page_title: FOXP2
section_title: History
hierarchical_section_title: FOXP2 / History
caption_attribution_description: English: FOXP2 gene. Cytogenetic Location: 7q31 The FOXP2 gene is located on the long (q) arm of chromosome 7 at position 31. More precisely, the FOXP2 gene is located from base pair 114,086,309 to base pair 114,693,771 on chromosome 7. http://ghr.nlm.nih.gov/gene/FOXP2
context_page_description: Forkhead box protein P2 is a protein that, in humans, is encoded by the FOXP2 gene. FOXP2 is a member of the forkhead box family of transcription factors, proteins that regulate gene expression by binding to DNA. It is expressed in the brain, heart, lungs and digestive system.
  FOXP2 is found in many vertebrates, where it plays an important role in mimicry in birds and echolocation in bats. FOXP2 is also required for the proper development of speech and language in humans. In humans, mutations in FOXP2 cause the severe speech and language disorder developmental verbal dyspraxia. Studies of the gene in mice and songbirds indicate that it is necessary for vocal imitation and the related motor learning. Outside the brain, FOXP2 has also been implicated in development of other tissues such as the lung and digestive system.
  Initially identified in 1998 as the genetic cause of a speech disorder in a British family designated the KE family, FOXP2 was the first gene discovered to be associated with speech and language and was subsequently dubbed "the language gene".
context_section_description: FOXP2 and its gene were discovered as a result of investigations on an English family known as the KE family, half of whom (15 individuals across three generations) suffered from a speech and language disorder called developmental verbal dyspraxia. Their case was studied at the Institute of Child Health of University College London. In 1990, Myrna Gopnik, Professor of Linguistics at McGill University, reported that the disorder-affected KE family had severe speech impediment with incomprehensible talk, largely characterized by grammatical deficits. She hypothesized that the basis was not of learning or cognitive disability, but due to genetic factors affecting mainly grammatical ability. (Her hypothesis led to a popularised existence of "grammar gene" and a controversial notion of grammar-specific disorder.) In 1995, the University of Oxford and the Institute of Child Health researchers found that the disorder was purely genetic. Remarkably, the inheritance of the disorder from one generation to the next was consistent with autosomal dominant inheritance, i.e., mutation of only a single gene on an autosome (non-sex chromosome) acting in a dominant fashion. This is one of the few known examples of Mendelian (monogenic) inheritance for a disorder affecting speech and language skills, which typically have a complex basis involving multiple genetic risk factors.
  In 1998, Oxford University geneticists Simon Fisher, Anthony Monaco, Cecilia S. L. Lai, Jane A. Hurst, and Faraneh Vargha-Khadem identified an autosomal dominant monogenic inheritance that is localized on a small region of chromosome 7 from DNA samples taken from the affected and unaffected members. The chromosomal region (locus) contained 70 genes. The locus was given the official name "SPCH1" (for speech-and-language-disorder-1) by the Human Genome Nomenclature committee. Mapping and sequencing of the chromosomal region was performed with the aid of bacterial artificial chromosome clones. Around this time, the researchers identified an individual who was unrelated to the KE family but had a similar type of speech and language disorder. In this case, the child, known as CS, carried a chromosomal rearrangement (a translocation) in which part of chromosome 7 had become exchanged with part of chromosome 5. The site of breakage of chromosome 7 was located within the SPCH1 region.
  In 2001, the team identified in CS that the mutation is in the middle of a protein-coding gene. Using a combination of bioinformatics and RNA analyses, they discovered that the gene codes for a novel protein belonging to the forkhead-box (FOX) group of transcription factors. As such, it was assigned with the official name of FOXP2. When the researchers sequenced the FOXP2 gene in the KE family, they found a heterozygous point mutation shared by all the affected individuals, but not in unaffected members of the family and other people. This mutation is due to an amino-acid substitution that inhibits the DNA-binding domain of the FOXP2 protein. Further screening of the gene identified multiple additional cases of FOXP2 disruption, including different point mutations and chromosomal rearrangements, providing evidence that damage to one copy of this gene is sufficient to derail speech and language development.
caption: The FOXP2 gene is located on the long (q) arm of chromosome 7, at position 31.
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