Imprinting
Global survey of genomic imprinting by transcriptome sequencing
Genomic imprinting is the restriction of gene expression to a paternal or maternal allele and is common to eutherian mammals, although the location and makeup of imprinted regions is not always identical between species. To date, ~90 imprinted transcripts have been identified in mouse, of which the majority were detected after intense interrogation of clusters of imprinted genes identified by phenotype-driven assays in mice with uniparental disomies [1]. Here we use selective priming and parallel sequencing to measure allelic bias in whole-transcriptomes. By distinguishing sex-specific from strain-specific bias in reciprocally crossed mouse embryos, we constructed a genome-wide map of imprinted transcription. This map was able to objectively locate over 80 percent of known imprinted loci and allowed the detection and confirmation of six novel imprinted genes. Even in the intensely studied E9.5 developmental stage that we analyzed, more than half of all imprinted SNPs did not overlap previously discovered imprinted transcripts; a large fraction of these represent novel noncoding RNAs within known imprinted loci. For example, a previously unnoticed, maternally-expressed antisense transcript was mapped within the Grb10 locus. This study demonstrates the feasibility of transcriptome sequencing for mapping and quantification of imprinted gene expression in physiologically normal animals. Such an approach will allow researchers to study imprinting without restricting themselves to individual loci or specific transcripts.