SVA Regulation of Transposable Element Clustered Transcription within the Major Histocompatibility Complex Genomic Class II Region of the Parkinson's Progression Markers Initiative.

SINE-VNTR-Alu (SVA) retrotransposons can regulate expression quantitative trait loci (eQTL) of coding and noncoding genes including transposable elements (TEs) distributed throughout the human genome. Previously, we reported that expressed SVAs and human leucocyte antigen (HLA) class II genotypes on chromosome 6 were associated significantly with Parkinson's disease (PD). Here, our aim was to follow-up our previous study and evaluate the SVA associations and their regulatory effects on the transcription of TEs within the HLA class II genomic region. We reanalyzed the transcriptome data of peripheral blood cells from the Parkinson's Progression Markers Initiative (PPMI) for 1530 subjects for TE and gene RNAs with publicly available computing packages. Four structurally polymorphic SVAs regulate the transcription of 20 distinct clusters of 235 TE loci represented by LINES (37%), SINES (28%), LTR/ERVs (23%), and ancient transposon DNA elements (12%) that are located in close proximity to HLA genes. The transcribed TEs were mostly short length, with an average size of 389 nucleotides. The numbers, types and profiles of positive and negative regulation of TE transcription varied markedly between the four regulatory SVAs. The expressed SVA and TE RNAs in blood cells appear to be enhancer-like elements that are coordinated differentially in the regulation of HLA class II genes. Future work on the mechanisms underlying their regulation and potential impact is essential for elucidating their roles in normal cellular processes and disease pathogenesis.

PBMC-engrafted humanized mice models for evaluating immune-related and anticancer drug delivery systems.

Immune-related drug delivery systems (DDSs) in humanized mouse models are at the forefront of cancer research and serve as bridges between preclinical studies and clinical applications. These systems offer unique platforms for exploring new therapies and understanding their interactions with human cells and the immune system. Here, we focus on a DDS and a peripheral blood mononuclear cell (PBMC)-engrafted humanized mouse model that we recently developed, and consider some of the key components, challenges, and applications to advance these systems towards better cancer treatment on the basis of a better understanding of the immune response. Our DDS is unique and has a dual function, an anticancer effect and a capacity to fine-tune the immune reaction. The PBL-NOG-hIL-4-Tg mouse system is superior to other available humanized mouse systems for the development of such multifunctional DDSs because it supports the rapid reconstruction of an individual donor's immunity and avoids the onset of graft-versus-host disease.

Genetic Links between Reproductive Traits and Amino Acid Pairwise Distances of Swine Leukocyte Antigen Alleles among Mating Partners in Microminipigs.

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.

Regulatory SVA retrotransposons and classical HLA genotyped-transcripts associated with Parkinson's disease.

Introduction: Parkinson's disease (PD) is a neurodegenerative and polygenic disorder characterised by the progressive loss of neural dopamine and onset of movement disorders. We previously described eight SINE-VNTR-Alu (SVA) retrotransposon-insertion-polymorphisms (RIPs) located and expressed within the Human Leucocyte Antigen (HLA) genomic region of chromosome 6 that modulate the differential co-expression of 71 different genes including the HLA classical class I and class II genes in a Parkinson's Progression Markers Initiative (PPMI) cohort. Aims and methods: In the present study, we (1) reanalysed the PPMI genomic and transcriptomic sequencing data obtained from whole blood of 1521 individuals (867 cases and 654 controls) to infer the genotypes of the transcripts expressed by eight classical HLA class I and class II genes as well as DRA and the DRB3/4/5 haplotypes, and (2) examined the statistical differences between three different PD subgroups (cases) and healthy controls (HC) for the HLA and SVA transcribed genotypes and inferred haplotypes. Results: Significant differences for 57 expressed HLA alleles (21 HLA class I and 36 HLA class II alleles) up to the three-field resolution and four of eight expressed SVA were detected at p<0.05 by the Fisher's exact test within one or other of three different PD subgroups (750 individuals with PD, 57 prodromes, 60 individuals who had scans without evidence of dopamine deficits [SWEDD]), when compared against a group of 654 HCs within the PPMI cohort and when not corrected by the Bonferroni test for multiple comparisons. Fourteen of 20 significant alleles were unique to the PD-HC comparison, whereas 31 of the 57 alleles overlapped between two or more different subgroup comparisons. Only the expressed HLA-DRA*01:01:01 and -DQA1*03:01:01 protective alleles (PD v HC), the -DQA1*03:03:01 risk (HC v Prodrome) or protective allele (PD v Prodrome), the -DRA*01:01:02 and -DRB4*01:03:02 risk alleles (SWEDD v HC), and the NR_SVA_381 present genotype (PD v HC) at a 5% homozygous insertion frequency near HLA-DPA1, were significant (Pc<0.1) after Bonferroni corrections. The homologous NR_SVA_381 insertion significantly decreased the transcription levels of HLA-DPA1 and HLA-DPB1 in the PPMI cohort and its presence as a homozygous genotype is a risk factor (Pc=0.012) for PD. The most frequent NR_SVA_381 insertion haplotype in the PPMI cohort was NR_SVA_381/DPA1*02/DPB1*01 (3.7%). Although HLA C*07/B*07/DRB5*01/DRB1*15/DQB1*06 was the most frequent HLA 5-loci phased-haplotype (n, 76) in the PPMI cohort, the NR_SVA_381 insertion was present in only six of them (8%). Conclusions: These data suggest that expressed SVA and HLA gene alleles in circulating white blood cells are coordinated differentially in the regulation of immune responses and the long-term onset and progression of PD, the mechanisms of which have yet to be elucidated.

HLA Genetics for the Human Diseases.

Highly polymorphic human leukocyte antigen (HLA) molecules (alleles) expressed by different classical HLA class I and class II genes have crucial roles in the regulation of innate and adaptive immune responses, transplant rejection and in the pathogenesis of numerous infectious and autoimmune diseases. To date, over 35,000 HLA alleles have been published from the IPD-IMGT/HLA database, and specific HLA alleles and HLA haplotypes have been reported to be associated with more than 100 different diseases and phenotypes. Next generation sequencing (NGS) technology developed in recent years has provided breakthroughs in various HLA genomic/gene studies and transplant medicine. In this chapter, we review the current information on the HLA genomic structure and polymorphisms, as well as the genetic context in which numerous disease associations have been identified in this region.

MHC-DRB alleles with amino acids Val11, Phe13, and the shared epitopes promote collagen-induced arthritis and a rapid IgG1 response in Filipino cynomolgus macaques.

Macaques are useful animal models for studying the pathogenesis of rheumatoid arthritis (RA) and the development of anti-rheumatic drugs. The purpose of this study was to identify the major histocompatibility complex (MHC) polymorphisms associated with the pathology of collagen-induced arthritis (CIA) and anti-collagen IgG induction in a cynomolgus macaque model, as MHC polymorphisms affect the onset of CIA in other animal models. Nine female Filipino cynomolgus macaques were immunized with bovine type II collagen (b-CII) to induce CIA, which was diagnosed clinically by scoring the symptoms of joint swelling over 9 weeks. MHC polymorphisms and anti-b-CII antibody titers were compared between symptomatic and asymptomatic macaques. Four of 9 (44%) macaques were defined as the CIA-affected group. Anti-b-CII IgG in the affected group increased in titer approximately 3 weeks earlier compared with the asymptomatic group. The mean plasma IgG1 titer in the CIA-affected group was significantly higher (p < 0.05) than that of the asymptomatic group. Furthermore, the cynomolgus macaque MHC (Mafa)-DRB1*10:05 or Mafa-DRB1*10:07 alleles, which contain the well-documented RA-susceptibility five amino acid sequence known as the shared epitope (SE) in positions 70 to 74, with valine at position 11 (Val11, V11) and phenylalanine at position 13 (Phe13, F13), were detected in the affected group. In contrast, no MHC polymorphisms specific to the asymptomatic group were identified. In conclusion, the presence of V11 and F13 along with SE in the MHC-DRB1 alleles seems essential for the production of IgG1 and the rapid induction of severe CIA in female Filipino cynomolgus macaques.

Regulation of expression quantitative trait loci by SVA retrotransposons within the major histocompatibility complex.

Genomic and transcriptomic studies of expression quantitative trait loci (eQTL) revealed that SINE-VNTR-Alu (SVA) retrotransposon insertion polymorphisms (RIPs) within human genomes markedly affect the co-expression of many coding and noncoding genes by coordinated regulatory processes. This study examined the polymorphic SVA modulation of gene co-expression within the major histocompatibility complex (MHC) genomic region where more than 160 coding genes are involved in innate and adaptive immunity. We characterized the modulation of SVA RIPs utilizing the genomic and transcriptomic sequencing data obtained from whole blood of 1266 individuals in the Parkinson's Progression Markers Initiative (PPMI) cohort that included an analysis of human leukocyte antigen (HLA)-A regulation in a subpopulation of the cohort. The regulatory properties of eight SVAs located within the class I and class II MHC regions were associated with differential co-expression of 71 different genes within and 75 genes outside the MHC region. Some of the same genes were affected by two or more different SVA. Five SVA are annotated in the human genomic reference sequence GRCh38.p14/hg38, whereas the other three were novel insertions within individuals. We also examined and found distinct structural effects (long and short variants and the CT internal variants) for one of the SVA (R_SVA_24) insertions on the differential expression of the HLA-A gene within a subpopulation (550 individuals) of the PPMI cohort. This is the first time that many HLA and non-HLA genes (multilocus expression units) and splicing mechanisms have been shown to be regulated by eight structurally polymorphic SVA within the MHC genomic region by applying precise statistical analysis of RNA data derived from the blood samples of a human cohort population. This study shows that SVA within the MHC region are important regulators or rheostats of gene co-expression that might have potential roles in diversity, health, and disease.

Large-Scale Polymorphism Analysis of Dog Leukocyte Antigen Class I and Class II Genes (DLA-88, DLA-12/88L and DLA-DRB1) and Comparison of the Haplotype Diversity between Breeds in Japan.

Polymorphisms of canine leukocyte antigen (DLA) class I (DLA-88 and DLA-12/88L) and class II (DLA-DRB1) genes are important for disease susceptibility studies, but information on the genetic diversity among dog breeds is still lacking. To better elucidate the polymorphism and genetic diversity between breeds, we genotyped DLA-88, DLA-12/88L, and DLA-DRB1 loci using 829 dogs of 59 breeds in Japan. Genotyping by Sanger sequencing identified 89, 43, and 61 alleles in DLA-88, DLA-12/88L, and DLA-DRB1 loci, respectively, and a total of 131 DLA-88-DLA-12/88L-DLA-DRB1 haplotypes (88-12/88L-DRB1) were detected more than once. Of the 829 dogs, 198 were homozygotes for one of the 52 different 88-12/88L-DRB1 haplotypes (homozygosity rate: 23.8%). Statistical modeling suggests that 90% of the DLA homozygotes or heterozygotes with one or other of the 52 different 88-12/88L-DRB1 haplotypes within somatic stem cell lines would benefit graft outcome after 88-12/88L-DRB1-matched transplantation. As previously reported for DLA class II haplotypes, the diversity of 88-12/88L-DRB1 haplotypes varied remarkably between breeds but was relatively conserved within most breeds. Therefore, the genetic characteristics of high DLA homozygosity rate and poor DLA diversity within a breed are useful for transplantation therapy, but they may affect biological fitness as homozygosity progresses.

Association of immune-mediated necrotizing myopathy with HLA polymorphisms.

Immune-mediated necrotizing myopathy (IMNM) is a type of autoimmune myositis typically characterized clinically by proximal muscle weakness with elevated creatine kinase levels, pathologically by myofiber necrosis and regeneration with paucity of lymphocytic cell infiltration, and serologically by the presence of either of two myositis-specific autoantibodies, anti-SRP, and anti-HMGCR antibodies. However, the HLA loci and alleles associated with IMNM are still not fully understood at least partly because IMNM was a relatively recently established condition. In this study, we genotyped the six HLA loci (HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1) in 250 patients (237 patients over age 18 years and 13 juvenile patients) diagnosed with IMNM based on clinicopathological features and autoantibody information and performed a case control study with Japanese healthy subjects. In the adult patients, specific HLA alleles associated with IMNM were identified at all HLA loci, with DRB1*08:03 showing the strongest association (OR = 2.5; p = 0.00000017). Furthermore, subgroup analysis with various clinical information showed that C*03:04 (OR = 3.7; p = 0.00012) was a higher risk allele for collagen disease in adult patients, and B*13:01 (OR = 23.2; p = 0.021) and C*03:04 (OR = 5.8; p = 0.0074) were higher risk for juvenile patients with anti-HMGCR antibody-positive IMNM. These findings will help to better understand the HLA genetic background and features of IMNM in designing future studies.

Nucleotide alterations in the HLA-C class I gene can cause aberrant splicing and marked changes in RNA levels in a polymorphic context-dependent manner.

Polymorphisms of HLA genes, which play a crucial role in presenting peptides with diverse sequences in their peptide-binding pockets, are also thought to affect HLA gene expression, as many studies have reported associations between HLA gene polymorphisms and their expression levels. In this study, we devised an ectopic expression assay for the HLA class I genes in the context of the entire gene, and used the assay to show that the HLA-C*03:03:01 and C*04:01:01 polymorphic differences observed in association studies indeed cause different levels of RNA expression. Subsequently, we investigated the C*03:23N null allele, which was previously noted for its reduced expression, attributed to an alternate exon 3 3' splice site generated by G/A polymorphism at position 781 within the exon 3. We conducted a thorough analysis of the splicing patterns of C*03:23N, and revealed multiple aberrant splicing, including the exon 3 alternative splicing, which overshadowed its canonical counterpart. After confirming a significant reduction in RNA levels caused by the G781A alteration in our ectopic assay, we probed the function of the G-rich sequence preceding the canonical exon 3 3' splice site. Substituting the G-rich sequence with a typical pyrimidine-rich 3' splice site sequence on C*03:23N resulted in a marked elevation in RNA levels, likely due to the enhanced preference for the canonical exon 3 3' splice site over the alternate site. However, the same substitution led to a reduction in RNA levels for C*03:03:01. These findings suggested the dual roles of the G-rich sequence in RNA expression, and furthermore, underscore the importance of studying polymorphism effects within the framework of the entire gene, extending beyond conventional mini-gene reporter assays.

Human leukocyte antigen super-locus: nexus of genomic supergenes, SNPs, indels, transcripts, and haplotypes.

The human Major Histocompatibility Complex (MHC) or Human Leukocyte Antigen (HLA) super-locus is a highly polymorphic genomic region that encodes more than 140 coding genes including the transplantation and immune regulatory molecules. It receives special attention for genetic investigation because of its important role in the regulation of innate and adaptive immune responses and its strong association with numerous infectious and/or autoimmune diseases. In recent years, MHC genotyping and haplotyping using Sanger sequencing and next-generation sequencing (NGS) methods have produced many hundreds of genomic sequences of the HLA super-locus for comparative studies of the genetic architecture and diversity between the same and different haplotypes. In this special issue on 'The Current Landscape of HLA Genomics and Genetics', we provide a short review of some of the recent analytical developments used to investigate the SNP polymorphisms, structural variants (indels), transcription and haplotypes of the HLA super-locus. This review highlights the importance of using reference cell-lines, population studies, and NGS methods to improve and update our understanding of the mechanisms, architectural structures and combinations of human MHC genomic alleles (SNPs and indels) that better define and characterise haplotypes and their association with various phenotypes and diseases.

Genetic Association between Farrowing Rates and Swine Leukocyte Antigen Alleles or Haplotypes in Microminipigs.

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.

Sequence Variations Within HLA-G and HLA-F Genomic Segments at the Human Leukocyte Antigen Telomeric End Associated With Acute Graft-Versus-Host Disease in Unrelated Bone Marrow Transplantation.

Acute graft-versus-host disease (aGVHD) is defined as a syndrome of an immunological response of graft to the host that occurs early after allogeneic hematopoietic stem cell transplantation (HCT). This disease is frequently observed even in HCT matched for human leukocyte antigen (HLA) alleles at multiple gene loci. Although the HLA region represents complex and diverse genomic characteristics, detailed association analysis is required for the identification of uncharacterized variants that are strongly associated with aGVHD. We genotyped three loci, OR2H2, HLA-F-AS1, and HLA-G, that are located in the 460 kb of HLA telomeric region and statistically analyzed the genotypes including HLA-DPB1 with clinical and transplantation outcomes using 338 unrelated bone marrow transplantation (UR-BMT) patient-donor pairs who were matched for HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 (HLA-10/10). Multivariate analyses demonstrated that HLA-F-AS1 and HLA-DPB1 mismatches were associated with grade II-IV aGVHD (hazard ratio (HR), 1.76; 95% CI, 1.07-2.88; p = 0.026; and HR, 1.59; CI, 1.02-2.49; p = 0.042, respectively). There was no confounding between HLA-F-AS1 and HLA-DPB1 (p = 0.512), suggesting that the HLA-F-AS1 mismatch has a strong effect on aGVHD independently of HLA-DPB1. Moreover, a stratified analysis suggested possible associations of HLA-F-AS1, HLA-DPB1, and/or HLA-G mismatches with grade II-IV aGVHD and the more severe grade III-IV aGVHD. These findings provide new insights into understanding the molecular mechanism of aGVHD caused by HLA-matched UR-BMT.

A novel swab storage gel is superior to dry swab DNA collection, and enables long-range high resolution next generation sequencing HLA typing from buccal cell samples.

HLA sequence-based DNA typing (SBT) by long-range PCR amplification (LR PCR) and next-generation sequencing (NGS) is a high-throughput DNA sequencing method (LR-NGS-SBT) for the efficient and sensitive detection of novel and null HLA alleles to the field-4 level of allelic resolution without phase ambiguity. However, the accuracy and reliability of the HLA typing results using buccal cells (BCs) and saliva as genetic source materials for the LR-NGS-SBT method are dependent largely on the quality of the extracted genomic DNA (gDNA) because a large degree of gDNA fragmentation can result in insufficient PCR amplification with the incorrect assignment of HLA alleles because of allele dropouts. In this study, we developed a new cost-efficient swab storage gel (SSG) for wet swab collection of BCs (BC-SSG) and evaluated its usefulness by performing different DNA analytical parameters including LR-NGS-SBT to compare the quality and quantity of gDNA extracted from BCs (in SSG or air dried), blood and saliva of 30 subjects. The BC-SSG samples after 5 days of storage revealed qualitative and quantitative DNA values equivalent to that of blood and/or saliva and better than swabs that were only air-dried (BC-nSSG). Moreover, all the gDNA extracted from blood, saliva and BC-SSG samples were HLA-typed successfully to an equivalent total of 408 alleles for each sample type. Therefore, the application of BC-SSG collection media for LR-NGS-SBT has benefits over BC dried samples (dry swabs) such as reducing retesting and the number of untestable BC samples because of insufficient DNA amplification.

Haplotype structures and polymorphisms of dog leukocyte antigen (DLA) class I loci shaped by intralocus and interlocus recombination events.

The dog leukocyte antigen (DLA) class I genomic region is located on chromosome 12, and the class I genomic region is composed of at least two distinct haplotypic gene structures, DLA-88-DLA-12 and DLA-88-DLA-88L. However, detailed information of the genomic differences among DLA-88, DLA-12, and DLA-88L are still lacking at the full-length gene level, and therefore, DLA allelic sequences classified for each of these loci are limited in number so far. In this study, we determined the DNA sequence of a 95-kb DLA class I genomic region including DLA-88, DLA-12/88L, and DLA-64 with three DLA homozygous dogs and of 37 full-length allelic gene sequences for DLA-88 and DLA-12/88L loci in 26 DLA class I homozygous dogs. Nucleotide diversity profiles of the 95-kb regions and sequence identity scores of the allelic sequences suggested that DLA-88L is a hybrid gene generated by interlocus and/or intralocus gene conversion between DLA-88 and DLA-12. The putative minimum conversion tract was estimated to be at least an 850-bp segment in length located from the 5´flanking untranslated region to the end of intron 2. In addition, at least one DLA-12 allele (DLA-12*004:01) was newly generated by interlocus gene conversion. In conclusion, the analysis for the occurrence of gene conversion within the dog DLA class I region revealed intralocus gene conversion tracts in 17 of 27 DLA-88 alleles and two of 10 DLA-12 alleles, suggesting that intralocus gene conversion has played an important role in expanding DLA allelic variations.

Identification of three novel HLA-DRA alleles by next-generation sequencing.

Three novel HLA-DRA alleles, DRA*01:03, DRA*01:04, and DRA*01:05 alleles with unique amino acid sequences.

Haplotypic Associations and Differentiation of MHC Class II Polymorphic Alu Insertions at Five Loci With HLA-DRB1 Alleles in 12 Minority Ethnic Populations in China.

The analysis of polymorphic variations in the human major histocompatibility complex (MHC) class II genomic region on the short-arm of chromosome 6 is a scientific enquiry to better understand the diversity in population structure and the effects of evolutionary processes such as recombination, mutation, genetic drift, demographic history, and natural selection. In order to investigate associations between the polymorphisms of HLA-DRB1 gene and recent Alu insertions (POALINs) in the HLA class II region, we genotyped HLA-DRB1 and five Alu loci (AluDPB2, AluDQA2, AluDQA1, AluDRB1, AluORF10), and determined their allele frequencies and haplotypic associations in 12 minority ethnic populations in China. There were 42 different HLA-DRB1 alleles for ethnic Chinese ranging from 12 alleles in the Jinuo to 28 in the Yugur with only DRB1∗08:03, DRB1∗09:01, DRB1∗12:02, DRB1∗14:01, DRB1∗15:01, and DRB1∗15:02 present in all ethnic groups. The POALINs varied in frequency between 0.279 and 0.514 for AluDPB2, 0 and 0.127 for AluDQA2, 0.777 and 0.995 for AluDQA1, 0.1 and 0.455 for AluDRB1 and 0.084 and 0.368 for AluORF10. By comparing the data of the five-loci POALIN in 13 Chinese ethnic populations (including Han-Yunnan published data) against Japanese and Caucasian published data, marked differences were observed between the populations at the allelic or haplotypic levels. Five POALIN loci were in significant linkage disequilibrium with HLA-DRB1 in different populations and AluDQA1 had the highest percentage association with most of the HLA-DRB1 alleles, whereas the nearby AluDRB1 indel was strongly haplotypic for only DRB1∗01, DRB1∗10, DRB1∗15 and DRB1∗16. There were 30 five-locus POALIN haplotypes inferred in all populations with H5 (no Alu insertions except for AluDQA1) and H21 (only AluDPB2 and AluDQA1 insertions) as the two predominant haplotypes. Neighbor joining trees and principal component analyses of the Alu and HLA-DRB1 polymorphisms showed that genetic diversity of these genomic markers is associated strongly with the population characteristics of language family, migration and sociality. This comparative study of HLA-DRB1 alleles and multilocus, lineage POALIN frequencies of Chinese ethnic populations confirmed that POALINs whether investigated alone or together with the HLA class II alleles are informative genetic and evolutionary markers for the identification of allele and haplotype lineages and genetic variations within the same and/or different populations.

Stillbirth rates and their association with swine leucocyte antigen class II haplotypes in Microminipigs.

OBJECTIVE: Microminipig (MMP) is a miniature pig with an extra small body size for experimental use. In the present study, the occurrence of stillbirths and their genetic association with swine leukocyte antigen (SLA) class II haplotypes were evaluated in a population of MMPs. METHODS: The occurrences of stillbirth and genetic association with SLA class II haplotypes using 483 stillborn and 2,246 live piglets, and their parents were compared among the three groups of newborn piglet litters; an all stillborn (AS) group consisting of only stillborn piglet litters, a partial stillborn (PS) group consisting of stillborn and live piglet litters, and an all alive (AA) group consisting of only live piglet litters. RESULTS: The incidence of stillborn piglets was 483/2,729 (17.7%). Distributions of litter sizes, numbers of stillborn piglets in a litter, parities, and gestation periods were distinct among the three groups. The frequencies of low resolution haplotype (Lr)-0.7 or Lr-0.23 were higher in the AS group than in the PS or AA groups. In sires, the frequency of Lr-0.7 associated with the AS group was significantly higher in the AS group than with the AA group. In dams, the frequency of Lr-0.23 was significantly higher in the AS group than in the PS or AA groups, whereas the frequency of Lr-0.7 was not significantly different. CONCLUSION: The incidence of stillborn piglets in MMPs appears to be higher than those in other pig breeds. Several traits related with stillbirths such as the number of stillborn piglets and parities of the AS group were different from those of the PS and AA groups. Specific SLA class II haplotypes were associated significantly with a high incidence of stillbirths and could be used as genetic markers to adopt breeding strategies to lower the rate of stillbirth in MMPs.