Whole-exome sequencing in maya indigenous families: variant in PPP1R3A is associated with type 2 diabetes

Abstract

It has been presumed that increased susceptibility in Mexicans to type 2 diabetes (T2D) is attributed to the Native American genetic ancestry. Nonetheless, it is not known if there are private genetic variants that confer susceptibility to develop T2D in our population. The Maya indigenous group has the highest proportion of Native American ancestry (98%) which makes it a representative group of the original peoples of Mexico. Thus, the aim of the present study is to identify new genetic variants associated with T2D in Maya families. Whole-exome sequencing was performed on DNA samples from Maya families with a third-generation family history of T2D only in one parental line. Four variants were identified for APOB, PPP1R3A, TPPP2, and GPR1 genes, and were further tested for association with T2D in 600 unrelated Maya in a case-control study. For the first time, rs1799999 in PPP1R3A was associated with risk of T2D in Mayan Mexican individuals (OR = 1.625, P = 0.014). Interestingly, carriers of rs1799999 presented increased values of HOMA-IR. In addition, rs1801702 in APOB was associated with total cholesterol and LDL-C (P = 0.019 and P = 0.020, respectively) in normoglycemic individuals; rs3732083 in GPR1 with HOMA-IR (P = 0.016) and rs9624 in TPPP2 with total cholesterol and triglycerides (P = 0.002 and P = 0.005, respectively) in T2D subjects. Overall, these findings support the idea that there are other genetic variants yet to be described, involved in T2D development in Maya population, being insulin resistance and lipid metabolism the main mechanisms implicated. Thus, these results can contribute to the understanding of diabetes genetic background in Mexican population.

Dietary Diversification and Specialization in Neotropical Bats Facilitated by Early Molecular Evolution

“…Of all mammals, bats offer unique opportunities for studying molecular adaptations associated with diet. As a taxonomic order, they show unparalleled dietary diversity and a suite of physiological and sensory adaptations for the acquisition and processing of food ( Dumont et al 2012 ; Fenton 2013 ; Jones et al 2013 ; McNab 2013 ; Santana and Cheung 2016 ). However, studies of molecular adaptation in metabolism-related genes in bats have been limited in scope, typically focusing on small numbers of genes or, more recently, larger gene sets but in fewer species ( Gutiérrez-Guerrero et al 2020 ; Wang et al 2020 ).…”

GWAS for Meat and Carcass Traits Using Imputed Sequence Level Genotypes in Pooled F2-Designs in Pigs

“…A third, rather minor QTL on SSC18, contains 21 variants downstream of MDFIC (min p-value 1.97 × 10 −15 ), a gene which has been linked to improved piglet birth weight (Zhang et al 2014). 25 intron and 42 downstream variants were found for the PPP1R3A gene (min p-value 6.92 × 10 −15 ), which in a whole exome sequencing study was found to be associated with type 2 diabetes in a Mayan population (Sánchez-Pozos et al 2018).…”

Variation in Actionable Pharmacogenetic Markers in Natives and Mestizos From Mexico

“…Comparative analyses among Mestizos, Natives, and continental populations, highlight the extent of our incomplete registry of pharmacogenetic variability within the country, but also indicate a closer completion for Mestizos than for Natives, because these have been much less studied (Cid-Soto et al, 2018; Sánchez-Pozos et al, 2018). For instance, Natives showed 2.4 functional novel variants on average per individual compared to 0.7 in Mestizos, which is in agreement with Romero-Hidalgo et al (2017) showing that damaging variation is 2× higher for unreported variants in Native Americans.…”