title: Noncanonical Genomic Imprinting Effects in Offspring.
abstract: Here, we describe an RNA-sequencing (RNA-seq)-based approach that accurately detects even modest maternal or paternal allele expression biases at the tissue level, which we call noncanonical genomic imprinting effects. We profile imprinting in the arcuate nucleus (ARN) and dorsal raphe nucleus of the female mouse brain as well as skeletal muscle (mesodermal) and liver (endodermal). Our study uncovers hundreds of noncanonical autosomal and X-linked imprinting effects. Noncanonical imprinting is highly tissue-specific and enriched in the ARN, but rare in the liver. These effects are reproducible across different genetic backgrounds and associated with allele-specific chromatin. Using in situ hybridization for nascent RNAs, we discover that autosomal noncanonical imprinted genes with a tissue-level allele bias exhibit allele-specific expression effects in subpopulations of neurons in the brain in vivo. We define noncanonical imprinted genes that regulate monoamine signaling and determine that these effects influence the impact of inherited mutations on offspring behavior.
authors.affiliation: Department of Neurobiology & Anatomy, University of Utah School of Medicine, Salt Lake City, UT 84132-3401, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Bonthuis
authors.affiliation: Department of Neurobiology & Anatomy, University of Utah School of Medicine, Salt Lake City, UT 84132-3401, USA.
authors.forename: Wei-Chao
authors.initials: WC
authors.lastname: Huang
authors.affiliation: Department of Neurobiology & Anatomy, University of Utah School of Medicine, Salt Lake City, UT 84132-3401, USA.
authors.forename: Cornelia N
authors.initials: CN
authors.lastname: Stacher Hörndli
authors.affiliation: Department of Neurobiology & Anatomy, University of Utah School of Medicine, Salt Lake City, UT 84132-3401, USA.
authors.forename: Elliott
authors.initials: E
authors.lastname: Ferris
authors.affiliation: Department of Neurobiology & Anatomy, University of Utah School of Medicine, Salt Lake City, UT 84132-3401, USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Cheng
authors.affiliation: Department of Neurobiology & Anatomy, University of Utah School of Medicine, Salt Lake City, UT 84132-3401, USA; Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84132-3401, USA. Electronic address: chris.gregg@neuro.utah.edu.
authors.forename: Christopher
authors.initials: C
authors.lastname: Gregg
mesh_terms: D000483:Alleles; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D005260:Female; D018392:Genomic Imprinting / Q000235:genetics*; D023281:Genomics / Q000379:methods*; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D015306:Biogenic Monoamines