Haplotype diversity generated by ancient recombination-like events in the MHC of Indian rhesus macaques

Doxiadis, Gaby G. M.; Groot, Nanine de; Otting, Nel; Vos-Rouweler, Annemiek J. M. de; Bolijn, Maria J.; Heijmans, Corrine M. C.; Groot, Natasja G. de; Wiel, Marit K. H. van der; Remarque, Edmond J.; Vangenot, Christelle; Nunes, José Manuel; Sanchez‐Mazas, Alicia; Bontrop, Ronald E.

doi:10.1007/s00251-013-0707-8

Cited by 45 publications

(83 citation statements)

References 64 publications

(100 reference statements)

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“…In Indian rhesus macaques, it has been shown that the reshuffling of A, B , and DR region segments by recombination-like events can generate ‘new’ haplotypes that accumulated over long evolutionary time spans (Doxiadis et al 2013). Here, we also observed haplotypes (e.g.…”

Section: Resultsmentioning

confidence: 99%

“…Recombinations within one region like the B region, however, which may be the reason for such patchwork haplotypes, have not often been observed when using Sanger sequencing (de Groot et al 2014; Doxiadis et al 2013). These are more easily visible with high resolution NGS techniques.…”

Section: Discussionmentioning

confidence: 99%

“…The B region in macaques shows even more CNV, and up to seven major and eight minor genes may be defined per haplotype. In contrast to the A region, however, a clear differentiation between major and minor B genes is difficult, as well as a definitive allocation of alleles to a certain locus (Budde et al 2010; Doxiadis et al 2011, 2013; Fernandez et al 2011; Karl et al 2013, 2017; Naruse et al 2010; O’Leary et al 2009; Otting et al 2005, 2007, 2009, 2012; Saito et al 2012; Shiina et al 2015). …”

Section: Introductionmentioning

confidence: 99%

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MHC class I diversity of olive baboons (Papio anubis) unravelled by next-generation sequencing

et al. 2018

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The olive baboon represents an important model system to study various aspects of human biology and health, including the origin and diversity of the major histocompatibility complex. After screening of a group of related animals for polymorphisms associated with a well-defined microsatellite marker, subsequent MHC class I typing of a selected population of 24 animals was performed on two distinct next-generation sequencing (NGS) platforms. A substantial number of 21 A and 80 B transcripts were discovered, about half of which had not been previously reported. Per animal, from one to four highly transcribed A alleles (majors) were observed, in addition to ones characterised by low transcripion levels (minors), such as members of the A*14 lineage. Furthermore, in one animal, up to 13 B alleles with differential transcription level profiles may be present. Based on segregation profiles, 16 Paan-AB haplotypes were defined. A haplotype encodes in general one or two major A and three to seven B transcripts, respectively. A further peculiarity is the presence of at least one copy of a B*02 lineage on nearly every haplotype, which indicates that B*02 represents a separate locus with probably a specialistic function. Haplotypes appear to be generated by recombination-like events, and the breakpoints map not only between the A and B regions but also within the B region itself. Therefore, the genetic makeup of the olive baboon MHC class I region appears to have been subject to a similar or even more complex expansion process than the one documented for macaque species.Electronic supplementary materialThe online version of this article (10.1007/s00251-018-1053-7) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MHC class I diversity of olive baboons (Papio anubis) unravelled by next-generation sequencing

et al. 2018

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“…Namely, in most species, there is a strong evolutionary pressure to maintain old allelic variation within MHC genes (trans-species polymorphism 3, 4, 9 ), which, if anything, is likely to slow down speciation rates because it increases the required size of the founder population 9 . If old allelic or haplotype variation can’t be maintained because of rapid speciation through small founder populations, it can be speculated that a species might benefit from an enhanced capacity for the creation of new MHC allelic and/or haplotype variation by duplications/deletions and recombination 10 between a high number of linked MHC gene copies. However, in that scenario it wouldn’t be the MHC organization which drives the speciation rate, as suggested by Malmstrøm et al 1 , but the other way around.…”

Section: Correspondencementioning

confidence: 99%

Major histocompatibility complex (MHC) fragment numbers alone – in Atlantic cod and in general - do not represent functional variability

Dijkstra

Grimholt

2018

F1000Res

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This correspondence concerns a publication by Malmstrøm et al. in Nature Genetics in October 2016. Malmstrøm et al. made an important contribution to fish phylogeny research by using low-coverage genome sequencing for comparison of 66 teleost (modern bony) fish species, with 64 of those 66 belonging to the species-rich clade Neoteleostei, and with 27 of those 64 belonging to the order Gadiformes. For these 66 species, Malmstrøm et al. estimated numbers of genes belonging to the major histocompatibility complex (MHC) class I lineages U and Z and concluded that in teleost fish these combined numbers are positively associated with, and a driving factor of, the rates of establishment of new fish species (speciation rates). They also claimed that functional genes for the MHC class II system molecules MHC IIA, MHC IIB, CD4 and CD74 were lost in early Gadiformes. Our main criticisms are (1) that the authors did not provide sufficient evidence for presence or absence of intact functional MHC class I or MHC class II system genes, (2) that they did not discuss that an MHC subpopulation gene number alone is a very incomplete measure of MHC variance, and (3) that the MHC system is more likely to reduce speciation rates than to enhance them. We conclude that their new model of MHC class I evolution, reflected in their title “Evolution of the immune system influences speciation rates in teleost fish”, is unsubstantiated. In addition, we explain that their “pinpointing” of the functional loss of the MHC class II system and all the important MHC class II system genes to the onset of Gadiformes is preliminary, because they did not sufficiently investigate the species at the clade border.

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“…For animals from the NEPRC colony, additional high-resolution sequencing was done using Roche 454 technologies on blood-derived lymphocyte cDNA Wiseman et al, 2013). In the case of the animals of BPRC, additional high-resolution Sanger sequencing had been performed beforehand and published previously (Otting et al, 2005;Doxiadis et al, 2013). Since the animals were members of breeding colonies, kinship coefficients and/or pedigrees of the animals are known, and some MHC haplotypes could be defined as well by segregation analysis.…”

Section: Mhc Typingmentioning

confidence: 99%

Spontaneous endometriosis in rhesus macaques: evidence for a genetic association with specific Mamu-A1 alleles

Kondova¹,

Braskamp²,

Heidt³

et al. 2017

Primate Biol.

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Abstract. Endometriosis is a poorly understood common debilitating women's reproductive disorder resulting from proliferative and ectopic endometrial tissue associated with variable clinical symptoms including dysmenorrhea (painful menstrual periods), dyspareunia (pain on intercourse), female infertility, and an increased risk of malignant transformation. The rhesus macaque (Macaca mulatta) develops a spontaneous endometriosis that is very similar to that seen in women. We hypothesized that specific major histocompatibility complex (MHC) alleles may contribute to the pathogenesis of endometriosis. As part of a collaboration between the Biomedical Primate Research Centre (BPRC) in the Netherlands and the New England Primate Research Center (NEPRC) in the United States, we analyzed DNA sequences of MHC class I (Macaca mulatta, Mamu-A1) and class II (Mamu-DRB) alleles from rhesus macaques with endometriosis and compared the allele frequencies with those of age-matched healthy macaques. We demonstrate that two MHC class I alleles are overrepresented in diseased macaques compared to controls: Mamu-A1*001, 33.3 % in BPRC animals with endometriosis vs. 11.6 % in healthy macaques (p = 0.007), and Mamu-A1*007, 21.9 % NEPRC rhesus macaques vs. 6.7 %, (p = 0.003). We provide evidence that select MHC class I alleles are associated with endometriosis in rhesus macaques and suggest that the disease pathogenesis contribution of MHC class I warrants further research.

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Haplotype diversity generated by ancient recombination-like events in the MHC of Indian rhesus macaques

Cited by 45 publications

References 64 publications

MHC class I diversity of olive baboons (Papio anubis) unravelled by next-generation sequencing

MHC class I diversity of olive baboons (Papio anubis) unravelled by next-generation sequencing

Major histocompatibility complex (MHC) fragment numbers alone – in Atlantic cod and in general - do not represent functional variability

Spontaneous endometriosis in rhesus macaques: evidence for a genetic association with specific Mamu-A1 alleles

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