University of British Columbia

About: University of British Columbia is a education organization based out in Vancouver, British Columbia, Canada. It is known for research contribution in the topics: Population & Health care. The organization has 89939 authors who have published 209679 publications receiving 9226862 citations. The organization is also known as: UBC & The University of British Columbia.

Multiwavelength study of massive galaxies at z~2. I. Star formation and galaxy growth

Abstract: Examining a sample of massive galaxies at 1.4 10 11 L⊙, show a mid-IR excess which is likely due to the presence of obscured active nuclei, as shown in a companion paper. There is a tight and roughly linear correlation between stellar mass and SFR for 24µm-detected galaxies. For a given mass, the SFR at z = 2 was larger by a factor of ∼ 4 and ∼ 30 relative to that in star forming galaxies at z = 1 and z = 0, respectively. Typical ultraluminous infrared galaxies (ULIRGs) at z = 2 are relatively ’transparent’ to ultraviolet light, and their activity is long lived ( > ∼ 400 Myr), unlike that in local ULIRGs and high redshift submillimeter-selected galaxies. ULIRGs are the common mode of star formation in massive galaxies at z = 2, and the high duty cycle suggests that major mergers are not the dominant trigger for this activity. Current galaxy formation models underpredict the normalization of the mass-SFR correlation by about a factor of 4, and the space density of ULIRGs by an order of magnitude, but give better agreement for z > 1.4 quiescent galaxies. Subject headings: galaxies: evolution — galaxies: formation — cosmology: observations — galaxies: starbursts — galaxies: high-redshift

Conserved role of intragenic DNA methylation in regulating alternative promoters

Abstract: Although it is known that the methylation of DNA in 5' promoters suppresses gene expression, the role of DNA methylation in gene bodies is unclear. In mammals, tissue- and cell type-specific methylation is present in a small percentage of 5' CpG island (CGI) promoters, whereas a far greater proportion occurs across gene bodies, coinciding with highly conserved sequences. Tissue-specific intragenic methylation might reduce, or, paradoxically, enhance transcription elongation efficiency. Capped analysis of gene expression (CAGE) experiments also indicate that transcription commonly initiates within and between genes. To investigate the role of intragenic methylation, we generated a map of DNA methylation from the human brain encompassing 24.7 million of the 28 million CpG sites. From the dense, high-resolution coverage of CpG islands, the majority of methylated CpG islands were shown to be in intragenic and intergenic regions, whereas less than 3% of CpG islands in 5' promoters were methylated. The CpG islands in all three locations overlapped with RNA markers of transcription initiation, and unmethylated CpG islands also overlapped significantly with trimethylation of H3K4, a histone modification enriched at promoters. The general and CpG-island-specific patterns of methylation are conserved in mouse tissues. An in-depth investigation of the human SHANK3 locus and its mouse homologue demonstrated that this tissue-specific DNA methylation regulates intragenic promoter activity in vitro and in vivo. These methylation-regulated, alternative transcripts are expressed in a tissue- and cell type-specific manner, and are expressed differentially within a single cell type from distinct brain regions. These results support a major role for intragenic methylation in regulating cell context-specific alternative promoters in gene bodies.

The landscape of cancer genes and mutational processes in breast cancer

Abstract: All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis, and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease.