Identification of loci affecting sexually dimorphic patterns for height and recurrent laryngeal neuropathy risk in American Belgian Draft Horses.

Equine recurrent laryngeal neuropathy (RLN) is a bilateral mononeuropathy with an unknown etiology. In Thoroughbreds (TB), we previously demonstrated that the haplotype association for height (LCORL/NCAPG locus on ECA3, which affects body size) and RLN was coincident. In the present study, we performed a genome-wide association scan (GWAS) for RLN in 458 American Belgian Draft Horses, a breed fixed for the LCORL/NCAPG risk alelle. In this breed, RLN risk is associated with sexually dimorphic differences in height, and we identified a novel locus contributing to height in a sex-specific manner: MYPN (ECA1). Yet this specific locus contributes little to RLN risk, suggesting that other growth traits correlated to height may underlie the correlation to this disease. Controlling for height, we identified a locus on ECA15 contributing to RLN risk specifically in males. These results suggest that loci with sex-specific gene expression play an important role in altering growth traits impacting RLN etiology, but not necessarily adult height. These newly identified genes are promising targets for novel preventative and treatment strategies.

Genomic analysis establishes correlation between growth and laryngeal neuropathy in Thoroughbreds.

BACKGROUND: Equine recurrent laryngeal neuropathy (RLN) is a bilateral mononeuropathy with an unknown pathogenesis that significantly affects performance in Thoroughbreds. A genetic contribution to the pathogenesis of RLN is suggested by the higher prevalence of the condition in offspring of RLN-affected than unaffected stallions. To better understand RLN pathogenesis and its genetic basis, we performed a genome-wide association (GWAS) of 282 RLN-affected and 268 control Thoroughbreds. RESULTS: We found a significant association of RLN with the LCORL/NCAPG locus on ECA3 previously shown to affect body size in horses. Using height at the withers of 505 of these horses, we confirmed the strong association of this locus with body size, and demonstrated a significant phenotypic and genetic correlation between height and RLN grade in this cohort. Secondary genetic associations for RLN on ECA18 and X did not correlate with withers height in our cohort, but did contain candidate genes likely influencing muscle physiology and growth: myostatin (MSTN) and integral membrane protein 2A (ITM2A). CONCLUSIONS: This linkage between body size and RLN suggests that selective breeding to reduce RLN prevalence would likely reduce adult size in this population. However, our results do not preclude the possibility of modifier loci that attenuate RLN risk without reducing size or performance, or that the RLN risk allele is distinct but tightly linked to the body size locus on ECA3. This study is both the largest body size GWAS and the largest RLN GWAS within Thoroughbred horses to date, and suggests that improved understanding of the relationship between genetics, equine growth rate, and RLN prevalence may significantly advance our understanding and management of this disease.

Further Characterization of Molecular Markers in Canine Dirofilaria immitis Infection.

Dirofilaria immitis is a common filarial parasite found in dogs and cats in the Americas, with the pathophysiological consequences of the infection differing somewhat between these 2 host species. Recent research efforts have been focused on determining if the microRNAs (miRNAs) released from adult Dirofilariae have a role as markers for distinguishing the intensity of adult worm infection, as well as determining the presence of new infections. This study expands previous work on 2 nematode miRNAs, miR34 and miR-71, by addressing their ability to discriminate between low and high D. immitis adult worm intensities in dogs. Serum samples were collected from 13 dogs, 8 of which carried known numbers of adult D. immitis at autopsy in their hearts and pulmonary vessels. Three groups of canine sera were created based on D. immitis burden: "control" (0 worms; 5 animals), "low intensity" (10-18 worms; mean ± SD = 12.3 ± 4.4; 4 animals), and "high intensity" (41-72 worms; mean 62.5 ± 15.1; 4 animals) groups. A qPCR analysis was performed on each sample to measure plasma levels of miR-34 and miR-71; however, no significant differences were observed between these groups in terms of levels of miRNAs, so the low- and high-intensity samples were then combined into a single "infected" category and compared to the "non-infected" controls. Copy numbers of both miR-34 and miR-71 were significantly higher in infected compared to uninfected animals ( P = 0.015 and P = 0.027, respectively). The Ct values of expression compared with the adult worm intensity for each miRNA revealed that both miR-34 and miR-71 significantly discriminate between the infected and non-infected groups ( P value < 0.0001 for both). These findings support the contention that miRNA 34 and miRNA 71, which are filarial-specific miRNAs, can both serve as biomarkers for the presence of D. immitis infection in dogs, but at this point they do not appear to reflect the actual intensity of adult parasites present.

A Serological Survey of Human Onchocerciasis in Yemen.

Yemen is a country that has been treating severe cases of oncho-dermatitis since 1992 and is now moving to a program aimed at the elimination of the transmission of Onchocerca volvulus. It is important to ensure that the currently acceptable tools used in epidemiological assessment of onchocerciasis in Africa and Latin America also apply to Yemen. Five hundred and ten blood samples from three known O. volvulus-endemic areas, locations that have never been under a mass treatment program, were tested for the presence of antibodies against a panel of O. volvulus-specific antigens using enzyme-linked immunosorbent assay (Ov16) and luciferase immunoprecipitation system (Ov-FAR-1 and Ov-MSA-1) assays. Overall, 31.4% of the samples tested were positive, with positivity increasing with age. Positivity was seen in 76.5% of those presenting with clinical onchocerciasis but importantly also in more than 28.5% of those defined as free of oncho-dermatitis; these latter individuals are likely to be serving as a source for persistent reinfection. This study supports the use of the current O. volvulus-specific serologic methodology in Yemen.