The common marmoset (Callithrix jacchus) is a New World monkey that is used frequently as a model for various human diseases. However, detailed knowledge about the MHC is still lacking. In this ...study, we sequenced and annotated a total of 854 kb of the common marmoset MHC region that corresponds to the HLA-A/G/F segment (Caja-G/F) between the Caja-G1 and RNF39 genes. The sequenced region contains 19 MHC class I genes, of which 14 are of the MHC-G (Caja-G) type, and 5 are of the MHC-F (Caja-F) type. Six putatively functional Caja-G and Caja-F genes (Caja-G1, Caja-G3, Caja-G7, Caja-G12, Caja-G13, and Caja-F4), 13 pseudogenes related either to Caja-G or Caja-F, three non-MHC genes (ZNRD1, PPPIR11, and RNF39), two miscRNA genes (ZNRD1-AS1 and HCG8), and one non-MHC pseudogene (ETF1P1) were identified. Phylogenetic analysis suggests segmental duplications of units consisting of basically five (four Caja-G and one Caja-F) MHC class I genes, with subsequent expansion/deletion of genes. A similar genomic organization of the Caja-G/F segment has not been observed in catarrhine primates, indicating that this genomic segment was formed in New World monkeys after the split of New World and Old World monkeys.
We have previously reported specific swine leukocyte antigen (SLA) haplotype associations with significant effects on several reproduction performance traits in a highly inbred miniature pig ...population of Microminipigs (MMPs). In this study, to clarify the effects on farrowing rates of SLA similarity between mating partners in the MMP population, we compared the farrowing rates as a measure of reproductive success after 1063-cumulative matings among the following three groups of mating partners: (1) completely sharing SLA class I or class II haplotypes or alleles between partners (CS), (2) only one sharing the haplotypes or alleles (OS), and (3) non-sharing the haplotypes or alleles (NS). Average farrowing rates in CS groups consisting of completely sharing SLA class II haplotypes or DRBI and DQB1 alleles were lowest in the three groups. Moreover, lower farrowing rates were indicated in mating pairs with smaller amino acid pairwise genetic distances of SLA-1, SLA-3, DRB1 and DQB1 alleles between the pairs. These results suggested that the dissimilarity of SLA class I and class II alleles between mating partners markedly improved reproductive performance; therefore, SLA alleles or haplotypes are potentially useful genetic markers for the selection of mating pairs in breeding programs and epistatic studies of reproductive traits of MMPs.
The class I major histocompatibility complex (MHC) presents self-developed peptides to specific T cells to induce cytotoxity against infection. The MHC proteins are encoded by multiple loci that ...express numerous alleles to preserve the variability of the antigen-presenting ability in each species. The mechanism regulating MHC mRNA and protein expression at each locus is difficult to analyze because of the structural and sequence similarities between alleles. In this study, we examined the correlation between the mRNA and surface protein expression of swine leukocyte antigen (SLA)-1*0401 after the stimulation of peripheral blood mononuclear cells (PBMCs) by Staphylococcus aureus superantigen toxic shock syndrome toxin-1 (TSST-1). We prepared a monoclonal antibody (mAb) against a domain composed of Y102, L103 and L109 in the α2 domain. The Hp-16.0 haplotype swine possess only SLA-1*0401, which has the mAb epitope, while other haplotypes possess 0 to 3 SLA classical class I loci with the mAb epitopes. When PBMCs from SLA-1*0401 homozygous pigs were stimulated, the SLA-1*0401 mRNA expression level increased until 24 hrs and decreased at 48 hrs. The kinetics of the interferon regulatory transcription factor-1 (IRF-1) mRNA level were similar to those of the SLA-1*0401 mRNA. However, the surface protein expression level continued to increase until 72 hrs. Similar results were observed in the Hp-10.0 pigs with three mAb epitopes. These results suggest that TSST-1 stimulation induced both mRNA and surface protein expression of class I SLA in the swine PBMCs differentially and that the surface protein level was sustained independently of mRNA regulation.
Highlights • We examined association of swine MHC (SLA) class II haplotypes with traits in pigs. • The line studied had improved resistance to mycoplasmal pneumonia of swine (MPS). • Two haplotypes ...showed increased frequency and decreased MPS lesions. • Two haplotypes, associated with increased MPS lesions, decreased in frequency. • SLA class II haplotypes are useful markers for breeding to decrease MPS lesions.
Despite their high degree of genomic similarity, reminiscent of their relatively recent separation from each other (≈6 million years ago), the molecular basis of traits unique to humans vs. their ...closest relative, the chimpanzee, is largely unknown. This report describes a large-scale single-contig comparison between human and chimpanzee genomes via the sequence analysis of almost one-half of the immunologically critical MHC. This 1,750,601-bp stretch of DNA, which encompasses the entire class I along with the telomeric part of the MHC class III regions, corresponds to an orthologous 1,870,955 bp of the human HLA region. Sequence analysis confirms the existence of a high degree of sequence similarity between the two species. However, and importantly, this 98.6% sequence identity drops to only 86.7% taking into account the multiple insertions/deletions (indels) dispersed throughout the region. This is functionally exemplified by a large deletion of 95 kb between the virtual locations of human MICA and MICB genes, which results in a single hybrid chimpanzee MIC gene, in a segment of the MHC genetically linked to species-specific handling of several viral infections (HIV/SIV, hepatitis B and C) as well as susceptibility to various autoimmune diseases. Finally, if generalized, these data suggest that evolution may have used the mechanistically more drastic indels instead of the more subtle single-nucleotide substitutions for shaping the recently emerged primate species.
CD117 is a cytokine receptor expressed on the surface of hematopoietic stem cells with a likely role in cell survival, proliferation and differentiation. In order to study the differentiation ...activity of porcine CD117 hematopoietic cells in vitro and in vivo we prepared an anti-swine CD117 Mab (2A1) with high specificity for flow-cytometrical analysis. The 2A1 Mab did not recognize mouse or human mast cells suggesting that 2A1 is species-specific. Swine bone marrow (BM) CD117+ cells differentiated in vitro mainly into erythroid and monocyte lineages in the methylcellulose-based colony assay. When the swine BM CD117+ cells were transplanted in vivo into immunodeficient NOG (NOD/SCID/IL-2gc-null) mice, a significant amount of swine CD45+ leukocytes, including CD3 positive T cells, were developed in the mice. These results revealed that the swine BM CD117+ cells possess hematopoietic stem/progenitor activity and when monitored in immunodeficient mice or in vitro they can develop into lymphoid, erythroid, and myeloid cells efficiently with the new monoclonal antibody.
Previously, we found that a greater dissimilarity in swine leukocyte antigen (SLA) class I and class II alleles between mating partners resulted in increased farrowing rates in a highly inbred ...population of Microminipigs (MMPs). In this follow-up study, we have analyzed the effects of dissimilarity in SLA alleles between mating partners for seven different reproductive traits, including litter size and the number of stillborn and live or dead weaned piglets. We determined the relationships among reproductive traits within each mating event and the amino acid distances of SLA alleles as markers of diversity between mating partners. Our results indicate that mating partners with greater amino acid pairwise genetic distances in the SLA-1 class I gene or DQB1 class II gene alleles were associated with significantly larger litter sizes and higher numbers of live piglets at birth and weaning. Also, partners with greater pairwise distances in the SLA-2 class I gene alleles exhibited fewer pre-weaning deaths. These findings suggest that the dissimilarity in SLA class I and class II alleles between mating partners may affect not only farrowing rates but also other key reproductive traits such as litter size and improved piglet survival rates. Consequently, SLA alleles could serve as valuable genetic markers for selecting mating partners in breeding programs and for conducting epistatic studies on various reproductive traits in MMPs.
: Background: Pigs with defined swine leukocyte antigen (SLA) haplotypes and their detailed information are useful for transplantation and immunological studies. We developed two herds of SLA ...homozygous Duroc pigs with novel SLA haplotypes and characterized their reproductive potential.
Methods: For selective inbreeding, a pair of Duroc pigs was chosen as initial breeders, and substantial breeding within progenies was carried out for eight generations. In the selective breeding Duroc pigs, SLA haplotypes were assigned by nucleotide sequence determination of reverse transcription polymerase chain reaction (RT‐PCR) products of three SLA classical class I genes and two class II genes. Based on this sequence information, we developed a rapid and simple SLA class II DNA typing method by polymerase chain reaction‐sequence specific primer (PCR‐SSP) technique. As a complementary method for the characterization of the SLA haplotypes, genetic polymorphisms of 36 microsatellite (MS) markers within the SLA region were also analyzed in the selective breeding pigs with SLA homozygous/heterozygous haplotypes.
Results: Among the selective breeding pigs from the third to fifth generations, only two SLA haplotypes were identified by the RT‐PCR based SLA typing method; Hp‐27.30 (SLA‐1*08an03, SLA‐1*06an04, SLA‐2*0102, SLA‐3*0101 DRB1*1101 and DQB1*0503) and Hp‐60.13 (SLA‐1*an02, SLA‐2*1002, SLA‐3*0502, DRB1*0403 and DQB1*0303). In these two SLA haplotypes, two class I haplotypes, Hp‐27.0 and Hp‐60.0, are novel. Furthermore, two class II haplotypes, Hp‐0.30 and Hp‐0.13, which were previously reported in Korean native pigs and pigs of Hanford breed, respectively, were also assigned by a simple assay using a PCR‐SSP technique in the entire selective breeding stock. Moreover, two haplotype specific MS patterns were observed across the entire SLA region in the selective breeding (homozygous/heterozygous) pigs. No morphological abnormalities were observed in selective breeding pigs. The theoretical inbreeding coefficient at the eighth generation was 78.5%. In all generations of selective breeding pigs, litter sizes were comparable and weaning weights from the fifth to eighth generation produced progenies significantly lighter (P < 0.01) than those in the non‐selective breeding pigs.
Conclusions: We established and characterized SLA homozygous Duroc herds with two kinds of haplotypes that can be used as a new resource for transplantation and other biomedical studies.
: Background: Inbred miniature swine with defined novel SLA haplotypes will be useful in allo‐ and xeno‐transplantation studies, which can be carried out representing variable combinations of SLA ...haplotypes.
Methods: In Clawn miniature swine, two haplotypes (c1 and c2) and one crossover haplotype (c3) have been assigned by nucleotide sequence determination of RT‐PCR products of the three SLA classical class I genes and two SLA class II genes. To select SLA class I and II homozygotes in Clawn miniature swine individuals, we developed a rapid and simple SLA‐class I‐ and II‐DNA typing method by a combination of polymerase chain reaction‐sequence specific primer (PCR‐SSP) and polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) techniques.
Results: Seven allele specific primer pairs were designed for amplification of the second exons of three SLA class I genes, SLA‐1, SLA‐2, and SLA‐3, and one SLA class II gene, DRB1. Furthermore, based on PCR‐RFLP patterns in the SLA‐DQB1 gene, two allelic variants were recognized in the second exon in the Clawn miniature swine. Three haplotypes, c1, c2 and c3, were simply identified by the combination of PCR‐SSP and PCR‐RFLP methods in 22 samples from five families. A single allele at each of the class I and II genes was also observed in seven samples as SLA class I and II homozygotes with either the c1 or c2 haplotype.
Conclusions: The combination of PCR‐SSP and PCR‐RFLP methods facilitate the rapid identification of the three haplotypes and SLA class I and II homozygotes in individual Clawn miniature swine.
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