title: Allelic Imbalance Is a Prevalent and Tissue-Specific Feature of the Mouse Transcriptome.
abstract: In mammals, several classes of monoallelic genes have been identified, including those subject to X-chromosome inactivation (XCI), genomic imprinting, and random monoallelic expression (RMAE). However, the extent to which these epigenetic phenomena are influenced by underlying genetic variation is unknown. Here we perform a systematic classification of allelic imbalance in mouse hybrids derived from reciprocal crosses of divergent strains. We observe that deviation from balanced biallelic expression is common, occurring in ∼20% of the mouse transcriptome in a given tissue. Allelic imbalance attributed to genotypic variation is by far the most prevalent class and typically is tissue-specific. However, some genotype-based imbalance is maintained across tissues and is associated with greater genetic variation, especially in 5' and 3' termini of transcripts. We further identify novel random monoallelic and imprinted genes and find that genotype can modify penetrance of parental origin even in the setting of large imprinted regions. Examination of nascent transcripts in single cells from inbred parental strains reveals that genes showing genotype-based imbalance in hybrids can also exhibit monoallelic expression in isogenic backgrounds. This surprising observation may suggest a competition between alleles and/or reflect the combined impact of cis- and trans-acting variation on expression of a given gene. Our findings provide novel insights into gene regulation and may be relevant to human genetic variation and disease.
authors: Howard Hughes Medical Institute, Chevy Chase, Maryland 20815-6789 Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114 Department of Genetics, Harvard Medical School, Boston, MA 02115.
authors: Stefan F
authors: http://orcid.org/0000-0003-4750-1403
authors: SF
authors: Pinter
authors: Howard Hughes Medical Institute, Chevy Chase, Maryland 20815-6789 Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114 Department of Genetics, Harvard Medical School, Boston, MA 02115.
authors: David
authors: D
authors: Colognori
authors: Department of Genetics, Harvard Medical School, Boston, MA 02115.
authors: Brian J
authors: http://orcid.org/0000-0003-1314-3118
authors: BJ
authors: Beliveau
authors: Howard Hughes Medical Institute, Chevy Chase, Maryland 20815-6789 Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114 Department of Genetics, Harvard Medical School, Boston, MA 02115.
authors: Ruslan I
authors: RI
authors: Sadreyev
authors: Howard Hughes Medical Institute, Chevy Chase, Maryland 20815-6789 Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114 Department of Genetics, Harvard Medical School, Boston, MA 02115.
authors: Bernhard
authors: http://orcid.org/0000-0002-4694-2082
authors: B
authors: Payer
authors: Howard Hughes Medical Institute, Chevy Chase, Maryland 20815-6789 Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114 Department of Genetics, Harvard Medical School, Boston, MA 02115.
authors: Eda
authors: E
authors: Yildirim
authors: Department of Genetics, Harvard Medical School, Boston, MA 02115.
authors: Chao-Ting
authors: CT
authors: Wu
authors: Howard Hughes Medical Institute, Chevy Chase, Maryland 20815-6789 Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114 Department of Genetics, Harvard Medical School, Boston, MA 02115 Department of Pathology, Harvard Medical School, Boston, MA 02115 lee@molbio.mgh.harvard.edu.
authors: Jeannie T
authors: JT
authors: Lee
mesh_terms: D000483:Alleles; D022981:Allelic Imbalance; D000818:Animals; D016000:Cluster Analysis; D003433:Crosses, Genetic; D020869:Gene Expression Profiling; D014644:Genetic Variation; D018392:Genomic Imprinting; D005838:Genotype; D051379:Mice; D009928:Organ Specificity / Q000235:genetics; D059467:Transcriptome
keywords: allele-specific RNA-seq; gene expression; genotype; imprinting; random monoallelic expression