Broad Institute

About: Broad Institute is a nonprofit organization based out in Cambridge, Massachusetts, United States. It is known for research contribution in the topics: Population & Genome-wide association study. The organization has 6584 authors who have published 11618 publications receiving 1522743 citations. The organization is also known as: Eli and Edythe L. Broad Institute of MIT and Harvard.

Evolution of pathogenicity and sexual reproduction in eight Candida genomes.

Abstract: Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine-to-serine genetic-code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the Candida albicans gene catalogue, identifying many new genes.

Local regulation of gene expression by lncRNA promoters, transcription and splicing

Abstract: Mammalian genomes are pervasively transcribed to produce thousands of long non-coding RNAs (lncRNAs) A few of these lncRNAs have been shown to recruit regulatory complexes through RNA-protein interactions to influence the expression of nearby genes, and it has been suggested that many other lncRNAs can also act as local regulators Such local functions could explain the observation that lncRNA expression is often correlated with the expression of nearby genes However, these correlations have been challenging to dissect and could alternatively result from processes that are not mediated by the lncRNA transcripts themselves For example, some gene promoters have been proposed to have dual functions as enhancers, and the process of transcription itself may contribute to gene regulation by recruiting activating factors or remodelling nucleosomes Here we use genetic manipulation in mouse cell lines to dissect 12 genomic loci that produce lncRNAs and find that 5 of these loci influence the expression of a neighbouring gene in cis Notably, none of these effects requires the specific lncRNA transcripts themselves and instead involves general processes associated with their production, including enhancer-like activity of gene promoters, the process of transcription, and the splicing of the transcript Furthermore, such effects are not limited to lncRNA loci: we find that four out of six protein-coding loci also influence the expression of a neighbour These results demonstrate that cross-talk among neighbouring genes is a prevalent phenomenon that can involve multiple mechanisms and cis-regulatory signals, including a role for RNA splice sites These mechanisms may explain the function and evolution of some genomic loci that produce lncRNAs and broadly contribute to the regulation of both coding and non-coding genes

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

Abstract: To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.

Identification of novel transcripts in annotated genomes using RNA-Seq

Abstract: Summary: We describe a new ‘reference annotation based transcript assembly’ problem for RNA-Seq data that involves assembling novel transcripts in the context of an existing annotation. This problem arises in the analysis of expression in model organisms, where it is desirable to leverage existing annotations for discovering novel transcripts. We present an algorithm for reference annotation-based transcript assembly and show how it can be used to rapidly investigate novel transcripts revealed by RNA-Seq in comparison with a reference annotation. Availability: The methods described in this article are implemented in the Cufflinks suite of software for RNA-Seq, freely available from http://bio.math.berkeley.edu/cufflinks. The software is released under the BOOST license. Contact:cole@broadinstitute.org; lpachter@math.berkeley.edu Supplementary Information:Supplementary data are available at Bioinformatics online.

A framework for the interpretation of de novo mutation in human disease

Abstract: Mark Daly and colleagues present a statistical framework to evaluate the role of de novo mutations in human disease by calibrating a model of de novo mutation rates at the individual gene level. The mutation probabilities defined by their model and list of constrained genes can be used to help identify genetic variants that have a significant role in disease.