Multi-omic studies on missense PLG variants in families with otitis media

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Univ Washington Ctr Mendelian Geno , Bootpetch , T C , Hafren , L , Elling , C L , Einarsdottir , E , Kere , J , Mattila , P S & Santos-Cortez , R L P 2020 , ' Multi-omic studies on missense PLG variants in families with otitis media ' , Scientific Reports , vol. 10 , no. 1 , 15035 .

Title: Multi-omic studies on missense PLG variants in families with otitis media
Author: Univ Washington Ctr Mendelian Geno; Bootpetch, Tori C.; Hafren, Lena; Elling, Christina L.; Einarsdottir, Elisabet; Kere, Juha; Mattila, Petri S.; Santos-Cortez, Regie Lyn P.
Contributor organization: Clinicum
HUS Head and Neck Center
University of Helsinki
Helsinki University Hospital Area
Department of Ophthalmology and Otorhinolaryngology
Päivi Marjaana Saavalainen / Principal Investigator
Research Programs Unit
STEMM - Stem Cells and Metabolism Research Program
Juha Kere / Principal Investigator
Korva-, nenä- ja kurkkutautien klinikka
Date: 2020-09-14
Language: eng
Number of pages: 12
Belongs to series: Scientific Reports
ISSN: 2045-2322
Abstract: Otitis media (OM), a very common disease in young children, can result in hearing loss. In order to potentially replicate previously reported associations between OM and PLG, exome and Sanger sequencing, RNA-sequencing of saliva and middle ear samples, 16S rRNA sequencing, molecular modeling, and statistical analyses including transmission disequilibrium tests (TDT) were performed in a multi-ethnic cohort of 718 families and simplex cases with OM. We identified four rare PLG variants c.112A > G (p.Lys38Glu), c.782G > A (p.Arg261His), c.1481C > T (p.Ala494Val) and c.2045 T > A (p.Ile682Asn), and one common variant c.1414G > A (p.Asp472Asn). However TDT analyses for these PLG variants did not demonstrate association with OM in 314 families. Additionally PLG expression is very low or absent in normal or diseased middle ear in mouse and human, and salivary expression and microbial a-diversity were non-significant in c.1414G > A (p.Asp472Asn) carriers. Based on molecular modeling, the novel rare variants particularly c.782G > A (p.Arg261His) and c.2045 T > A (p.Ile682Asn) were predicted to affect protein structure. Exploration of other potential disease mechanisms will help elucidate how PLG contributes to OM susceptibility in humans. Our results underline the importance of following up findings from genome-wide association through replication studies, preferably using multi-omic datasets.
3125 Otorhinolaryngology, ophthalmology
1184 Genetics, developmental biology, physiology
3123 Gynaecology and paediatrics
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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