Monoallelic expression of the human FOXP2 speech gene

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 112; no. 22; pp. 6848 - 6854
• Main Authors: Adegbola, Abidemi A, Cox, Gerald F, Bradshaw, Elizabeth M, Hafler, David A, Gimelbrant, Alexander, Chess, Andrew
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 02.06.2015; National Acad Sciences
• Subjects: Apraxias - genetics; Biological Sciences; Chromosomes; Comparative Genomic Hybridization; Epigenetic Changes in the Developing Brain: Effects on Behavior Sackler; Female; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Developmental - genetics; Gene Expression Regulation, Developmental - physiology; Genes, X-Linked - genetics; Genetic disorders; Genomes; Genotype & phenotype; Humans; Mutation; Polymorphism, Single Nucleotide - genetics; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, DNA; Sequence Deletion - genetics; Speech - physiology; X Chromosome Inactivation - physiology; language; speech; random monoallelic expression; FOXP2; developmental verbal dyspraxia
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1411270111

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.