Fine mapping of loci on BTA8 associated to antibody response to Mycobacterium avium paratuberculosis in cattle

Paratuberculosis (ParaTB) or Johne's disease, caused by Mycobacterium avium subspecies paratuberculosis commonly known as MAP in cattle, is a chronic gastroenteritis characterized by diarrhoea, decreased milk production and ultimately death. MAP is responsible for huge economic losses, particularly in dairy cattle herds. Susceptibility to MAP infection has been found to be heritable with heritability estimates ranging from 0.06 to 0.102. The definition of an infected animal can be based either on the presence of anti-MAP antibodies in the serum, or by direct demonstration of MAP in tissue or faeces by culture or PCR. Several studies have addressed the identification of genetic loci associated with MAP susceptibility. The objective of this study was to refine a locus associated with antibody response to Mycobacterium avium paratuberculosi (MAP). Using a genome- wide association analysis, a single nucleotide polymorphism on Bos taurus autosome BTA8 namely the SNP rs43161947 at posi- tion 35398490 with a p-value of 7.02 e-05, has previously been identified by the authors as associated with MAP infection. Fine mapping of the region was conducted with 100 single nucleotide polymorphisms spanning a region between BTA8: 34422912 and BTA8: 364553881 covering 2 Mega bases (Mb) designed in to cover 1 Mb ahead and after the SNP identified on BTA8. The 2 Mb region on BTA8 was evaluated within a group of 966 Holstein cows collected from routine ParaTB screening in the province of Lodi in Italy, in an area with a high prevalence of ParaTB. Animals were defined as ParaTB positive based on the detection of serum antibodies produced in response to MAP infection using the ID-screen® ELISA test (ID VET Montpellier, France). Of the 966 samples, 483 were MAP antibody positive (cases) and 483 MAP antibody negative (MAP negative controls). All animals were female, and cases and MAP negative controls were from the same farm tested on the same day.Using a single marker associ- ation analysis, conducted within the R statistical environment, we identified 3 different QTLs within the 2 Mega base region, under the main QTL on BTA8 associated with antibody response to MAP, in position 34.700.000, 35.800.000 and 36.400.000 bp. This reveals the complexity of the genetic architecture of thetrait and confirms the need to further explore the genome with fine mapping approaches, or by the use of whole genome sequencing to investigate complex traits, such as disease resistance.