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

Show full item record



Permalink

http://hdl.handle.net/10138/320494

Citation

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 . https://doi.org/10.1038/s41598-020-70498-w

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: University of Helsinki, Clinicum
University of Helsinki, Biosciences
University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
University of Helsinki, HUS Head and Neck Center
Date: 2020-09-14
Language: eng
Number of pages: 12
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/320494
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.
Subject: HUMAN PLASMINOGEN
GENE
NETWORKANALYST
CONSEQUENCES
PREDICTION
MUTATIONS
FRAMEWORK
CHILDREN
DATABASE
LINKAGE
3125 Otorhinolaryngology, ophthalmology
1184 Genetics, developmental biology, physiology
3123 Gynaecology and paediatrics
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
s41598_020_70498_w.pdf 1.231Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record