Rare A2ML1 variants confer susceptibility to otitis media.

TitleRare A2ML1 variants confer susceptibility to otitis media.
Publication TypeJournal Article
Year of Publication2015
AuthorsSantos-Cortez, RLyn P, Chiong, CM, Reyes-Quintos, MRina T, Tantoco, MLeah C, Wang, X, Acharya, A, Abbe, I, Giese, AP, Smith, JD, E Allen, K, Li, B, de la Paz, EMaria Cuti, Garcia, MCristy, Llanes, EGonzalo D, Labra, PJohn, Gloria-Cruz, TLuisa I, Chan, AL, Wang, GT, Daly, KA, Shendure, J, Bamshad, MJ, Nickerson, DA, Patel, JA, Riazuddin, S, Sale, MM, Chonmaitree, T, Ahmed, ZM, Abes, GT, Leal, SM
Corporate AuthorsUniversity of Washington Center for Mendelian Genomics
JournalNat Genet
Volume47
Issue8
Pagination917-20
Date Published2015 Aug
ISSN1546-1718
Keywordsalpha-Macroglobulins, Animals, Base Sequence, Child, Cochlea, Exome, Family Health, Female, Gene Duplication, Gene Frequency, Genetic Predisposition to Disease, Genotype, Haplotypes, Humans, Male, Mice, Inbred C57BL, Models, Molecular, Otitis Media, Pedigree, Principal Component Analysis, Protein Conformation, Sequence Analysis, DNA
Abstract

A duplication variant within the middle ear-specific gene A2ML1 cosegregates with otitis media in an indigenous Filipino pedigree (LOD score = 7.5 at reduced penetrance) and lies within a founder haplotype that is also shared by 3 otitis-prone European-American and Hispanic-American children but is absent in non-otitis-prone children and >62,000 next-generation sequences. We identified seven additional A2ML1 variants in six otitis-prone children. Collectively, our studies support a role for A2ML1 in the pathophysiology of otitis media.

DOI10.1038/ng.3347
Alternate JournalNat. Genet.
PubMed ID26121085
PubMed Central IDPMC4528370
Grant ListU54 HG006493 / HG / NHGRI NIH HHS / United States
R01 DC011651 / DC / NIDCD NIH HHS / United States
R01 DC005841 / DC / NIDCD NIH HHS / United States
R01 DC012564 / DC / NIDCD NIH HHS / United States
F27 / / Action on Hearing Loss / United Kingdom
R01 DC003166 / DC / NIDCD NIH HHS / United States
R01 DC003594 / DC / NIDCD NIH HHS / United States
R01 DK084350 / DK / NIDDK NIH HHS / United States
UM1 HG006493 / HG / NHGRI NIH HHS / United States
R01 DC011803 / DC / NIDCD NIH HHS / United States