Adapting Genotyping-by-Sequencing and Variant Calling for Heterogeneous Stock Rats

The heterogeneous stock (HS) is an outbred rat population derived from eight inbred rat strains. HS rats are ideally suited for genome wide association studies; however, only a few genotyping microarrays have ever been designed for rats and none of them are currently in production. To address the ne...

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Main Authors: Alexander F. Gileta, Jianjun Gao, Apurva S. Chitre, Hannah V. Bimschleger, Celine L. St. Pierre, Shyam Gopalakrishnan, Abraham A. Palmer
Format: Article
Language:English
Published: Oxford University Press 2020-07-01
Series:G3: Genes, Genomes, Genetics
Subjects:
Online Access:http://g3journal.org/lookup/doi/10.1534/g3.120.401325
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author Alexander F. Gileta
Jianjun Gao
Apurva S. Chitre
Hannah V. Bimschleger
Celine L. St. Pierre
Shyam Gopalakrishnan
Abraham A. Palmer
author_facet Alexander F. Gileta
Jianjun Gao
Apurva S. Chitre
Hannah V. Bimschleger
Celine L. St. Pierre
Shyam Gopalakrishnan
Abraham A. Palmer
author_sort Alexander F. Gileta
collection DOAJ
description The heterogeneous stock (HS) is an outbred rat population derived from eight inbred rat strains. HS rats are ideally suited for genome wide association studies; however, only a few genotyping microarrays have ever been designed for rats and none of them are currently in production. To address the need for an efficient and cost effective method of genotyping HS rats, we have adapted genotype-by-sequencing (GBS) to obtain genotype information at large numbers of single nucleotide polymorphisms (SNPs). In this paper, we have outlined the laboratory and computational steps we took to optimize double digest genotype-by-sequencing (ddGBS) for use in rats. We evaluated multiple existing computational tools and explain the workflow we have used to call and impute over 3.7 million SNPs. We have also compared various rat genetic maps, which are necessary for imputation, including a recently developed map specific to the HS. Using our approach, we obtained concordance rates of 99% with data obtained using data from a genotyping array. The principles and computational pipeline that we describe could easily be adapted for use in other species for which reliable reference genome sets are available.
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spelling doaj.art-3aa4bd3693ad45488193d7ee910dee762022-12-21T20:04:46ZengOxford University PressG3: Genes, Genomes, Genetics2160-18362020-07-011072195220510.1534/g3.120.4013257Adapting Genotyping-by-Sequencing and Variant Calling for Heterogeneous Stock RatsAlexander F. GiletaJianjun GaoApurva S. ChitreHannah V. BimschlegerCeline L. St. PierreShyam GopalakrishnanAbraham A. PalmerThe heterogeneous stock (HS) is an outbred rat population derived from eight inbred rat strains. HS rats are ideally suited for genome wide association studies; however, only a few genotyping microarrays have ever been designed for rats and none of them are currently in production. To address the need for an efficient and cost effective method of genotyping HS rats, we have adapted genotype-by-sequencing (GBS) to obtain genotype information at large numbers of single nucleotide polymorphisms (SNPs). In this paper, we have outlined the laboratory and computational steps we took to optimize double digest genotype-by-sequencing (ddGBS) for use in rats. We evaluated multiple existing computational tools and explain the workflow we have used to call and impute over 3.7 million SNPs. We have also compared various rat genetic maps, which are necessary for imputation, including a recently developed map specific to the HS. Using our approach, we obtained concordance rates of 99% with data obtained using data from a genotyping array. The principles and computational pipeline that we describe could easily be adapted for use in other species for which reliable reference genome sets are available.http://g3journal.org/lookup/doi/10.1534/g3.120.401325genotyping-by-sequencingheterogeneous stockratimputation
spellingShingle Alexander F. Gileta
Jianjun Gao
Apurva S. Chitre
Hannah V. Bimschleger
Celine L. St. Pierre
Shyam Gopalakrishnan
Abraham A. Palmer
Adapting Genotyping-by-Sequencing and Variant Calling for Heterogeneous Stock Rats
G3: Genes, Genomes, Genetics
genotyping-by-sequencing
heterogeneous stock
rat
imputation
title Adapting Genotyping-by-Sequencing and Variant Calling for Heterogeneous Stock Rats
title_full Adapting Genotyping-by-Sequencing and Variant Calling for Heterogeneous Stock Rats
title_fullStr Adapting Genotyping-by-Sequencing and Variant Calling for Heterogeneous Stock Rats
title_full_unstemmed Adapting Genotyping-by-Sequencing and Variant Calling for Heterogeneous Stock Rats
title_short Adapting Genotyping-by-Sequencing and Variant Calling for Heterogeneous Stock Rats
title_sort adapting genotyping by sequencing and variant calling for heterogeneous stock rats
topic genotyping-by-sequencing
heterogeneous stock
rat
imputation
url http://g3journal.org/lookup/doi/10.1534/g3.120.401325
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