Multilocus definition of MHC haplotypes in pedigreed cynomolgus macaques (Macaca fascicularis)

Otting, Nel; Groot, Nanine de; Vos-Rouweler, Annemiek J. M. de; Louwerse, Annet L.; Doxiadis, Gaby G. M.; Bontrop, Ronald E.

doi:10.1007/s00251-012-0632-2

Cited by 15 publications

(55 citation statements)

References 47 publications

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“…Although the low number of informative meioses observed in a previous study ( N = 332) (Otting et al 2012) and in the present analysis may not allow statistically relevant conclusions, the recombination frequencies of the class I region in Indonesian/Indochinese cynomolgus macaques (~0.6 %) are apparently higher than those observed in humans and rhesus macaques. The difference between both macaque species becomes even more pronounced when recombination rates between the class III and II regions are taken into account.…”

Section: Discussioncontrasting

confidence: 91%

Differential recombination dynamics within the MHC of macaque species

et al. 2014

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A panel of 15 carefully selected microsatellites (short tandem repeats, STRs) has allowed us to study segregation and haplotype stability in various macaque species. The STRs span the major histocompatibility complex (MHC) region and map in more detail from the centromeric part of the Mhc-A to the DR region. Two large panels of Indian rhesus and Indonesian/Indochinese cynomolgus macaques have been subjected to pedigree analysis, allowing the definition of 161 and 36 different haplotypes and the physical mapping of 10 and 5 recombination sites, respectively. Although most recombination sites within the studied section of the Indian rhesus monkey MHC are situated between the Mhc-A and Mhc-B regions, the resulting recombination rate for this genomic segment is low and similar to that in humans. In contrast, in Indonesian/Indochinese macaques, two recombination sites, which appear to be absent in rhesus macaques, map between the class III and II regions. As a result, the mean recombination frequency of the core MHC, Mhc-A to class II, is higher in Indonesian/Indochinese cynomolgus than in Indian rhesus macaques, but as such is comparable to that in humans. The present communication demonstrates that the dynamics of recombination ‘hot/cold spots’ in the MHC, as well as their frequencies, may differ substantially between highly related macaque species.Electronic supplementary materialThe online version of this article (doi:10.1007/s00251-014-0783-4) contains supplementary material, which is available to authorized users.

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Section: Discussioncontrasting

confidence: 91%

Differential recombination dynamics within the MHC of macaque species

et al. 2014

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“…Though many studies have examined the lists of MHC class I transcripts expressed in cynomolgus macaques of multiple geographic origins, few have studied the haplotype structures in those animals (Budde et al 2010; Campbell et al 2008; Otting et al 2009, 2012; Saito et al 2012; Shiina et al 2015). The best-characterized population of cynomolgus macaques is from the island of Mauritius, where a limited number of founding animals were deposited on the island in the 1500s.…”

Section: Resultsmentioning

confidence: 99%

“…Among the remaining Mafa-B haplotypes, 14 (19%) were exclusive to Vietnamese-origin animals, 26 (35%) exclusive to Cambodian-origin, and 13 (18%) were observed only in the mixed Cambodian/Indonesian-origin individuals. No previous MHC haplotype studies have been performed in either Vietnamese- or Cambodian-origin cynomolgus macaques, but limited studies have characterized haplotypes in Filipino, Indonesian, and Malaysian cynomolgus macaques (Campbell et al 2008; Otting et al 2009, 2012; Saito et al 2012; Shiina et al 2015). The cohorts studied here appear more MHC diverse than those sampled from the previously described insular and extremely southern continental Asian populations (it is unclear from precisely where the Malaysian cohort was initially derived).…”

Section: Resultsmentioning

confidence: 99%

“…In macaques, the MHC class I region is highly polymorphic and extensively duplicated (Daza-Vamenta et al 2004; Otting et al 2005), with different chromosomes carrying different numbers of functional Mafa-A and Mafa-B genes. Many investigators have examined the MHC class I region of cynomolgus macaques from various origins (Budde et al 2010; Campbell et al 2008; Kita et al 2009; Lawrence et al 2012; Ling et al 2012; Otting et al 2007, 2009, 2012; Pendley et al 2008; Saito et al 2012; Shiina et al 2015; Uda et al 2004, 2005; Zhang et al 2012; Zhuo et al 2011), but only a limited number of studies have looked at cynomolgus macaques from Chinese breeding facilities (Krebs et al 2005; Westbrook et al 2015). …”

Section: Introductionmentioning

confidence: 99%

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Major histocompatibility complex haplotyping and long-amplicon allele discovery in cynomolgus macaques from Chinese breeding facilities

et al. 2017

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Very little is currently known about the major histocompatibility complex (MHC) region of cynomolgus macaques (Macaca fascicularis; Mafa) from Chinese breeding centers. We performed comprehensive MHC class I haplotype analysis of 100 cynomolgus macaques from two different centers, with animals from different reported original geographic origins (Vietnamese, Cambodian, and Cambodian/Indonesian mixed-origin). Many of the samples were of known relation to each other (sire, dam, and progeny sets), making it possible to characterize lineage-level haplotypes in these animals. We identified 52 Mafa-A and 74 Mafa-B haplotypes in this cohort, many of which were restricted to specific sample origins. We also characterized full-length MHC class I transcripts using Pacific Biosciences (PacBio) RS II single-molecule real-time (SMRT) sequencing. This technology allows for complete read-through of unfragmented MHC class I transcripts (~1,100 bp in length), so no assembly is required to unambiguously resolve novel full-length sequences. Overall, we identified 311 total full-length transcripts in a subset of 72 cynomolgus macaques from these Chinese breeding facilities; 130 of these sequences were novel and an additional 115 extended existing short database sequences to span the complete open reading frame. This significantly expands the number of Mafa-A, Mafa-B, and Mafa-I full-length alleles in the official cynomolgus macaque MHC class I database. The PacBio technique described here represents a general method for full-length allele discovery and genotyping that can be extended to other complex immune loci such as MHC class II, killer immunoglobulin-like receptors, and Fc gamma receptors.

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“…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%

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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Multilocus definition of MHC haplotypes in pedigreed cynomolgus macaques (Macaca fascicularis)

Cited by 15 publications

References 47 publications

Differential recombination dynamics within the MHC of macaque species

Differential recombination dynamics within the MHC of macaque species

Major histocompatibility complex haplotyping and long-amplicon allele discovery in cynomolgus macaques from Chinese breeding facilities

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

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