Autosomal monoallelic expression: genetics of epigenetic diversity?
In mammals, relative expression of the two parental alleles of many genes is controlled by one of three major epigenetic phenomena: X chromosome inactivation, imprinting, and mitotically stable autosomal monoallelic expression (MAE). MAE affects a large fraction of human autosomal genes and introduces enormous epigenetic heterogeneity in otherwise similar cell populations. Despite its prevalence, many functional and mechanistic aspects of MAE biology remain unknown. Several lines of evidence imply that MAE establishment and maintenance are controlled by a variety of genetic elements. Based on known genomic features regulating X-inactivation and imprinting, we outline likely features of MAE-controlling elements. We also assess implications of MAE for genotype-phenotype relationship, with a focus on haploinsufficiency.
Department of Cancer Biology, Dana-Farber Cancer Institute, Department of Genetics, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, United States.
Virginia
V
Savova
Sébastien
S
Vigneau
Alexander A
AA
Gimelbrant
D000483:Alleles; D000818:Animals; D044127:Epigenesis, Genetic / Q000235:genetics*; D015870:Gene Expression; D014644:Genetic Variation; D016678:Genome / Q000235:genetics*; D057895:Haploinsufficiency; D006801:Humans; D008957:Models, Genetic; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*