Candidate genes and genetic architecture of symbiotic and agronomic traits revealed by whole-genome, sequence-based association genetics in Medicago truncatula.

Genome-wide association study (GWAS) has revolutionized the search for the genetic basis of complex traits. To date, GWAS have generally relied on relatively sparse sampling of nucleotide diversity, which is likely to bias results by preferentially sampling high-frequency SNPs not in complete linkag...

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Autores principales:	John Stanton-Geddes, Timothy Paape, Brendan Epstein, Roman Briskine, Jeremy Yoder, Joann Mudge, Arvind K Bharti, Andrew D Farmer, Peng Zhou, Roxanne Denny, Gregory D May, Stephanie Erlandson, Mohammed Yakub, Masayuki Sugawara, Michael J Sadowsky, Nevin D Young, Peter Tiffin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a020c55984bd4830a1307e50ee1f0ab6
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spelling	oai:doaj.org-article:a020c55984bd4830a1307e50ee1f0ab62021-11-18T07:43:23ZCandidate genes and genetic architecture of symbiotic and agronomic traits revealed by whole-genome, sequence-based association genetics in Medicago truncatula.1932-620310.1371/journal.pone.0065688https://doaj.org/article/a020c55984bd4830a1307e50ee1f0ab62013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23741505/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Genome-wide association study (GWAS) has revolutionized the search for the genetic basis of complex traits. To date, GWAS have generally relied on relatively sparse sampling of nucleotide diversity, which is likely to bias results by preferentially sampling high-frequency SNPs not in complete linkage disequilibrium (LD) with causative SNPs. To avoid these limitations we conducted GWAS with >6 million SNPs identified by sequencing the genomes of 226 accessions of the model legume Medicago truncatula. We used these data to identify candidate genes and the genetic architecture underlying phenotypic variation in plant height, trichome density, flowering time, and nodulation. The characteristics of candidate SNPs differed among traits, with candidates for flowering time and trichome density in distinct clusters of high linkage disequilibrium (LD) and the minor allele frequencies (MAF) of candidates underlying variation in flowering time and height significantly greater than MAF of candidates underlying variation in other traits. Candidate SNPs tagged several characterized genes including nodulation related genes SERK2, MtnodGRP3, MtMMPL1, NFP, CaML3, MtnodGRP3A and flowering time gene MtFD as well as uncharacterized genes that become candidates for further molecular characterization. By comparing sequence-based candidates to candidates identified by in silico 250K SNP arrays, we provide an empirical example of how reliance on even high-density reduced representation genomic makers can bias GWAS results. Depending on the trait, only 30-70% of the top 20 in silico array candidates were within 1 kb of sequence-based candidates. Moreover, the sequence-based candidates tagged by array candidates were heavily biased towards common variants; these comparisons underscore the need for caution when interpreting results from GWAS conducted with sparsely covered genomes.John Stanton-GeddesTimothy PaapeBrendan EpsteinRoman BriskineJeremy YoderJoann MudgeArvind K BhartiAndrew D FarmerPeng ZhouRoxanne DennyGregory D MayStephanie ErlandsonMohammed YakubMasayuki SugawaraMichael J SadowskyNevin D YoungPeter TiffinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e65688 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q John Stanton-Geddes Timothy Paape Brendan Epstein Roman Briskine Jeremy Yoder Joann Mudge Arvind K Bharti Andrew D Farmer Peng Zhou Roxanne Denny Gregory D May Stephanie Erlandson Mohammed Yakub Masayuki Sugawara Michael J Sadowsky Nevin D Young Peter Tiffin Candidate genes and genetic architecture of symbiotic and agronomic traits revealed by whole-genome, sequence-based association genetics in Medicago truncatula.
description	Genome-wide association study (GWAS) has revolutionized the search for the genetic basis of complex traits. To date, GWAS have generally relied on relatively sparse sampling of nucleotide diversity, which is likely to bias results by preferentially sampling high-frequency SNPs not in complete linkage disequilibrium (LD) with causative SNPs. To avoid these limitations we conducted GWAS with >6 million SNPs identified by sequencing the genomes of 226 accessions of the model legume Medicago truncatula. We used these data to identify candidate genes and the genetic architecture underlying phenotypic variation in plant height, trichome density, flowering time, and nodulation. The characteristics of candidate SNPs differed among traits, with candidates for flowering time and trichome density in distinct clusters of high linkage disequilibrium (LD) and the minor allele frequencies (MAF) of candidates underlying variation in flowering time and height significantly greater than MAF of candidates underlying variation in other traits. Candidate SNPs tagged several characterized genes including nodulation related genes SERK2, MtnodGRP3, MtMMPL1, NFP, CaML3, MtnodGRP3A and flowering time gene MtFD as well as uncharacterized genes that become candidates for further molecular characterization. By comparing sequence-based candidates to candidates identified by in silico 250K SNP arrays, we provide an empirical example of how reliance on even high-density reduced representation genomic makers can bias GWAS results. Depending on the trait, only 30-70% of the top 20 in silico array candidates were within 1 kb of sequence-based candidates. Moreover, the sequence-based candidates tagged by array candidates were heavily biased towards common variants; these comparisons underscore the need for caution when interpreting results from GWAS conducted with sparsely covered genomes.
format	article
author	John Stanton-Geddes Timothy Paape Brendan Epstein Roman Briskine Jeremy Yoder Joann Mudge Arvind K Bharti Andrew D Farmer Peng Zhou Roxanne Denny Gregory D May Stephanie Erlandson Mohammed Yakub Masayuki Sugawara Michael J Sadowsky Nevin D Young Peter Tiffin
author_facet	John Stanton-Geddes Timothy Paape Brendan Epstein Roman Briskine Jeremy Yoder Joann Mudge Arvind K Bharti Andrew D Farmer Peng Zhou Roxanne Denny Gregory D May Stephanie Erlandson Mohammed Yakub Masayuki Sugawara Michael J Sadowsky Nevin D Young Peter Tiffin
author_sort	John Stanton-Geddes
title	Candidate genes and genetic architecture of symbiotic and agronomic traits revealed by whole-genome, sequence-based association genetics in Medicago truncatula.
title_short	Candidate genes and genetic architecture of symbiotic and agronomic traits revealed by whole-genome, sequence-based association genetics in Medicago truncatula.
title_full	Candidate genes and genetic architecture of symbiotic and agronomic traits revealed by whole-genome, sequence-based association genetics in Medicago truncatula.
title_fullStr	Candidate genes and genetic architecture of symbiotic and agronomic traits revealed by whole-genome, sequence-based association genetics in Medicago truncatula.
title_full_unstemmed	Candidate genes and genetic architecture of symbiotic and agronomic traits revealed by whole-genome, sequence-based association genetics in Medicago truncatula.
title_sort	candidate genes and genetic architecture of symbiotic and agronomic traits revealed by whole-genome, sequence-based association genetics in medicago truncatula.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/a020c55984bd4830a1307e50ee1f0ab6
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Candidate genes and genetic architecture of symbiotic and agronomic traits revealed by whole-genome, sequence-based association genetics in Medicago truncatula.

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