Extent of linkage disequilibrium in the domestic cat, Felis silvestris catus, and its breeds
Open accessAbstract
Domestic cats have a unique breeding history and can be used as models for human hereditary and infectious diseases. In the current era of genome-wide association studies, insights regarding linkage disequilibrium (LD) are essential for efficient association studies. The objective of this study is to investigate the extent of LD in the domestic cat, Felis silvestris catus, particularly within its breeds. A custom illumina GoldenGate Assay consisting of 1536 single nucleotide polymorphisms (SNPs) equally divided over ten 1 Mb chromosomal regions was developed, and genotyped across 18 globally recognized cat breeds and two distinct random bred populations. The pair-wise LD descriptive measure (r(2)) was calculated between the SNPs in each region and within each population independently. LD decay was estimated by determining the non-linear least-squares of all pair-wise estimates as a function of distance using established models. The point of 50% decay of r(2) was used to compare the extent of LD between breeds. The longest extent of LD was observed in the Burmese breed, where the distance at which r(2) ≈ 0.25 was ∼380 kb, comparable to several horse and dog breeds. The shortest extent of LD was found in the Siberian breed, with an r(2) ≈ 0.25 at approximately 17 kb, comparable to random bred cats and human populations. A comprehensive haplotype analysis was also conducted. The haplotype structure of each region within each breed mirrored the LD estimates. The LD of cat breeds largely reflects the breeds' population history and breeding strategies. Understanding LD in diverse populations will contribute to an efficient use of the newly developed SNP array for the cat in the design of genome-wide association studies, as well as to the interpretation of results for the fine mapping of disease and phenotypic traits.
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The study mitigated genetic drift effects by combining sequence data from 22 cats from six phylogenetically and geographically dispersed domestic breeds before variant detection and performing selection analyses relative to variants detected within a pool of European and Near Eastern wildcats.
“We mitigated this effect by combining sequence data from a collection of 22 cats (∼58× coverage) from six phylogenetically and geographically dispersed domestic breeds (42) before variant detection and performed selection analyses relative to variants detected within a pool of European (F.silvestris silvestris) and Near Eastern (F.silvestris lybica) wildcats (∼7× coverage; Figs. S4 and S5 and S2.1”
From Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication (2014) · cites this paper as [42]
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Montague, M. J., Li, G., Gandolfi, B., Khan, R., Aken, B. L., Searle, S. M. J., Minx, P., Hillier, L. W., Koboldt, D. C., Davis, B. W., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1410083111 · Cited by 340 · see citing works
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- Authors
- Alhaddad, H., Khan, R., Grahn, R. A., Gandolfi, B., Mullikin, J. C., Cole, S. A., Gruffydd-Jones, T. J., Häggström, J., Lohi, H., Longeri, M., & Lyons, L. A.
- Affiliations
- University of California, Davis (US)
- National Institutes of Health (US)
- Texas Biomedical Research Institute (US)
- University of Bristol (GB)
- Swedish University of Agricultural Sciences (SE)
- University of Helsinki (FI)
- University of Milan (IT)
- Corresponding author
- Lyons, Leslie A.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-01-07
- Volume
- 8
- Issue
- 1
- Pages
- e53537
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3538540
- OpenAlex
- W2033178168
- Cited by
- 62
- References
- 63
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 2 · 2021: 6 · 2020: 5 · 2019: 6 · 2018: 1 · 2017: 2 · 2016: 12 · 2015: 7 · 2014: 6 · 2013: 4
- FWCI
- 6.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Figshare (submittedVersion, cc-by)
- Työväentutkimus Vuosikirja (submittedVersion, other-oa)
- Funders
- San Francisco Foundation
- National Institutes of Health (R24OD010928, 1c06rr013556-01)
- University of California, Davis
- National Human Genome Research Institute
- National Center for Research Resources (R24RR016094, C06 RR-013556, RR13556, C06 RR-13556, RR016094)
- Center for Companion Animal Health, University of California, Davis
- Office of Research Infrastructure Programs, National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
- Keywords
- linkage disequilibrium, cats, cat breeds, single nucleotide polymorphisms, SNP array, haplotype structure, LD decay, demographic history, breeding strategies, genome-wide association study, disease mapping
- MeSH terms
- Alleles, Animals, Breeding, Cats, Chromosome Mapping, Gene Frequency, Haplotypes, Humans, Phenotype, Phylogeny, Linkage Disequilibrium, Least-Squares Analysis, Polymorphism, Single Nucleotide, Chromosomes, Mammalian, Microarray Analysis, Genome-Wide Association Study
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