Editing FOXP2 (section)

== History ==
''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) had a speech and language disorder called [[developmental verbal dyspraxia]]. Their case was studied at the [[UCL Institute of Child Health|Institute of Child Health of University College London]].<ref name = "Hurst_1990">{{cite journal | vauthors = Hurst JA, Baraitser M, Auger E, Graham F, Norell S | title = An extended family with a dominantly inherited speech disorder | journal = Developmental Medicine and Child Neurology | volume = 32 | issue = 4 | pages = 352–5 | date = April 1990 | pmid = 2332125 | doi = 10.1111/j.1469-8749.1990.tb16948.x | s2cid = 2654363 }}</ref> 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.<ref>{{cite journal | vauthors = Gopnik M | title = Genetic basis of grammar defect | journal = Nature | volume = 347 | issue = 6288 | pages = 26 | date = September 1990 | pmid = 2395458 | doi = 10.1038/347026a0 | s2cid = 4323390 | doi-access = free | bibcode = 1990Natur.347...26G }}</ref> She hypothesized that the basis was not of learning or cognitive disability, but due to genetic factors affecting mainly grammatical ability.<ref>{{cite journal | vauthors = Gopnik M | title = Feature-blind grammar and dysphagia | journal = Nature | volume = 344 | issue = 6268 | pages = 715 | date = April 1990 | pmid = 2330028 | doi = 10.1038/344715a0 | s2cid = 4360334 | bibcode = 1990Natur.344..715G | doi-access = free }}</ref> (Her hypothesis led to a popularised existence of "grammar gene" and a controversial notion of grammar-specific disorder.<ref>{{cite book| vauthors = Cowie F |title=What's Within?: Nativism Reconsidered|year=1999|publisher=Oxford University Press|location=New York, US|isbn=978-0-19-515978-3|pages=290–291|url=https://books.google.com/books?id=xb1pvz1JhQYC}}</ref><ref>{{cite book| vauthors = Jenkins L |title=Biolinguistics: Exploring the Biology of Language|year=2000|publisher=Cambridge University Press|location=Cambridge, UK|isbn=978-0-521-00391-9|pages=98–99|edition=Revised|url=https://books.google.com/books?id=Z2AN2f6GPFQC}}</ref>) In 1995, the [[University of Oxford]] and the Institute of Child Health researchers found that the disorder was purely genetic.<ref>{{cite journal | vauthors = Vargha-Khadem F, Watkins K, Alcock K, Fletcher P, Passingham R | title = Praxic and nonverbal cognitive deficits in a large family with a genetically transmitted speech and language disorder | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 92 | issue = 3 | pages = 930–3 | date = January 1995 | pmid = 7846081 | pmc = 42734 | doi = 10.1073/pnas.92.3.930 | doi-access = free | bibcode = 1995PNAS...92..930V }}</ref> 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.<ref name = "Fisher_2003">{{cite journal | vauthors = Fisher SE, Lai CS, Monaco AP | title = Deciphering the genetic basis of speech and language disorders | journal = Annual Review of Neuroscience | volume = 26 | pages = 57–80 | year = 2003 | pmid = 12524432 | doi = 10.1146/annurev.neuro.26.041002.131144 | hdl-access = free | s2cid = 1276712 | hdl = 11858/00-001M-0000-0012-CB7E-4 }}</ref>

[[File:FOXP2 location.png|thumb|left|The ''FOXP2'' gene is located on the long (q) arm of [[Chromosome 7 (human)|chromosome 7]], at position 31.]]
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.<ref name="Fisher_1998"/> The chromosomal region (locus) contained 70 genes.<ref>{{cite web|title=Genes that are essential for speech|url=http://thebrain.mcgill.ca/flash/d/d_10/d_10_m/d_10_m_lan/d_10_m_lan.html|website=The Brain from Top to Bottom|access-date=31 October 2014}}</ref> 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.<ref name="Lai_2000"/> 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 [[Chromosomal translocation|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.<ref name="Lai_2000"/>

In 2001, the team identified in CS that the mutation is in the middle of a protein-coding gene.<ref name="Lai_2001"/> 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.<ref name="Lai_2001"/> This mutation is due to an amino-acid substitution that inhibits the DNA-binding domain of the ''FOXP2'' protein.<ref name = "Vernes_2006">{{cite journal | vauthors = Vernes SC, Nicod J, Elahi FM, Coventry JA, Kenny N, Coupe AM, Bird LE, Davies KE, Fisher SE | title = Functional genetic analysis of mutations implicated in a human speech and language disorder | journal = Human Molecular Genetics | volume = 15 | issue = 21 | pages = 3154–67 | date = November 2006 | pmid = 16984964 | doi = 10.1093/hmg/ddl392 | doi-access = free | hdl = 11858/00-001M-0000-0012-CB23-C | hdl-access = free }}</ref> Further screening of the gene identified multiple additional cases of ''FOXP2'' disruption, including different point mutations<ref name="MacDermot_2005"/> and chromosomal rearrangements,<ref name="Feuk_2006">{{cite journal | vauthors = Feuk L, Kalervo A, Lipsanen-Nyman M, Skaug J, Nakabayashi K, Finucane B, Hartung D, Innes M, Kerem B, Nowaczyk MJ, Rivlin J, Roberts W, Senman L, Summers A, Szatmari P, Wong V, Vincent JB, Zeesman S, Osborne LR, Cardy JO, Kere J, Scherer SW, Hannula-Jouppi K | title = Absence of a paternally inherited FOXP2 gene in developmental verbal dyspraxia | journal = American Journal of Human Genetics | volume = 79 | issue = 5 | pages = 965–72 | date = November 2006 | pmid = 17033973 | pmc = 1698557 | doi = 10.1086/508902 }}</ref> providing evidence that damage to one copy of this gene is sufficient to derail speech and language development.