RESUMO
Toll-like receptors (TLRs) and members of their signaling pathway are important in the initiation of the innate immune response to a wide variety of pathogens. The adaptor protein Mal (also known as TIRAP), encoded by TIRAP (MIM 606252), mediates downstream signaling of TLR2 and TLR4 (refs. 4-6). We report a case-control study of 6,106 individuals from the UK, Vietnam and several African countries with invasive pneumococcal disease, bacteremia, malaria and tuberculosis. We genotyped 33 SNPs, including rs8177374, which encodes a leucine substitution at Ser180 of Mal. We found that heterozygous carriage of this variant associated independently with all four infectious diseases in the different study populations. Combining the study groups, we found substantial support for a protective effect of S180L heterozygosity against these infectious diseases (N = 6,106; overall P = 9.6 x 10(-8)). We found that the Mal S180L variant attenuated TLR2 signal transduction.
Assuntos
Bacteriemia/genética , Malária/genética , Proteínas de Membrana Transportadoras/genética , Proteínas da Mielina/genética , Infecções Pneumocócicas/genética , Polimorfismo de Nucleotídeo Único , Proteolipídeos/genética , Tuberculose/genética , África , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Desequilíbrio de Ligação , Glicoproteínas de Membrana/genética , Proteínas de Membrana Transportadoras/fisiologia , Modelos Moleculares , Proteínas da Mielina/fisiologia , Proteínas Proteolipídicas Associadas a Linfócitos e Mielina , Polimorfismo de Nucleotídeo Único/fisiologia , Proteolipídeos/fisiologia , Receptores de Interleucina-1/genética , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Reino Unido , VietnãRESUMO
The genome of bread wheat (Triticum aestivum) is predicted to be greater than 16 Gbp in size and consist predominantly of repetitive elements, making the sequencing and assembly of this genome a major challenge. We have reduced genome sequence complexity by isolating chromosome arm 7DS and applied second-generation technology and appropriate algorithmic analysis to sequence and assemble low copy and genic regions of this chromosome arm. The assembly represents approximately 40% of the chromosome arm and all known 7DS genes. Comparison of the 7DS assembly with the sequenced genomes of rice (Oryza sativa) and Brachypodium distachyon identified large regions of conservation. The syntenic relationship between wheat, B. distachyon and O. sativa, along with available genetic mapping data, has been used to produce an annotated draft 7DS syntenic build, which is publicly available at http://www.wheatgenome.info. Our results suggest that the sequencing of isolated chromosome arms can provide valuable information of the gene content of wheat and is a step towards whole-genome sequencing and variation discovery in this important crop.
Assuntos
Genoma de Planta/genética , Mapeamento Físico do Cromossomo , Sintenia/genética , Triticum/genética , Algoritmos , Brachypodium/genética , Cromossomos de Plantas/genética , DNA de Plantas/química , DNA de Plantas/genética , Sequenciamento de Nucleotídeos em Larga Escala , Meristema/genética , Anotação de Sequência Molecular , Oryza/genética , Plântula/genética , Análise de Sequência de DNARESUMO
Coral disease outbreaks contribute to the ongoing degradation of reef ecosystems, however, microbial mechanisms underlying the onset and progression of most coral diseases are poorly understood. Black band disease (BBD) manifests as a cyanobacterial-dominated microbial mat that destroys coral tissues as it rapidly spreads over coral colonies. To elucidate BBD pathogenesis, we apply a comparative metagenomic and metatranscriptomic approach to identify taxonomic and functional changes within microbial lesions during in-situ development of BBD from a comparatively benign stage termed cyanobacterial patches. Results suggest that photosynthetic CO2-fixation in Cyanobacteria substantially enhances productivity of organic matter within the lesion during disease development. Photosynthates appear to subsequently promote sulfide-production by Deltaproteobacteria, facilitating the major virulence factor of BBD. Interestingly, our metagenome-enabled transcriptomic analysis reveals that BBD-associated cyanobacteria have a putative mechanism that enables them to adapt to higher levels of hydrogen sulfide within lesions, underpinning the pivotal roles of the dominant cyanobacterium within the polymicrobial lesions during the onset of BBD. The current study presents sequence-based evidence derived from whole microbial communities that unravel the mechanism of development and progression of BBD.
Assuntos
Antozoários/genética , Antozoários/microbiologia , Genômica , Animais , Cianobactérias/metabolismo , Perfilação da Expressão Gênica , Metagenoma , Metagenômica , Modelos Biológicos , Fotossíntese , Sulfetos/metabolismo , Transcriptoma/genéticaRESUMO
The caste system has persisted in Indian Hindu society for around 3,500 years. Like the Y chromosome, caste is defined at birth, and males cannot change their caste. In order to investigate the genetic consequences of this system, we have analysed male-lineage variation in a sample of 227 Indian men of known caste, 141 from the Jaunpur district of Uttar Pradesh and 86 from the rest of India. We typed 131 Y-chromosomal binary markers and 16 microsatellites. We find striking evidence for male substructure: in particular, Brahmins and Kshatriyas (but not other castes) from Jaunpur each show low diversity and the predominance of a single distinct cluster of haplotypes. These findings confirm the genetic isolation and drift within the Jaunpur upper castes, which are likely to result from founder effects and social factors. In the other castes, there may be either larger effective population sizes, or less strict isolation, or both.