Concordance rate between copy number variants detected using either high- or medium-density single nucleotide polymorphism genotype panels and the potential of imputing copy number variants from flanking high density single nucleotide polymorphism haplotypes in cattle
The trading of individual animal genotype information often involves only the exchange of the called genotypes and not necessarily the additional information required to effectively call structural variants. The main aim here was to determine if it is possible to impute copy number variants (CNVs) u...
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| Published in | BMC genomics Vol. 21; no. 1; p. 205 |
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| Language | English |
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BioMed Central Ltd
04.03.2020
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| Abstract | The trading of individual animal genotype information often involves only the exchange of the called genotypes and not necessarily the additional information required to effectively call structural variants. The main aim here was to determine if it is possible to impute copy number variants (CNVs) using the flanking single nucleotide polymorphism (SNP) haplotype structure in cattle. While this objective was achieved using high-density genotype panels (i.e., 713,162 SNPs), a secondary objective investigated the concordance of CNVs called with this high-density genotype panel compared to CNVs called from a medium-density panel (i.e., 45,677 SNPs in the present study). This is the first study to compare CNVs called from high-density and medium-density SNP genotypes from the same animals. High (and medium-density) genotypes were available on 991 Holstein-Friesian, 1015 Charolais, and 1394 Limousin bulls. The concordance between CNVs called from the medium-density and high-density genotypes were calculated separately for each animal. A subset of CNVs which were called from the high-density genotypes was selected for imputation. Imputation was carried out separately for each breed using a set of high-density SNPs flanking the midpoint of each CNV. A CNV was deemed to be imputed correctly when the called copy number matched the imputed copy number.
For 97.0% of CNVs called from the high-density genotypes, the corresponding genomic position on the medium-density of the animal did not contain a called CNV. The average accuracy of imputation for CNV deletions was 0.281, with a standard deviation of 0.286. The average accuracy of imputation of the CNV normal state, i.e. the absence of a CNV, was 0.982 with a standard deviation of 0.022. Two CNV duplications were imputed in the Charolais, a single CNV duplication in the Limousins, and a single CNV duplication in the Holstein-Friesians; in all cases the CNV duplications were incorrectly imputed.
The vast majority of CNVs called from the high-density genotypes were not detected using the medium-density genotypes. Furthermore, CNVs cannot be accurately predicted from flanking SNP haplotypes, at least based on the imputation algorithms routinely used in cattle, and using the SNPs currently available on the high-density genotype panel. |
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| AbstractList | Background The trading of individual animal genotype information often involves only the exchange of the called genotypes and not necessarily the additional information required to effectively call structural variants. The main aim here was to determine if it is possible to impute copy number variants (CNVs) using the flanking single nucleotide polymorphism (SNP) haplotype structure in cattle. While this objective was achieved using high-density genotype panels (i.e., 713,162 SNPs), a secondary objective investigated the concordance of CNVs called with this high-density genotype panel compared to CNVs called from a medium-density panel (i.e., 45,677 SNPs in the present study). This is the first study to compare CNVs called from high-density and medium-density SNP genotypes from the same animals. High (and medium-density) genotypes were available on 991 Holstein-Friesian, 1015 Charolais, and 1394 Limousin bulls. The concordance between CNVs called from the medium-density and high-density genotypes were calculated separately for each animal. A subset of CNVs which were called from the high-density genotypes was selected for imputation. Imputation was carried out separately for each breed using a set of high-density SNPs flanking the midpoint of each CNV. A CNV was deemed to be imputed correctly when the called copy number matched the imputed copy number. Results For 97.0% of CNVs called from the high-density genotypes, the corresponding genomic position on the medium-density of the animal did not contain a called CNV. The average accuracy of imputation for CNV deletions was 0.281, with a standard deviation of 0.286. The average accuracy of imputation of the CNV normal state, i.e. the absence of a CNV, was 0.982 with a standard deviation of 0.022. Two CNV duplications were imputed in the Charolais, a single CNV duplication in the Limousins, and a single CNV duplication in the Holstein-Friesians; in all cases the CNV duplications were incorrectly imputed. Conclusion The vast majority of CNVs called from the high-density genotypes were not detected using the medium-density genotypes. Furthermore, CNVs cannot be accurately predicted from flanking SNP haplotypes, at least based on the imputation algorithms routinely used in cattle, and using the SNPs currently available on the high-density genotype panel. Keywords: CNV, Bovine, PennCNV, QuantiSNP, Beagle, FImpute, SNP, Imputation Abstract Background The trading of individual animal genotype information often involves only the exchange of the called genotypes and not necessarily the additional information required to effectively call structural variants. The main aim here was to determine if it is possible to impute copy number variants (CNVs) using the flanking single nucleotide polymorphism (SNP) haplotype structure in cattle. While this objective was achieved using high-density genotype panels (i.e., 713,162 SNPs), a secondary objective investigated the concordance of CNVs called with this high-density genotype panel compared to CNVs called from a medium-density panel (i.e., 45,677 SNPs in the present study). This is the first study to compare CNVs called from high-density and medium-density SNP genotypes from the same animals. High (and medium-density) genotypes were available on 991 Holstein-Friesian, 1015 Charolais, and 1394 Limousin bulls. The concordance between CNVs called from the medium-density and high-density genotypes were calculated separately for each animal. A subset of CNVs which were called from the high-density genotypes was selected for imputation. Imputation was carried out separately for each breed using a set of high-density SNPs flanking the midpoint of each CNV. A CNV was deemed to be imputed correctly when the called copy number matched the imputed copy number. Results For 97.0% of CNVs called from the high-density genotypes, the corresponding genomic position on the medium-density of the animal did not contain a called CNV. The average accuracy of imputation for CNV deletions was 0.281, with a standard deviation of 0.286. The average accuracy of imputation of the CNV normal state, i.e. the absence of a CNV, was 0.982 with a standard deviation of 0.022. Two CNV duplications were imputed in the Charolais, a single CNV duplication in the Limousins, and a single CNV duplication in the Holstein-Friesians; in all cases the CNV duplications were incorrectly imputed. Conclusion The vast majority of CNVs called from the high-density genotypes were not detected using the medium-density genotypes. Furthermore, CNVs cannot be accurately predicted from flanking SNP haplotypes, at least based on the imputation algorithms routinely used in cattle, and using the SNPs currently available on the high-density genotype panel. Abstract Background The trading of individual animal genotype information often involves only the exchange of the called genotypes and not necessarily the additional information required to effectively call structural variants. The main aim here was to determine if it is possible to impute copy number variants (CNVs) using the flanking single nucleotide polymorphism (SNP) haplotype structure in cattle. While this objective was achieved using high-density genotype panels (i.e., 713,162 SNPs), a secondary objective investigated the concordance of CNVs called with this high-density genotype panel compared to CNVs called from a medium-density panel (i.e., 45,677 SNPs in the present study). This is the first study to compare CNVs called from high-density and medium-density SNP genotypes from the same animals. High (and medium-density) genotypes were available on 991 Holstein-Friesian, 1015 Charolais, and 1394 Limousin bulls. The concordance between CNVs called from the medium-density and high-density genotypes were calculated separately for each animal. A subset of CNVs which were called from the high-density genotypes was selected for imputation. Imputation was carried out separately for each breed using a set of high-density SNPs flanking the midpoint of each CNV. A CNV was deemed to be imputed correctly when the called copy number matched the imputed copy number. Results For 97.0% of CNVs called from the high-density genotypes, the corresponding genomic position on the medium-density of the animal did not contain a called CNV. The average accuracy of imputation for CNV deletions was 0.281, with a standard deviation of 0.286. The average accuracy of imputation of the CNV normal state, i.e. the absence of a CNV, was 0.982 with a standard deviation of 0.022. Two CNV duplications were imputed in the Charolais, a single CNV duplication in the Limousins, and a single CNV duplication in the Holstein-Friesians; in all cases the CNV duplications were incorrectly imputed. Conclusion The vast majority of CNVs called from the high-density genotypes were not detected using the medium-density genotypes. Furthermore, CNVs cannot be accurately predicted from flanking SNP haplotypes, at least based on the imputation algorithms routinely used in cattle, and using the SNPs currently available on the high-density genotype panel. The trading of individual animal genotype information often involves only the exchange of the called genotypes and not necessarily the additional information required to effectively call structural variants. The main aim here was to determine if it is possible to impute copy number variants (CNVs) using the flanking single nucleotide polymorphism (SNP) haplotype structure in cattle. While this objective was achieved using high-density genotype panels (i.e., 713,162 SNPs), a secondary objective investigated the concordance of CNVs called with this high-density genotype panel compared to CNVs called from a medium-density panel (i.e., 45,677 SNPs in the present study). This is the first study to compare CNVs called from high-density and medium-density SNP genotypes from the same animals. High (and medium-density) genotypes were available on 991 Holstein-Friesian, 1015 Charolais, and 1394 Limousin bulls. The concordance between CNVs called from the medium-density and high-density genotypes were calculated separately for each animal. A subset of CNVs which were called from the high-density genotypes was selected for imputation. Imputation was carried out separately for each breed using a set of high-density SNPs flanking the midpoint of each CNV. A CNV was deemed to be imputed correctly when the called copy number matched the imputed copy number. For 97.0% of CNVs called from the high-density genotypes, the corresponding genomic position on the medium-density of the animal did not contain a called CNV. The average accuracy of imputation for CNV deletions was 0.281, with a standard deviation of 0.286. The average accuracy of imputation of the CNV normal state, i.e. the absence of a CNV, was 0.982 with a standard deviation of 0.022. Two CNV duplications were imputed in the Charolais, a single CNV duplication in the Limousins, and a single CNV duplication in the Holstein-Friesians; in all cases the CNV duplications were incorrectly imputed. The vast majority of CNVs called from the high-density genotypes were not detected using the medium-density genotypes. Furthermore, CNVs cannot be accurately predicted from flanking SNP haplotypes, at least based on the imputation algorithms routinely used in cattle, and using the SNPs currently available on the high-density genotype panel. BACKGROUNDThe trading of individual animal genotype information often involves only the exchange of the called genotypes and not necessarily the additional information required to effectively call structural variants. The main aim here was to determine if it is possible to impute copy number variants (CNVs) using the flanking single nucleotide polymorphism (SNP) haplotype structure in cattle. While this objective was achieved using high-density genotype panels (i.e., 713,162 SNPs), a secondary objective investigated the concordance of CNVs called with this high-density genotype panel compared to CNVs called from a medium-density panel (i.e., 45,677 SNPs in the present study). This is the first study to compare CNVs called from high-density and medium-density SNP genotypes from the same animals. High (and medium-density) genotypes were available on 991 Holstein-Friesian, 1015 Charolais, and 1394 Limousin bulls. The concordance between CNVs called from the medium-density and high-density genotypes were calculated separately for each animal. A subset of CNVs which were called from the high-density genotypes was selected for imputation. Imputation was carried out separately for each breed using a set of high-density SNPs flanking the midpoint of each CNV. A CNV was deemed to be imputed correctly when the called copy number matched the imputed copy number. RESULTSFor 97.0% of CNVs called from the high-density genotypes, the corresponding genomic position on the medium-density of the animal did not contain a called CNV. The average accuracy of imputation for CNV deletions was 0.281, with a standard deviation of 0.286. The average accuracy of imputation of the CNV normal state, i.e. the absence of a CNV, was 0.982 with a standard deviation of 0.022. Two CNV duplications were imputed in the Charolais, a single CNV duplication in the Limousins, and a single CNV duplication in the Holstein-Friesians; in all cases the CNV duplications were incorrectly imputed. CONCLUSIONThe vast majority of CNVs called from the high-density genotypes were not detected using the medium-density genotypes. Furthermore, CNVs cannot be accurately predicted from flanking SNP haplotypes, at least based on the imputation algorithms routinely used in cattle, and using the SNPs currently available on the high-density genotype panel. Background The trading of individual animal genotype information often involves only the exchange of the called genotypes and not necessarily the additional information required to effectively call structural variants. The main aim here was to determine if it is possible to impute copy number variants (CNVs) using the flanking single nucleotide polymorphism (SNP) haplotype structure in cattle. While this objective was achieved using high-density genotype panels (i.e., 713,162 SNPs), a secondary objective investigated the concordance of CNVs called with this high-density genotype panel compared to CNVs called from a medium-density panel (i.e., 45,677 SNPs in the present study). This is the first study to compare CNVs called from high-density and medium-density SNP genotypes from the same animals. High (and medium-density) genotypes were available on 991 Holstein-Friesian, 1015 Charolais, and 1394 Limousin bulls. The concordance between CNVs called from the medium-density and high-density genotypes were calculated separately for each animal. A subset of CNVs which were called from the high-density genotypes was selected for imputation. Imputation was carried out separately for each breed using a set of high-density SNPs flanking the midpoint of each CNV. A CNV was deemed to be imputed correctly when the called copy number matched the imputed copy number. Results For 97.0% of CNVs called from the high-density genotypes, the corresponding genomic position on the medium-density of the animal did not contain a called CNV. The average accuracy of imputation for CNV deletions was 0.281, with a standard deviation of 0.286. The average accuracy of imputation of the CNV normal state, i.e. the absence of a CNV, was 0.982 with a standard deviation of 0.022. Two CNV duplications were imputed in the Charolais, a single CNV duplication in the Limousins, and a single CNV duplication in the Holstein-Friesians; in all cases the CNV duplications were incorrectly imputed. Conclusion The vast majority of CNVs called from the high-density genotypes were not detected using the medium-density genotypes. Furthermore, CNVs cannot be accurately predicted from flanking SNP haplotypes, at least based on the imputation algorithms routinely used in cattle, and using the SNPs currently available on the high-density genotype panel. The trading of individual animal genotype information often involves only the exchange of the called genotypes and not necessarily the additional information required to effectively call structural variants. The main aim here was to determine if it is possible to impute copy number variants (CNVs) using the flanking single nucleotide polymorphism (SNP) haplotype structure in cattle. While this objective was achieved using high-density genotype panels (i.e., 713,162 SNPs), a secondary objective investigated the concordance of CNVs called with this high-density genotype panel compared to CNVs called from a medium-density panel (i.e., 45,677 SNPs in the present study). This is the first study to compare CNVs called from high-density and medium-density SNP genotypes from the same animals. High (and medium-density) genotypes were available on 991 Holstein-Friesian, 1015 Charolais, and 1394 Limousin bulls. The concordance between CNVs called from the medium-density and high-density genotypes were calculated separately for each animal. A subset of CNVs which were called from the high-density genotypes was selected for imputation. Imputation was carried out separately for each breed using a set of high-density SNPs flanking the midpoint of each CNV. A CNV was deemed to be imputed correctly when the called copy number matched the imputed copy number. For 97.0% of CNVs called from the high-density genotypes, the corresponding genomic position on the medium-density of the animal did not contain a called CNV. The average accuracy of imputation for CNV deletions was 0.281, with a standard deviation of 0.286. The average accuracy of imputation of the CNV normal state, i.e. the absence of a CNV, was 0.982 with a standard deviation of 0.022. Two CNV duplications were imputed in the Charolais, a single CNV duplication in the Limousins, and a single CNV duplication in the Holstein-Friesians; in all cases the CNV duplications were incorrectly imputed. The vast majority of CNVs called from the high-density genotypes were not detected using the medium-density genotypes. Furthermore, CNVs cannot be accurately predicted from flanking SNP haplotypes, at least based on the imputation algorithms routinely used in cattle, and using the SNPs currently available on the high-density genotype panel. |
| ArticleNumber | 205 |
| Audience | Academic |
| Author | Parnell, Andrew C Kearney, John Francis Rafter, Pierce Berry, Donagh P Gormley, Isobel Claire |
| Author_xml | – sequence: 1 givenname: Pierce surname: Rafter fullname: Rafter, Pierce organization: UCD School of Mathematics and Statistics, University College Dublin, Belfield, Dublin 4, Ireland – sequence: 2 givenname: Isobel Claire surname: Gormley fullname: Gormley, Isobel Claire organization: UCD School of Mathematics and Statistics, University College Dublin, Belfield, Dublin 4, Ireland – sequence: 3 givenname: Andrew C surname: Parnell fullname: Parnell, Andrew C organization: Hamilton Institute Maynooth University, Maynooth, Kildare, Ireland – sequence: 4 givenname: John Francis surname: Kearney fullname: Kearney, John Francis organization: Irish Cattle Breeding Federation, Highfield House, Shinagh, Bandon, Co., Cork, Ireland – sequence: 5 givenname: Donagh P orcidid: 0000-0003-4349-1447 surname: Berry fullname: Berry, Donagh P email: Donagh.Berry@teagasc.ie organization: Animal & Grassland Research and Innovation Centre, Teagasc, Moorepark, Fermoy, Co. Cork, Ireland. Donagh.Berry@teagasc.ie |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32131735$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_3390_ani12111435 crossref_primary_10_1186_s12864_021_08075_2 crossref_primary_10_3389_fgene_2021_761503 crossref_primary_10_3168_jds_2020_19879 crossref_primary_10_1093_jas_skaa337 crossref_primary_10_1371_journal_pone_0284085 crossref_primary_10_3168_jds_2023_24295 crossref_primary_10_1016_j_gene_2022_147111 |
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| Keywords | Bovine SNP CNV FImpute Imputation QuantiSNP PennCNV Beagle |
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| Snippet | The trading of individual animal genotype information often involves only the exchange of the called genotypes and not necessarily the additional information... Abstract Background The trading of individual animal genotype information often involves only the exchange of the called genotypes and not necessarily the... Background The trading of individual animal genotype information often involves only the exchange of the called genotypes and not necessarily the additional... BACKGROUNDThe trading of individual animal genotype information often involves only the exchange of the called genotypes and not necessarily the additional... Abstract Background The trading of individual animal genotype information often involves only the exchange of the called genotypes and not necessarily the... |
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| SubjectTerms | Algorithms Beagle Beef cattle Bovine Cattle CNV Copy number Copy number variations Density FImpute Gene polymorphism Genetic polymorphisms Genomics Genotypes Haplotypes Identification and classification Nucleotides PennCNV Polymorphism QuantiSNP Single nucleotide polymorphisms Single-nucleotide polymorphism Standard deviation Vertebrates |
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| Title | Concordance rate between copy number variants detected using either high- or medium-density single nucleotide polymorphism genotype panels and the potential of imputing copy number variants from flanking high density single nucleotide polymorphism haplotypes in cattle |
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