Whole-Exome Sequencing in Family Trios Reveals De Novo Mutations Associated with Type 1 Diabetes Mellitus

Author:

Mousa Mira1ORCID,Albarguthi Sara12,Albreiki Mohammed1,Farooq Zenab3,Sajid Sameeha3,El Hajj Chehadeh Sarah1,ElBait Gihan Daw1,Tay Guan1,Deeb Asma Al34,Alsafar Habiba12ORCID

Affiliation:

1. Center of Biotechnology, Khalifa University of Science and Technology, Abu Dhabi 127788, United Arab Emirates

2. Department of Biomedical Engineering, Khalifa University of Science and Technology, Abu Dhabi 127788, United Arab Emirates

3. College of Medicine and Health Sciences, Khalifa University, Abu Dhabi 127788, United Arab Emirates

4. Department of Endocrinology, Mafraq Hospital, Abu Dhabi 127788, United Arab Emirates

Abstract

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by insulin deficiency and loss of pancreatic islet β-cells. The objective of this study is to identify de novo mutations in 13 trios from singleton families that contribute to the genetic basis of T1DM through the application of whole-exome sequencing (WES). Of the 13 families sampled for this project, 12 had de novo variants, with Family 7 having the highest number (nine) of variants linked to T1DM/autoimmune pathways, whilst Family 4 did not have any variants past the filtering steps. There were 10 variants of 7 genes reportedly associated with T1DM (MST1; TDG; TYRO3; IFIHI; GLIS3; VEGFA; TYK2). There were 20 variants of 13 genes that were linked to endocrine, metabolic, or autoimmune diseases. Our findings demonstrate that trio-based WES is a powerful approach for identifying new candidate genes for the pathogenesis of T1D. Genotyping and functional annotation of the discovered de novo variants in a large cohort is recommended to ascertain their association with disease pathogenesis.

Funder

Khalifa University

Publisher

MDPI AG

Subject

General Agricultural and Biological Sciences,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology

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