Genome-wide association mapping to candidate polymorphism resolution in the unsequenced barley genome

James Cockram, Jon White, DL Zuluaga, David Smith, J Comadran , M Macaulay, Z Lou, MJ Kearsey, P Werner, D Harrap, C Tapsell, Liu H, PE Hedley, N Stein, DE Schulte, B Steuernagel, David Marshall, WBT Thomas, Ramsay L, Ian MackayDavid Balding

Research output: Contribution to journalArticle

181 Citations (Scopus)

Abstract

Although commonplace in human disease genetics, genome-wide association (GWA) studies have only relatively recently been applied to plants. Using 32 phenotypes in the inbreeding crop barley, we report GWA mapping of 15 morphological traits across ∼500 cultivars genotyped with 1,536 SNPs. In contrast to the majority of human GWA studies, we observe high levels of linkage disequilibrium within and between chromosomes. Despite this, GWA analysis readily detected common alleles of high penetrance. To investigate the potential of combining GWA mapping with comparative analysis to resolve traits to candidate polymorphism level in unsequenced genomes, we fine-mapped a selected phenotype (anthocyanin pigmentation) within a 140-kb interval containing three genes. Of these, resequencing the putative anthocyanin pathway gene HvbHLH1 identified a deletion resulting in a premature stop codon upstream of the basic helix-loop-helix domain, which was diagnostic for lack of anthocyanin in our association and biparental mapping populations. The methodology described here is transferable to species with limited genomic resources, providing a paradigm for reducing the threshold of map-based cloning in unsequenced crops.
Original languageEnglish
Pages (from-to)21611-21616
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number50
DOIs
Publication statusPrint publication - 14 Dec 2010

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Anthocyanins
Genome-Wide Association Study
Hordeum
Genome
Helix-Loop-Helix Motifs
Phenotype
Inbreeding
Penetrance
Nonsense Codon
Linkage Disequilibrium
Medical Genetics
Pigmentation
Human Genome
Genes
Single Nucleotide Polymorphism
Organism Cloning
Chromosomes
Alleles
Population

Cite this

Cockram, James ; White, Jon ; Zuluaga, DL ; Smith, David ; Comadran , J ; Macaulay, M ; Lou, Z ; Kearsey, MJ ; Werner, P ; Harrap, D ; Tapsell, C ; H, Liu ; Hedley, PE ; Stein, N ; Schulte, DE ; Steuernagel, B ; Marshall, David ; Thomas, WBT ; L, Ramsay ; Mackay, Ian ; Balding, David. / Genome-wide association mapping to candidate polymorphism resolution in the unsequenced barley genome. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 50. pp. 21611-21616.
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abstract = "Although commonplace in human disease genetics, genome-wide association (GWA) studies have only relatively recently been applied to plants. Using 32 phenotypes in the inbreeding crop barley, we report GWA mapping of 15 morphological traits across ∼500 cultivars genotyped with 1,536 SNPs. In contrast to the majority of human GWA studies, we observe high levels of linkage disequilibrium within and between chromosomes. Despite this, GWA analysis readily detected common alleles of high penetrance. To investigate the potential of combining GWA mapping with comparative analysis to resolve traits to candidate polymorphism level in unsequenced genomes, we fine-mapped a selected phenotype (anthocyanin pigmentation) within a 140-kb interval containing three genes. Of these, resequencing the putative anthocyanin pathway gene HvbHLH1 identified a deletion resulting in a premature stop codon upstream of the basic helix-loop-helix domain, which was diagnostic for lack of anthocyanin in our association and biparental mapping populations. The methodology described here is transferable to species with limited genomic resources, providing a paradigm for reducing the threshold of map-based cloning in unsequenced crops.",
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Cockram, J, White, J, Zuluaga, DL, Smith, D, Comadran , J, Macaulay, M, Lou, Z, Kearsey, MJ, Werner, P, Harrap, D, Tapsell, C, H, L, Hedley, PE, Stein, N, Schulte, DE, Steuernagel, B, Marshall, D, Thomas, WBT, L, R, Mackay, I & Balding, D 2010, 'Genome-wide association mapping to candidate polymorphism resolution in the unsequenced barley genome', Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 50, pp. 21611-21616. https://doi.org/10.1073/pnas.1010179107

Genome-wide association mapping to candidate polymorphism resolution in the unsequenced barley genome. / Cockram, James; White, Jon; Zuluaga, DL; Smith, David; Comadran , J; Macaulay, M; Lou, Z; Kearsey, MJ; Werner, P; Harrap, D; Tapsell, C; H, Liu; Hedley, PE; Stein, N; Schulte, DE; Steuernagel, B; Marshall, David; Thomas, WBT; L, Ramsay; Mackay, Ian; Balding, David.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 50, 14.12.2010, p. 21611-21616.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genome-wide association mapping to candidate polymorphism resolution in the unsequenced barley genome

AU - Cockram, James

AU - White, Jon

AU - Zuluaga, DL

AU - Smith, David

AU - Comadran , J

AU - Macaulay, M

AU - Lou, Z

AU - Kearsey, MJ

AU - Werner, P

AU - Harrap, D

AU - Tapsell, C

AU - H, Liu

AU - Hedley, PE

AU - Stein, N

AU - Schulte, DE

AU - Steuernagel, B

AU - Marshall, David

AU - Thomas, WBT

AU - L, Ramsay

AU - Mackay, Ian

AU - Balding, David

PY - 2010/12/14

Y1 - 2010/12/14

N2 - Although commonplace in human disease genetics, genome-wide association (GWA) studies have only relatively recently been applied to plants. Using 32 phenotypes in the inbreeding crop barley, we report GWA mapping of 15 morphological traits across ∼500 cultivars genotyped with 1,536 SNPs. In contrast to the majority of human GWA studies, we observe high levels of linkage disequilibrium within and between chromosomes. Despite this, GWA analysis readily detected common alleles of high penetrance. To investigate the potential of combining GWA mapping with comparative analysis to resolve traits to candidate polymorphism level in unsequenced genomes, we fine-mapped a selected phenotype (anthocyanin pigmentation) within a 140-kb interval containing three genes. Of these, resequencing the putative anthocyanin pathway gene HvbHLH1 identified a deletion resulting in a premature stop codon upstream of the basic helix-loop-helix domain, which was diagnostic for lack of anthocyanin in our association and biparental mapping populations. The methodology described here is transferable to species with limited genomic resources, providing a paradigm for reducing the threshold of map-based cloning in unsequenced crops.

AB - Although commonplace in human disease genetics, genome-wide association (GWA) studies have only relatively recently been applied to plants. Using 32 phenotypes in the inbreeding crop barley, we report GWA mapping of 15 morphological traits across ∼500 cultivars genotyped with 1,536 SNPs. In contrast to the majority of human GWA studies, we observe high levels of linkage disequilibrium within and between chromosomes. Despite this, GWA analysis readily detected common alleles of high penetrance. To investigate the potential of combining GWA mapping with comparative analysis to resolve traits to candidate polymorphism level in unsequenced genomes, we fine-mapped a selected phenotype (anthocyanin pigmentation) within a 140-kb interval containing three genes. Of these, resequencing the putative anthocyanin pathway gene HvbHLH1 identified a deletion resulting in a premature stop codon upstream of the basic helix-loop-helix domain, which was diagnostic for lack of anthocyanin in our association and biparental mapping populations. The methodology described here is transferable to species with limited genomic resources, providing a paradigm for reducing the threshold of map-based cloning in unsequenced crops.

UR - http://www.mendeley.com/research/genomewide-association-mapping-candidate-polymorphism-resolution-unsequenced-barley-genome

U2 - 10.1073/pnas.1010179107

DO - 10.1073/pnas.1010179107

M3 - Article

VL - 107

SP - 21611

EP - 21616

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 50

ER -