tailieunhanh - Báo cáo y học: "Exome sequencing identifies a missense mutation in Isl1 associated with low penetrance otitis media in dearisch mice"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: Exome sequencing identifies a missense mutation in Isl1 associated with low penetrance otitis media in dearisch mice. | Hilton et al. Genome Biology 2011 12 R90 http 2011 12 9 R90 Genome Biology RESEARCH Open Access Exome sequencing identifies a missense mutation in Isl1 associated with low penetrance otitis media in deariseh mice 1 1 1 1 3 Jennifer M Hilton Morag A Lewis M hamed Grati Neil Ingham Selina Pearson Roman A Laskowski David J Adams1 and Karen P Steel1 Abstract Background Inflammation of the middle ear otitis media is very common and can lead to serious complications if not resolved. Genetic studies suggest an inherited component but few of the genes that contribute to this condition are known. Mouse mutants have contributed significantly to the identification of genes predisposing to otitis media Results The dearisch mouse mutant is an ENU-induced mutant detected by its impaired Preyer reflex ear flick in response to sound . Auditory brainstem responses revealed raised thresholds from as early as three weeks old. Pedigree analysis suggested a dominant but partially penetrant mode of inheritance. The middle ear of dearisch mutants shows a thickened mucosa and cellular effusion suggesting chronic otitis media with effusion with superimposed acute infection. The inner ear including the sensory hair cells appears normal. Due to the low penetrance of the phenotype normal backcross mapping of the mutation was not possible. Exome sequencing was therefore employed to identify a non-conservative tyrosine to cysteine Y71C missense mutation in the Isletl gene Isl1Drsh. Isl1 is expressed in the normal middle ear mucosa. The findings suggest the Isl1Drshmutation is likely to predispose carriers to otitis media. Conclusions Dearisch Isl1Drsh represents the first point mutation in the mouse Isll gene and suggests a previously unrecognized role for this gene. It is also the first recorded exome sequencing of the C3HeB FeJ background relevant to many ENU-induced mutants. Most importantly the power of exome resequencing to identify ENU-induced mutations without a .