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

The reproductive success of a Quercus petraea ×\times Q. robur F1-hybrid in back-crossing situations

International audienc

Population genetics and spatial autocorrelation in an unmanaged stand of Quercus petraea in Denmark

An unmanaged stand of Quercus petraea (Matt.) Liebl. in Denmark was studied for morphological and microsatellite variation. The sample of 339 trees, which is part of a European network of similar oak stands, revealed a unimodal (single) distribution of Q. petraea but found evidence for extreme morphological variation expressed by a number of trees. While hybridization with Quercus robur may be one reason for such a pattern of variation, other possibilities exist. Variation at six microsatellite loci indicated no correlation with any of the nine morphological traits investigated, and showed only small deviations from Hardy /Weinberg proportions. The levels of observed heterozygosity and allelic diversity were similar to those found within other stands of Q. petraea in central Europe, and no reduction in diversity was evident for the Danish stand despite its being situated at the margin of the distribution of the species. Weak, but significant, spatial genetic structure was identified using Moran’s index, but the level of spatial autocorrelation was found to be dependent on locus, allele frequency and sample size, which should be greater than 100 trees to identify spatial patterns. Spatial genetic structure was found to be higher for trees with a diameter at breast height (dbh) of B/40 cm than for larger trees ( /40 cm dbh) and this is thought to reflect a balance between the influence of limited seed dispersal, which will act to establish genetic structure in younger generations, and selection, which will disrupt genetic structure in older generations. The life history of the stand is discussed in relation to the observed genetic parameters.Jan Svejgaard Jensen, Ditte Christina Olrik, Hans R. Siegismund and Andrew J. Low