Identification of common genetic variants that account for transcript isoform variation between human populations

Wei Zhang, Shiwei Duan, Wasim K. Bleibel, Steven A. Wisel, R. Stephanie Huang, Xiaolin Wu, Lijun He, Tyson A. Clark, Tina X. Chen, Anthony C. Schweitzer, John E. Blume, M. Eileen Dolan, Nancy J. Cox

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)81-93
Number of pages13
JournalHuman Genetics
Issue number1
StatePublished - 2009

Bibliographical note

Funding Information:
Acknowledgments This Pharmacogenetics of Anticancer Agents Research (PAAR) Group ( study was supported by NIH/NIGMS grants U01 GM61393 and U01 GM61374. We are grateful to Dr. Jeong-Ah Kang for maintaining cell lines, Cheryl A. Roe for reviewing the manuscript and Drs. James Fackenthal and Emily Kistner for helpful discussion. T.A.C., T.X.C., A.C.S., and J.E.B. are employees of Affymetrix, Inc.


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