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1.
de Groot N Doxiadis GG de Vos-Rouweler AJ de Groot NG Verschoor EJ Bontrop RE 《Immunogenetics》2008,60(12):737-748
The DRB region of the major histocompatibility complex (MHC) of cynomolgus and rhesus macaques is highly plastic, and extensive copy
number variation together with allelic polymorphism makes it a challenging enterprise to design a typing protocol. All intact
DRB genes in cynomolgus monkeys (Mafa) appear to possess a compound microsatellite, DRB-STR, in intron 2, which displays extensive length polymorphism. Therefore,
this STR was studied in a large panel of animals, comprising pedigreed families as well. Sequencing analysis resulted in the
detection of 60 Mafa-DRB exon 2 sequences that were unambiguously linked to the corresponding microsatellite. Its length is often allele specific
and follows Mendelian segregation. In cynomolgus and rhesus macaques, the nucleotide composition of the DRB-STR is in concordance
with the phylogeny of exon 2 sequences. As in humans and rhesus monkeys, this protocol detects specific combinations of different
DRB-STR lengths that are unique for each haplotype. In the present panel, 22 Mafa-DRB region configurations could be defined, which exceeds the number detected in a comparable cohort of Indian rhesus macaques.
The results suggest that, in cynomolgus monkeys, even more frequently than in rhesus macaques, new haplotypes are generated
by recombination-like events. Although both macaque species are known to share several identical DRB exon 2 sequences, the lengths of the corresponding microsatellites often differ. Thus, this method allows not only fast and
accurate DRB haplotyping but may also permit discrimination between highly related macaque species. 相似文献
2.
Doxiadis GG Rouweler AJ de Groot NG Louwerse A Otting N Verschoor EJ Bontrop RE 《Immunogenetics》2006,58(4):259-268
In contrast to rhesus monkeys, substantial knowledge on cynomolgus monkey major histocompatibility complex (MHC) class II haplotypes is lacking. Therefore, 17 animals, including one pedigreed family, were thoroughly characterized for polymorphic Mhc class II region genes as well as their mitochondrial DNA (mtDNA) sequences. Different cynomolgus macaque populations appear to exhibit unique mtDNA profiles reflecting their geographic origin. Within the present panel, 10 Mafa-DPB1, 14 Mafa-DQA1, 12 Mafa-DQB1, and 35 Mafa-DRB exon 2 sequences were identified. All of these alleles cluster into lineages that were previously described for rhesus macaques. Moreover, about half of the Mafa-DPB1, Mafa-DQA1, and Mafa-DQB1 alleles and one third of the Mafa-DRB exon 2 sequences are identical to rhesus macaque orthologues. Such a high level of Mhc class II allele sharing has not been reported for primate species. Pedigree analysis allowed the characterization of nine distinct Mafa class II haplotypes, and seven additional ones could be deduced. Two of these haplotypes harbor a duplication of the Mafa-DQB1 locus. Despite extensive allele sharing, rhesus and cynomolgus monkeys do not appear to possess identical Mhc class II haplotypes, thus illustrating that new haplotypes were generated after speciation by recombination-like processes. 相似文献
3.
MHC class I A region diversity and polymorphism in macaque species 总被引:11,自引:7,他引:4
Otting N de Vos-Rouweler AJ Heijmans CM de Groot NG Doxiadis GG Bontrop RE 《Immunogenetics》2007,59(5):367-375
The HLA-A locus represents a single copy gene that displays abundant allelic polymorphism in the human population, whereas, in contrast, a nonhuman primate species such as the rhesus macaque (Macaca mulatta) possesses multiple HLA-A-like (Mamu-A) genes, which parade varying degrees of polymorphism. The number and combination of transcribed Mamu-A genes present per chromosome display diversity in a population of Indian animals. At present, it is not clearly understood whether these different A region configurations are evolutionarily stable entities. To shed light on this issue, rhesus macaques from a Chinese population and a panel of cynomolgus monkeys (Macaca fascicularis) were screened for various A region-linked variations. Comparisons demonstrated that most A region configurations are old entities predating macaque speciation, whereas most allelic variation (>95%) is of more recent origin. The latter situation contrasts the observations of the major histocompatibility complex class II genes in rhesus and cynomolgus macaques, which share a high number of identical alleles (>30%) as defined by exon 2 sequencing. 相似文献
4.
The human major histocompatibility complex (MHC) contains a variety of genes, many of which are highly polymorphic and of
immunological importance. A database of MHC extended haplotypes was used to integrate experimental, cell line, and population
data. Three alleles of the human TNF-beta (lymphotoxin-alpha) gene were identified, named TNFB
*1SL, TNFB
*2LL, and TNFB
*1LS, each representing a different lineage in the evolution of TNF region haplotypes. Lower variability in the length of the associated microsatellite alleles indicates that *1SL characterizes the youngest of the three haplotype lineages. Microsatellite haplotypes in the two older lineages show evidence
for a coevolution of alleles through concerted expansions. Genetic predispositions to high and low TNF-alpha (cachectin) responses
seem to have evolved independently in more than one lineage. The literature data suggest different, or even opposite, associations
concerning the regulation of TNF-alpha in macrophages and lymphoid cells. Microsatellite ud may be the most informative marker for studies of the associations of individual TNF region markers with secretion levels, immunity, and disease.
Received: 10 December 1996 / Revised: 21 May 1997 相似文献
5.
Major histocompatibility complex (MHC) class I genes play a crucial role in the immune defence against intracellular pathogens. An important evolutionary strategy is to generate and maintain a high level of diversity in these genes. Humans express three highly polymorphic classical MHC class I genes (HLA-A, HLA-B and HLA-C). In contrast, some species, for example rat and rhesus macaque, maintain diversity by generation of haplotypes that vary considerably with regard to the number and combination of transcribed genes. Cattle appear to use both strategies. We show that various combinations of six apparently classical genes, three of which are highly polymorphic, are transcribed on different haplotypes. Although additional sequences were identified in both cDNA and gDNA, it was not possible to assign them to any of these defined genes. Most were highly divergent or were non-classical class I genes. Thus, we found little evidence for frequent duplication and deletion of classical class I genes as reported in some other species. However, the maintenance of class I diversity in cattle may involve limited gene shuffling and deletion, possibly as a result of unequal crossing-over within the class I region.The first two authors made an equal contribution to this work. 相似文献
6.
7.
Ilka Hoof Bjoern Peters John Sidney Lasse Eggers Pedersen Alessandro Sette Ole Lund Søren Buus Morten Nielsen 《Immunogenetics》2009,61(1):1-13
Binding of peptides to major histocompatibility complex (MHC) molecules is the single most selective step in the recognition
of pathogens by the cellular immune system. The human MHC genomic region (called HLA) is extremely polymorphic comprising
several thousand alleles, each encoding a distinct MHC molecule. The potentially unique specificity of the majority of HLA
alleles that have been identified to date remains uncharacterized. Likewise, only a limited number of chimpanzee and rhesus
macaque MHC class I molecules have been characterized experimentally. Here, we present NetMHCpan-2.0, a method that generates quantitative predictions of the affinity of any peptide–MHC class I interaction. NetMHCpan-2.0 has been trained on the hitherto largest set of quantitative MHC binding data available, covering HLA-A and HLA-B, as well
as chimpanzee, rhesus macaque, gorilla, and mouse MHC class I molecules. We show that the NetMHCpan-2.0 method can accurately predict binding to uncharacterized HLA molecules, including HLA-C and HLA-G. Moreover, NetMHCpan-2.0 is demonstrated to accurately predict peptide binding to chimpanzee and macaque MHC class I molecules. The power of NetMHCpan-2.0 to guide immunologists in interpreting cellular immune responses in large out-bred populations is demonstrated. Further,
we used NetMHCpan-2.0 to predict potential binding peptides for the pig MHC class I molecule SLA-1*0401. Ninety-three percent of the predicted
peptides were demonstrated to bind stronger than 500 nM. The high performance of NetMHCpan-2.0 for non-human primates documents the method’s ability to provide broad allelic coverage also beyond human MHC molecules.
The method is available at .
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
8.
Evolutionary stability of MHC class II haplotypes in diverse rhesus macaque populations 总被引:12,自引:10,他引:2
Doxiadis GG Otting N de Groot NG de Groot N Rouweler AJ Noort R Verschoor EJ Bontjer I Bontrop RE 《Immunogenetics》2003,55(8):540-551
A thoroughly characterized breeding colony of 172 pedigreed rhesus macaques was used to analyze exon 2 of the polymorphic Mamu-DPB1, -DQA1, -DQB1, and -DRB loci. Most of the monkeys or their ancestors originated in India, though the panel also included animals from Burma and China, as well as some of unknown origin and mixed breeds. In these animals, mtDNA appears to correlate with the aforementioned geographic origin, and a large number of Mamu class II alleles were observed. The different Mamu-DPB1 alleles were largely shared between monkeys of different origin, whereas in humans particular alleles appear to be unique for ethnic populations. In contrast to Mamu-DPB1, the highly polymorphic -DQA1/DQB1 alleles form tightly linked pairs that appear to be about two-thirds population specific. For most of the DQA1/DQB1 pairs, Mamu-DRB region configurations present on the same chromosome have been ascertained, resulting in 41 different -DQ/DRB haplotypes. These distinct DQ/DRB haplotypes seem to be specific for monkeys of a determined origin. Thus, in evolutionary terms, the Mamu-DP, -DQ, and -DR regions show increasing instability with regard to allelic polymorphism, such as for -DP/DQ, or gene content and allelic polymorphism, such as for -DR, resulting in population-specific class II haplotypes. Furthermore, novel haplotypes are generated by recombination-like events. The results imply that mtDNA analysis in combination with Mhc typing is a helpful tool for selecting animals for biomedical experiments.The sequences reported in this paper have been deposited in the EMBL database (accession nos. AJ534296–AJ534304, AJ 564564, and AJ557455–AJ557511) 相似文献
9.
10.
Huber I Walter L Wimmer R Pasantes JJ Günther E Schempp W 《Cytogenetic and genome research》2003,103(1-2):144-149
Applying fluorescence in situ hybridisation (FISH), six cosmid clones of rhesus macaque origin containing the genes SACM2L, RING1, BAT1 and MIC2, MIC3, MICD, and MOG of the major histocompatibility complex (MHC) were localised to the long arm of the rhesus macaque chromosome 6 in 6q24, the orthologous region to human 6p21.3. Furthermore, centromere to telomere orientation of the rhesus macaque MHC as well as the internal order of the MHC genes tested are the same as in human. Fiber-FISH allows a rough estimate of distances between these MHC genes in the rhesus macaque, and, as in the human, the rhesus macaque MHC comprises about 3 to 4 Mb. 相似文献
11.
MHC polymorphism under host-pathogen coevolution 总被引:9,自引:0,他引:9
The genes encoding major histocompatibility (MHC) molecules are among the most polymorphic genes known for vertebrates. Since MHC molecules play an important role in the induction of immune responses, the evolution of MHC polymorphism is often explained in terms of increased protection of hosts against pathogens. Two selective pressures that are thought to be involved are (1) selection favoring MHC heterozygous hosts, and (2) selection for rare MHC alleles by host-pathogen coevolution. We have developed a computer simulation of coevolving hosts and pathogens to study the relative impact of these two mechanisms on the evolution of MHC polymorphism. We found that heterozygote advantage per se is insufficient to explain the high degree of polymorphism at the MHC, even in very large host populations. Host-pathogen coevolution, on the other hand, can easily account for realistic polymorphisms of more than 50 alleles per MHC locus. Since evolving pathogens mainly evade presentation by the most common MHC alleles in the host population, they provide a selective pressure for a large variety of rare MHC alleles. Provided that the host population is sufficiently large, a large set of MHC alleles can persist over many host generations under host-pathogen coevolution, despite the fact that allele frequencies continuously change.Electronic Supplementary Material Supplementary material is available in the online version of this article at 相似文献
12.
Lymphocytes of a New World primate, the cotton-top tamarin (Saguinus oedipus), express classical G–related major histocompatibility complex (MHC) class I molecules with unusually limited polymorphism and variability. Three
G-related loci, an F locus, an E locus, and two pseudogenes (So-N1 and So-N3) have been identified by cDNA library screening and extensive PCR analysis of both cDNA and genomic DNA from the cotton-top
tamarin. Furthermore, each genus of the subfamily Callitrichinae (tamarins and marmosets) appears to express its own unique
set of MHC class I genes, likely due to a rapid turnover of loci. The rapid emergence of unique MHC class I genes in the Callitrichinae
genera, resulting from an active process of duplication and inactivation of loci, may account for the limited diversity of
the MHC class I genes in the cotton-top tamarin. To determine the nature of the entire complement of MHC class I genes in
the cotton-top tamarin, we synthesized a genomic DNA library and screened it with MHC class I-specific probes. We isolated
nine new MHC class I pseudogenes from this library. These newly isolated tamarin G–related MHC class I pseudogenes are not closely related to any of their functional counterparts in the tamarin, suggesting
that they do not share a recent common ancestral gene with the tamarin's currently expressed MHC class I loci. In addition,
these tamarin sequences display a high rate of nonsynonymous substitutions in their putative peptide binding region. This
indicates that the genes from which they have derived were likely subject to positive selection and, therefore, were once
functional. Our data support the notion that an extremely high rate of loci turnover is largely responsible for the limited
diversity of the MHC class I genes in the cotton-top tamarin.
Received: 15 September 1997 / Revised: 2 July 1998 相似文献
13.
14.
Unprecedented intraspecific diversity of the MHC class I region of a teleost medaka, Oryzias latipes
Tsukamoto K Hayashi S Matsuo MY Nonaka MI Kondo M Shima A Asakawa S Shimizu N Nonaka M 《Immunogenetics》2005,57(6):420-431
The major histocompatibility complex (MHC) is present at a single chromosomal locus of all jawed vertebrate analyzed so far,
from sharks to mammals, except for teleosts whose orthologs of the mammalian MHC-encoded genes are dispersed at several chromosomal
loci. Even in teleosts, several class IA genes and those genes directly involved in class I antigen presentation preserve
their linkage, defining the teleost MHC class I region. We determined the complete nucleotide sequence of the MHC class I
region of the inbred HNI strain of medaka, Oryzias latipes (northern Japan population-derived), from four overlapping bacterial artificial chromosome (BAC) clones spanning 540,982 bp,
and compared it with the published sequence of the corresponding region of the inbred Hd-rR strain of medaka (425,935 bp,
southern Japan population-derived) as the first extensive study of intraspecies polymorphisms of the ectotherm MHC regions.
A segment of about 100 kb in the middle of the compared sequences encompassing two class Ia genes and two immunoproteasome
subunit genes, PSMB8 and PSMB10, was so divergent between these two inbred strains that a reliable sequence alignment could not be made. The rest of the
compared region (about 320 kb) showed a fair correspondence, and an approximately 96% nucleotide identity was observed upon
gap-free segmental alignment. These results indicate that the medaka MHC class I region contains an ∼100-kb polymorphic core,
which is most probably evolving adaptively by accumulation of point mutations and extensive genetic rearrangements such as
insertions, deletions and duplications.
The nucleotide sequence data of HNI MHC class I region reported in this paper have been submitted to the DDBJ/EMBL/GenBank
and were assigned the accession number AB183488. 相似文献
15.
目的建立非人灵长类动物胃镜检测技术。方法复方氯胺酮麻醉动物,将内镜经口腔、咽依次进入食管、胃、十二指肠,观察粘膜状况后在胃、十二指肠分别取材,术后清洗消毒内镜,动物即时苏醒。结果内镜顺利进入食管、胃及十二指肠,进镜深度分别约10cm、30cm、50cm,各段粘膜光滑平整,未见明显异常。术后动物未发生不良反应及并发症。结论非人灵长类动物胃镜检测技术的建立,为研究非人灵长类动物上消化道疾病搭建了良好的技术平台。 相似文献
16.
Genetic rearrangement by recombination is one of the major driving forces for genome
evolution, and recombination is known to occur in non-random, discreet recombination sites
within the genome. Mapping of recombination sites has proved to be difficult,
particularly, in the human MHC region that is complicated by both population variation and
highly polymorphic HLA genes. To overcome these problems, HLA-typed individuals
from three representative populations: Asian, European and African were used to generate
phased HLA haplotypes. Extended haplotype homozygosity (EHH) plots constructed from the
phased haplotype data revealed discreet EHH drops corresponding to recombination events
and these signatures were observed to be different for each population. Surprisingly, the
majority of recombination sites detected are unique to each population, rather than being
common. Unique recombination sites account for 56.8% (21/37 of total sites) in
the Asian cohort, 50.0% (15/30 sites) in Europeans and 63.2% (24/38
sites) in Africans. Validation carried out at a known sperm typing recombination site of
45 kb (HLA-F-telomeric) showed that EHH was an efficient method to narrow
the recombination region to 826 bp, and this was further refined to 660 bp
by resequencing. This approach significantly enhanced mapping of the genomic architecture
within the human MHC, and will be useful in studies to identify disease risk genes. 相似文献
17.
18.
Kaizu M Borchardt GJ Glidden CE Fisk DL Loffredo JT Watkins DI Rehrauer WM 《Immunogenetics》2007,59(9):693-703
The utility of the rhesus macaque as an animal model in both HIV vaccine development and pathogenesis studies necessitates the development of accurate and efficient major histocompatibility complex (MHC) genotyping technologies. In this paper, we describe the development and application of allele-specific polymerase chain reaction (PCR) amplification for the simultaneous detection of eight MHC class I alleles from the rhesus macaque (Macaca mulatta) of Indian descent. These alleles were selected, as they have been implicated in the restriction of CD8(+) T cell epitopes of simian immunodeficiency virus (SIV). Molecular typing of Mamu-A 01, Mamu-A 02, Mamu-A 08, Mamu-A 11, Mamu-B 01, Mamu-B 03, Mamu-B 04, and Mamu-B 17 was conducted in a high throughput fashion using genomic DNA. Our amplification strategy included a conserved internal control target to minimize false negative results and can be completed in less than 5 h. We have genotyped over 4,000 animals to establish allele frequencies from colonies all over the western hemisphere. The ability to identify MHC-defined rhesus macaques will greatly enhance investigation of the immune responses, which are responsible for the control of viral replication. Furthermore, application of this technically simple and accurate typing method should facilitate selection, utilization, and breeding of rhesus macaques for AIDS virus pathogenesis and vaccine studies. 相似文献
19.
Porntip Chaichompoo Pavel Bostik Susan Stephenson Jaruda Kobkitjaroen Aftab A. Ansari 《Cellular immunology》2010,263(2):176-187
Innate immune mechanisms play a deterministic role in the rate of disease progression during acute infection in HIV infected humans and SIV infection of non-human primates. The role NK cells play in mediating such an effect has thus gained importance. One of the major sets of molecules that regulate NK cell function are the killer cell immunoglobulin-like molecules (KIR’s). Our laboratory has previously shown an association of KIR3DL alleles 13 and 14 with high plasma viral loads in a cohort of SIV-infected rhesus macaques. To gain a more detailed understanding of the role of KIR polymorphisms, our laboratory herein conducted studies of three additional KIR loci and show that select KIR3DH alleles appear to be more strongly associated with high plasma viral loads than KIR3DL alleles 13 and 14. In addition, we herein document the existence of additional new alleles for the KIR1D, KIR2DL4, and the KIR3DH loci. 相似文献