Influence of functional polymorphisms on susceptibility and chronic progression in the spirochetes induced hoof disease bovine digital dermatitis

• Applicant: Dr. Diana Oelschlägel
• Subject Area: Animal Breeding, Animal Nutrition, Animal Husbandry
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 533845368

Bovine digital dermatitis (BDD) is an infectious painful disease of the hoof in cattle with multifactorial etiology and a polygenic influence with respect to susceptibility and progression. A genome-wide association study performed by our working group led to the identification of two significantly associated single nucleotide polymorphisms. One polymorphism is located in the fifth exon of ASB16, the other downstream of CMPK2. Both of the mentioned genes are expected to be involved in immunological processes. Animals with these polymorphisms show a significantly higher probability to suffer from BDD and to develop chronical lesions. The findings on the genomic background concerning the pathogenesis will be an aid to establish a BDD pre-screening test and could be used in cattle breeding programs in the long term. In addition, further investigation of genetic factors and their effects will be addressed in order to improve existing therapeutic approaches and thus reduce the suffering of affected animals already in the short term. Currently, antibiotics offer a limited possibility for symptomatic treatment. However, permanent cure can only be achieved to a limited extent, as chronic reactivation of the painful inflammatory process often occurs after a period of rest. The aim of our proposed project is to gain more insight into the influence of identified polymorphisms on disease progression in the context of regulation of immunological signaling pathways and communication of locally involved cell types. The focus is on macrophages and keratinocytes, two important cell types involved in the inflammatory process. Transcriptome analyses from cell samples of animals with favorable or unfavorable genotype constellations will provide new information on differentially expressed inflammatory modulators, which will allow conclusions on the intercellular communication ability and the physiological functions of the cells and will be investigated and validated with appropriate follow-up experiments. Detailed knowledge about genetic variants and their cell biological effect on disease susceptibility and progression is also important for human medicine. Members of the bacterial class of spirochetes which include the BDD-associated Treponema species, are also involved in inflammatory, partially chronical diseases in humans, such as Lyme disease, syphilis or periodontitis. Therefore, polymorphisms are already being investigated as genetic predisposing factors in these infections since individual disease progression and variable efficiency of classical antibiotic therapies are known. Finally, with information on significantly associated polymorphisms and their effects at the molecular level, development of more effective, individualized prevention and treatment options for BDD will be enhanced, and bovine research could also provide useful insights across species.

• DFG Programme: Research Grants