Extent of linkage disequilibrium in the domestic cat, Felis silvestris catus, and its breeds.

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 t...

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Main Authors: Hasan Alhaddad, Razib Khan, Robert A Grahn, Barbara Gandolfi, James C Mullikin, Shelley A Cole, Timothy J Gruffydd-Jones, Jens Häggström, Hannes Lohi, Maria Longeri, Leslie A Lyons
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3538540?pdf=render
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author Hasan Alhaddad
Razib Khan
Robert A Grahn
Barbara Gandolfi
James C Mullikin
Shelley A Cole
Timothy J Gruffydd-Jones
Jens Häggström
Hannes Lohi
Maria Longeri
Leslie A Lyons
author_facet Hasan Alhaddad
Razib Khan
Robert A Grahn
Barbara Gandolfi
James C Mullikin
Shelley A Cole
Timothy J Gruffydd-Jones
Jens Häggström
Hannes Lohi
Maria Longeri
Leslie A Lyons
author_sort Hasan Alhaddad
collection DOAJ
description 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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spelling doaj.art-1d5f4d3f614b414e82519543dbddf7012022-12-21T17:23:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5353710.1371/journal.pone.0053537Extent of linkage disequilibrium in the domestic cat, Felis silvestris catus, and its breeds.Hasan AlhaddadRazib KhanRobert A GrahnBarbara GandolfiJames C MullikinShelley A ColeTimothy J Gruffydd-JonesJens HäggströmHannes LohiMaria LongeriLeslie A LyonsDomestic 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.http://europepmc.org/articles/PMC3538540?pdf=render
spellingShingle Hasan Alhaddad
Razib Khan
Robert A Grahn
Barbara Gandolfi
James C Mullikin
Shelley A Cole
Timothy J Gruffydd-Jones
Jens Häggström
Hannes Lohi
Maria Longeri
Leslie A Lyons
Extent of linkage disequilibrium in the domestic cat, Felis silvestris catus, and its breeds.
PLoS ONE
title Extent of linkage disequilibrium in the domestic cat, Felis silvestris catus, and its breeds.
title_full Extent of linkage disequilibrium in the domestic cat, Felis silvestris catus, and its breeds.
title_fullStr Extent of linkage disequilibrium in the domestic cat, Felis silvestris catus, and its breeds.
title_full_unstemmed Extent of linkage disequilibrium in the domestic cat, Felis silvestris catus, and its breeds.
title_short Extent of linkage disequilibrium in the domestic cat, Felis silvestris catus, and its breeds.
title_sort extent of linkage disequilibrium in the domestic cat felis silvestris catus and its breeds
url http://europepmc.org/articles/PMC3538540?pdf=render
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