Candidate gene variant effects on language disorders in Robinson Crusoe Island

Abstract

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 founderbrothers, 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 Here we report a comprehensive examination of genes directly implicated in languagerelated 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.

Pedigree-Based Gene Mapping Supports Previous Loci and Reveals Novel Suggestive Loci in Specific Language Impairment

“…In the context of the many candidate SLI regions and genes already reported, only one candidate gene NOP9 overlapped with our three reported suggestive regions, though other regions with LOD scores greater than 1.2 in four families (315, 387, 430, and 489) are also noted if they coincided with previously reported regions or candidate genes associated with SLI, RD, NWR performance, ASD, and CAS (see Supplemental Table S1 ; Chen et al, 2017 ; Mountford & Newbury, 2018 ; Mountford et al, 2019 ). A few candidate genes of note overlapped with the regions showing markers with LOD scores above 1.2 including ROBO1 , ROBO2 , and FOXP1 (see Supplemental Table S1 ; Chen et al, 2017 ; Mountford & Newbury, 2018 ; Mountford et al, 2019 ).…”

“…Across the reported linkage regions, many candidate genes have been identified and these studies indicate that more genes are involved in SLI than previously expected (Chen et al, 2017;Mountford & Newbury, 2018;Mountford et al, 2019). The current list of language impairment candidate genes is extensive, although across studies and reviews about 30 candidates are more consistently and recently discussed (Chen et al, 2017;Mountford & Newbury, 2018;Mountford et al, 2019).…”

“…Such studies have provided strong evidence for candidate genes including TM4SF20 , NFXL1 , and SETBP1 ( Rakhlin et al, 2013 ; Villanueva et al, 2015 ; Wiszniewski et al, 2013 ). One study of note is the family-based Robinson Crusoe Island investigation of a founder population, which underscores the need for further family-based study ( Mountford et al, 2019 ; Villanueva et al, 2011 , 2015 ). Genetic studies in the founder population identified a protein coding change in NFXL1 with a higher frequency in individuals from the population with language impairment ( Villanueva et al, 2015 ).…”

The Effects of Reading and Language Intervention on Literacy Skills in Children in a Remote Community: A Randomized Controlled Trial

“…Difficulties are reported across a range of linguistic measures including phonological production and expressive and receptive morphology (De Barbieri et al, 2018). Further, the language difficulties observed in this population aggregate within families from the last island colonization which suggests the influence of genetic risk factors (Villanueva et al, 2015), although the contributory genetic mechanisms have yet to be fully characterized (Mountford et al, 2019).…”

Human biology and ancient DNA: exploring disease, domestication and movement

“…Their results challenge the assumption that Neanderthal admixture has negatively impacted on modern human health, and suggest that maternal survival may have been an important selective pressure for the persistence of hypercoagulability alleles in modern Europeans. Mountford et al (2019) examine the genetics underlying our ability to communicate and interact with the world. They ask whether small population isolates help us to detect genes associated with developmental disorders of language and, thus, better understand their evolution in ancient genomic data.…”