Decoding the genetics of speech and language

Abstract

Researchers are beginning to uncover the neurogenetic pathways that underlie our unparalleled capacity for spoken language. Initial clues come from identification of genetic risk factors implicated in developmental language disorders. The underlying genetic architecture is complex, involving a range of molecular mechanisms. For example, rare protein-coding mutations of the FOXP2 transcription factor cause severe problems with sequencing of speech sounds, while common genetic risk variants of small effect size in genes like CNTNAP2, ATP2C2 and CMIP are associated with typical forms of language impairment. In this article, we describe how investigations of these and other candidate genes, in humans, animals and cellular models, are unravelling the connections between genes and cognition. This depends on interdisciplinary research at multiple levels, from determining molecular interactions and functional roles in neural cell-biology all the way through to effects on brain structure and activity.

Heterozygous deletion of the LRFN2 gene is associated with working memory deficits

“…1,2 However, most of the genetic determinants of higher cognitive functions including learning, attention, memory and executive function remain unknown. 3,4 Working memory (WM) is a neural system that provides temporary active maintenance of necessary information while performing complex cognitive tasks such as reasoning, learning, understanding, thinking, decision making, and planning. [5][6][7] Although selective WM deficit is a rare condition, many studies have shown that poor WM performance can have an impact on academic performance.…”

Insights into the Genetic Foundations of Human Communication

“…A framework for bridging the gap between genetics and behavior is provided by a decade of research into FOXP2 (Fisher and Scharff 2009;Graham and Fisher 2013). It is still not fully understood why disruption of one copy of this gene should lead to a severe speech and language disorder, but considerable progress has been made in elucidating both molecular-level effects and consequences for higher-level brain function.…”

“…There is evidence that these substitutions affect target regulation and synaptic plasticity, but the molecular mechanism of these effects is still unknown (Konopka et al 2009;Enard et al 2009;ReimersKipping et al 2011). Interestingly, a selective sweep may have occurred at the FOXP2 locus within the last 200,000 years, but is not explained by the amino acid substitutions and may instead relate to non-coding changes affecting FOXP2 regulation, or may be a false-positive finding (Coop et al 2008;Maricic et al 2013;Graham and Fisher 2013).…”

A Molecular Genetic Perspective on Speech and Language

“…Thus, the identification of FOXP2 may have been something of a paradigm shift for the language sciences because it facilitated a series of innovative molecular investigations into the neurobiological pathways and evolutionary history of spoken language using this gene as a unique entry point (Fisher & Scharff, 2009). Such work has called on a diverse array of experimental strategies and model systems, ranging from neuronal cells investigated at a laboratory bench, to genetic manipulations in animals, to studies of humans (Graham & Fisher, 2013).…”

“…Arguments for a genetic basis have drawn from an array of diverse fields and approaches, marshaling threads of evidence taken from formal linguistics, child development, twin studies, biological anthropology, comparative psychology, and so on. In recent years, through advances in molecular biology techniques, it has become possible to move beyond these indirect sources and let the genome speak for itself (Graham & Fisher, 2013). In particular, by studying neurodevelopmental disorders that disproportionately disturb speech and language skills, researchers started to identify individual genes that may be involved in the relevant neurobiological pathways.…”