Mostrando recursos 1 - 20 de 98.083
Common Genetic Variation in the 3 '-BCL11B Gene Desert Is Associated With Carotid-Femoral Pulse Wave Velocity and Excess Cardiovascular Disease Risk The AortaGen Consortium
Mitchell, GF; Verwoert, GC; Tarasov, KV; Isaacs, A; Smith, AV; Yasmin,; Rietzschel, ER; Tanaka, T; Liu, Y; Parsa, A; Najjar, SS; O'Shaughnessy, KM; Sigurdsson, S; De Buyzere, ML; Larson, MG; Sie, MPS; Andrews, JS; Post, WS; Mattace-Raso, FUS; McEniery, CM; Eiriksdottir, G; Segers, P; Vasan, RS; van Rijn, MJE; Howard, TD; McArdle, PF; Dehghan, A; Jewell, ES; Newhouse, SJ; Bekaert, S; Hamburg, NM; Newman, AB; Hofman, A; Scuteri, A; De Bacquer, D; Ikram, MA; Psaty, BM; Fuchsberger, C; Olden, M; Wain, LV; Elliott, P; Smith, NL; Felix, JF; Erdmann, J; Vita, JA; Sutton-Tyrrell, K; Sijbrands, EJG; Sanna, S; Launer, LJ; De Meyer, T; Johnson, AD; Schut, AFC; Herrington, DM; Rivadeneira, F; Uda, M; Wilkinson, IB; Aspelund, T; Gillebert, TC; Van Bortel, L; Benjamin, EJ; Oostra, BA; Ding, J; Gibson, Q; Uitterlinden, AG; Abecasis, GR; Cockcroft, JR; Gudnason, V; De Backer, GG; Ferrucci, L; Harris, TB; Shuldiner, AR; van Duijn, CM; Levy, D; Lakatta, EG; Witteman, JCM
Robson, EA; Chetcuti, P; Hirst, RA; Mitchison, H; Moya, E; Peckham, D; Robinson, PJ; Rutman, A; O'Callaghan, C
© 2017 Elsevier Ltd.PCD is a rare autosomal recessive disorder of ciliary function. It is characterised by progressive sino-pulmonary disease, fertility problems and disorders of organ laterality. Clinical phenotype and disease course can vary significantly. A daily chronic wet cough that never goes away is invariably present, with most suffering from persistent and significant rhinosinusitis. Middle ear effusion and hearing difficulty are seen in a proportion of patients. Bronchiectasis is reported in approximately 70% of children.Diagnosis can be difficult and often requires specialist centre input. In patients with a suggestive clinical phenotype a combination of nasal nitric oxide, high-speed video...
An alternative promoter in the mouse major histocompatibility complex class II I-Abeta gene: implications for the origin of CpG islands.
Macleod, D; Ali, RR; Bird, A
Nonmethylated CpG islands are generally located at the 5' ends of genes, but a CpG island in the mouse major histocompatibility complex class II I-Abeta gene is remote from the promoter and covers exon 2. We have found that this CpG island includes a novel intronic promoter that is active in embryonic and germ cells. The resulting transcript potentially encodes a severely truncated protein which would lack the signal peptide and external beta1 domains. The functional significance of the internal CpG island may be to facilitate gene conversion, thereby sustaining the high level of polymorphism seen at exon 2. Deletions...
Hospenthal, MK; Costa, TRD; Waksman, G
Pili are crucial virulence factors for many Gram-negative pathogens. These surface structures provide bacteria with a link to their external environments by enabling them to interact with, and attach to, host cells, other surfaces or each other, or by providing a conduit for secretion. Recent high-resolution structures of pilus filaments and the machineries that produce them, namely chaperone-usher pili, type IV pili, conjugative type IV secretion pili and type V pili, are beginning to explain some of the intriguing biological properties that pili exhibit, such as the ability of chaperone-usher pili and type IV pili to stretch in response to...
Meschia, JF; Woo, D; Werring, D
Genetic analysis of an Indian family with members affected with juvenile-onset primary open-angle glaucoma.
Markandaya, M; Ramesh, TK; Selvaraju, V; Dorairaj, SK; Prakash, R; Shetty, J; Kumar, A
PURPOSE: Glaucoma is the second leading cause of blindness. In India, approximately 1.5 million people are blind due to glaucoma. Mutations in the MYOC gene located at the GLC1A locus on chromosome 1q21-q31 have been found in patients with juvenile-onset primary open-angle glaucoma (J-POAG). The purpose of the present study was to identify the genetic cause of glaucoma in a four-generation Indian family affected with J-POAG. METHODS: Peripheral blood samples were obtained from individuals for genomic DNA isolation. To determine if this family was linked to the GLC1A locus, haplotyping analysis was carried out using microsatellite markers from the GLC1A...
Haplotype reference consortium panel: Practical implications of imputations with large reference panels.
Iglesias, AI; van der Lee, SJ; Bonnemaijer, PWM; Höhn, R; Nag, A; Gharahkhani, P; Khawaja, AP; Broer, L; International Glaucoma Genetics Consortium (IGGC),; Foster, PJ; Hammond, CJ; Hysi, PG; van Leeuwen, EM; MacGregor, S; Mackey, DA; Mazur, J; Nickels, S; Uitterlinden, AG; Klaver, CCW; Amin, N; van Duijn, CM
Recently, the Haplotype Reference Consortium (HRC) released a large imputation panel that allows more accurate imputation of genetic variants. In this study, we compared a set of directly assayed common and rare variants from an exome array to imputed genotypes, i.e., 1000 genomes project (1000GP) and HRC. We showed that imputation using the HRC panel improved the concordance between assayed and imputed genotypes at common, and especially, low-frequency variants. Furthermore, we performed a genome-wide association meta-analysis of vertical cup-disc ratio (VCDR), a highly heritable endophenotype of glaucoma, in four cohorts using 1000GP and HRC imputations. We compared the results of...
Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function
Wild, PS; Felix, JF; Schillert, A; Teumer, A; Chen, M-H; Leening, MJG; Voelker, U; Grossmann, V; Brody, JA; Irvin, MR; Shah, SJ; Pramana, S; Lieb, W; Schmidt, R; Stanton, AV; Malzahn, D; Smith, AV; Sundstrom, J; Minelli, C; Ruggiero, D; Lyytikainen, L-P; Tiller, D; Smith, JG; Monnereau, C; Di Tullio, MR; Musani, SK; Morrison, AC; Pers, TH; Morley, M; Kleber, ME; Aragam, J; Benjamin, EJ; Bis, JC; Bisping, E; Broeckel, U; Cheng, S; Deckers, JW; Del Greco, F; Edelmann, F; Fornage, M; Franke, L; Friedrich, N; Harris, TB; Hofer, E; Hofman, A; Huang, J; Hughes, AD; Kahonen, M; Kruppa, J; Lackner, KJ; Lannfelt, L; Laskowski, R; Launer, LJ; Leosdottir, M; Lin, H; Lindgren, CM; Loley, C; MacRae, CA; Mascalzoni, D; Mayet, J; Medenwald, D; Morris, AP; Mueller, C; Mueller-Nurasyid, M; Nappo, S; Nilsson, PM; Nuding, S; Nutile, T; Peters, A; Pfeufer, A; Pietzner, D; Pramstaller, PP; Raitakari, OT; Rice, KM; Rivadeneira, F; Rotter, JI; Ruohonen, ST; Sacco, RL; Samdarshi, TE; Schmidt, H; Sharp, ASP; Shields, DC; Sorice, R; Sotoodehnia, N; Stricker, BH; Surendran, P; Thom, S; Toeglhofer, AM; Uitterlinden, AG; Wachter, R; Voelzke, H; Ziegler, A; Muenzel, T; Maerz, W; Cappola, TP; Hirschhorn, JN; Mitchell, GF; Smith, NL; Fox, ER; Dueker, ND; Jaddoe, VWV; Melander, O; Russ, M; Lehtimaki, T; Ciullo, M; Hicks, AA; Lind, L; Gudnason, V; Pieske, B; Barron, AJ; Zweiker, R; Schunkert, H; Ingelsson, E; Liu, K; Arnett, DK; Psaty, BM; Blankenberg, S; Larson, MG; Felix, SB; Franco, OH; Zeller, T; Vasan, RS; Doerr, M
11,670 whole-genome sequences representative of the Han Chinese population from the CONVERGE project
Cai, N; Bigdeli, TB; Kretzschmar, WW; Li, Y; Liang, J; Hu, J; Peterson, RE; Bacanu, S; Webb, BT; Riley, B; Li, Q; Marchini, J; Mott, R; Kendler, KS; Flint, J
The China, Oxford and Virginia Commonwealth University Experimental Research on Genetic Epidemiology (CONVERGE) project on Major Depressive Disorder (MDD) sequenced 11,670 female Han Chinese at low-coverage (1.7X), providing the first large-scale whole genome sequencing resource representative of the largest ethnic group in the world. Samples are collected from 58 hospitals from 23 provinces around China. We are able to call 22 million high quality single nucleotide polymorphisms (SNP) from the nuclear genome, representing the largest SNP call set from an East Asian population to date. We use these variants for imputation of genotypes across all samples, and this has allowed...
Dawson, E; Abecasis, GR; Bumpstead, S; Chen, Y; Hunt, S; Beare, DM; Pabial, J; Dibling, T; Tinsley, E; Kirby, S; Carter, D; Papaspyridonos, M; Livingstone, S; Ganske, R; Lõhmussaar, E; Zernant, J; Tõnisson, N; Remm, M; Mägi, R; Puurand, T; Vilo, J; Kurg, A; Rice, K; Deloukas, P; Mott, R; Metspalu, A; Bentley, DR; Cardon, LR; Dunham, I
DNA sequence variants in specific genes or regions of the human genome are responsible for a variety of phenotypes such as disease risk or variable drug response. These variants can be investigated directly, or through their non-random associations with neighbouring markers (called linkage disequilibrium (LD)). Here we report measurement of LD along the complete sequence of human chromosome 22. Duplicate genotyping and analysis of 1,504 markers in Centre d'Etude du Polymorphisme Humain (CEPH) reference families at a median spacing of 15 kilobases (kb) reveals a highly variable pattern of LD along the chromosome, in which extensive regions of nearly complete...
Hui, WWI; Jiang, P; Tong, YK; Lee, W-S; Cheng, YKY; New, MI; Kadir, RA; Chan, KCA; Leung, TY; Lo, YMD; Chiu, RWK
BACKGROUND: Researchers have developed approaches for the noninvasive prenatal testing of single gene diseases. One approach that allows for the noninvasive assessment of both maternally and paternally inherited mutations involves the analysis of single nucleotide polymorphisms (SNPs) in maternal plasma DNA with reference to parental haplotype information. In the past, parental haplotypes were resolved by complex experimental methods or inferential approaches, such as through the analysis of DNA from other affected family members. Recently, microfluidics-based linked-read sequencing technology has become available and allows the direct haplotype phasing of the whole genome rapidly. We explored the feasibility of applying this direct...
Comparative Genomics of Amphibian-like Ranaviruses, Nucleocytoplasmic Large DNA Viruses of Poikilotherms
Recent research on genome evolution of large DNA viruses has highlighted a number of incredibly dynamic processes that can facilitate rapid adaptation. The genomes of amphibian-like ranaviruses – double-stranded DNA viruses infecting amphibians, reptiles, and fish (family Iridoviridae) – were examined to assess variation in genome content and evolutionary processes. The viruses studied were closely related, but their genome content varied considerably, with 29 genes identified that were not present in all of the major clades. Twenty-one genes had evidence of recombination, while a virus isolated from a captive reptile appeared to be a mosaic of two divergent parents. Positive...
Flint, J; Shifman, S; Munafo, M; Mott, R
Major depression is one of the most common and most debilitating disorders in the world. A wealth of data indicate that additive genetic effects contribute to at least 30% of the variance in liability to major depression, yet attempts to identify the molecular basis of susceptibility using standard family based linkage and genetic association methodologies have had limited success. Alternative approaches have recently been advocated, such as the inclusion of gene by environment interactions and the use of endophenotypes. Our own data indicate that the genetic architecture of affective illness is more complex than expected. A whole genome association study...
Baud, A; Calderari, S; Mott, R; Flint, J; Gauguier, D; Rat Genome Sequencing and Mapping Consortium,
Relationships between angry-impulsive personality traits and genetic polymorphisms of the dopamine transporter
Joyce, PR; McHugh, PC; Light, KJ; Rowe, S; Miller, AL; Kennedy, MA
Background: The 9-repeat variable number tandem repeat allele of the dopamine transporter has recently been associated with borderline personality disorder (BPD) in depressed patients. Methods: We investigated the association between the 9-repeat allele of the dopamine transporter and angry-impulsive personality traits in a family study with 512 subjects on the molecular genetics of depression and personality. Results: Across the whole sample, the 9-repeat allele of the dopamine transporter was associated with angry-impulsive personality traits (p = .002). This association was stronger in subjects with no history of mood disorders or BPD (odds ratio [OR] = 4.85, p = .008) than...
Busby, GBJ; Hellenthal, G; Montinaro, F; Tofanelli, S; Bulayeva, K; Rudan, I; Zemunik, T; Hayward, C; Toncheva, D; Karachanak-Yankova, S; Nesheva, D; Anagnostou, P; Cali, F; Brisighelli, F; Romano, V; Lefranc, G; Buresi, C; Ben Chibani, J; Haj-Khelil, A; Denden, S; Ploski, R; Krajewski, P; Hervig, T; Moen, T; Herrera, RJ; Wilson, JF; Myers, S; Capelli, C
Protease inhibitor monotherapy for long-term management of HIV infection: a randomised, controlled, open-label, non-inferiority trial
Paton, NI; Stöhr, W; Arenas-Pinto, A; Fisher, M; Williams, I; Johnson, M; Orkin, C; Chen, F; Lee, V; Winston, A; Gompels, M; Fox, J; Scott, K; Dunn, DT
BACKGROUND: Standard-of-care antiretroviral therapy (ART) uses a combination of drugs deemed essential to minimise treatment failure and drug resistance. Protease inhibitors are potent, with a high genetic barrier to resistance, and have potential use as monotherapy after viral load suppression is achieved with combination treatment. We aimed to assess clinical risks and benefits of protease inhibitor monotherapy in long-term clinical use: in particular, the effect on drug resistance and future treatment options. METHODS: In this pragmatic, parallel-group, randomised, controlled, open-label, non-inferiority trial, we enrolled adults (≥18 years of age) positive for HIV attending 43 public sector treatment centres in the...
Barr, ET; Harman, M; Jia, Y; Marginean, A; Petke, J
Automated transplantation would open many exciting avenues for software development: suppose we could autotrans-plant code from one system into another, entirely unrelated, system. This paper introduces a theory, an algorithm, and a tool that achieve this. Leveraging lightweight annotation, program analysis identifies an organ (interesting behavior to transplant); testing validates that the organ exhibits the desired behavior during its extraction and after its implantation into a host. While we do not claim automated transplantation is now a solved problem, our results are encouraging: we report that in 12 of 15 experiments, involving 5 donors and 3 hosts (all popular real-world...
Drosophila comes of age as a model system for understanding the function of cytoskeletal proteins in cells, tissues, and organisms
Rodal, Avital A.; Del Signore, Steven J.; Martin, Adam C
For the last 100 years, Drosophila melanogaster has been a powerhouse genetic system for understanding mechanisms of inheritance, development, and behavior in animals. In recent years, advances in imaging and genetic tools have led to Drosophila becoming one of the most effective systems for unlocking the subcellular functions of proteins (and particularly cytoskeletal proteins) in complex developmental settings. In this review, written for non-Drosophila experts, we will discuss critical technical advances that have enabled these cell biological insights, highlighting three examples of cytoskeletal discoveries that have arisen as a result: (1) regulation of Arp2/3 complex in myoblast fusion, (2) cooperation...