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Individual differences |
Methods | Statistics | Clinical | Educational | Industrial | Professional items | World psychology |
|forkhead box P2|
|Symbol(s):||FOXP2 TNRC10, SPCH1|
FOXP2 is a member of the large FOX family of transcription factors. Information from known human mutations and mouse studies suggest that FOXP2 regulates genes involved in the development of tissues such as brain, lung, and gut. The exact identity of the genes FOXP2 regulates is still not known, however.
FOXP2 and human diseaseEdit
Several cases of developmental verbal dyspraxia in humans have been linked to mutations in the FOXP2 gene. Individuals have little or no cognitive handicaps but are unable to correctly perform the coordinated movements required for speech. fMRI analysis of these individuals performing silent verb generation and spoken word repetition tasks showed underactivation of Broca's area and the putamen, brain centers thought to be involved in language tasks. Because of this, FOXP2 has been dubbed the "speech and language gene". Scientists have also looked for associations between FOXP2 and autism but so far no evidence has found.
There is some evidence that the linguistic impairments associated with a mutation of the FOXP2 gene are not simply the result of a fundamental deficit in motor control. For example:
- the impairments include difficulties in comprehension;
- brain imaging of affected individuals indicates functional abnormalities in language-related cortical and basal/ganglia regions, demonstrating that the problems extend beyond the motor system.
FOXP2 is required for proper brain and lung development. Knockout mice with only one functional copy of the FOXP2 gene have significantly reduced vocalizations as pups. Knockout mice with no functional copies of FOXP2 are runted, display abnormalities in brain regions such as the Purkinje layer, and die 21 days after birth from inadequate lung development.
Different studies of FOXP2 in songbirds suggest that FOXP2 may regulate genes involved in neuroplasticity: during song learning FoxP2 is upregulated in a brain regions critical for song learning in young zebra finches. Similarily, in adult canaries higher FoxP2 levels also correlate with song changes  In addition, levels of FOXP2 in adult zebra finches are significantly lower when males direct their song to females than when they sing song in other contexts .
FOXP2 has also been implicated in the development of bat echolocation.A recent extraction of DNA from Neanderthal bones indicates that Neanderthals had the same version (allele) of the FOXP2 gene that is known to play a role in human language.
The FOXP2 protein sequence is highly conserved. Similar FOXP2 proteins can be found in songbirds, fish, and reptiles such as alligators. Aside from a polyglutamine tract, human FOXP2 differs from chimp FOXP2 by only two amino acids, mouse FOXP2 by only 3 amino acids, and zebra finch FOXP2 by only 7 amino acids. Some researchers have speculated that the two amino acid differences between chimps and humans led to the evolution of language in humans. Others, however, have been unable to find a clear association between species with learned vocalizations and similar mutations in FOXP2. Both human mutations occur in an exon with no known function.
The search for the gene was initially started as a result of the investigations into the KE (or K) family. Certain members of this family suffered from an inherited speech and language disorder and living members stretched back three generations. Closer inspection of the family revealed the disorder to be autosomal dominant.
A scan was performed of the genome of the affected and some of the unaffected family members. This initial scan limited the affected region to a spot on chromosome 7, which the team called "SPCH1". Sequencing of this region was done with the aid of bacterial artificial chromosome clones. At this point, another individual was located who had a similar disorder but was unrelated to the family. The genome of this individual was mapped and it was discovered that there was a break in chromosome 7.
Further investigation discovered a point mutation in this chromosome. Sequenced and analysed, this is now referred to as the FOXP2 gene.
See also Edit
- FOX proteins
- Broca's area
- Evolution of Homo sapiens
- Genetics and language
- Human evolutionary genetics
- Human Genome Project
- Chimpanzee genome project
- Origin of language
- ↑ Lai C, Fisher S, Hurst J, Levy E, Hodgson S, Fox M, Jeremiah S, Povey S, Jamison D, Green E, Vargha-Khadem F, Monaco A (2000). The SPCH1 region on human 7q31: genomic characterization of the critical interval and localization of translocations associated with speech and language disorder. Am J Hum Genet 67 (2): 357-68.
- ↑ Vargha-Khadem F, Gadian DG, Copp A, Mishkin M (2005). FOXP2 and the neuroanatomy of speech and language. Nature Reviews Neuroscience 6: 131-137.
- ↑ Newbury DF, Bonora E, Lamb JA, Fisher SE, Lai CS, Baird G, Jannoun L, Slonims V, Stott CM, Merricks MJ, Bolton PF, Bailey AJ, Monaco AP (2002). FOXP2 is not a major susceptibility gene for autism or specific language impairment. Am J Hum Genet 70 (5): 1318-27.
- ↑ Shu W, Cho JY, Jiang Y, Zhang M, Weisz D, Elder GA, Schmeidler J, De Gasperi R, Sosa MA, Rabidou D, Santucci AC, Perl D, Morrisey E, Buxbaum JD (2005). Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene. Proc Natl Acad Sci U S A 102 (27): 9643-8.
- ↑ Shu W, Lu MM, Zhang Y, Tucker PW, Zhou D, Morrisey EE (2007). Foxp2 and Foxp1 cooperatively regulate lung and esophagus development. Development 134 (10): 1991-2000.
- ↑ Haesler S, Wada K, Nshdejan A,Morrisey EE, Lints T, Jarvis ED, Scharff C (2004). FoxP2 expression in avian vocal learners and non-learners. J Neurosci. (24): 3164-75.
- ↑ Teramitsu I, White SA (2006). FoxP2 regulation during undirected singing in adult songbirds. J Neurosci 26 (28): 7390-4.
- ↑ Li, Gang; Wang, Jinhong; Rossiter, Stephen J.; Jones, Gareth; Zhang, Shuyi (2007), Accelerated FoxP2 Evolution in Echolocating Bats, http://www.plosone.org/article/fetchArticle.action?articleURI=info:doi/10.1371/journal.pone.0000900, retrieved on 2007-9-19
- ↑ Neanderthals Had Important Speech Gene, DNA Evidence Shows
- ↑ 10.0 10.1 Webb DM, Zhang J (2005). FoxP2 in song-learning birds and vocal-learning mammals. J Hered. 96 (3): 212-6.
- ↑ 11.0 11.1 Scharff C, Haesler S (2004). An evolutionary perspective on FoxP2: strictly for the birds?. Curr Opin Neurobiol 15 (6): 694-703.
- ↑ 12.0 12.1 Enard W, Przeworski M, Fisher S, Lai C, Wiebe V, Kitano T, Monaco A, Pääbo S (2002). Molecular evolution of FOXP2, a gene involved in speech and language. Nature 418 (6900): 869-72.
- ↑ 13.0 13.1 Teramitsu I, Kudo LC, London SE, Geschwind DH, White SA (2004). Parallel FoxP1 and FoxP2 expression in songbird and human brain predicts functional interaction. J Neurosci. 24 (13): 3152-63.
Constitutive androstane receptor - Core binding factor - E2F - Farnesoid X receptor - Kruppel-like factors - Nanog - NF-kB - Oct-4 - P300/CBP - Peroxisome proliferator-activated - PIT-1 - Rho factor - R-SMAD - Sigma factor - Sox2 - Sp1 - STAT protein
Steroid hormone receptors
Type I: Glucocorticoid receptor - Mineralocorticoid receptor - Sex hormone receptor (Androgen receptor, Estrogen receptor, Progesterone receptor)
Type II: Calcitriol receptor - Retinoid receptor (Retinoic acid receptor, Retinoid X receptor) - Thyroid hormone receptor
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