title: Genetic susceptibility to infectious disease in East African Shorthorn Zebu: a genome-wide analysis of the effect of heterozygosity and exotic introgression.
abstract: BACKGROUND
  Positive multi-locus heterozygosity-fitness correlations have been observed in a number of natural populations. They have been explained by the correlation between heterozygosity and inbreeding, and the negative effect of inbreeding on fitness (inbreeding depression). Exotic introgression in a locally adapted population has also been found to reduce fitness (outbreeding depression) through the breaking-up of co-adapted genes, or the introduction of non-locally adapted gene variants. In this study we examined the inter-relationships between genome-wide heterozygosity, introgression, and death or illness as a result of infectious disease in a sample of calves from an indigenous population of East African Shorthorn Zebu (crossbred Bos taurus x Bos indicus) in western Kenya. These calves were observed from birth to one year of age as part of the Infectious Disease in East African Livestock (IDEAL) project. Some of the calves were found to be genetic hybrids, resulting from the recent introgression of European cattle breed(s) into the indigenous population. European cattle are known to be less well adapted to the infectious diseases present in East Africa. If death and illness as a result of infectious disease have a genetic basis within the population, we would expect both a negative association of these outcomes with introgression and a positive association with heterozygosity.
  
  
  RESULTS
  In this indigenous livestock population we observed negative associations between heterozygosity and both death and illness as a result of infectious disease and a positive association between European taurine introgression and episodes of clinical illness.
  
  
  CONCLUSIONS
  We observe the effects of both inbreeding and outbreeding depression in the East African Shorthorn Zebu, and therefore find evidence of a genetic component to vulnerability to infectious disease. These results indicate that the significant burden of infectious disease in this population could, in principle, be reduced by altered breeding practices.
authors.affiliation: Institute of Evolutionary Biology, and Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3JT, UK. ggrm2@cam.ac.uk.
authors.forename: Gemma G R
authors.initials: GG
authors.lastname: Murray
authors.forename: Mark E J
authors.initials: ME
authors.lastname: Woolhouse
authors.forename: Miika
authors.initials: M
authors.lastname: Tapio
authors.forename: Mary N
authors.initials: MN
authors.lastname: Mbole-Kariuki
authors.forename: Tad S
authors.initials: TS
authors.lastname: Sonstegard
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Thumbi
authors.forename: Amy E
authors.initials: AE
authors.lastname: Jennings
authors.forename: Ilana Conradie
authors.initials: IC
authors.lastname: van Wyk
authors.forename: Margo
authors.initials: M
authors.lastname: Chase-Topping
authors.forename: Henry
authors.initials: H
authors.lastname: Kiara
authors.forename: Phil
authors.initials: P
authors.lastname: Toye
authors.forename: Koos
authors.initials: K
authors.lastname: Coetzer
authors.forename: Barend M
authors.initials: BM
authors.lastname: deC Bronsvoort
authors.forename: Olivier
authors.initials: O
authors.lastname: Hanotte
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics* / Q000401:mortality; D003141:Communicable Diseases / Q000235:genetics / Q000401:mortality / Q000662:veterinary*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006579:Heterozygote; D007178:Inbreeding; D007630:Kenya; D020641:Polymorphism, Single Nucleotide