title: Genetic and functional evaluation of the level of inbreeding of the Westran pig: a herd with potential for use in xenotransplantation.
abstract: BACKGROUND
  The Westran pig has been purposely inbred for use in xenotransplantation. The herd originated in the wild from a limited gene pool and has been inbred by repeated full-sib matings for nine generations.
  
  
  METHODS
  The aim of this study was to evaluate the level of inbreeding by functional assays, such as bi-directional MLR and reciprocal skin grafts between herd members, and by genetic analysis using highly polymorphic genetic markers to calculate the level of inbreeding.
  
  
  RESULTS
  The MLR between herd members were non-reactive whereas there was a prompt response to third party pig lymphocytes, indicative of a normal immune responsiveness in Westran pigs but isogenicity of the major histocompatibility complex. Skin grafts between male siblings or female sibling skin grafts on male recipients showed prolonged survival but with few exceptions did not survive beyond 100 days suggesting that by the fifth generation the Westran herd was still mismatched at minor histocompatibility antigens. This level of functional inbreeding was confirmed by microsatellite analysis of highly polymorphic markers, which showed that 52 of 53 chromosomally dispersed markers were fixed by the ninth generation. This level of fixation was consistent with 19 to 20 generations of full-sibling inbreeding. The calculated inbreeding coefficient at generation 10 was 0.98159.
  
  
  CONCLUSIONS
  This analysis confirms that the Westran pig is highly inbred and we propose that analysis of chromosomally dispersed highly polymorphic markers is an accurate and reproducible method for assessing the level of inbreeding of a pig herd.
authors.affiliation: Centre for Transplant and Renal Research, Westmead Millennium Institute, University of Sydney at Westmead Hospital, Westmead, NSW, Australia. philip_oconnell@wsahs.nsw.gov.au
authors.forename: Philip J
authors.initials: PJ
authors.lastname: O'Connell
authors.forename: Wayne J
authors.initials: WJ
authors.lastname: Hawthorne
authors.forename: Denbigh
authors.initials: D
authors.lastname: Simond
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Chapman
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Chen
authors.forename: Anita T
authors.initials: AT
authors.lastname: Patel
authors.forename: Stacey N
authors.initials: SN
authors.lastname: Walters
authors.forename: Jane
authors.initials: J
authors.lastname: Burgess
authors.forename: Lyanne
authors.initials: L
authors.lastname: Weston
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Stokes
authors.forename: Chris
authors.initials: C
authors.lastname: Moran
authors.forename: Richard
authors.initials: R
authors.lastname: Allen
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D005260:Female; D007178:Inbreeding; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree; D011110:Polymorphism, Genetic / Q000235:genetics; D035781:Siblings; D016038:Skin Transplantation; D013552:Swine / Q000145:classification* / Q000235:genetics* / Q000276:immunology / Q000601:surgery; D014183:Transplantation, Heterologous / Q000276:immunology*