title: Identification of common genetic variants that account for transcript isoform variation between human populations.
abstract: In addition to the differences between populations in transcriptional and translational regulation of genes, alternative pre-mRNA splicing (AS) is also likely to play an important role in regulating gene expression and generating variation in mRNA and protein isoforms. Recently, the genetic contribution to transcript isoform variation has been reported in individuals of recent European descent. We report here results of an investigation of the differences in AS patterns between human populations. AS patterns in 176 HapMap lymphoblastoid cell lines derived from individuals of European and African ancestry were evaluated using the Affymetrix GeneChip Human Exon 1.0 ST Array. A variety of biological processes such as response to stimulus and transcription were found to be enriched among the differentially spliced genes. The differentially spliced genes also include some involved in human diseases that have different prevalence or susceptibility between populations. The genetic contribution to the population differences in transcript isoform variation was then evaluated by a genome-wide association using the HapMap genotypic data on single nucleotide polymorphisms (SNPs). The results suggest that local and distant genetic variants account for a substantial fraction of the observed transcript isoform variation between human populations. Our findings provide new insights into the complexity of the human genome as well as the health disparities between the two populations.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Box MC6091, 5841 S. Maryland Ave., Chicago, IL 60637, USA. wzhang1@uchicago.edu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Shiwei
authors.initials: S
authors.lastname: Duan
authors.forename: Wasim K
authors.initials: WK
authors.lastname: Bleibel
authors.forename: Steven A
authors.initials: SA
authors.lastname: Wisel
authors.forename: R Stephanie
authors.initials: RS
authors.lastname: Huang
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wu
authors.forename: Lijun
authors.initials: L
authors.lastname: He
authors.forename: Tyson A
authors.initials: TA
authors.lastname: Clark
authors.forename: Tina X
authors.initials: TX
authors.lastname: Chen
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Schweitzer
authors.forename: John E
authors.initials: JE
authors.lastname: Blume
authors.forename: M Eileen
authors.initials: ME
authors.lastname: Dolan
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
mesh_terms: D017398:Alternative Splicing; D044383:Black People / Q000235:genetics; D016000:Cluster Analysis; D005828:Genetics, Population; D015894:Genome, Human; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D020033:Protein Isoforms