Association mapping of partitioning loci in barley

James Cockram, Jon White, Fiona J Leigh, Vincent J Lea, Elena Chiapparino, David A Laurie, Ian J Mackay, Wayne Powell, Donal M O'Sullivan

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

BACKGROUND: Association mapping, initially developed in human disease genetics, is now being applied to plant species. The model species Arabidopsis provided some of the first examples of association mapping in plants, identifying previously cloned flowering time genes, despite high population sub-structure. More recently, association genetics has been applied to barley, where breeding activity has resulted in a high degree of population sub-structure. A major genotypic division within barley is that between winter- and spring-sown varieties, which differ in their requirement for vernalization to promote subsequent flowering. To date, all attempts to validate association genetics in barley by identifying major flowering time loci that control vernalization requirement (VRN-H1 and VRN-H2) have failed. Here, we validate the use of association genetics in barley by identifying VRN-H1 and VRN-H2, despite their prominent role in determining population sub-structure.

RESULTS: By taking barley as a typical inbreeding crop, and seasonal growth habit as a major partitioning phenotype, we develop an association mapping approach which successfully identifies VRN-H1 and VRN-H2, the underlying loci largely responsible for this agronomic division. We find a combination of Structured Association followed by Genomic Control to correct for population structure and inflation of the test statistic, resolved significant associations only with VRN-H1 and the VRN-H2 candidate genes, as well as two genes closely linked to VRN-H1 (HvCSFs1 and HvPHYC).

CONCLUSION: We show that, after employing appropriate statistical methods to correct for population sub-structure, the genome-wide partitioning effect of allelic status at VRN-H1 and VRN-H2 does not result in the high levels of spurious association expected to occur in highly structured samples. Furthermore, we demonstrate that both VRN-H1 and the candidate VRN-H2 genes can be identified using association mapping. Discrimination between intragenic VRN-H1 markers was achieved, indicating that candidate causative polymorphisms may be discerned and prioritised within a larger set of positive associations. This proof of concept study demonstrates the feasibility of association mapping in barley, even within highly structured populations. A major advantage of this method is that it does not require large numbers of genome-wide markers, and is therefore suitable for fine mapping and candidate gene evaluation, especially in species for which large numbers of genetic markers are either unavailable or too costly.

Original languageEnglish
Article number16
JournalBMC Genetics
Volume9
DOIs
Publication statusPrint publication - 18 Feb 2008
Externally publishedYes

Fingerprint

Hordeum
Population
Genes
Genome
Internal-External Control
Inbreeding
Chromosome Mapping
Economic Inflation
Medical Genetics
Feasibility Studies
Genetic Markers
Arabidopsis
Habits
Breeding
Phenotype
Growth

Keywords

  • Chromosome Mapping/methods
  • Genetic Markers/genetics
  • Genome, Plant
  • Hordeum/genetics
  • Linkage Disequilibrium
  • Phenotype
  • Polymorphism, Genetic
  • Quantitative Trait Loci/genetics

Cite this

Cockram, J., White, J., Leigh, F. J., Lea, V. J., Chiapparino, E., Laurie, D. A., ... O'Sullivan, D. M. (2008). Association mapping of partitioning loci in barley. BMC Genetics, 9, [16]. https://doi.org/10.1186/1471-2156-9-16
Cockram, James ; White, Jon ; Leigh, Fiona J ; Lea, Vincent J ; Chiapparino, Elena ; Laurie, David A ; Mackay, Ian J ; Powell, Wayne ; O'Sullivan, Donal M. / Association mapping of partitioning loci in barley. In: BMC Genetics. 2008 ; Vol. 9.
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Cockram, J, White, J, Leigh, FJ, Lea, VJ, Chiapparino, E, Laurie, DA, Mackay, IJ, Powell, W & O'Sullivan, DM 2008, 'Association mapping of partitioning loci in barley', BMC Genetics, vol. 9, 16. https://doi.org/10.1186/1471-2156-9-16

Association mapping of partitioning loci in barley. / Cockram, James; White, Jon; Leigh, Fiona J; Lea, Vincent J; Chiapparino, Elena; Laurie, David A; Mackay, Ian J; Powell, Wayne; O'Sullivan, Donal M.

In: BMC Genetics, Vol. 9, 16, 18.02.2008.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association mapping of partitioning loci in barley

AU - Cockram, James

AU - White, Jon

AU - Leigh, Fiona J

AU - Lea, Vincent J

AU - Chiapparino, Elena

AU - Laurie, David A

AU - Mackay, Ian J

AU - Powell, Wayne

AU - O'Sullivan, Donal M

PY - 2008/2/18

Y1 - 2008/2/18

N2 - BACKGROUND: Association mapping, initially developed in human disease genetics, is now being applied to plant species. The model species Arabidopsis provided some of the first examples of association mapping in plants, identifying previously cloned flowering time genes, despite high population sub-structure. More recently, association genetics has been applied to barley, where breeding activity has resulted in a high degree of population sub-structure. A major genotypic division within barley is that between winter- and spring-sown varieties, which differ in their requirement for vernalization to promote subsequent flowering. To date, all attempts to validate association genetics in barley by identifying major flowering time loci that control vernalization requirement (VRN-H1 and VRN-H2) have failed. Here, we validate the use of association genetics in barley by identifying VRN-H1 and VRN-H2, despite their prominent role in determining population sub-structure.RESULTS: By taking barley as a typical inbreeding crop, and seasonal growth habit as a major partitioning phenotype, we develop an association mapping approach which successfully identifies VRN-H1 and VRN-H2, the underlying loci largely responsible for this agronomic division. We find a combination of Structured Association followed by Genomic Control to correct for population structure and inflation of the test statistic, resolved significant associations only with VRN-H1 and the VRN-H2 candidate genes, as well as two genes closely linked to VRN-H1 (HvCSFs1 and HvPHYC).CONCLUSION: We show that, after employing appropriate statistical methods to correct for population sub-structure, the genome-wide partitioning effect of allelic status at VRN-H1 and VRN-H2 does not result in the high levels of spurious association expected to occur in highly structured samples. Furthermore, we demonstrate that both VRN-H1 and the candidate VRN-H2 genes can be identified using association mapping. Discrimination between intragenic VRN-H1 markers was achieved, indicating that candidate causative polymorphisms may be discerned and prioritised within a larger set of positive associations. This proof of concept study demonstrates the feasibility of association mapping in barley, even within highly structured populations. A major advantage of this method is that it does not require large numbers of genome-wide markers, and is therefore suitable for fine mapping and candidate gene evaluation, especially in species for which large numbers of genetic markers are either unavailable or too costly.

AB - BACKGROUND: Association mapping, initially developed in human disease genetics, is now being applied to plant species. The model species Arabidopsis provided some of the first examples of association mapping in plants, identifying previously cloned flowering time genes, despite high population sub-structure. More recently, association genetics has been applied to barley, where breeding activity has resulted in a high degree of population sub-structure. A major genotypic division within barley is that between winter- and spring-sown varieties, which differ in their requirement for vernalization to promote subsequent flowering. To date, all attempts to validate association genetics in barley by identifying major flowering time loci that control vernalization requirement (VRN-H1 and VRN-H2) have failed. Here, we validate the use of association genetics in barley by identifying VRN-H1 and VRN-H2, despite their prominent role in determining population sub-structure.RESULTS: By taking barley as a typical inbreeding crop, and seasonal growth habit as a major partitioning phenotype, we develop an association mapping approach which successfully identifies VRN-H1 and VRN-H2, the underlying loci largely responsible for this agronomic division. We find a combination of Structured Association followed by Genomic Control to correct for population structure and inflation of the test statistic, resolved significant associations only with VRN-H1 and the VRN-H2 candidate genes, as well as two genes closely linked to VRN-H1 (HvCSFs1 and HvPHYC).CONCLUSION: We show that, after employing appropriate statistical methods to correct for population sub-structure, the genome-wide partitioning effect of allelic status at VRN-H1 and VRN-H2 does not result in the high levels of spurious association expected to occur in highly structured samples. Furthermore, we demonstrate that both VRN-H1 and the candidate VRN-H2 genes can be identified using association mapping. Discrimination between intragenic VRN-H1 markers was achieved, indicating that candidate causative polymorphisms may be discerned and prioritised within a larger set of positive associations. This proof of concept study demonstrates the feasibility of association mapping in barley, even within highly structured populations. A major advantage of this method is that it does not require large numbers of genome-wide markers, and is therefore suitable for fine mapping and candidate gene evaluation, especially in species for which large numbers of genetic markers are either unavailable or too costly.

KW - Chromosome Mapping/methods

KW - Genetic Markers/genetics

KW - Genome, Plant

KW - Hordeum/genetics

KW - Linkage Disequilibrium

KW - Phenotype

KW - Polymorphism, Genetic

KW - Quantitative Trait Loci/genetics

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DO - 10.1186/1471-2156-9-16

M3 - Article

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VL - 9

JO - BMC Genetics

JF - BMC Genetics

SN - 1471-2156

M1 - 16

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Cockram J, White J, Leigh FJ, Lea VJ, Chiapparino E, Laurie DA et al. Association mapping of partitioning loci in barley. BMC Genetics. 2008 Feb 18;9. 16. https://doi.org/10.1186/1471-2156-9-16