FOXP2

FOXP2 ("forkhead box P2") is a gene that is implicated in the development of language skills, including grammatical competence.

Introduction
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 disease
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.

Function
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.

Evolution
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.

History
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.