title: Monoallelic expression of the human FOXP2 speech gene.
abstract: The recent descriptions of widespread random monoallelic expression (RMAE) of genes distributed throughout the autosomal genome indicate that there are more genes subject to RMAE on autosomes than the number of genes on the X chromosome where X-inactivation dictates RMAE of X-linked genes. Several of the autosomal genes that undergo RMAE have independently been implicated in human Mendelian disorders. Thus, parsing the relationship between allele-specific expression of these genes and disease is of interest. Mutations in the human forkhead box P2 gene, FOXP2, cause developmental verbal dyspraxia with profound speech and language deficits. Here, we show that the human FOXP2 gene undergoes RMAE. Studying an individual with developmental verbal dyspraxia, we identify a deletion 3 Mb away from the FOXP2 gene, which impacts FOXP2 gene expression in cis. Together these data suggest the intriguing possibility that RMAE impacts the haploinsufficiency phenotypes observed for FOXP2 mutations.
authors.affiliation: Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY 10029; Center for Autism, Philadelphia, PA 19131;
authors.forename: Abidemi A
authors.initials: AA
authors.lastname: Adegbola
authors.affiliation: Division of Genetics and Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115; Department of Clinical Development, Genzyme, a Sanofi Company, Cambridge, MA 02142;
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Cox
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Bradshaw
authors.affiliation: Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT 06520;
authors.forename: David A
authors.initials: DA
authors.lastname: Hafler
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215; Department of Genetics, Harvard Medical School, Boston, MA 02115; and.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gimelbrant
authors.affiliation: Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY 10029; Fishberg Department of Neuroscience, Department of Genetics and Genomic Sciences, Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY 10029 andrew.chess@mssm.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Chess
mesh_terms: D001072:Apraxias / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D050172:Genes, X-Linked / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics; D013060:Speech / Q000502:physiology*; D049951:X Chromosome Inactivation / Q000502:physiology*
chemical_list: C465448:FOXP2 protein, human; D051858:Forkhead Transcription Factors
keywords: FOXP2; developmental verbal dyspraxia; language; random monoallelic expression; speech