Dataset Information

Heritability of alternative splicing in the human genome

ABSTRACT: Alternative pre-mRNA splicing increases proteomic diversity and provides a potential mechanism underlying both phenotypic diversity and susceptibility to genetic disorders in human populations. To investigate the variation in splicing among humans on a genomewide scale, we use a comprehensive exon-targeted microarray to examine alternative splicing in lymphoblasts derived from the CEPH HapMap population. We show the identification of transcripts containing annotated and novel sequence verified exon skipping, intron retention, and cryptic splice site usage that are specific between individuals. Using family-based linkage analysis, we demonstrate Mendelian inheritance and segregation of specific splice isoforms with regulatory haplotypes for three genes. Allelic association was further used to identify individual SNPs or regulatory haplotype blocks linked to the alternative splicing event, taking advantage of the high-resolution genotype information from the CEPH HapMap population. Keywords: Comparative genomic hybridiation within a 3 generation pedigree We used 14 individuals from the 3 generation CEPH/UTAH 1444 pedigree for our analysis of looking at heritability of differentially spliced exons within the family. 3 biological growths of individuals NA12739, NA12740, NA12750, and NA12751 were used and a single biological growth for the remaining 10 individuals.

ORGANISM(S): Homo sapiens

SUBMITTER: Tony Kwan Jacek Majewski

PROVIDER: E-GEOD-7952 | ArrayExpress | 2007-08-07

SECONDARY ACCESSION(S): GSE7952PRJNA100135

REPOSITORIES: GEO, ArrayExpress

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Heritability of alternative splicing in the human genome.

Kwan Tony T Benovoy David D Dias Christel C Gurd Scott S Serre David D Zuzan Harry H Clark Tyson A TA Schweitzer Anthony A Staples Michelle K MK Wang Hui H Blume John E JE Hudson Thomas J TJ Sladek Rob R Majewski Jacek J

Genome research 20070801 8

Alternative pre-mRNA splicing increases proteomic diversity and provides a potential mechanism underlying both phenotypic diversity and susceptibility to genetic disorders in human populations. To investigate the variation in splicing among humans on a genome-wide scale, we use a comprehensive exon-targeted microarray to examine alternative splicing in lymphoblastoid cell lines (LCLs) derived from the CEPH HapMap population. We show the identification of transcripts containing sequence verified ...[more]

PMID: 17671095

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