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Diverse Non-genetic, Allele-Specific Expression Effects Shape Genetic Architecture at the Cellular Level in the Mammalian Brain
- Publication Year :
- 2017
-
Abstract
- Summary Interactions between genetic and epigenetic effects shape brain function, behavior, and the risk for mental illness. Random X inactivation and genomic imprinting are epigenetic allelic effects that are well known to influence genetic architecture and disease risk. Less is known about the nature, prevalence, and conservation of other potential epigenetic allelic effects in vivo in the mouse and primate brain. Here we devise genomics, in situ hybridization, and mouse genetics strategies to uncover diverse allelic effects in the brain that are not caused by imprinting or genetic variation. We found allelic effects that are developmental stage and cell type specific, that are prevalent in the neonatal brain, and that cause mosaics of monoallelic brain cells that differentially express wild-type and mutant alleles for heterozygous mutations. Finally, we show that diverse non-genetic allelic effects that impact mental illness risk genes exist in the macaque and human brain. Our findings have potential implications for mammalian brain genetics. Video Abstract
- Subjects :
- 0301 basic medicine
Genotype
Genomics
Mice, Transgenic
Biology
Article
03 medical and health sciences
Genomic Imprinting
X Chromosome Inactivation
Genetic variation
Animals
Humans
Epigenetics
Allele
Behavioural genetics
Alleles
Genetics
Mammals
General Neuroscience
Brain
Genetic Variation
Genetic architecture
030104 developmental biology
Mutation
Macaca
Genomic imprinting
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....b78d760f62510c960c62211b570b317c