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Forkhead box protein P2 (FOXP2) is a protein that, in humans, is encoded by the ''FOXP2'' gene, also known as ''CAGH44'', ''SPCH1'' or ''TNRC10'', and is required for proper development of speech and language. Initially identified as the genetic factor of speech disorder in KE family, its gene is the first gene discovered associated with speech and language. The gene is located on chromosome 7 (7q31, at the ''SPCH1'' locus), and is expressed in fetal and adult brain, heart, lung and gut. ''FOXP2'' orthologs have also been identified in other mammals for which complete genome data are available. The ''FOXP2'' protein contains a forkhead-box DNA-binding domain, making it a member of the FOX group of transcription factors, involved in regulation of gene expression. In addition to this characteristic forkhead-box domain, the protein contains a polyglutamine tract, a zinc finger and a leucine zipper. The gene is more active in females than in males, to which could be attributed better language learning in females. In humans, mutations of ''FOXP2'' cause a severe speech and language disorder.〔 Versions of ''FOXP2'' exist in similar forms in distantly related vertebrates; functional studies of the gene in mice and in songbirds indicate that it is important for modulating plasticity of neural circuits. Outside the brain ''FOXP2'' has also been implicated in development of other tissues such as the lung and gut.〔 ''FOXP2'' is popularly dubbed the "language gene", but this is only partly correct since there are other genes involved in language development. It directly regulates a number of other genes, including ''CNTNAP2'', ''CTBP1'', and ''SRPX2''. Two amino acid substitutions distinguish the human ''FOXP2'' protein from that found in chimpanzees, but only one of these two changes is unique to humans.〔 Evidence from genetically manipulated mice and human neuronal cell models suggests that these changes affect the neural functions of ''FOXP2''. == Discovery == ''FOXP2'' and its gene were discovered as a result of investigations on an English family known as the KE family, half of whom (fifteen 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 London College. 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.〔(【引用サイトリンク】url=http://thebrain.mcgill.ca/flash/d/d_10/d_10_m/d_10_m_lan/d_10_m_lan.html )〕 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. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「FOXP2」の詳細全文を読む スポンサード リンク
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