Expanding Possibilities for Intervention against Small Ruminant Lentiviruses through Genetic Marker-Assisted Selective Breeding
Abstract
:1. Small Ruminant Lentiviruses: Background & Existing Intervention Strategies
1.1. Background on Small Ruminant Lentiviruses
1.2. Existing Intervention Strategies for Small Ruminant Lentiviruses
1.3. Advantages of Genetic Marker Tests as Interventions for Small Ruminant Lentiviruses
2. Development of Genetic Marker Tests for Small Ruminant Lentiviruses
2.1. General Background on Development of Genetic Marker Tests
2.1.1. Definition of Phenotypes
2.1.2. Evidence-Based Stages for Development of Genetic Marker Tests
Stage | Goal | Types of markers potentially involved | Concerns | Marker-Assisted Selection (MAS) |
---|---|---|---|---|
1 | Initial discovery of genetic association | Functional variants, markers in linkage disequilibrium (LD; inherited together) with functional variants, spurious associations | (A) Initial association in one animal set directs additional research. (B) Association could be spurious. | Not recommended |
2A | Replication of association in validation animal sets | Functional variants, markers in LD with functional variants a | (A) Do markers have predictive value in the sense of consistent trait association? (B) Are there conditions under which predictive value might break down? | Supported by data for traits with replicated association, avoiding conditions where replication of association fails |
2B | Assess potential correlated responses to selection | Functional variants, markers in LD with functional variants a | Are there trade-offs where some traits could be improved at the expense of other traits? | Conditions for use refined by assessment of potential trade-offs |
2.2.Example of Genetic Marker Tests for Infectious Disease in Sheep: Classical Scrapie
Species | Trait(s) | Gene | Haplotype & Variant | Effect Size | Mode of Inheritance | Breeds | Management | Locale | Potential Correlated Responses to Selection Examined |
---|---|---|---|---|---|---|---|---|---|
Sheep | [Common Reference Haplotype] | PRNP | ARQ haplotype Contains: A136 R154 Q171 | [Common Reference Haplotype] | [Common Reference Haplotype] | Many | Many | Many | [Common Reference Haplotype] |
Sheep | Probability of infection | PRNP | ARR haplotype Contains: R171 | Strong resistance [115,116,117] | Dominant, except to VRQ haplotype | Many | Many | Many | Many |
Sheep | Probability of infection | PRNP | VRQ haplotype Contains: V136 | Strong susceptibility Often 10-fold increased risk [115,116,117] | Largely Dominant | Many | Many | Many | Many |
Sheep | Probability of infection | PRNP | AHQ haplotype Contains: H154 | 3–7 fold risk reduction [115,116,117,122] | Partial Dominant, except to ARR or VRQ | Many | Many | Many | Many |
2.3. Current State of Genetic Marker Tests in Sheep for Ovine Lentivirus
Species | Trait | Gene/Region | Specific variant | Effect Size | Mode of Inheritance | Breeds | Management | Locations | Potential Correlated Responses to Selection Examined |
---|---|---|---|---|---|---|---|---|---|
Sheep | Probability of infection | TMEM154 | Haplotype 1 Contains: K35 Substitution | Genotypic relative risk: 2 copies confer 2.85-fold reduced risk under field exposure [75] | Possibly Recessive | Columbia, Dorset, Finnsheep, MARCIII, Rambouillet, Romanov, Suffolk, Texel, Dorper a, Katahdin a | Extensive, Semi-intensive with variable levels of confinement during lambing | Nebraska, USA Iowa, USA Idaho, USA | Research needed |
Sheep | Research needed | TMEM154 | Haplotype 4 Contains: Codon 4 Frameshift | Research needed | Research needed | Research needed | Research needed | Research needed | Research needed |
Sheep | Research needed | TMEM154 | Haplotype 6 Contains: Codon 82 Frameshift | Research needed | Research needed | Research needed | Research needed | Research needed | Research needed |
3. Future Opportunities and Needs
3.1. Continued Development of Existing Genetic Tests Based on TMEM154
3.2. Expanded Virus/Host Interaction Data
3.3. Additional Genetic Tests
Species | Trait | Gene/Region | Specific variant | Breeds | Locations | Reference |
---|---|---|---|---|---|---|
Sheep | Probability of disease | MHC-Class I | OMHC1*205 | Latxa | Araba, Spain Gipuzkoa, Spain | [85] |
Sheep | Probability of disease | MHC-DRB2 | DRB2*275 | Latxa | Araba, Spain Gipuzkoa, Spain | [85] |
Sheep | Probability of disease | MHC-DRB1 | Haplotype *0325 | Latxa | Araba, Spain Gipuzkoa, Spain | [84] |
Sheep | Proviral concentration | MHC-DRB1 | Haplotypes *0403 and *07012 | Rambouillet, Polypay, Columbia | Idaho, USA | [34] |
Sheep | Proviral concentration | CCR5 | rs119102753 | Rambouillet, Polypay, Columbia | Idaho, USA | [74] |
Sheep | Probability of infection | DPPA2, DPPA4 | OAR1_185953850 | Rambouillet, Polypay, Columbia | Idaho, USA | [77] |
Sheep | Probability of infection | SYTL3, GTF2H5, DYNLT1, TMEM181, EZR | OAR8_88021348 | Rambouillet | Idaho, USA | [77] |
Sheep | Proviral concentration | C19orf42, TMEM38A, NWD1, MED26, SLC35E1, CHERP | s27054 | Polypay | Idaho, USA | [77] |
Sheep | Proviral concentration | ZNF192, ZSCAN16, ZNF165, ZNF389 | s65956 | Rambouillet | Idaho, USA | [77] |
3.4. Additional Phenotypes to Address Superspreader Hypothesis with OvLV
3.5. Additional Studies on Other Small Ruminants
3.6. Possibilities for Genomic Selection
4. Conclusions
Acknowledgments
Conflicts of Interest
References and Notes
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White, S.N.; Knowles, D.P. Expanding Possibilities for Intervention against Small Ruminant Lentiviruses through Genetic Marker-Assisted Selective Breeding. Viruses 2013, 5, 1466-1499. https://doi.org/10.3390/v5061466
White SN, Knowles DP. Expanding Possibilities for Intervention against Small Ruminant Lentiviruses through Genetic Marker-Assisted Selective Breeding. Viruses. 2013; 5(6):1466-1499. https://doi.org/10.3390/v5061466
Chicago/Turabian StyleWhite, Stephen N., and Donald P. Knowles. 2013. "Expanding Possibilities for Intervention against Small Ruminant Lentiviruses through Genetic Marker-Assisted Selective Breeding" Viruses 5, no. 6: 1466-1499. https://doi.org/10.3390/v5061466