Misidentification of runs of homozygosity islands in cattle caused by interference with copy number variation or large intermarker distances
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1186/s12711-018-0414-x http://hdl.handle.net/11449/176734 |
Resumo: | Background: Runs of homozygosity (ROH) islands are stretches of homozygous sequence in the genome of a large proportion of individuals in a population. Algorithms for the detection of ROH depend on the similarity of haplotypes. Coverage gaps and copy number variants (CNV) may result in incorrect identification of such similarity, leading to the detection of ROH islands where none exists. Misidentified hemizygous regions will also appear as homozygous based on sequence variation alone. Our aim was to identify ROH islands influenced by marker coverage gaps or CNV, using Illumina BovineHD BeadChip (777 K) single nucleotide polymorphism (SNP) data for Austrian Brown Swiss, Tyrol Grey and Pinzgauer cattle. Methods: ROH were detected using clustering, and ROH islands were determined from population inbreeding levels for each marker. CNV were detected using a multivariate copy number analysis method and a hidden Markov model. SNP coverage gaps were defined as genomic regions with intermarker distances on average longer than 9.24 kb. ROH islands that overlapped CNV regions (CNVR) or SNP coverage gaps were considered as potential artefacts. Permutation tests were used to determine if overlaps between CNVR with copy losses and ROH islands were due to chance. Diversity of the haplotypes in the ROH islands was assessed by haplotype analyses. Results: In Brown Swiss, Tyrol Grey and Pinzgauer, we identified 13, 22, and 24 ROH islands covering 26.6, 389.0 and 35.8 Mb, respectively, and we detected 30, 50 and 71 CNVR derived from CNV by using both algorithms, respectively. Overlaps between ROH islands, CNVR or coverage gaps occurred for 7, 14 and 16 ROH islands, respectively. About 37, 44 and 52% of the ROH islands coverage in Brown Swiss, Tyrol Grey and Pinzgauer, respectively, were affected by copy loss. Intersections between ROH islands and CNVR were small, but significantly larger compared to ROH islands at random locations across the genome, implying an association between ROH islands and CNVR. Haplotype diversity for reliable ROH islands was lower than for ROH islands that intersected with copy loss CNVR. Conclusions: Our findings show that a significant proportion of the ROH islands in the bovine genome are artefacts due to CNV or SNP coverage gaps. |
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Misidentification of runs of homozygosity islands in cattle caused by interference with copy number variation or large intermarker distancesBackground: Runs of homozygosity (ROH) islands are stretches of homozygous sequence in the genome of a large proportion of individuals in a population. Algorithms for the detection of ROH depend on the similarity of haplotypes. Coverage gaps and copy number variants (CNV) may result in incorrect identification of such similarity, leading to the detection of ROH islands where none exists. Misidentified hemizygous regions will also appear as homozygous based on sequence variation alone. Our aim was to identify ROH islands influenced by marker coverage gaps or CNV, using Illumina BovineHD BeadChip (777 K) single nucleotide polymorphism (SNP) data for Austrian Brown Swiss, Tyrol Grey and Pinzgauer cattle. Methods: ROH were detected using clustering, and ROH islands were determined from population inbreeding levels for each marker. CNV were detected using a multivariate copy number analysis method and a hidden Markov model. SNP coverage gaps were defined as genomic regions with intermarker distances on average longer than 9.24 kb. ROH islands that overlapped CNV regions (CNVR) or SNP coverage gaps were considered as potential artefacts. Permutation tests were used to determine if overlaps between CNVR with copy losses and ROH islands were due to chance. Diversity of the haplotypes in the ROH islands was assessed by haplotype analyses. Results: In Brown Swiss, Tyrol Grey and Pinzgauer, we identified 13, 22, and 24 ROH islands covering 26.6, 389.0 and 35.8 Mb, respectively, and we detected 30, 50 and 71 CNVR derived from CNV by using both algorithms, respectively. Overlaps between ROH islands, CNVR or coverage gaps occurred for 7, 14 and 16 ROH islands, respectively. About 37, 44 and 52% of the ROH islands coverage in Brown Swiss, Tyrol Grey and Pinzgauer, respectively, were affected by copy loss. Intersections between ROH islands and CNVR were small, but significantly larger compared to ROH islands at random locations across the genome, implying an association between ROH islands and CNVR. Haplotype diversity for reliable ROH islands was lower than for ROH islands that intersected with copy loss CNVR. Conclusions: Our findings show that a significant proportion of the ROH islands in the bovine genome are artefacts due to CNV or SNP coverage gaps.Division of Livestock Sciences (NUWI) University of Natural Resources and Life Sciences, Gregor-Mendel Strasse 33Lilongwe University of Agriculture and Natural Resources, P. O. Box 219School of Agricultural and Veterinarian Sciences Jaboticabal Department of Preventive Veterinary Medicine and Animal Reproduction São Paulo State University (UNESP)National Livestock Resources Research Institute, P.O Box 96Department of Animal Breeding and Genetics Swedish University of Agricultural Sciences, Box 7023Department of Animal Science Faculty of Agriculture University of Zagreb, Svetošimunska cesta 25School of Veterinary Medicine Araçatuba Department of Support Production and Animal Health São Paulo State University (UNESP)Animal Genomics and Improvement LaboratorySchool of Agricultural and Veterinarian Sciences Jaboticabal Department of Preventive Veterinary Medicine and Animal Reproduction São Paulo State University (UNESP)School of Veterinary Medicine Araçatuba Department of Support Production and Animal Health São Paulo State University (UNESP)University of Natural Resources and Life SciencesLilongwe University of Agriculture and Natural ResourcesUniversidade Estadual Paulista (Unesp)National Livestock Resources Research InstituteSwedish University of Agricultural SciencesUniversity of ZagrebAnimal Genomics and Improvement LaboratoryNandolo, WilsonUtsunomiya, Yuri T. [UNESP]Mészáros, GáborWurzinger, MariaKhayadzadeh, NegarTorrecilha, Rafaela B. P. [UNESP]Mulindwa, Henry A.Gondwe, Timothy N.Waldmann, PatrikFerenčaković, MajaGarcia, José F. [UNESP]Rosen, Benjamin D.Bickhart, DerekVan Tassell, Curt P.Curik, InoSölkner, Johann2018-12-11T17:22:15Z2018-12-11T17:22:15Z2018-08-22info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1186/s12711-018-0414-xGenetics Selection Evolution, v. 50, n. 1, 2018.1297-96860999-193Xhttp://hdl.handle.net/11449/17673410.1186/s12711-018-0414-x2-s2.0-850519480462-s2.0-85051948046.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengGenetics Selection Evolution1,745info:eu-repo/semantics/openAccess2024-09-04T19:15:52Zoai:repositorio.unesp.br:11449/176734Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-09-04T19:15:52Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Misidentification of runs of homozygosity islands in cattle caused by interference with copy number variation or large intermarker distances |
title |
Misidentification of runs of homozygosity islands in cattle caused by interference with copy number variation or large intermarker distances |
spellingShingle |
Misidentification of runs of homozygosity islands in cattle caused by interference with copy number variation or large intermarker distances Nandolo, Wilson |
title_short |
Misidentification of runs of homozygosity islands in cattle caused by interference with copy number variation or large intermarker distances |
title_full |
Misidentification of runs of homozygosity islands in cattle caused by interference with copy number variation or large intermarker distances |
title_fullStr |
Misidentification of runs of homozygosity islands in cattle caused by interference with copy number variation or large intermarker distances |
title_full_unstemmed |
Misidentification of runs of homozygosity islands in cattle caused by interference with copy number variation or large intermarker distances |
title_sort |
Misidentification of runs of homozygosity islands in cattle caused by interference with copy number variation or large intermarker distances |
author |
Nandolo, Wilson |
author_facet |
Nandolo, Wilson Utsunomiya, Yuri T. [UNESP] Mészáros, Gábor Wurzinger, Maria Khayadzadeh, Negar Torrecilha, Rafaela B. P. [UNESP] Mulindwa, Henry A. Gondwe, Timothy N. Waldmann, Patrik Ferenčaković, Maja Garcia, José F. [UNESP] Rosen, Benjamin D. Bickhart, Derek Van Tassell, Curt P. Curik, Ino Sölkner, Johann |
author_role |
author |
author2 |
Utsunomiya, Yuri T. [UNESP] Mészáros, Gábor Wurzinger, Maria Khayadzadeh, Negar Torrecilha, Rafaela B. P. [UNESP] Mulindwa, Henry A. Gondwe, Timothy N. Waldmann, Patrik Ferenčaković, Maja Garcia, José F. [UNESP] Rosen, Benjamin D. Bickhart, Derek Van Tassell, Curt P. Curik, Ino Sölkner, Johann |
author2_role |
author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
University of Natural Resources and Life Sciences Lilongwe University of Agriculture and Natural Resources Universidade Estadual Paulista (Unesp) National Livestock Resources Research Institute Swedish University of Agricultural Sciences University of Zagreb Animal Genomics and Improvement Laboratory |
dc.contributor.author.fl_str_mv |
Nandolo, Wilson Utsunomiya, Yuri T. [UNESP] Mészáros, Gábor Wurzinger, Maria Khayadzadeh, Negar Torrecilha, Rafaela B. P. [UNESP] Mulindwa, Henry A. Gondwe, Timothy N. Waldmann, Patrik Ferenčaković, Maja Garcia, José F. [UNESP] Rosen, Benjamin D. Bickhart, Derek Van Tassell, Curt P. Curik, Ino Sölkner, Johann |
description |
Background: Runs of homozygosity (ROH) islands are stretches of homozygous sequence in the genome of a large proportion of individuals in a population. Algorithms for the detection of ROH depend on the similarity of haplotypes. Coverage gaps and copy number variants (CNV) may result in incorrect identification of such similarity, leading to the detection of ROH islands where none exists. Misidentified hemizygous regions will also appear as homozygous based on sequence variation alone. Our aim was to identify ROH islands influenced by marker coverage gaps or CNV, using Illumina BovineHD BeadChip (777 K) single nucleotide polymorphism (SNP) data for Austrian Brown Swiss, Tyrol Grey and Pinzgauer cattle. Methods: ROH were detected using clustering, and ROH islands were determined from population inbreeding levels for each marker. CNV were detected using a multivariate copy number analysis method and a hidden Markov model. SNP coverage gaps were defined as genomic regions with intermarker distances on average longer than 9.24 kb. ROH islands that overlapped CNV regions (CNVR) or SNP coverage gaps were considered as potential artefacts. Permutation tests were used to determine if overlaps between CNVR with copy losses and ROH islands were due to chance. Diversity of the haplotypes in the ROH islands was assessed by haplotype analyses. Results: In Brown Swiss, Tyrol Grey and Pinzgauer, we identified 13, 22, and 24 ROH islands covering 26.6, 389.0 and 35.8 Mb, respectively, and we detected 30, 50 and 71 CNVR derived from CNV by using both algorithms, respectively. Overlaps between ROH islands, CNVR or coverage gaps occurred for 7, 14 and 16 ROH islands, respectively. About 37, 44 and 52% of the ROH islands coverage in Brown Swiss, Tyrol Grey and Pinzgauer, respectively, were affected by copy loss. Intersections between ROH islands and CNVR were small, but significantly larger compared to ROH islands at random locations across the genome, implying an association between ROH islands and CNVR. Haplotype diversity for reliable ROH islands was lower than for ROH islands that intersected with copy loss CNVR. Conclusions: Our findings show that a significant proportion of the ROH islands in the bovine genome are artefacts due to CNV or SNP coverage gaps. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-12-11T17:22:15Z 2018-12-11T17:22:15Z 2018-08-22 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1186/s12711-018-0414-x Genetics Selection Evolution, v. 50, n. 1, 2018. 1297-9686 0999-193X http://hdl.handle.net/11449/176734 10.1186/s12711-018-0414-x 2-s2.0-85051948046 2-s2.0-85051948046.pdf |
url |
http://dx.doi.org/10.1186/s12711-018-0414-x http://hdl.handle.net/11449/176734 |
identifier_str_mv |
Genetics Selection Evolution, v. 50, n. 1, 2018. 1297-9686 0999-193X 10.1186/s12711-018-0414-x 2-s2.0-85051948046 2-s2.0-85051948046.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Genetics Selection Evolution 1,745 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
repositoriounesp@unesp.br |
_version_ |
1810021404909764608 |