title: Genome-wide analysis of transcript isoform variation in humans.
abstract: We have performed a genome-wide analysis of common genetic variation controlling differential expression of transcript isoforms in the CEU HapMap population using a comprehensive exon tiling microarray covering 17,897 genes. We detected 324 genes with significant associations between flanking SNPs and transcript levels. Of these, 39% reflected changes in whole gene expression and 55% reflected transcript isoform changes such as splicing variants (exon skipping, alternative splice site use, intron retention), differential 5' UTR (initiation of transcription) use, and differential 3' UTR (alternative polyadenylation) use. These results demonstrate that the regulatory effects of genetic variation in a normal human population are far more complex than previously observed. This extra layer of molecular diversity may account for natural phenotypic variation and disease susceptibility.
authors.affiliation: Department of Human Genetics, McGill University, 740 Dr. Penfield, Room 7210, Montréal, Québec H3A 1A4, Canada.
authors.forename: Tony
authors.initials: T
authors.lastname: Kwan
authors.forename: David
authors.initials: D
authors.lastname: Benovoy
authors.forename: Christel
authors.initials: C
authors.lastname: Dias
authors.forename: Scott
authors.initials: S
authors.lastname: Gurd
authors.forename: Cathy
authors.initials: C
authors.lastname: Provencher
authors.forename: Patrick
authors.initials: P
authors.lastname: Beaulieu
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hudson
authors.forename: Rob
authors.initials: R
authors.lastname: Sladek
authors.forename: Jacek
authors.initials: J
authors.lastname: Majewski
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000483:Alleles; D017398:Alternative Splicing; D016009:Chi-Square Distribution; D018388:Codon, Terminator; D005091:Exons; D020224:Expressed Sequence Tags; D015870:Gene Expression; D005787:Gene Frequency; D005819:Genetic Markers; D014644:Genetic Variation; D015894:Genome, Human; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007438:Introns; D016014:Linear Models; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms / Q000032:analysis* / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D012337:RNA, Ribosomal, 18S / Q000235:genetics; D015203:Reproducibility of Results; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D018388:Codon, Terminator; D005819:Genetic Markers; D020033:Protein Isoforms; D012337:RNA, Ribosomal, 18S; C483041:PARP2 protein, human; D011065:Poly(ADP-ribose) Polymerases