The Genetics of Language Acquisition

This chapter focuses on the understanding of the role of genetics in language and explores how genetics contribute to language, and shows how new genetic techniques can offer inroads into the molecular basis of language acquisition. It discusses some of the key findings of gene x environment studies and provides a snapshot of the understanding in the field, considering some of the limitations of the type of study design. The chapter describes the field of play in the genetics of language acquisition and explains the heritability of language and the role of family and twin studies in the understanding of language. It also explores the inheritance mechanisms that are implicated in language development. The chapter considers how modern DNA sequencing approaches are revolutionizing the field of language genetics. Heritability studies have provided many key insights into the genetics of both language acquisition and language disorders. Insights into mechanisms can also come from the opposite end of the language ability spectrum

The genomic landscape of language disorders: Insights into evolution

Studies of severe, monogenic forms of language disorders have revealed important insights into the mechanisms that underpin language development and evolution. It is clear that monogenic mutations in genes such as FOXP2 and CNTNAP2 only account for a small proportion of language disorders seen in children, and the genetic basis of language in modern humans is highly complex and poorly understood. In this review, we examine why we understand so little of the genetic landscape of language disorders, and how the genetic background of an individual greatly affects the way in which a genetic change is expressed. We discuss how the underlying genetics of language disorders has informed our understanding of language evolution, and how recent advances may obtain a clearer picture of language capacity in ancient hominins

Genetic studies of language disorders

Developmental language disorder (DLD) is estimated to affect 8 per cent of primary school-aged children, and has lasting impacts on academic achievement and social-emotional and behavioural outcomes. DLD is classified as a severe and persistent impairment in the acquisition, understanding, production or use of language, occurring in the absence of comorbid neurodevelopmental disorder. The phenotype of DLD is well established, yet there is relatively limited understanding of its aetiology. A complex interaction of genetic variants and environmental factors is thought to be the cause. To date, linkage and association analyses have implicated a handful of genes in DLD populations, including CMIP and ATP2C2. While many of these variants are common in DLD, they are not consistently associated with severe language impairment, and many overlap with chromosome regions commonly associated with neurodevelopmental disorders such as intellectual disability. The effects of alternate genetic models such as copy number and rare variants may provide a gateway to understanding the complex genetic pathways of this disorder. Pleiotropy and generalisation are also important considerations in understanding the genetic architecture of DLD. Here we outline the phenotype of DLD and provide an overview of recently identified gene pathways implicated in this disorder

Copy number variation burden does not predict severity of neurodevelopmental phenotype in children with a sex chromosome trisomy

Sex chromosome trisomies (SCTs) (XXX, XXY, and XYY karyotypes) are associated with an elevated risk of neurodevelopmental disorders. The range of severity of the phenotype is substantial. We considered whether this variable outcome was related to the presence of copy number variants (CNVs)—stretches of duplicated or deleted DNA. A sample of 125 children with an SCT were compared with 181 children of normal karyotype who had been given the same assessments. First, we compared the groups on measures of overall CNV burden: number of CNVs, total span of CNVs, and likely functional impact (probability of loss‐of‐function intolerance, pLI, summed over CNVs). Differences between groups were small relative to within‐group variance and not statistically significant on overall test. Next, we considered whether a measure of general neurodevelopmental impairment was predicted by pLI summed score, SCT versus comparison group, or the interaction between them. There was a substantial effect of SCT/comparison status but the pLI score was not predictive of outcomes in either group. We conclude that variable presence of CNVs is not a likely explanation for the wide phenotypic variation in children with SCTs. We discuss methodological challenges of testing whether CNVs are implicated in causing neurodevelopmental problems

Candidate gene variant effects on language disorders in Robinson Crusoe Island

Robinson Crusoe Island is a geographically and socially isolated settlement located over 600km west of the Port of Valparíso, Chile. An unusually high incidence (30%) of the Chilean equivalent of developmental language disorder (TEL) has been reported in Islander children, with 90% of these affected children found to be direct descendants of a pair of original founder-brothers, therefore strongly suggesting a shared genetic basis. Here we utilise whole-genome sequencing to investigate potential underlying variants in a panel of thirty-four genes known to play a role in language disorders, in seven TEL affected and ten unaffected islanders. We use this targeted approach to look for rare, shared variants that may underlie the diagnosis of TEL in a Mendelian genetic model. We go on to test whether the overall burden of rare variants is enriched in individuals affected by TEL or with Islanders related to the founder-brother lineage. In the absence of explanatory rare variants, we further investigate these candidate genes within a complex model of inheritance, where inheriting a small number of moderate impact common variants may increase susceptibility of developing TEL. We examine if any variants segregate with affection status or with founder-brother-related status, and therefore may increase risk of developing a language disorder. Finally, we perform a pooled, gene-based tests to evaluate relationships between combined variation across candidate genes and TEL affection status. Here we report a comprehensive examination of genes directly implicated in language-related mechanisms to identify ‘low hanging fruit’ of causative monogenic Mendelian variants, and complex association model of increased susceptibility in developmental language disorder found on Robinson Crusoe Island

The genetic and molecular basis of developmental language disorder: A review

Language disorders are highly heritable and are influenced by complex interactions between genetic and environmental factors. Despite more than twenty years of research, we still lack critical understanding of the biological underpinnings of language. This review provides an overview of the genetic landscape of developmental language disorders (DLD), with an emphasis on the importance of defining the specific features (the phenotype) of DLD to inform gene discovery. We review the specific phenotype of DLD in the genetic literature, and the influence of historic variation in diagnostic inclusion criteria on researchers’ ability to compare and replicate genotype-phenotype studies. This review provides an overview of the recently identified gene pathways in populations with DLD and explores current state-of-the-art approaches to genetic analysis based on the hypothesized architecture of DLD. We will show how recent global efforts to unify diagnostic criteria have vastly increased sample size and allow for large multi-cohort metanalyses, leading the identification of a growing number of contributory loci. We emphasize the important role of estimating the genetic architecture of DLD to decipher underlying genetic associations. Finally, we explore the potential for epigenetics and environmental interactions to further unravel the biological basis of language disorders.

The effects of prenatal smoke exposure on language development- a systematic review

The negative health effects cigarette smoking during pregnancy (SDP) on the foetus are well known. Despite previous reports of poor cognitive performance in offspring exposed to SDP, few studies specifically consider language outcomes according to maternal smoking. In this study, we systematically review the literature to assess the relationships between SDP and child language. Of the 14 studies reviewed, 13 (93%) reported significant associations between maternal smoking or exposure and language outcomes. Despite this consistent association, only 8 of the 13 studies reporting associations (62%) concluded direct relationships between exposure and outcome. The remaining studies suggested that the relationship between smoking and language could be explained by factors such as maternal IQ, socioeconomic status (SES) and parental age. Future studies should apply careful study designs allowing for confounding factors across child, parental, environmental and genetic influences. Our review suggests that smoking cessation is likely to positively affect child language outcomes

The genetic population structure of Robinson Crusoe Island, Chile

Studies examining genetic conditions common in Latin America are highly underrepresented in the scientific literature. Understanding of the population structure is limited, particularly Chile, in part due to the lack of available population specific data. An important first-step in elucidating disease mechanisms in Latin America countries is to understand the genetic structure of isolated populations. Robinson Crusoe Island (RCI) is a small land mass off the coast of Chile. The current population of over 900 inhabitants are primarily descended from a small number of founders who colonized the island in the late 1800s. Extensive genealogical records can trace the ancestry of almost the entire population. We perform a comprehensive genetic analysis to investigate the ancestry of the island population, examining ancestral mitochondrial and Y chromosome haplogroups, as well as autosomal admixture. Mitochondrial and Y chromosome haplogroups indicated a substantial European genetic contribution to the current RCI population. Analysis of the mitochondrial haplogroups found in the present-day population revealed that 79.1% of islanders carried European haplogroups, compared to 60.0% of the mainland Chilean controls from Santiago. Both groups showed a substantially lower contribution of indigenous haplogroups than expected. Analysis of the Y chromosome haplogroups also showed predominantly European haplogroups detected in 92.3% of male islanders and 86.7% of mainland Chilean controls. Using the near-complete genealogical data collected from the RCI population, we successfully inferred the ancestral haplogroups of 16/23 founder individuals, revealing genetic ancestry from Northern and Southern Europe. As mitochondrial and Y investigations only provide information for direct maternal and paternal lineages, we expanded this to investigate genetic admixture using the autosomes. Admixture analysis identified substantial indigenous genetic admixture in the RCI population (46.9%), higher than that found in the Santiago mainland Chilean controls (43.4%), but lower than a more representative Chilean population (Chile_GRU) (49.1%). Our study revealed the Robinson Crusoe Island population show a substantial genetic contribution for indigenous Chileans, similar to the level reported in mainland Chileans. However, direct maternal and paternal haplogroup analysis revealed strong European genetic contributions consistent with the history of the Island