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Sökning: WFRF:(Frank S. S.) > (2020-2024) > The role of CDHR3 i...

  • Hirsch, S. D. (författare)

The role of CDHR3 in susceptibility to otitis media

  • Artikel/kapitelEngelska2021

Förlag, utgivningsår, omfång ...

  • 2021-07-28
  • Springer Nature,2021
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:kth-310703
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-310703URI
  • https://doi.org/10.1007/s00109-021-02118-7DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:147183910URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • QC 20220428
  • Abstract: Otitis media (OM) is common in young children and can cause hearing loss and speech, language, and developmental delays. OM has high heritability; however, little is known about OM-related molecular and genetic processes. CDHR3 was previously identified as a locus for OM susceptibility, but to date, studies have focused on how the CDHR3 p.Cys529Tyr variant increases epithelial binding of rhinovirus-C and risk for lung or sinus pathology. In order to further delineate a role for CDHR3 in OM, we performed the following: exome sequencing using DNA samples from OM-affected individuals from 257 multi-ethnic families; Sanger sequencing, logistic regression and transmission disequilibrium tests for 407 US trios or probands with OM; 16S rRNA sequencing and analysis for middle ear and nasopharyngeal samples; and single-cell RNA sequencing and differential expression analyses for mouse middle ear. From exome sequence data, we identified a novel pathogenic CDHR3 splice variant that co-segregates with OM in US and Finnish families. Additionally, a frameshift and six missense rare or low-frequency variants were identified in Finnish probands. In US probands, the CDHR3 p.Cys529Tyr variant was associated with the absence of middle ear fluid at surgery and also with increased relative abundance of Lysobacter in the nasopharynx and Streptomyces in the middle ear. Consistent with published data on airway epithelial cells and our RNA-sequence data from human middle ear tissues, Cdhr3 expression is restricted to ciliated epithelial cells of the middle ear and is downregulated after acute OM. Overall, these findings suggest a critical role for CDHR3 in OM susceptibility. Key messages: • Novel rare or low-frequency CDHR3 variants putatively confer risk for otitis media. • Pathogenic variant CDHR3 c.1653 + 3G > A was found in nine families with otitis media. • CDHR3 p.Cys529Tyr was associated with lack of effusion and bacterial otopathogens. • Cdhr3 expression was limited to ciliated epithelial cells in mouse middle ear. • Cdhr3 was downregulated 3 h after infection of mouse middle ear.

Ämnesord och genrebeteckningar

  • MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
  • MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
  • CDHR3
  • Expression
  • Microbiome
  • Middle ear
  • Otitis media
  • rs6967330
  • antibiotic agent
  • messenger RNA
  • RNA 16S
  • cadherin related protein
  • CDHR3 protein
  • human
  • membrane protein
  • transcriptome
  • acute otitis media
  • airway epithelium cell
  • allergic rhinitis
  • Article
  • bacterial microbiome
  • Caucasian
  • cdhr3 gene
  • child
  • cohort analysis
  • Colorado
  • differential expression analysis
  • DNA sequencing
  • ear tissue
  • ethnicity
  • exome
  • female
  • Finland
  • gene
  • gene frequency
  • gene function
  • gene identification
  • gene linkage disequilibrium
  • genetic susceptibility
  • genetic variability
  • genotype
  • Hispanic
  • human
  • human tissue
  • loss of function mutation
  • Lysobacter
  • major clinical study
  • male
  • Minnesota
  • nasopharynx
  • nontypeable Haemophilus influenzae
  • otoscopy
  • Pakistani
  • pathogenesis
  • population abundance
  • preschool child
  • recurrent disease
  • RNA sequencing
  • Sanger sequencing
  • single cell RNA seq
  • single nucleotide polymorphism
  • Streptomyces
  • Texas
  • tympanometry
  • whole exome sequencing
  • animal
  • C57BL mouse
  • genetic predisposition
  • genetics
  • infant
  • microbiology
  • microflora
  • mutation
  • Animals
  • Cadherin Related Proteins
  • Child
  • Preschool
  • Genetic Predisposition to Disease
  • Humans
  • Membrane Proteins
  • Mice
  • Inbred C57BL
  • Microbiota
  • RNA
  • Ribosomal
  • 16S

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Elling, C. L. (författare)
  • Bootpetch, T. C. (författare)
  • Scholes, M. A. (författare)
  • Hafrén, L. (författare)
  • Streubel, S. -O (författare)
  • Pine, H. S. (författare)
  • Wine, T. M. (författare)
  • Szeremeta, W. (författare)
  • Prager, J. D. (författare)
  • Einarsdottir, ElisabetKTH,Genteknologi,Science for Life Laboratory, SciLifeLab,Folkhälsan Institute of Genetics and Molecular Neurology Research Program, University of Helsinki, PO Box 63, Biomedicum 1, 3rd floor, Haartmaninkatu 8, 00014, Helsinki, Finland; Department of Biosciences and Nutrition, Karolinska Institute, 141 86, Huddinge, Stockholm, Sweden.(Swepub:kth)u1jgep5v (författare)
  • Yousaf, A. (författare)
  • Baschal, E. E. (författare)
  • Rehman, S. (författare)
  • Bamshad, M. J. (författare)
  • Nickerson, D. A. (författare)
  • Riazuddin, S. (författare)
  • Leal, S. M. (författare)
  • Ahmed, Z. M. (författare)
  • Yoon, P. J. (författare)
  • Kere, J.Karolinska Institutet (författare)
  • Chan, K. H. (författare)
  • Mattila, P. S. (författare)
  • Friedman, N. R. (författare)
  • Chonmaitree, T. (författare)
  • Frank, D. N. (författare)
  • Ryan, A. F. (författare)
  • Santos-Cortez, R. L. P. (författare)
  • KTHGenteknologi (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of Molecular Medicine: Springer Nature99:11, s. 1571-15830946-27161432-1440

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