Defining genetic diversity of rhesus macaque Fcγ receptors with long-read RNA sequencing
Fcγ receptors (FcγRs) are membrane-bound glycoproteins that bind to the fragment crystallizable (Fc) constant regions of IgG antibodies. Interactions between IgG immune complexes and FcγRs can initiate signal transduction that mediates important components of the immune response including activation...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1306292/full |
| _version_ | 1797361292588089344 |
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| author | Haleigh E. Conley Haleigh E. Conley Max M. He David Easterhoff Hélène Fradin Kirshner Sarah L. Cocklin Jacob Meyer Taylor Hoxie Madison Berry Todd Bradley William D. Tolbert Marzena Pazgier Georgia D. Tomaras Georgia D. Tomaras Joern E. Schmitz Michael Anthony Moody Kevin Wiehe Justin Pollara Justin Pollara |
| author_facet | Haleigh E. Conley Haleigh E. Conley Max M. He David Easterhoff Hélène Fradin Kirshner Sarah L. Cocklin Jacob Meyer Taylor Hoxie Madison Berry Todd Bradley William D. Tolbert Marzena Pazgier Georgia D. Tomaras Georgia D. Tomaras Joern E. Schmitz Michael Anthony Moody Kevin Wiehe Justin Pollara Justin Pollara |
| author_sort | Haleigh E. Conley |
| collection | DOAJ |
| description | Fcγ receptors (FcγRs) are membrane-bound glycoproteins that bind to the fragment crystallizable (Fc) constant regions of IgG antibodies. Interactions between IgG immune complexes and FcγRs can initiate signal transduction that mediates important components of the immune response including activation of immune cells for clearance of opsonized pathogens or infected host cells. In humans, many studies have identified associations between FcγR gene polymorphisms and risk of infection, or progression of disease, suggesting a gene-level impact on FcγR-dependent immune responses. Rhesus macaques are an important translational model for most human health interventions, yet little is known about the breadth of rhesus macaque FcγR genetic diversity. This lack of knowledge prevents evaluation of the impact of FcγR polymorphisms on outcomes of preclinical studies performed in rhesus macaques. In this study we used long-read RNA sequencing to define the genetic diversity of FcγRs in 206 Indian-origin Rhesus macaques, Macaca mulatta. We describe the frequency of single nucleotide polymorphisms, insertions, deletions, frame-shift mutations, and isoforms. We also index the identified diversity using predicted and known rhesus macaque FcγR and Fc-FcγR structures. Future studies that define the functional significance of this genetic diversity will facilitate a better understanding of the correlation between human and macaque FcγR biology that is needed for effective translation of studies with antibody-mediated outcomes performed in rhesus macaques. |
| first_indexed | 2024-03-08T15:51:46Z |
| format | Article |
| id | doaj.art-7ca88bbcf7974541b140d919d5470520 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T15:51:46Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-7ca88bbcf7974541b140d919d54705202024-01-09T04:27:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-01-011410.3389/fimmu.2023.13062921306292Defining genetic diversity of rhesus macaque Fcγ receptors with long-read RNA sequencingHaleigh E. Conley0Haleigh E. Conley1Max M. He2David Easterhoff3Hélène Fradin Kirshner4Sarah L. Cocklin5Jacob Meyer6Taylor Hoxie7Madison Berry8Todd Bradley9William D. Tolbert10Marzena Pazgier11Georgia D. Tomaras12Georgia D. Tomaras13Joern E. Schmitz14Michael Anthony Moody15Kevin Wiehe16Justin Pollara17Justin Pollara18Department of Surgery, Duke University School of Medicine, Duke University, Durham, NC, United StatesDuke Human Vaccine Institute, Duke University School of Medicine, Duke University, Durham, NC, United StatesDuke Human Vaccine Institute, Duke University School of Medicine, Duke University, Durham, NC, United StatesDuke Human Vaccine Institute, Duke University School of Medicine, Duke University, Durham, NC, United StatesDuke Human Vaccine Institute, Duke University School of Medicine, Duke University, Durham, NC, United StatesCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United StatesDuke Human Vaccine Institute, Duke University School of Medicine, Duke University, Durham, NC, United StatesDuke Human Vaccine Institute, Duke University School of Medicine, Duke University, Durham, NC, United StatesDuke Human Vaccine Institute, Duke University School of Medicine, Duke University, Durham, NC, United StatesGenomic Medicine Center, Children’s Mercy Kansas City, Kansas City, MO, United StatesInfectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United StatesInfectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United StatesDepartment of Surgery, Duke University School of Medicine, Duke University, Durham, NC, United StatesDuke Human Vaccine Institute, Duke University School of Medicine, Duke University, Durham, NC, United StatesCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United StatesDuke Human Vaccine Institute, Duke University School of Medicine, Duke University, Durham, NC, United StatesDuke Human Vaccine Institute, Duke University School of Medicine, Duke University, Durham, NC, United StatesDepartment of Surgery, Duke University School of Medicine, Duke University, Durham, NC, United StatesDuke Human Vaccine Institute, Duke University School of Medicine, Duke University, Durham, NC, United StatesFcγ receptors (FcγRs) are membrane-bound glycoproteins that bind to the fragment crystallizable (Fc) constant regions of IgG antibodies. Interactions between IgG immune complexes and FcγRs can initiate signal transduction that mediates important components of the immune response including activation of immune cells for clearance of opsonized pathogens or infected host cells. In humans, many studies have identified associations between FcγR gene polymorphisms and risk of infection, or progression of disease, suggesting a gene-level impact on FcγR-dependent immune responses. Rhesus macaques are an important translational model for most human health interventions, yet little is known about the breadth of rhesus macaque FcγR genetic diversity. This lack of knowledge prevents evaluation of the impact of FcγR polymorphisms on outcomes of preclinical studies performed in rhesus macaques. In this study we used long-read RNA sequencing to define the genetic diversity of FcγRs in 206 Indian-origin Rhesus macaques, Macaca mulatta. We describe the frequency of single nucleotide polymorphisms, insertions, deletions, frame-shift mutations, and isoforms. We also index the identified diversity using predicted and known rhesus macaque FcγR and Fc-FcγR structures. Future studies that define the functional significance of this genetic diversity will facilitate a better understanding of the correlation between human and macaque FcγR biology that is needed for effective translation of studies with antibody-mediated outcomes performed in rhesus macaques.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1306292/fullrhesus macaquesFc receptorLong-read RNA sequencingFcγR SNPsFcγR structuresgenetic diversity |
| spellingShingle | Haleigh E. Conley Haleigh E. Conley Max M. He David Easterhoff Hélène Fradin Kirshner Sarah L. Cocklin Jacob Meyer Taylor Hoxie Madison Berry Todd Bradley William D. Tolbert Marzena Pazgier Georgia D. Tomaras Georgia D. Tomaras Joern E. Schmitz Michael Anthony Moody Kevin Wiehe Justin Pollara Justin Pollara Defining genetic diversity of rhesus macaque Fcγ receptors with long-read RNA sequencing Frontiers in Immunology rhesus macaques Fc receptor Long-read RNA sequencing FcγR SNPs FcγR structures genetic diversity |
| title | Defining genetic diversity of rhesus macaque Fcγ receptors with long-read RNA sequencing |
| title_full | Defining genetic diversity of rhesus macaque Fcγ receptors with long-read RNA sequencing |
| title_fullStr | Defining genetic diversity of rhesus macaque Fcγ receptors with long-read RNA sequencing |
| title_full_unstemmed | Defining genetic diversity of rhesus macaque Fcγ receptors with long-read RNA sequencing |
| title_short | Defining genetic diversity of rhesus macaque Fcγ receptors with long-read RNA sequencing |
| title_sort | defining genetic diversity of rhesus macaque fcγ receptors with long read rna sequencing |
| topic | rhesus macaques Fc receptor Long-read RNA sequencing FcγR SNPs FcγR structures genetic diversity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1306292/full |
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