Evolution and functional impact of rare coding variation from deep sequencing of human exomes

As a first step toward understanding how rare variants contribute to risk for complex diseases, we sequenced 15,585 human protein-coding genes to an average median depth of 111× in 2440 individuals of European (n = 1351) and African (n = 1088) ancestry. We identified over 500,000 single-nucleotide variants (SNVs), the majority of which were rare (86% with a minor allele frequency less than 0.5%), previously unknown (82%), and population-specific (82%). On average, 2.3% of the 13,595 SNVs each person carried were predicted to affect protein function of ~313 genes per genome, and ~95.7% of SNVs predicted to be functionally important were rare. This excess of rare functional variants is due to the combined effects of explosive, recent accelerated population growth and weak purifying selection. Furthermore, we show that large sample sizes will be required to associate rare variants with complex traits.     

MOTION-CORRECTION TECHNIQUES FOR STANDING EQUINE MRI

Magnetic resonance imaging (MRI) of the distal extremities of the standing, sedated horse would be desirable if diagnostic quality images could be obtained. With the availability of extremity and special purpose magnet designs on the market, a system to safely accommodate the standing horse may gain increasing popularity. This paper considers the issue of motion that will need to be addressed to achieve successful, diagnostic quality images. The motion of the carpus and tarsus of five standing, sedated horses was quantified. The obtained motion records were then used to induce motion in cadaveric joint specimens during several MRI scans. The measured dorsal-palmar/plantar, medial-lateral, and proximal-distal random wobbling motions in the standing sedated horse were several centimeters in magnitude and generated severe motion-artifacts during axial MRI of the cadaveric specimens. Two retrospective motion-correction techniques (autocorrection and navigator-based adaptive correction) were used to correct the corrupted images. The motion artifacts were nearly eliminated with the use of both techniques in series. Although significant hurdles remain, these results suggest promise for allowing diagnostic quality MRI of the carpus and tarsus in the standing horse.     

Severity and persistence of footrot in Merino sheep experimentally infected with a protease thermostable strain of Dichelobacter nodosus at five sites

Objective To test the hypothesis that ovine footrot associated with a thermostable protease strain of Dichelobacter nodosus undergoes self cure or is sustained as an annually recurring disease, depending on the environment.
Design and procedure Forty Merino sheep from a single blood line were infected with a protease thermostable strain of D nodosus a t each of five sites in Western Australia. Footrot lesions and microscopic evidence of D nodosus were recorded every fortnight for 2.5 years, supplemented by laboratory culture. Rainfall, soil and air temperature, pasture quantity and composition and soil types were also recorded. Flocks that apparently self cured were relocated to a more favourable site for footrot in the final spring season.
Results The maximum prevalence of feet with clinical footrot lesions was 80.6, 1.3, 14.4, 3.8 and 88.1% at the five sites. Severe footrot occurred for three consecutive spring seasons at one site that had clay loam soil and at least 3500 kg/ha total pasture dry matter annually. However, the infection was asymptomatic for up to 10 weeks between outbreaks. D nodosus was isolated from flocks for 2.5 years at only two sites, although there was microscopic evidence of the organism at other sites in the final year. A thermolabile variant (strain U6) of D nodosus was isolated from the two sites where footrot persisted.
Conclusion Depending on time and location, ovine footrot induced by a protease thermostable strain of D nodosus either self cured or persisted as annual outbreaks interspersed with periods of asymptomatic infection.     

Investigation of parrot papillomavirus in cloacal and oral papillomas of psittacine birds

Cloacal and oral papillomas from 27 psittacine birds of various species were examined for the presence of parrot papillomavirus by DNA in situ hybridization, DNA in situ polymerase chain reaction, and nested polymerase chain reaction. Parrot papillomavirus was detected in one oral papilloma from an African grey parrot by all three techniques. In addition, rare basophilic intranuclear inclusions were observed by light microscopy in tissue sections of the oral papilloma from this parrot. The remaining lesions were negative for parrot papillomavirus DNA. This study suggests that parrot papillomavirus may be involved in the development of papillomas in African grey parrots, but apparently is not responsible for development of similar lesions in unrelated species of psittacine birds.