A DNA Regulatory Element Haplotype at Zinc Finger Genes Is Associated with Host Resilience to Small Ruminant Lentivirus in Two Sheep Populations
Small ruminant lentivirus (SRLV) causes Maedi-Visna or Ovine Progressive Pneumonia in sheep and creates insidious livestock production losses. This retrovirus is closely related to human immunodeficiency virus and currently has no vaccines or cure. Genetic marker assisted selection for sheep disease...
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MDPI AG
2021-06-01
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| Series: | Animals |
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| Online Access: | https://www.mdpi.com/2076-2615/11/7/1907 |
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| author | Alisha T. Massa Michelle R. Mousel Codie J. Durfee Maria K. Herndon Kaneesha M. Hemmerling J. Bret Taylor Holly L. Neibergs Stephen N. White |
| author_facet | Alisha T. Massa Michelle R. Mousel Codie J. Durfee Maria K. Herndon Kaneesha M. Hemmerling J. Bret Taylor Holly L. Neibergs Stephen N. White |
| author_sort | Alisha T. Massa |
| collection | DOAJ |
| description | Small ruminant lentivirus (SRLV) causes Maedi-Visna or Ovine Progressive Pneumonia in sheep and creates insidious livestock production losses. This retrovirus is closely related to human immunodeficiency virus and currently has no vaccines or cure. Genetic marker assisted selection for sheep disease resiliency presents an attractive management solution. Previously, we identified a region containing a cluster of zinc finger genes that had association with ovine SRLV proviral concentration. Trait-association analysis validated a small insertion/deletion variant near <i>ZNF389</i> (rs397514112) in multiple sheep breeds. In the current study, 543 sheep from two distinct populations were genotyped at 34 additional variants for fine mapping of the regulatory elements within this locus. Variants were selected based on ChIP-seq annotation data from sheep alveolar macrophages that defined active cis-regulatory elements predicted to influence zinc finger gene expression. We present a haplotype block of variants within regulatory elements that have improved associations and larger effect sizes (up to 4.7-fold genotypic difference in proviral concentration) than the previously validated <i>ZNF389</i> deletion marker. Hypotheses for the underlying causal mutation or mutations are presented based on changes to in silico transcription factor binding sites. These variants offer alternative markers for selective breeding and are targets for future functional mutation assays. |
| first_indexed | 2024-03-10T10:02:00Z |
| format | Article |
| id | doaj.art-cb48519b24bb4fafa554cde9cdccf1df |
| institution | Directory Open Access Journal |
| issn | 2076-2615 |
| language | English |
| last_indexed | 2024-03-10T10:02:00Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Animals |
| spelling | doaj.art-cb48519b24bb4fafa554cde9cdccf1df2023-11-22T01:54:11ZengMDPI AGAnimals2076-26152021-06-01117190710.3390/ani11071907A DNA Regulatory Element Haplotype at Zinc Finger Genes Is Associated with Host Resilience to Small Ruminant Lentivirus in Two Sheep PopulationsAlisha T. Massa0Michelle R. Mousel1Codie J. Durfee2Maria K. Herndon3Kaneesha M. Hemmerling4J. Bret Taylor5Holly L. Neibergs6Stephen N. White7Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99163, USAAnimal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Pullman, WA 99163, USAAnimal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Pullman, WA 99163, USADepartment of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99163, USADepartment of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99163, USARange Sheep Production Efficiency Research, Agricultural Research Service, United States Department of Agriculture, Dubois, ID 83423, USADepartment of Animal Science, Washington State University, Pullman, WA 99163, USAAnimal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Pullman, WA 99163, USASmall ruminant lentivirus (SRLV) causes Maedi-Visna or Ovine Progressive Pneumonia in sheep and creates insidious livestock production losses. This retrovirus is closely related to human immunodeficiency virus and currently has no vaccines or cure. Genetic marker assisted selection for sheep disease resiliency presents an attractive management solution. Previously, we identified a region containing a cluster of zinc finger genes that had association with ovine SRLV proviral concentration. Trait-association analysis validated a small insertion/deletion variant near <i>ZNF389</i> (rs397514112) in multiple sheep breeds. In the current study, 543 sheep from two distinct populations were genotyped at 34 additional variants for fine mapping of the regulatory elements within this locus. Variants were selected based on ChIP-seq annotation data from sheep alveolar macrophages that defined active cis-regulatory elements predicted to influence zinc finger gene expression. We present a haplotype block of variants within regulatory elements that have improved associations and larger effect sizes (up to 4.7-fold genotypic difference in proviral concentration) than the previously validated <i>ZNF389</i> deletion marker. Hypotheses for the underlying causal mutation or mutations are presented based on changes to in silico transcription factor binding sites. These variants offer alternative markers for selective breeding and are targets for future functional mutation assays.https://www.mdpi.com/2076-2615/11/7/1907small ruminant lentivirussheeppost-infection controlgenetic fine mapvalidation |
| spellingShingle | Alisha T. Massa Michelle R. Mousel Codie J. Durfee Maria K. Herndon Kaneesha M. Hemmerling J. Bret Taylor Holly L. Neibergs Stephen N. White A DNA Regulatory Element Haplotype at Zinc Finger Genes Is Associated with Host Resilience to Small Ruminant Lentivirus in Two Sheep Populations Animals small ruminant lentivirus sheep post-infection control genetic fine map validation |
| title | A DNA Regulatory Element Haplotype at Zinc Finger Genes Is Associated with Host Resilience to Small Ruminant Lentivirus in Two Sheep Populations |
| title_full | A DNA Regulatory Element Haplotype at Zinc Finger Genes Is Associated with Host Resilience to Small Ruminant Lentivirus in Two Sheep Populations |
| title_fullStr | A DNA Regulatory Element Haplotype at Zinc Finger Genes Is Associated with Host Resilience to Small Ruminant Lentivirus in Two Sheep Populations |
| title_full_unstemmed | A DNA Regulatory Element Haplotype at Zinc Finger Genes Is Associated with Host Resilience to Small Ruminant Lentivirus in Two Sheep Populations |
| title_short | A DNA Regulatory Element Haplotype at Zinc Finger Genes Is Associated with Host Resilience to Small Ruminant Lentivirus in Two Sheep Populations |
| title_sort | dna regulatory element haplotype at zinc finger genes is associated with host resilience to small ruminant lentivirus in two sheep populations |
| topic | small ruminant lentivirus sheep post-infection control genetic fine map validation |
| url | https://www.mdpi.com/2076-2615/11/7/1907 |
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