A QTL for number of teats shows breed specific effects on number of vertebrae in pigs: Bridging the gap between molecular and quantitative genetics

Maren Van Son, Marcos S. Lopes, Henry J. Martell, Martijn F.L. Derks, Lars Erik Gangsei, Jorgen Kongsro, Mark N. Wass, Eli H. Grindflek, Barbara Harlizius

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Modern breeding schemes for livestock species accumulate a large amount of genotype and phenotype data which can be used for genome-wide association studies (GWAS). Many chromosomal regions harboring effects on quantitative traits have been reported from these studies, but the underlying causative mutations remain mostly undetected. In this study, we combine large genotype and phenotype data available from a commercial pig breeding scheme for three different breeds (Duroc, Landrace, and Large White) to pinpoint functional variation for a region on porcine chromosome 7 affecting number of teats (NTE). Our results show that refining trait definition by counting number of vertebrae (NVE) and ribs (RIB) helps to reduce noise from other genetic variation and increases heritability from 0.28 up to 0.62 NVE and 0.78 RIB in Duroc. However, in Landrace, the effect of the same QTL on NTE mainly affects NVE and not RIB, which is reflected in reduced heritability for RIB (0.24) compared to NVE (0.59). Further, differences in allele frequencies and accuracy of rib counting influence genetic parameters. Correction for the top SNP does not detect any other QTL effect on NTE, NVE, or RIB in Landrace or Duroc. At the molecular level, haplotypes derived from 660K SNP data detects a core haplotype of seven SNPs in Duroc. Sequence analysis of 16 Duroc animals shows that two functional mutations of the Vertnin (VRTN) gene known to increase number of thoracic vertebrae (ribs) reside on this haplotype. In Landrace, the linkage disequilibrium (LD) extends over a region of more than 3 Mb also containing both VRTN mutations. Here, other modifying loci are expected to cause the breed-specific effect. Additional variants found on the wildtype haplotype surrounding the VRTN region in all sequenced Landrace animals point toward breed specific differences which are expected to be present also across the whole genome. This Landrace specific haplotype contains two missense mutations in the ABCD4 gene, one of which is expected to have a negative effect on the protein function. Together, the integration of largescale genotype, phenotype and sequence data shows exemplarily how population parameters are influenced by underlying variation at the molecular level.

LanguageEnglish
Article number00272
JournalFrontiers in Genetics
Volume10
Issue numberMAR
DOIs
Publication statusPublished - 26 Mar 2019

Fingerprint

Ribs
Molecular Biology
Spine
Swine
Haplotypes
Single Nucleotide Polymorphism
Genotype
Phenotype
Mutation
Breeding
Thoracic Vertebrae
Chromosomes, Human, Pair 7
Genome-Wide Association Study
Linkage Disequilibrium
Livestock
Missense Mutation
Gene Frequency
Genes
Sequence Analysis
Noise

Keywords

  • Fine mapping
  • Mammary gland
  • QTL
  • Ribs
  • Spine development
  • SSC7
  • Teats
  • Vertebrae

Cite this

Van Son, Maren ; Lopes, Marcos S. ; Martell, Henry J. ; Derks, Martijn F.L. ; Gangsei, Lars Erik ; Kongsro, Jorgen ; Wass, Mark N. ; Grindflek, Eli H. ; Harlizius, Barbara. / A QTL for number of teats shows breed specific effects on number of vertebrae in pigs: Bridging the gap between molecular and quantitative genetics. In: Frontiers in Genetics. 2019 ; Vol. 10, No. MAR.
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abstract = "Modern breeding schemes for livestock species accumulate a large amount of genotype and phenotype data which can be used for genome-wide association studies (GWAS). Many chromosomal regions harboring effects on quantitative traits have been reported from these studies, but the underlying causative mutations remain mostly undetected. In this study, we combine large genotype and phenotype data available from a commercial pig breeding scheme for three different breeds (Duroc, Landrace, and Large White) to pinpoint functional variation for a region on porcine chromosome 7 affecting number of teats (NTE). Our results show that refining trait definition by counting number of vertebrae (NVE) and ribs (RIB) helps to reduce noise from other genetic variation and increases heritability from 0.28 up to 0.62 NVE and 0.78 RIB in Duroc. However, in Landrace, the effect of the same QTL on NTE mainly affects NVE and not RIB, which is reflected in reduced heritability for RIB (0.24) compared to NVE (0.59). Further, differences in allele frequencies and accuracy of rib counting influence genetic parameters. Correction for the top SNP does not detect any other QTL effect on NTE, NVE, or RIB in Landrace or Duroc. At the molecular level, haplotypes derived from 660K SNP data detects a core haplotype of seven SNPs in Duroc. Sequence analysis of 16 Duroc animals shows that two functional mutations of the Vertnin (VRTN) gene known to increase number of thoracic vertebrae (ribs) reside on this haplotype. In Landrace, the linkage disequilibrium (LD) extends over a region of more than 3 Mb also containing both VRTN mutations. Here, other modifying loci are expected to cause the breed-specific effect. Additional variants found on the wildtype haplotype surrounding the VRTN region in all sequenced Landrace animals point toward breed specific differences which are expected to be present also across the whole genome. This Landrace specific haplotype contains two missense mutations in the ABCD4 gene, one of which is expected to have a negative effect on the protein function. Together, the integration of largescale genotype, phenotype and sequence data shows exemplarily how population parameters are influenced by underlying variation at the molecular level.",
keywords = "Fine mapping, Mammary gland, QTL, Ribs, Spine development, SSC7, Teats, Vertebrae",
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A QTL for number of teats shows breed specific effects on number of vertebrae in pigs: Bridging the gap between molecular and quantitative genetics. / Van Son, Maren; Lopes, Marcos S.; Martell, Henry J.; Derks, Martijn F.L.; Gangsei, Lars Erik; Kongsro, Jorgen; Wass, Mark N.; Grindflek, Eli H.; Harlizius, Barbara.

In: Frontiers in Genetics, Vol. 10, No. MAR, 00272, 26.03.2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - A QTL for number of teats shows breed specific effects on number of vertebrae in pigs: Bridging the gap between molecular and quantitative genetics

AU - Van Son, Maren

AU - Lopes, Marcos S.

AU - Martell, Henry J.

AU - Derks, Martijn F.L.

AU - Gangsei, Lars Erik

AU - Kongsro, Jorgen

AU - Wass, Mark N.

AU - Grindflek, Eli H.

AU - Harlizius, Barbara

PY - 2019/3/26

Y1 - 2019/3/26

N2 - Modern breeding schemes for livestock species accumulate a large amount of genotype and phenotype data which can be used for genome-wide association studies (GWAS). Many chromosomal regions harboring effects on quantitative traits have been reported from these studies, but the underlying causative mutations remain mostly undetected. In this study, we combine large genotype and phenotype data available from a commercial pig breeding scheme for three different breeds (Duroc, Landrace, and Large White) to pinpoint functional variation for a region on porcine chromosome 7 affecting number of teats (NTE). Our results show that refining trait definition by counting number of vertebrae (NVE) and ribs (RIB) helps to reduce noise from other genetic variation and increases heritability from 0.28 up to 0.62 NVE and 0.78 RIB in Duroc. However, in Landrace, the effect of the same QTL on NTE mainly affects NVE and not RIB, which is reflected in reduced heritability for RIB (0.24) compared to NVE (0.59). Further, differences in allele frequencies and accuracy of rib counting influence genetic parameters. Correction for the top SNP does not detect any other QTL effect on NTE, NVE, or RIB in Landrace or Duroc. At the molecular level, haplotypes derived from 660K SNP data detects a core haplotype of seven SNPs in Duroc. Sequence analysis of 16 Duroc animals shows that two functional mutations of the Vertnin (VRTN) gene known to increase number of thoracic vertebrae (ribs) reside on this haplotype. In Landrace, the linkage disequilibrium (LD) extends over a region of more than 3 Mb also containing both VRTN mutations. Here, other modifying loci are expected to cause the breed-specific effect. Additional variants found on the wildtype haplotype surrounding the VRTN region in all sequenced Landrace animals point toward breed specific differences which are expected to be present also across the whole genome. This Landrace specific haplotype contains two missense mutations in the ABCD4 gene, one of which is expected to have a negative effect on the protein function. Together, the integration of largescale genotype, phenotype and sequence data shows exemplarily how population parameters are influenced by underlying variation at the molecular level.

AB - Modern breeding schemes for livestock species accumulate a large amount of genotype and phenotype data which can be used for genome-wide association studies (GWAS). Many chromosomal regions harboring effects on quantitative traits have been reported from these studies, but the underlying causative mutations remain mostly undetected. In this study, we combine large genotype and phenotype data available from a commercial pig breeding scheme for three different breeds (Duroc, Landrace, and Large White) to pinpoint functional variation for a region on porcine chromosome 7 affecting number of teats (NTE). Our results show that refining trait definition by counting number of vertebrae (NVE) and ribs (RIB) helps to reduce noise from other genetic variation and increases heritability from 0.28 up to 0.62 NVE and 0.78 RIB in Duroc. However, in Landrace, the effect of the same QTL on NTE mainly affects NVE and not RIB, which is reflected in reduced heritability for RIB (0.24) compared to NVE (0.59). Further, differences in allele frequencies and accuracy of rib counting influence genetic parameters. Correction for the top SNP does not detect any other QTL effect on NTE, NVE, or RIB in Landrace or Duroc. At the molecular level, haplotypes derived from 660K SNP data detects a core haplotype of seven SNPs in Duroc. Sequence analysis of 16 Duroc animals shows that two functional mutations of the Vertnin (VRTN) gene known to increase number of thoracic vertebrae (ribs) reside on this haplotype. In Landrace, the linkage disequilibrium (LD) extends over a region of more than 3 Mb also containing both VRTN mutations. Here, other modifying loci are expected to cause the breed-specific effect. Additional variants found on the wildtype haplotype surrounding the VRTN region in all sequenced Landrace animals point toward breed specific differences which are expected to be present also across the whole genome. This Landrace specific haplotype contains two missense mutations in the ABCD4 gene, one of which is expected to have a negative effect on the protein function. Together, the integration of largescale genotype, phenotype and sequence data shows exemplarily how population parameters are influenced by underlying variation at the molecular level.

KW - Fine mapping

KW - Mammary gland

KW - QTL

KW - Ribs

KW - Spine development

KW - SSC7

KW - Teats

KW - Vertebrae

U2 - 10.3389/fgene.2019.00272

DO - 10.3389/fgene.2019.00272

M3 - Article

VL - 10

JO - Frontiers in Genetics Livestock Genomics

T2 - Frontiers in Genetics Livestock Genomics

JF - Frontiers in Genetics Livestock Genomics

SN - 1664-8021

IS - MAR

M1 - 00272

ER -