Whole-Genome association analysis of susceptibility to paratuberculosis in Holstein cattle

Abstract

The objective of this study was to identify genetic markers and genomic regions associated with susceptibility to Mycobacterium avium ssp. paratuberculosis (MAP) infection in Holstein cattle. Associated single nucleotide polymorphisms (SNPs) were identified by genotyping 521 MAP-infected Holstein cows and comparing SNP allele frequencies of these infected cows with allele frequencies estimated from specific reference populations. Reference population allele frequency estimates used Holstein sire genotype data and were weighted estimates based on sire usage within the population in question. The 521 infected cows were 233 and 288 cows from two resource populations of approximately 5000 cows each, collected independently. Population 1 was comprised primarily of daughters of twelve Holstein artificial insemination sires used heavily within the US dairy cattle population. Samples were obtained from 300 co-operating commercial dairy herds throughout the US and were tested by both MAP faecal culture and blood-enzyme-linked immunosorbent assay (ELISA). Population 2 consisted of dairy cattle from six co-operating dairy herds in Wisconsin, with all animals in the herds tested by blood enzyme-linked immunosorbent assay (ELISA) for MAP infection. Genotyping was performed with the Illumina Bovine SNP50 Bead Chip, providing genotypes for 35,772 informative SNPs. Data from the two resource populations were analysed both in separate and combined analyses. The most significant autosomal markers from the individual and combined analyses (n=197, nominal P<0.001) were used in a stepwise logistic regression analysis to identify a set of 51 SNPs that could be used as a predictor of genetics for Holstein cattle susceptibility to MAP infection.

Phenotype definition is a main point in genome-wide association studies for bovine Mycobacterium avium ssp. paratuberculosis infection status

“…None of these genes were found in previous published GWA studies (summarized in Supplementary Table S1). Also there is no functional candidate gene described in the literature within 1 Mbp region of the SNPs in the present study (Settles et al, 2009;Minozzi et al, 2010;Pant et al, 2010;Kirkpatrick et al, 2011;Minozzi et al, 2012;van Hulzen et al, 2012). This supports once more the conclusion that paratuberculosis is probably affected by a large number of genes.…”

“…In this study, regions on BTA 3 and 9 were identified with a high significance to MAP status tested by MAP culture in feces and tissue in US Holsteins. In different GWA studies several associations were found on different chromosomes (Minozzi et al, 2010;Pant et al, 2010;Kirkpatrick et al, 2011;Minozzi et al, 2012;van Hulzen et al, 2012), summarized in Supplementary Table S1. These studies provide in general evidence for the existence of genomic regions associated with MAP infection in dairy cows.…”

Predicted accuracy of and response to genomic selection for new traits in dairy cattle

“…For new traits, depending on the cost of a single phenotypic measurement, composing reference populations may only be feasible for perhaps a few thousand cows with a single phenotypic measurement. Examples of such new traits are reduction of methane emission (Wall et al, 2010), energy balance (Verbyla et al, 2010), progesterone profiles as a proxy for fertility (Berry et al, 2012) and susceptibility to paratuberculosis (Johne's disease; Kirkpatrick et al, 2011). On the basis of such reference populations consisting of 600 to 2000 cows with single phenotypic measurements, accuracy of direct genomic values (DGV) was reported to be in the range of 0.3 to 0.5 (Verbyla et al, 2010;de Haas et al, 2011).…”

First insights in the genetics of caseous lymphadenitis in goats

“…From an economical and epidemiological point of view it would be important to select for disease resistant animals in order to decrease steadily the presence of CLA in goat herds. Although the application of genomic technologies, mainly applied in dairy cattle, can decrease the generation interval and boost genetic gain compared with traditional phenotypic selection, it is still important to perform genome wide association studies for infectious diseases to pinpoint and localise the genetic variations that have an effect on health traits, in cases where no effective therapy or prophylaxis are available, as in the case of bovine tuberculosis (Allen et al 2010;Finlay et al 2012;Bermingham et al 2014;Zare et al 2014;Richardson et al 2016) and bovine paratuberculosis (Settles et al 2009;Kirkpatrick et al 2011;Minozzi et al 2012;van Hulzen et al 2012;Alpay et al 2014;Pauciullo et al 2015), allowing the possibility to include the genetic approach as a complementary aid for disease incidence reduction. Recent developments in the animal genome sequencing technologies have allowed the application of a series of methods designed to identify regions of the genome linked or that affect certain characters of economic interest in cattle (e.g., production and/or resistance to diseases in dairy cattle) (Minozzi et al 2013) and in small ruminants, suitable when pedigree information is not available or unreliable.…”