Submitted to: Immunogenetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/22/2008
Publication Date: 6/17/2008
Citation: Ando, A., Uenishi, H., Kawata, H., Tanaka, M., Shigenari, A., Flori, L., Chardon, P., Lunney, J.K., Kulski, J.K., Inoko, H. 2008. Microsatellite diversity and crossover regions within homozygous and heterozygous sla haplotypes of different pig breeds. Immunogenetics.60:399-407. Interpretive Summary: Effective animal vaccine and infectious disease responses require that the vaccine or infectious organisms be recognized by the immune system. This requires that the vaccine or microbial antigens be processed and presented to the immune system by host proteins, termed the major histocompatibility complex (MHC) antigens. For swine the MHC is called the Swine Leukocyte Antigen (SLA) complex. This manuscript presents a new method to genetically type the SLA complex, using highly polymorphic microsatellite probes that identify alleles within each of the three SLA regions, the class I, II and III regions. Combined sets of SLA class I, II and III genes are termed haplotypes. Swine with different SLA haplotypes have been shown to develop different, SLA dependent titers of complement and antibodies in response to immunization with defined antigens and vaccines. Thus it is important to know the SLA haplotypes for pigs involved in disease and vaccine studies. This genetic typing approach for identifying SLA alleles is also important for further development of basic research in swine immunology and for use of the swine as a transplantation model for humans and as a xenotranplantation (cross-species) donor for humans, since SLA matching is required for acceptance of cell and solid organ transplants. Overall, this genetic typing approach for defining SLA alleles and haplotypes will be very useful for providing background data for researchers designing vaccines and biotherapeutics. It will help stimulate research into effective protective immunity for infectious diseases in every pig.
Technical Abstract: Our aim was to investigate microsatellite (MS) diversity and find crossover regions at 42 polymorphic MS loci in the SLA genomic region of 72 pigs with different homozygous and heterozygous well-defined SLA haplotypes. We analyzed the genetic polymorphisms of the 42 MS markers in 23 SLA homozygous/heterozygous, common pig breeds with 12 SLA serological haplotypes and 49 NIH and Clawn homozygous/heterozygous miniature pigs with nine SLA serological or genotyped haplotypes including four recombinant haplotypes. In comparing the same and different haplotypes both haplospecific patterns and allelic variations were observed at the MS loci. Some of the haplotypes were found to share large haplotype blocks extended over 2-Mb, suggesting the existence of strong linkage disequilibrium (LD) in the entire SLA region. Crossing over regions were easily defined by the MS markers within the class I and/or III region in pigs with the NIH and Clawn recombinant haplotypes. The present haplotype comparison shows that our set of MS markers provides a fast and cost-efficient alternative or complementary method to the serological or sequence based determination of the SLA alleles for the characterization of SLA haplotypes and/or the crossing over regions between different haplotypes.