The Acquisition of Speech and Language Is Highly Developed in Humans.

The acquisition of speech and language is highly developed in humans.

Outline how the identification of genes important for these abilities have been

characterised and how disorders of speech and language development have aided

this research.

The acquisition of speech and language is highly developed in humans. Very little was known about the genetic basis of language production before the discovery of the FOXP2 gene in 2001. The analysis of a family with language disabilities aided in the finding of this gene as well as aiding in the research into the identification of genes important for language and speech abilities. The identification of this first ‘language’ gene lead to discoveries about specific brain regions and systems involved in speech production. The analysis of speech disorders was crucial to the discovery of these elements of the acquisition of speech as the areas where defects were found could be compared to normal functioning brain.

Finding the FOXP2 gene

The identification of genes important for speech and language in humans were identified in 2001 by examining a family, known as KE, over three generations, where nearly half of the members (15 individuals) suffered from a speech disorder known as childhood apraxia of speech (CAS) or developmental verbal dypraxia (DVD). Some of their symptoms included ‘garbled pronunciation, putting words in the wrong order and difficulty understand speech’ (Marcus & Fisher, 2003). They also displayed difficulty in comprehension and writing as well as language expression.

Many behavior and medical test were conducted to examine the behavioral and neural phenotypes of affected and unaffected members of the KE family. Behavioral tests consisted of analysis of pronunciation, grammar, semantics and IQ. Overall members thought to be affected had significantly impaired results compared to unaffected members. However affected members tended to have greater impaired results for tests for language production compared to tests for comprehension. It was also found that overall members with speech disorders had a lower IQ than members with no speech disorders. The results of these tests distinguished the affected members from the unaffected, which provided a base that allowed the groups to be compared on a genetic level, which ultimately lead to the discovery of the FOXP2 gene.

If was found that affected members had a greater deficit when they tried to repeat multisyllabic words compared to monosyllabic words. This indicated that a core difference between affected and unaffected members was a higher order orofacial motor impairment as speech requires accurate selection, coordination and timing of sequences of rapid facial movements. (Vargha-Khadem, Gadian, Copp, & Mishkin, 2005)

It was noticed that affected KE members verbal and orofacial dyspraxia was very similar to that of people with Broca’s aphasia. Broca’s aphasia is when the Broca’s area is damaged resulting in difficultly articulating speech and preforming facial motor movements. This indicated that the factor causing speech disorders in affected members affects the Broca’s area in affected KE members.

Multiples medical test were conducted on participants to provide information about the neuropathological basis of the speech defects as well as identifying neural sites that underlie the acquisition. Findings from behavioral tests would suggest that the underlying neuropathology would involve multiple components of the motor system. (Vargha-Khadem, Gadian, Copp, & Mishkin, 2005). Tests included MRI, functional MRI (fMRI) and PET scans, which found that members with speech disorders had some underactive brain regions when compared to unaffected members. These regions included the left supplementary motor area (SMA), the subjacent cingulate cortex on the left and the left pre SMA/cingulate cortex. (Nudel & Newbury, 2013)

MRI scans also found structural differences between affected and unaffected KE members. Multiple regions of different levels of grey matter between affected and unaffected members were found. These included more grey matter in the Wernicke’s area, angular gyrus and the lenitfom in affected members as well as less grey matter in the Broca’s area, ventral cerebellum and the caudate nucleus^[a].

By examining the DNA of affected and unaffected individuals of the family a genome-wide linkage analysis study was conducted. This study found evidence of linkage on the long arm of chromosome 7. Fine mapping of the region found a 5.6 region in chromosomal band 7q31 called SPCH1. Further study of this region using polymorphic markers revealed that the breakpoint was located inside the FOXP2 gene. (Nudel & Newbury, 2013)

Further examination found a missense mutation of base changes from G to A in exon 14, this results in an arginine-to-histidine substitution in the fork head DNA-binding domain of the FOXP2 gene. This mutation was found in a glutamine-rich region consisting of two polygutamine tracks, encoded by CAG and CAA repeats, which are known to have high mutation rates. (Enard, et al., 2002). This mutation leads to a truncated FOXP2 protein product.

Two other candidates with speech disorders outside of the KE family were also examined, one of the candidate had a chromosomal translocation with a breakpoint at the same location as other affected KE members, therefore further indicating that region is involved in speech and language disorders.

All affected members of the KE family were heterozygous for the mutation, which indicates that inheritance of speech disorders is dominant. The inheritance of speech disorders in the KE family appears to be a result of monogenic inheritance with the involvement of a dominant single gene on an autosome (Marcus & Fisher, 2003).

Mutations and chromosomal rearrangements involving the FOXP2 gene are associated with the central nervous system and impact the development of speech and language abilities.

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The FOXP2 gene

The FOXP2 gene is responsible for the production of a protein called forkhead box P2. This protein is a transcription factor and aids in a range of functions including cellular differentiation and proliferation, pattern formation and signal transduction.

FOXP2 controls the expression and activity of other genes by binding to DNA through its forkhead domain. Genes consist of coding regions and regulatory region; the coding region acts as a template for the production of specific proteins. The production of proteins is controlled by transcription factors, in this FOXP2 protein is the transcription factor. Transcription factors affect the levels of proteins transcribed. FOXP2 acts as a repressor and inhibits transcription of downstream genes when bound to the regulatory region, as shown in figure 2. The regulatory region of the gene is responsible for determining the level of protein produced. Transcription factors allow cells of an organism to have diverse function and morphology by regulating the levels of expression of genes at different points of development and location.