Whole exome sequencing identifies the novel putative gene variants related with type 2 diabetes in Mizo population, northeast India

The contribution of genes towards T2D development varies among different population groups across the world. It has been reported that a number of loci involved in T2D susceptibility are common across certain population groups, but ethnicity specific variants are also observed. The population of Mizoram has an independent ethnic identity and there are no scientific records about the history of the Mizo people; which makes this ethnic group unique and interesting to study. The aim of the study focuses on the identification of the gene variants which may contribute to T2D susceptibility in Mizo-Mongloid ethnic tribe of North east India through whole exome sequencing. The variants like 328G > C (KRT18), 997G > T (CYP4A11), 2368 T > C (SLC4A3), 508G > A (SLC26A5), 1659C > T (KCNS1), 650C > A (ABCD1) 821A > T (YTHDC2), 931G > T (PINX1), 3280C > A (TNRC6A), 48C > A(TACO1), 6035A > T(LAMA1), 805C > A(ACP7) and 806A > G(ACP7) variants were not reported for any disease in the database and were found to be pathogenic in different insilico analysis softwares. The changes in protein stability upon mutation has been predicted where 35.71% increases the stability of the protein, while 64.28% of the variants decrease the stability of the protein. These findings present the population specific variants which might involve in the susceptibility to T2D in Mizo population. Further, in this study some gene variants have contribution as a possible diagnostic or prognostic marker for other diseases as well, which suggests the need for performing association analysis for different disease manifestations in Mizo population in the near future.

Automated summary

The study aimed to identify gene variants contributing to T2D susceptibility in the Mizo-Mongloid ethnic tribe through whole exome sequencing. Rare pathogenic variants were discovered, some of which could potentially serve as diagnostic or prognostic markers for other diseases. Predictions showed that these variants either increased or decreased protein stability, highlighting their potential impact on disease susceptibility.