Journal ArticleDOI
Natural variation in human gene expression assessed in lymphoblastoid cells
Vivian G. Cheung,Laura K. Conlin,Teresa M. Weber,Melissa Arcaro,Kuang-Yu Jen,Michael Morley,Richard S. Spielman +6 more
TLDR
There is evidence for familial aggregation of expression phenotype by comparing variation among unrelated individuals, among siblings within families and between monozygotic twins, which suggests that there is a genetic contribution to polymorphic variation in the level of gene expression.Abstract:
The sequencing of the human genome has resulted in greater attention to genetic variation among individuals, and variation at the DNA sequence level is now being extensively studied. At the same time, it has become possible to study variation at the level of gene expression by various methods. At present, it is largely unknown how widespread this variation in transcript levels is over the entire genome and to what extent individual differences in expression level are genetically determined. In the present study, we used lymphoblastoid cells to examine variation in gene expression and identified genes whose transcript levels differed greatly among unrelated individuals. We also found evidence for familial aggregation of expression phenotype by comparing variation among unrelated individuals, among siblings within families and between monozygotic twins. These observations suggest that there is a genetic contribution to polymorphic variation in the level of gene expression.read more
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MicroRNA signatures in human cancers
George A. Calin,Carlo M. Croce +1 more
TL;DR: MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment and has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein-coding genes involved in cancer.
Journal Article
MicroRNA signatures in human cancers
George A. Calin,Carlo M. Croce +1 more
TL;DR: The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery as discussed by the authors.
Journal ArticleDOI
Five years of GWAS discovery
Peter M. Visscher,Peter M. Visscher,Matthew A. Brown,Mark I. McCarthy,Mark I. McCarthy,Jian Yang +5 more
TL;DR: The past five years have seen many scientific and biological discoveries made through the experimental design of genome-wide association studies (GWASs), which were aimed at detecting variants at genomic loci that are associated with complex traits in the population and, in particular, at detecting associations between common single-nucleotide polymorphisms (SNPs) and common diseases such as heart disease, diabetes, auto-immune diseases, and psychiatric disorders.
Journal ArticleDOI
Heritability in the genomics era — concepts and misconceptions
TL;DR: This work has shown that despite continuous misunderstandings and controversies over its use and application, heritability remains key to the response to selection in evolutionary biology and agriculture, and to the prediction of disease risk in medicine.
Journal ArticleDOI
Understanding mechanisms underlying human gene expression variation with RNA sequencing
Joseph K. Pickrell,John C. Marioni,Athma A. Pai,Jacob F. Degner,Barbara E. Engelhardt,Everlyne Nkadori,Jean-Baptiste Veyrieras,Matthew Stephens,Yoav Gilad,Jonathan K. Pritchard +9 more
TL;DR: It is demonstrated that eQTLs near genes generally act by a mechanism involving allele-specific expression, and that variation that influences the inclusion of an exon is enriched within and near the consensus splice sites.
References
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Journal ArticleDOI
Gene Ontology: tool for the unification of biology
M Ashburner,Catherine A. Ball,Judith A. Blake,David Botstein,Heather Butler,J. M. Cherry,Allan Peter Davis,Kara Dolinski,Selina S. Dwight,J.T. Eppig,Midori A. Harris,David P. Hill,Laurie Issel-Tarver,Andrew Kasarskis,Suzanna E. Lewis,John C. Matese,Joel E. Richardson,M. Ringwald,Gerald M. Rubin,Gavin Sherlock +19 more
TL;DR: The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing.
Journal ArticleDOI
Quantitative monitoring of gene expression patterns with a complementary DNA microarray.
TL;DR: A high-capacity system was developed to monitor the expression of many genes in parallel by means of simultaneous, two-color fluorescence hybridization, which enabled detection of rare transcripts in probe mixtures derived from 2 micrograms of total cellular messenger RNA.
Journal ArticleDOI
A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms
Ravi Sachidanandam,David Weissman,Steven Schmidt,Jerzy M. Kakol,Lincoln Stein,Gabor T. Marth,Steve Sherry,James C. Mullikin,Beverley J. Mortimore,David Willey,Sarah E. Hunt,Charlotte G. Cole,Penny Coggill,Catherine M. Rice,Zemin Ning,Jane Rogers,David R. Bentley,Pui-Yan Kwok,Elaine R. Mardis,Raymond T. Yeh,Brian Schultz,Lisa Cook,Ruth Davenport,Michael Dante,Lucinda Fulton,LaDeana W. Hillier,Robert H. Waterston,John Douglas Mcpherson,Brian Gilman,Stephen F. Schaffner,William J. Van Etten,David Reich,John M. Higgins,Mark J. Daly,Brendan Blumenstiel,Jennifer Baldwin,Nicole Stange-Thomann,Michael C. Zody,Lauren Linton,Eric S. Lander,David Altshuler +40 more
TL;DR: This high-density SNP map provides a public resource for defining haplotype variation across the genome, and should help to identify biomedically important genes for diagnosis and therapy.
Journal ArticleDOI
Genetic dissection of transcriptional regulation in budding yeast.
TL;DR: To begin to understand the genetic architecture of natural variation in gene expression, genetic linkage analysis of genomewide expression patterns in a cross between a laboratory strain and a wild strain of Saccharomyces cerevisiae was carried out.
Journal ArticleDOI
CYTOCHROME P-450 3A4: Regulation and Role in Drug Metabolism
TL;DR: Several issues remain to be resolved regarding the catalytic activity of the P-450 3A4 protein, including rate-limiting steps and the need for cytochrome b5, divalent cations, and acidic phospholipid systems for optimal activity.
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