4 research outputs found
Middle ear microbiome differences in indigenous Filipinos with chronic otitis media due to a duplication in the A2ML1 gene
Middle ear microbial profiles of indigenous Filipinos with chronic otitis media. All panels compare carriers with non-carriers of the A2ML1 duplication variant. Panel description: (A) ÃŽÄ…-diversity by observed OTUs; (B) ÃŽÄ…-diversity by the Shannon diversity index; (C) ÃŽË›-diversity from unweighted UniFrac principal coordinate analysis; (D) ÃŽË›-diversity from weighted UniFrac principal coordinate analysis. (PDF 1019 kb
A2ML1 and otitis media : novel variants, differential expression, and relevant pathways
A genetic basis for otitis media is established, however, the role of rare variants in disease etiology is largely unknown. Previously a duplication variant within A2ML1 was identified as a significant risk factor for otitis media in an indigenous Filipino population and in US children. In this report exome and Sanger sequencing was performed using DNA samples from the indigenous Filipino population, Filipino cochlear implantees, US probands, Finnish, and Pakistani families with otitis media. Sixteen novel, damaging A2ML1 variants identified in otitis media patients were rare or low-frequency in population-matched controls. In the indigenous population, both gingivitis and A2ML1 variants including the known duplication variant and the novel splice variant c.4061 + 1 G>C were independently associated with otitis media. Sequencing of salivary RNA samples from indigenous Filipinos demonstrated lower A2ML1 expression according to the carriage of A2ML1 variants. Sequencing of additional salivary RNA samples from US patients with otitis media revealed differentially expressed genes that are highly correlated with A2ML1 expression levels. In particular, RND3 is upregulated in both A2ML1 variant carriers and high-A2ML1 expressors. These findings support a role for A2ML1 in keratinocyte differentiation within the middle ear as part of otitis media pathology and the potential application of ROCK inhibition in otitis media.Peer reviewe
Additional file 3: Figure S2. of Middle ear microbiome differences in indigenous Filipinos with chronic otitis media due to a duplication in the A2ML1 gene
Comparison of right and left ears from five individuals with bilateral ear samples. Plots comparing the most abundant phyla and genera in the outer and middle ears show very similar profiles between right and left ears. Blue bars represent taxa that are more abundant in the right ear, green bars for the left ear. Only phylum Firmicutes (P = 0.02) and genus Alcaligenaceae which belongs to phylum Proteobacteria (P = 0.02) were significantly different between right and left outer ear swabs from these five individuals, however p-values were non-significant for all comparisons after correction for multiple testing. For the five individuals with bilateral samples, only right ear swabs were included in microbial analyses by genotype. (PDF 750 kb