A Genome Wide Association Scan of Bovine Tuberculosis Susceptibility in Holstein-Friesian Dairy Cattle

Abstract

BackgroundBovine tuberculosis is a significant veterinary and financial problem in many parts of the world. Although many factors influence infection and progression of the disease, there is a host genetic component and dissection of this may enlighten on the wider biology of host response to tuberculosis. However, a binary phenotype of presence/absence of infection presents a noisy signal for genomewide association study.Methodology/Principal FindingsWe calculated a composite phenotype of genetic merit for TB susceptibility based on disease incidence in daughters of elite sires used for artificial insemination in the Irish dairy herd. This robust measure was compared with 44,426 SNP genotypes in the most informative 307 subjects in a genome wide association analysis. Three SNPs in a 65 kb genomic region on BTA 22 were associated (i.e. p<10−5, peaking at position 59588069, p = 4.02×10−6) with tuberculosis susceptibility.Conclusions/SignificanceA genomic region on BTA 22 was suggestively associated with tuberculosis susceptibility; it contains the taurine transporter gene SLC6A6, or TauT, which is known to function in the immune system but has not previously been investigated for its role in tuberculosis infection.

Admixture mapping of tuberculosis and pigmentation-related traits in an African–European hybrid cattle population

“…Additionally, several genome regions identified as candidates in genome wide association studies of BTB traits in British and Irish herds showed no correspondence here (Finlay et al, 2012; Bermingham et al, 2014). These disjunct results may not be surprising given that the present study is designed to detect variants segregating between zebu and European cattle breeds which are likely different to those that segregate within European herds.…”

Association between microsatellite markers and bovine tuberculosis in Chadian Zebu cattle

“…We identified six microsatellite markers significantly associated with at least one BTB trait (see Tables 3-5 A recent study of genome-wide association which used high density SNPs (single nucleotide polymorphisms) has identified three SNPs in a 65 kb genomic region on chromosome 22 associated with bovine tuberculosis susceptibility in Irish dairy cattle [14]. This genomic region has been found to contain gene SLC6A6 which is known to function in host immune systems.…”

“…Although there is no particular gene known to be responsible for differences in BTB infection susceptibility in cattle, natural resistant associated macrophage protein 1 (NRAMP1) was a known candidate gene; it is associated with natural resistance to infection with Mycobacterium spp., in cattle [12,13]. Recently, a genome-wide association study on Holstein-Friesian herds in Irish cattle that used the bovine 50 k SNP chip has identified three SNPs in a 65 kb genomic region on chromosome 22 associated with BTB susceptibility [14]. These studies provide substantial evidence that polymorphisms in the genome sequence play an essential role in determining resistance/ susceptibility to BTB infection.…”

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.…”