The domestic dog, Canis familiaris, exhibits profound phenotypic diversity and is an ideal model organism for the genetic dissection of simple and complex traits. However, some of the most interesting phenotypes are fixed in particular breeds and are therefore less tractable to genetic analysis using classical segregation-based mapping approaches. We implemented an across breed mapping approach using a moderately dense SNP array, a low number of animals and breeds carefully selected for the phenotypes of interest to identify genetic variants responsible for breed-defining characteristics. Using a modest number of affected (10–30) and control (20–60) samples from multiple breeds, the correct chromosomal assignment was identified in a proof of concept experiment using three previously defined loci; hyperuricosuria, white spotting and chondrodysplasia. Genome-wide association was performed in a similar manner for one of the most striking morphological traits in dogs: brachycephalic head type. Although candidate gene approaches based on comparable phenotypes in mice and humans have been utilized for this trait, the causative gene has remained elusive using this method. Samples from nine affected breeds and thirteen control breeds identified strong genome-wide associations for brachycephalic head type on Cfa 1. Two independent datasets identified the same genomic region. Levels of relative heterozygosity in the associated region indicate that it has been subjected to a selective sweep, consistent with it being a breed defining morphological characteristic. Genotyping additional dogs in the region confirmed the association. To date, the genetic structure of dog breeds has primarily been exploited for genome wide association for segregating traits. These results demonstrate that non-segregating traits under strong selection are equally tractable to genetic analysis using small sample numbers.
Hair is a unique structure, characteristic of mammals, controlling body homeostasis, as well as cell and tissue integration. Previous studies in dog, mouse, and rat have identified polymorphisms in Keratin 71 (KRT71) as responsible for the curly/wavy phenotypes. The coding sequence and the 3′ UTR of KRT71 were directly sequenced in randomly bred and pedigreed domestic cats with different pelage mutations, including hairless varieties. A SNP altering a splice site was identified in the Sphynx breed and suggested to be the hairless (hr) allele, and a complex sequence alteration, also causing a splice variation, was identified in the Devon Rex breed and suggested to be the curly (re) allele. The polymorphisms were genotyped in approximately 200 cats. All the Devon Rex were homozygous for the complex alterations and most of the Sphynx were either homozygous for the hr allele or compound heterozygotes with the Devon-associated re allele, suggesting that the phenotypes are a result of the identified SNPs. Two Sphynx carrying the proposed hr mutation did not carry the Devon-associated alteration. No other causative mutations for eight different rexoid and hairless cat phenotypes were identified. The allelic series KRT71+ > KRT71hr > KRT71re is suggested.Electronic supplementary materialThe online version of this article (doi:10.1007/s00335-010-9290-6) contains supplementary material, which is available to authorized users.
The John Day Basin of central Oregon contains a remarkably detailed and welldated Early Eocene-Late Miocene sedimentary sequence, known for its superb fossils. This fi eld trip examines plant fossil assemblages from throughout the sequence in the context of their geological and taphonomic setting and regional and global signifi cance. The Early to Late Eocene (>54-39.7 Ma) Clarno Formation contains fossil plants and animals that occupied an active volcanic landscape near sea level, interspersed with meandering rivers and lakes. Clarno assemblages, including the ca. 44 Ma Nut Beds fl ora, record near-tropical "Boreotropical" rainforest, which was replaced during late Clarno time by more open and seasonal subtropical forest. The overlying John Day Formation (39.7-18.2 Ma) was deposited in a backarc landscape of low hills dotted with lakes and showered by ashfalls from the Western Cascades. Fossils and paleosols record the advent of the "Icehouse" Earth during the earliest Oligocene, with decreasing winter temperature and more seasonal rainfall that supported open deciduous and coniferous forest, much like that of the southern Chinese highlands today. Sixteen and a half million years ago the Picture Gorge fl ood basalt covered the region. Animals and plants fossilized in the overlying (ca. 16 to >12 Ma) Mascall Formation occupied a relatively fl at landscape during a warm and moist period known as the Middle Miocene Climatic Optimum. In total this sequence preserves a detailed series of time slices illustrating regional biotic and landscape evolution during the Cenozoic that is highly relevant for deciphering regional and global biotic, climatic, and geological trends.
Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent public health threat. We evaluated the capacity of the Carba NP test to detect carbapenemase production in 206 isolates: 143 Enterobacteriaceae identified by Oregon's CRE surveillance program in 2013 and 63 known carbapenemase-positive organisms. Overall, test sensitivity and specificity were 89% (59/66 isolates; 95% confidence interval [CI], 81 to 97%) and 100% (140/140 isolates; 95% CI, 98 to 100%), respectively. All KPC, NDM-1, VIM, and IMP producers but no (0/7 isolates) OXA-48-like strains were Carba NP positive prior to a post hoc protocol modification. We subsequently incorporated Carba NP into Oregon's CRE screening algorithm.
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