Next Generation Exome Sequencing of Pediatric Asthma Identifies Rare and Novel Variants in Candidate Genes.

Neda M Bogari,Amr A Amin,Abdellatif Bouazzaoui,Luke O’Gorman,Faisal A Al-Allaf,John W Holloway,Husni H Rayes,Mohiuddin M Taher,Ahmed Abdelmotelb,Peng Fei Li

doi:10.1155/2021/8884229

Abstract

Multiple genes have been implicated to have a role in asthma predisposition by association studies. Pediatric patients often manifest a more extensive form of this disease and a particularly severe disease course. It is likely that genetic predisposition could play a more substantial role in this group. This study is aimed at identifying the spectrum of rare and novel variation in known pediatric asthma susceptibility genes using whole exome sequencing analysis in nine individual cases of childhood onset allergic asthma. DNA samples from the nine children with a history of bronchial asthma diagnosis underwent whole exome sequencing on Ion Proton. For each patient, the entire complement of rare variation within strongly associated candidate genes was catalogued. The analysis showed 21 variants in the subjects, 13 had been previously identified, and 8 were novel. Also, among of which, nineteen were nonsynonymous and 2 were nonsense. With regard to the novel variants, the 2 nonsynonymous variants in the PRKG1 gene (PRKG1: p.C519W and PRKG1: p.G520W) were presented in 4 cases, and a nonsynonymous variant in the MAVS gene (MAVS: p.A45V) was identified in 3 cases. The variants we found in this study will enrich the variant spectrum and build up the database in the Saudi population. Novel eight variants were identified in the study which provides more evidence in the genetic susceptibility in asthma among Saudi children, providing a genetic screening map for the molecular genetic determinants of allergic disease in Saudi children, with the goal of reducing the impact of chronic diseases on the health and the economy. We believe that the advanced specified statistical filtration/annotation programs used in this study succeeded to release such results in a preliminary study, exploring the genetic map of that disease in Saudi children.

Highlights

Asthma and other allergic diseases, including allergic rhinitis, eczema, and food allergy, cause a substantial burden of disease in childhood
It has been reported that there are more than 100 candidate genes in every chromosome which are identified to have a linkage with asthma and the strength of association of these single-nucleotide polymorphisms (SNPs) with asthma varieties in different parts of the world [3,4,5]
Exome sequencing of eight children in this study has identified 21 potentially deleterious SNPs in known asthma genes; among them, eight novel variants and 13 variants previously deposited in dbSNP

Summary

Introduction

Asthma and other allergic diseases, including allergic rhinitis, eczema, and food allergy, cause a substantial burden of disease in childhood. A rapid increase in asthma and allergies has been identified over the latter part of the 20th century, the reasons for this are still unknown [1]. Recent changes in environmental factors and their interactions with genetic profiles have been suggested as major factors responsible for the increase in asthma and allergic diseases [2]. A chronic inflammatory respiratory condition characterized by hyperresponsive airways and reversible airflow obstruction, is a substantial public health problem that affects nearly 155 million individuals worldwide with the Disease Markers prevalence of current asthma and is higher in children compared than adults [3,4,5]. Environmental factors are important, there are strong genetic predispositions for the development of allergic diseases. A better knowledge of asthma susceptibility will hold promise for a better understanding of the pathology, diagnosis, prevention, treatment, and management of this increasingly frequent disease

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