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727 results on '"Bontrop, Ronald E."'

1. Longitudinal positron emission tomography and postmortem analysis reveals widespread neuroinflammation in SARS-CoV-2 infected rhesus macaques

Author

Nieuwland, Juliana M., Nutma, Erik, Philippens, Ingrid H. C. H. M., Böszörményi, Kinga P., Remarque, Edmond J., Bakker, Jaco, Meijer, Lisette, Woerdman, Noor, Fagrouch, Zahra C., Verstrepen, Babs E., Langermans, Jan A. M., Verschoor, Ernst J., Windhorst, Albert D., Bontrop, Ronald E., de Vries, Helga E., Stammes, Marieke A., and Middeldorp, Jinte

Published
2023
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4. Medical imaging of pulmonary disease in SARS-CoV-2-exposed non-human primates

Author

Stammes, Marieke A., Lee, Ji Hyun, Meijer, Lisette, Naninck, Thibaut, Doyle-Meyers, Lara A., White, Alexander G., Borish, H. Jacob, Hartman, Amy L., Alvarez, Xavier, Ganatra, Shashank, Kaushal, Deepak, Bohm, Rudolf P., le Grand, Roger, Scanga, Charles A., Langermans, Jan A.M., Bontrop, Ronald E., Finch, Courtney L., Flynn, JoAnne L., Calcagno, Claudia, Crozier, Ian, and Kuhn, Jens H.

Published
2022
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10. Extreme selective sweeps independently targeted the X chromosomes of the great apes

Author

Nam, Kiwoong, Munch, Kasper, Hobolth, Asger, Dutheil, Julien Yann, Veeramah, Krishna R, Woerner, August E, Hammer, Michael F, Mailund, Thomas, Schierup, Mikkel Heide, Prado-Martinez, Javier, Sudmant, Peter H, Kidd, Jeffrey M, Li, Heng, Kelley, Joanna L, Lorente-Galdos, Belen, O’Connor, Timothy D, Santpere, Gabriel, Cagan, Alexander, Theunert, Christoph, Casals, Ferran, Laayouni, Hafid, Halager, Anders E, Malig, Maika, Hernandez-Rodriguez, Jessica, Hernando-Herraez, Irene, Prüfer, Kay, Pybus, Marc, Johnstone, Laurel, Lachmann, Michael, Alkan, Can, Twigg, Dorina, Petit, Natalia, Baker, Carl, Hormozdiari, Fereydoun, Fernandez-Callejo, Marcos, Dabad, Marc, Wilson, Michael L, Stevison, Laurie, Camprubí, Cristina, Carvalho, Tiago, Ruiz-Herrera, Aurora, Vives, Laura, Mele, Marta, Abello, Teresa, Kondova, Ivanela, Bontrop, Ronald E, Pusey, Anne, Lankester, Felix, Kiyang, John A, Bergl, Richard A, Lonsdorf, Elizabeth, Myers, Simon, Ventura, Mario, Gagneux, Pascal, Comas, David, Siegismund, Hans, Blanc, Julie, Agueda-Calpena, Lidia, Gut, Marta, Fulton, Lucinda, Tishkoff, Sarah A, Mullikin, James C, Wilson, Richard K, Gut, Ivo G, Gonder, Mary Katherine, Ryder, Oliver A, Hahn, Beatrice H, Navarro, Arcadi, Akey, Joshua M, Bertranpetit, Jaume, Reich, David, Schierup, Mikkel H, Hvilsom, Christina, Andrés, Aida M, Wall, Jeffrey D, Bustamante, Carlos D, Eichler, Evan E, and Marques-Bonet, Tomas

Subjects
Human Genome, Genetics, Animals, Computational Biology, Databases, Genetic, Genetic Variation, Genetics, Population, Hominidae, Models, Genetic, Polymorphism, Genetic, Selection, Genetic, Species Specificity, X Chromosome, Great Ape Genome Diversity Project, X-chromosome evolution, ampliconic genes, great apes, meiotic drive, selective sweeps
Abstract

The unique inheritance pattern of the X chromosome exposes it to natural selection in a way that is different from that of the autosomes, potentially resulting in accelerated evolution. We perform a comparative analysis of X chromosome polymorphism in 10 great ape species, including humans. In most species, we identify striking megabase-wide regions, where nucleotide diversity is less than 20% of the chromosomal average. Such regions are found exclusively on the X chromosome. The regions overlap partially among species, suggesting that the underlying targets are partly shared among species. The regions have higher proportions of singleton SNPs, higher levels of population differentiation, and a higher nonsynonymous-to-synonymous substitution ratio than the rest of the X chromosome. We show that the extent to which diversity is reduced is incompatible with direct selection or the action of background selection and soft selective sweeps alone, and therefore, we suggest that very strong selective sweeps have independently targeted these specific regions in several species. The only genomic feature that we can identify as strongly associated with loss of diversity is the location of testis-expressed ampliconic genes, which also have reduced diversity around them. We hypothesize that these genes may be responsible for selective sweeps in the form of meiotic drive caused by an intragenomic conflict in male meiosis.

Published
2015

13. Great ape genetic diversity and population history.

Author

Prado-Martinez, Javier, Sudmant, Peter H, Kidd, Jeffrey M, Li, Heng, Kelley, Joanna L, Lorente-Galdos, Belen, Veeramah, Krishna R, Woerner, August E, O'Connor, Timothy D, Santpere, Gabriel, Cagan, Alexander, Theunert, Christoph, Casals, Ferran, Laayouni, Hafid, Munch, Kasper, Hobolth, Asger, Halager, Anders E, Malig, Maika, Hernandez-Rodriguez, Jessica, Hernando-Herraez, Irene, Prüfer, Kay, Pybus, Marc, Johnstone, Laurel, Lachmann, Michael, Alkan, Can, Twigg, Dorina, Petit, Natalia, Baker, Carl, Hormozdiari, Fereydoun, Fernandez-Callejo, Marcos, Dabad, Marc, Wilson, Michael L, Stevison, Laurie, Camprubí, Cristina, Carvalho, Tiago, Ruiz-Herrera, Aurora, Vives, Laura, Mele, Marta, Abello, Teresa, Kondova, Ivanela, Bontrop, Ronald E, Pusey, Anne, Lankester, Felix, Kiyang, John A, Bergl, Richard A, Lonsdorf, Elizabeth, Myers, Simon, Ventura, Mario, Gagneux, Pascal, Comas, David, Siegismund, Hans, Blanc, Julie, Agueda-Calpena, Lidia, Gut, Marta, Fulton, Lucinda, Tishkoff, Sarah A, Mullikin, James C, Wilson, Richard K, Gut, Ivo G, Gonder, Mary Katherine, Ryder, Oliver A, Hahn, Beatrice H, Navarro, Arcadi, Akey, Joshua M, Bertranpetit, Jaume, Reich, David, Mailund, Thomas, Schierup, Mikkel H, Hvilsom, Christina, Andrés, Aida M, Wall, Jeffrey D, Bustamante, Carlos D, Hammer, Michael F, Eichler, Evan E, and Marques-Bonet, Tomas

Subjects
Animals, Animals, Wild, Animals, Zoo, Hominidae, Gorilla gorilla, Humans, Pan paniscus, Pan troglodytes, Inbreeding, Genetics, Population, Population Density, Evolution, Molecular, Phylogeny, Polymorphism, Single Nucleotide, Genome, Africa, Asia, Southeastern, Gene Flow, Genetic Variation, General Science & Technology
Abstract

Most great ape genetic variation remains uncharacterized; however, its study is critical for understanding population history, recombination, selection and susceptibility to disease. Here we sequence to high coverage a total of 79 wild- and captive-born individuals representing all six great ape species and seven subspecies and report 88.8 million single nucleotide polymorphisms. Our analysis provides support for genetically distinct populations within each species, signals of gene flow, and the split of common chimpanzees into two distinct groups: Nigeria-Cameroon/western and central/eastern populations. We find extensive inbreeding in almost all wild populations, with eastern gorillas being the most extreme. Inferred effective population sizes have varied radically over time in different lineages and this appears to have a profound effect on the genetic diversity at, or close to, genes in almost all species. We discover and assign 1,982 loss-of-function variants throughout the human and great ape lineages, determining that the rate of gene loss has not been different in the human branch compared to other internal branches in the great ape phylogeny. This comprehensive catalogue of great ape genome diversity provides a framework for understanding evolution and a resource for more effective management of wild and captive great ape populations.

Published
2013

27. Nomenclature for the KIR of non-human species

Author

Robinson, James, Guethlein, Lisbeth A., Maccari, Giuseppe, Blokhuis, Jeroen, Bimber, Benjamin N., de Groot, Natasja G., Sanderson, Nicholas D., Abi-Rached, Laurent, Walter, Lutz, Bontrop, Ronald E., Hammond, John A., Marsh, Steven G. E., and Parham, Peter

Published
2018
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28. The KIR repertoire of a West African chimpanzee population is characterized by limited gene, allele, and haplotype variation

Author

Sub Theoretical Biology, Theoretical Biology and Bioinformatics, de Groot, Natasja G., Heijmans, Corrine M.C., van der Wiel, Marit K.H., Bruijnesteijn, Jesse, Bontrop, Ronald E., Sub Theoretical Biology, Theoretical Biology and Bioinformatics, de Groot, Natasja G., Heijmans, Corrine M.C., van der Wiel, Marit K.H., Bruijnesteijn, Jesse, and Bontrop, Ronald E.

Published
2023

29. Longitudinal positron emission tomography and postmortem analysis reveals widespread neuroinflammation in SARS-CoV-2 infected rhesus macaques

Author

AISS Animal Welfare, Sub Theoretical Biology, Theoretical Biology and Bioinformatics, AISS – Animal Welfare, Nieuwland, Juliana M, Nutma, Erik, Philippens, Ingrid H C H M, Böszörményi, Kinga P, Remarque, Edmond J, Bakker, Jaco, Meijer, Lisette, Woerdman, Noor, Fagrouch, Zahra C, Verstrepen, Babs E, Langermans, Jan A M, Verschoor, Ernst J, Windhorst, Albert D, Bontrop, Ronald E, de Vries, Helga E, Stammes, Marieke A, Middeldorp, Jinte, AISS Animal Welfare, Sub Theoretical Biology, Theoretical Biology and Bioinformatics, AISS – Animal Welfare, Nieuwland, Juliana M, Nutma, Erik, Philippens, Ingrid H C H M, Böszörményi, Kinga P, Remarque, Edmond J, Bakker, Jaco, Meijer, Lisette, Woerdman, Noor, Fagrouch, Zahra C, Verstrepen, Babs E, Langermans, Jan A M, Verschoor, Ernst J, Windhorst, Albert D, Bontrop, Ronald E, de Vries, Helga E, Stammes, Marieke A, and Middeldorp, Jinte

Published
2023

30. Correction to: Nomenclature report 2019: major histocompatibility complex genes and alleles of great and small ape and old and new world monkey species

Author

de Groot, Natasja G., Otting, Nel, Maccari, Giuseppe, Robinson, James, Hammond, John A., Blancher, Antoine, Lafont, Bernard A. P., Guethlein, Lisbeth A., Wroblewski, Emily E., Marsh, Steven G. E., Shiina, Takashi, Walter, Lutz, Vigilant, Linda, Parham, Peter, O’Connor, David H., and Bontrop, Ronald E.

Published
2020
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35. Medical imaging of pulmonary disease in SARS-CoV-2-exposed non-human primates

Author

Theoretical Biology and Bioinformatics, AISS LAS/3'R Centre ULS, Sub Theoretical Biology, Stammes, Marieke A, Lee, Ji Hyun, Meijer, Lisette, Naninck, Thibaut, Doyle-Meyers, Lara A, White, Alexander G, Borish, H Jacob, Hartman, Amy L, Alvarez, Xavier, Ganatra, Shashank, Kaushal, Deepak, Bohm, Rudolf P, le Grand, Roger, Scanga, Charles A, Langermans, Jan A M, Bontrop, Ronald E, Finch, Courtney L, Flynn, JoAnne L, Calcagno, Claudia, Crozier, Ian, Kuhn, Jens H, Theoretical Biology and Bioinformatics, AISS LAS/3'R Centre ULS, Sub Theoretical Biology, Stammes, Marieke A, Lee, Ji Hyun, Meijer, Lisette, Naninck, Thibaut, Doyle-Meyers, Lara A, White, Alexander G, Borish, H Jacob, Hartman, Amy L, Alvarez, Xavier, Ganatra, Shashank, Kaushal, Deepak, Bohm, Rudolf P, le Grand, Roger, Scanga, Charles A, Langermans, Jan A M, Bontrop, Ronald E, Finch, Courtney L, Flynn, JoAnne L, Calcagno, Claudia, Crozier, Ian, and Kuhn, Jens H

Published
2022

37. Dynamic evolution of Mhc haplotypes in cynomolgus macaques of different geographic origins

Author

Theoretical Biology and Bioinformatics, Sub Theoretical Biology, de Groot, Natasja G, de Groot, Nanine, de Vos-Rouweler, Annemiek J M, Louwerse, Annet, Bruijnesteijn, Jesse, Bontrop, Ronald E, Theoretical Biology and Bioinformatics, Sub Theoretical Biology, de Groot, Natasja G, de Groot, Nanine, de Vos-Rouweler, Annemiek J M, Louwerse, Annet, Bruijnesteijn, Jesse, and Bontrop, Ronald E

Published
2022

38. Brain Inflammation and Intracellular α-Synuclein Aggregates in Macaques after SARS-CoV-2 Infection

Author

Philippens, Ingrid H. C. H. M., primary, Böszörményi, Kinga P., additional, Wubben, Jacqueline A. M., additional, Fagrouch, Zahra C., additional, van Driel, Nikki, additional, Mayenburg, Amber Q., additional, Lozovagia, Diana, additional, Roos, Eva, additional, Schurink, Bernadette, additional, Bugiani, Marianna, additional, Bontrop, Ronald E., additional, Middeldorp, Jinte, additional, Bogers, Willy M., additional, de Geus-Oei, Lioe-Fee, additional, Langermans, Jan A. M., additional, Verschoor, Ernst J., additional, Stammes, Marieke A., additional, and Verstrepen, Babs E., additional

Published
2022
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39. Comparative genetics of the major histocompatibility complex in humans and nonhuman primates

Author

Heijmans, Corrine M.c., Groot, Natasja G., Bontrop, Ronald E., Theoretical Biology and Bioinformatics, and Sub Theoretical Biology

Subjects
Primates, Immunology, Human leukocyte antigen, Major histocompatibility complex, polymorphism, Evolution, Molecular, Major Histocompatibility Complex, Polymorphism (computer science), Lesser apes, Genetics, Animals, Humans, histocompatibility, Allele, Molecular Biology, Gene, Alleles, Phylogeny, Genetics (clinical), nonhuman, biology, Hominidae, General Medicine, Histocompatibility, biology.protein, Mammalian genome
Abstract

The major histocompatibility complex (MHC) is one of the most gene-dense regions of the mammalian genome. Multiple genes within the human MHC (HLA) show extensive polymorphism, and currently, more than 26,000 alleles divided over 39 different genes are known. Nonhuman primate (NHP) species are grouped into great and lesser apes and Old and New World monkeys, and their MHC is studied mostly because of their important role as animal models in preclinical research or in connection with conservation biology purposes. The evolutionary equivalents of many of the HLA genes are present in NHP species, and these genes may also show abundant levels of polymorphism. This review is intended to provide a comprehensive comparison relating to the organization and polymorphism of human and NHP MHC regions.

Published
2020

44. The Genomic Organization of the LILR Region Remained Largely Conserved Throughout Primate Evolution: Implications for Health And Disease

Author

Storm, Lisanne, Bruijnesteijn, Jesse, de Groot, Natasja G., Bontrop, Ronald E., Sub Theoretical Biology, and Theoretical Biology and Bioinformatics

Subjects
Immunology, killer immunoglobulin-like receptor (KIR), Immunology and Allergy, non-human primates (NHP), human, leukocyte immunoglobulin-like receptor (LILR), leukocyte receptor complex (LRC), immunoglobulin Ig-like superfamily (IgSF)
Abstract

The genes of the leukocyte immunoglobulin-like receptor (LILR) family map to the leukocyte receptor complex (LRC) on chromosome 19, and consist of both activating and inhibiting entities. These receptors are often involved in regulating immune responses, and are considered to play a role in health and disease. The human LILR region and evolutionary equivalents in some rodent and bird species have been thoroughly characterized. In non-human primates, the LILR region is annotated, but a thorough comparison between humans and non-human primates has not yet been documented. Therefore, it was decided to undertake a comprehensive comparison of the human and non-human primate LILR region at the genomic level. During primate evolution the organization of the LILR region remained largely conserved. One major exception, however, is provided by the common marmoset, a New World monkey species, which seems to feature a substantial contraction of the number of LILR genes in both the centromeric and the telomeric region. Furthermore, genomic analysis revealed that the killer-cell immunoglobulin-like receptor gene KIR3DX1, which maps in the LILR region, features one copy in humans and great ape species. A second copy, which might have been introduced by a duplication event, was observed in the lesser apes, and in Old and New World monkey species. The highly conserved gene organization allowed us to standardize the LILR gene nomenclature for non-human primate species, and implies that most of the receptors encoded by these genes likely fulfill highly preserved functions.

Published
2021

45. Rapid Characterization of Complex Killer Cell Immunoglobulin-Like Receptor (KIR) Regions Using Cas9 Enrichment and Nanopore Sequencing

Author

Bruijnesteijn, Jesse, van der Wiel, Marit, de Groot, Natasja G., Bontrop, Ronald E., Sub Theoretical Biology, Theoretical Biology and Bioinformatics, Sub Theoretical Biology, and Theoretical Biology and Bioinformatics

Subjects
Genotype, Immunology, Killer-cell immunoglobulin-like receptor, Mononuclear, Receptors, KIR/genetics, Computational biology, Nanopore Sequencing/methods, Biology, Genome, Deep sequencing, Epigenesis, Genetic, Receptors, KIR, Genetic, Gene cluster, Receptors, Leukocytes, Immunology and Allergy, Animals, Humans, Copy-number variation, Cas9, Gene, Original Research, Sequence Analysis, DNA, KIR/genetics, DNA, DNA Methylation, RC581-607, recombination, KIR, Haplotypes, targeted enrichment, Multigene Family, nanopore sequencing, Leukocytes, Mononuclear, Macaca, Nanopore sequencing, CRISPR-Cas Systems, Immunologic diseases. Allergy, Sequence Analysis, Reference genome, Epigenesis
Abstract

Long-read sequencing approaches have considerably improved the quality and contiguity of genome assemblies. Such platforms bear the potential to resolve even extremely complex regions, such as multigenic immune families and repetitive stretches of DNA. Deep sequencing coverage, however, is required to overcome low nucleotide accuracy, especially in regions with high homopolymer density, copy number variation, and sequence similarity, such as the MHC and KIR gene clusters of the immune system. Therefore, we have adapted a targeted enrichment protocol in combination with long-read sequencing to efficiently annotate complex KIR gene regions. Using Cas9 endonuclease activity, segments of the KIR gene cluster were enriched and sequenced on an Oxford Nanopore Technologies platform. This provided sufficient coverage to accurately resolve and phase highly complex KIR haplotypes. Our strategy eliminates PCR-induced amplification errors, facilitates rapid characterization of large and complex multigenic regions, including its epigenetic footprint, and is applicable in multiple species, even in the absence of a reference genome.

Published
2021

46. The Post-Acute Phase of SARS-CoV-2 Infection in Two Macaque Species Is Associated with Signs of Ongoing Virus Replication and Pathology in Pulmonary and Extrapulmonary Tissues

Author

Böszörményi, Kinga, Stammes, Marieke, Fagrouch, Zahra C., Kiemenyi-Kayere, Gwendoline, Niphuis, Henk, Mortier, Daniella, Driel, Nikki van, Nieuwenhuis, Ivonne, Vervenne, Richard A. W., Haaksma, Tom, Ouwerling, Boudewijn, Adema, Deborah, Acar, Roja Fidel, Zuiderwijk-Sick, Ella, Meijer, Lisette, Mooij, Petra, Remarque, Ed J., Oostermeijer, Herman, Hoste, Alexis C. R., Sastre, Patricia, Haagmans, Bart, Bontrop, Ronald E., Langermans, Jan, Bogers, Willy, Kondova, Ivanela, Verschoor, Ernst, Verstrepen, Babs E, Sub Theoretical Biology, AISS LAS/3'R Centre ULS, and Theoretical Biology and Bioinformatics

Subjects
NHPs, Infectious Diseases, SARS-CoV-2, Virology, COVID-19, Animal models, Non-human primates
Abstract

The post-acute phase of SARS-CoV-2 infection was investigated in rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis). During the acute phase of infection, SARS-CoV-2 was shed via the nose and throat, and viral RNA was occasionally detected in feces. This phase coincided with a transient change in systemic immune activation. Even after the alleged resolution of the infection, computed tomography (CT) and positron emission tomography (PET)-CT revealed pulmonary lesions and activated tracheobronchial lymph nodes in all animals. Post-mortem histological examination of the lung tissue revealed mostly marginal or resolving minimal lesions that were indicative of SARS-CoV-2 infection. Evidence for SARS-CoV-2-induced histopathology was also found in extrapulmonary tissue samples, such as conjunctiva, cervical, and mesenteric lymph nodes. However, 5–6 weeks after SARS-CoV-2 exposure, upon necropsy, viral RNA was still detectable in a wide range of tissue samples in 50% of the macaques and included amongst others the heart, the respiratory tract and surrounding lymph nodes, salivary gland, and conjunctiva. Subgenomic messenger RNA was detected in the lungs and tracheobronchial lymph nodes, indicative of ongoing virus replication during the post-acute phase. These results could be relevant for understanding the long-term consequences of COVID-19 in humans.

Published
2021

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