title: Digital RNA allelotyping reveals tissue-specific and allele-specific gene expression in human.
abstract: We developed a digital RNA allelotyping method for quantitatively interrogating allele-specific gene expression. This method involves ultra-deep sequencing of padlock-captured single-nucleotide polymorphisms (SNPs) from the transcriptome. We characterized four cell lines established from two human subjects in the Personal Genome Project. Approximately 11-22% of the heterozygous mRNA-associated SNPs showed allele-specific expression in each cell line and 4.3-8.5% were tissue-specific, suggesting the presence of tissue-specific cis regulation. When we applied allelotyping to two pairs of sibling human embryonic stem cell lines, the sibling lines were more similar in allele-specific expression than were the genetically unrelated lines. We found that the variation of allelic ratios in gene expression among different cell lines was primarily explained by genetic variations, much more so than by specific tissue types or growth conditions. Comparison of expressed SNPs on the sense and antisense transcripts suggested that allelic ratios are primarily determined by cis-regulatory mechanisms on the sense transcripts.
authors.affiliation: Department of Bioengineering, University of California at San Diego, La Jolla, California, USA. kzhang@bioeng.ucsd.edu
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Jin Billy
authors.initials: JB
authors.lastname: Li
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.forename: Dieter
authors.initials: D
authors.lastname: Egli
authors.forename: Bin
authors.initials: B
authors.lastname: Xie
authors.forename: Jie
authors.initials: J
authors.lastname: Deng
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
authors.forename: Je-Hyuk
authors.initials: JH
authors.lastname: Lee
authors.forename: John
authors.initials: J
authors.lastname: Aach
authors.forename: Emily M
authors.initials: EM
authors.lastname: Leproust
authors.forename: Kevin
authors.initials: K
authors.lastname: Eggan
authors.forename: George M
authors.initials: GM
authors.lastname: Church
mesh_terms: D000483:Alleles; D002460:Cell Line; D004277:DNA, Single-Stranded / Q000235:genetics; D005260:Female; D015870:Gene Expression; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA
chemical_list: D004277:DNA, Single-Stranded; D012333:RNA, Messenger