Exome Evaluation of Autism-Associated Genes in Amazon American Populations

Abstract

Autism spectrum disorder is a neurodevelopmental disorder, affecting one in 160 children worldwide. The causes of autism are still poorly understood, but research shows the relevance of genetic factors in its pathophysiology, including the CHD8, SCN2A, FOXP1 and SYNGAP1 genes. Information about the genetic influence on various diseases, including autism, in the Amerindian population from Amazon, is still scarce. We investigated 35 variants of the CHD8, SCN2A, FOXP1, and SYNGAP1 gene in Amazonian Amerindians in comparison with publicly available population frequencies from the 1000 Genomes Project database. Our study identified 16 variants in the Amerindian population of the Amazon with frequencies significantly different from the other populations. Among them, the SCN2A (rs17183814, rs75109281, and rs150453735), FOXP1 (rs56850311 and rs939845), and SYNGAP1 (rs9394145 and rs115441992) variants presented higher frequency than all other populations analyzed. In addition, nine variants were found with lower frequency among the Amerindians: CHD8 (rs35057134 and rs10467770), SCN2A (rs3769951, rs2304014, rs1838846, and rs7593568), FOXP1 (rs112773801 and rs56850311), and SYNGAP1 (rs453590). These data show the unique genetic profile of the indigenous population of the Brazilian Amazon. Knowledge of these variants can help to understand the pathophysiology and diagnosis of autism among Amerindians, Brazilians, and in admixed populations that have contributions from this ethnic group.

Pharmacogenomic Profile of Amazonian Amerindians

“…These findings agree with the history of human evolution: Amerindians are more genetically similar to American and East Asian populations and more genetically distant from African populations [ 67 , 68 ]. This pattern of genetic profile between Amazonian Amerindians and other global population corroborates with other genetic association studies [ 12 , 24 , 25 ].…”

“…However, some population groups remain underrepresented in these types of investigations, such as Native American populations. Recently, some efforts have been made to include genetic information about allelic frequencies of Native American populations and their influence on susceptibility to diseases, such as severe forms of COVID-19 [ 23 ], psychological disorders [ 24 ], oncological diseases [ 25 , 26 ], and also on different types of pharmacological treatments [ 12 , 13 , 27 , 28 ]. Most of these studies are focused on one or a few group of genes.…”

A scoping review of the landscape of health-related open datasets in Latin America

“…5 datasets were created for Colombia: 1 with social determinants of health and nutrition data for Public Health tasks [ 21 ], and 4 with a more clinical point of view which are a muscle dysmorphia dataset [ 22 ], body fat measurement [ 23 ], endoscopic ultrasound scans [ 24 ], and a treatment of Helicobacter pylori dataset [ 25 ]. 8 datasets were created for Brazil: 2 from a Public Health perspective which are BASICS [ 26 ] with epidemiologic data, and the dataset on child vaccination [ 27 ]; 1 dataset of laboratory exams [ 28 ]; 1 dataset of images of leprosy called AI4Leprosy [ 29 ]; 1 open dataset with electronic health records called ORBDA [ 30 ]; 2 datasets for genomics [ 31 , 32 ]; and one trial with the effects of BCG vaccination for COVID-19 to [ 33 ]. Of note, 4 datasets were created for Mexico, followed by Cuba (1) and Honduras (1).…”

“…Of the total datasets in Latin America, only 7 (5%) require credentialing. Three of these correspond to databases created in research papers ( Table 2 ): SELAdb database [ 31 , 32 ], the Helicobacter pylori dataset [ 25 ], and the Cuban Human Brain Mapping Project (CHBMP) [ 42 ].…”

“…Exome Evaluation of Autism-Associated Genes in Amazon American Populations Brazil A database that includes genetic variants of CHD8, SCN2A, FOXP1, and SYNGAP1 genes in the Amazonian Amerindian population. [31,32] SELAdb Brazil A genomic database that includes a cohort of 523 unrelated individuals, mainly of mixed Latin American origin. [31,32] (Continued )…”