Using data from the Mars Exploration Rovers, we show that bright dust deposits on opposite sides of the planet are part of a global unit and not dominated by the composition of local rocks. Dark soil deposits at both sites have similar basaltic mineralogies, and could reflect either a global component or the general similarity in the compositions of the rocks from which they were derived. Increased levels of bromine are consistent with mobilization of soluble salts by thin films of liquid water, but the presence of olivine in analysed soil samples indicates that the extent of aqueous alteration of soils has been limited. Nickel abundances are enhanced at the immediate surface and indicate that the upper few millimetres of soil could contain up to one per cent meteoritic material. 相似文献
8.
TGFB2 mutations cause familial thoracic aortic aneurysms and dissections associated with mild systemic features of Marfan syndrome 总被引:1,自引:0,他引:1
C Boileau DC Guo N Hanna ES Regalado D Detaint L Gong M Varret SK Prakash AH Li H d'Indy AC Braverman B Grandchamp CS Kwartler L Gouya RL Santos-Cortez M Abifadel SM Leal C Muti J Shendure MS Gross MJ Rieder A Vahanian DA Nickerson JB Michel;National Heart Lung Blood Institute 《Nature genetics》2012,44(8):916-921
A predisposition for thoracic aortic aneurysms leading to acute aortic dissections can be inherited in families in an autosomal dominant manner. Genome-wide linkage analysis of two large unrelated families with thoracic aortic disease followed by whole-exome sequencing of affected relatives identified causative mutations in TGFB2. These mutations-a frameshift mutation in exon 6 and a nonsense mutation in exon 4-segregated with disease with a combined logarithm of odds (LOD) score of 7.7. Sanger sequencing of 276 probands from families with inherited thoracic aortic disease identified 2 additional TGFB2 mutations. TGFB2 encodes transforming growth factor (TGF)-β2, and the mutations are predicted to cause haploinsufficiency for TGFB2; however, aortic tissue from cases paradoxically shows increased TGF-β2 expression and immunostaining. Thus, haploinsufficiency for TGFB2 predisposes to thoracic aortic disease, suggesting that the initial pathway driving disease is decreased cellular TGF-β2 levels leading to a secondary increase in TGF-β2 production in the diseased aorta. 相似文献
9.
MJ Emond T Louie J Emerson W Zhao RA Mathias MR Knowles FA Wright MJ Rieder HK Tabor DA Nickerson KC Barnes;National Heart Lung Blood Institute 《Nature genetics》2012,44(8):886-889
Exome sequencing has become a powerful and effective strategy for the discovery of genes underlying Mendelian disorders. However, use of exome sequencing to identify variants associated with complex traits has been more challenging, partly because the sample sizes needed for adequate power may be very large. One strategy to increase efficiency is to sequence individuals who are at both ends of a phenotype distribution (those with extreme phenotypes). Because the frequency of alleles that contribute to the trait are enriched in one or both phenotype extremes, a modest sample size can potentially be used to identify novel candidate genes and/or alleles. As part of the National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP), we used an extreme phenotype study design to discover that variants in DCTN4, encoding a dynactin protein, are associated with time to first P. aeruginosa airway infection, chronic P. aeruginosa infection and mucoid P. aeruginosa in individuals with cystic fibrosis. 相似文献
10.
Summary The effect of -aminocaproic acid on EAE of rabbits was investigated. A partial inhibition, dependent on the dose administered by intravenous injection, can be proved. The formation of antibodies is not significantly impaired, whereas an inhibition of local granulomatosis is obvious. The results obtained can be interpreted as an inhibition of delayed immune reaction. 相似文献