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Title: Genome-Wide Association Study Reveals Complex Genetic Architecture of Cadmium and Mercury Accumulation and Tolerance Traits in Medicago truncatula

Abstract

Heavy metals are an increasing problem due to contamination from human sources that and can enter the food chain by being taken up by plants. Understanding the genetic basis of accumulation and tolerance in plants is important for reducing the uptake of toxic metals in crops and crop relatives, as well as for removing heavy metals from soils by means of phytoremediation. Following exposure of Medicago truncatula seedlings to cadmium (Cd) and mercury (Hg), we conducted a genome-wide association study using relative root growth (RRG) and leaf accumulation measurements. Cd and Hg accumulation and RRG had heritability ranging 0.44 – 0.72 indicating high genetic diversity for these traits. The Cd and Hg trait associations were broadly distributed throughout the genome, indicated the traits are polygenic and involve several quantitative loci. For all traits, candidate genes included several membrane associated ATP-binding cassette transporters, P-type ATPase transporters, oxidative stress response genes, and stress related UDP-glycosyltransferases. The P-type ATPase transporters and ATP-binding cassette protein-families have roles in vacuole transport of heavy metals, and our findings support their wide use in physiological plant responses to heavy metals and abiotic stresses. We also found associations between Cd RRG with the genes CAX3 and PDR3, twomore » linked adjacent genes, and leaf accumulation of Hg associated with the genes NRAMP6 and CAX9. When plant genotypes with the most extreme phenotypes were compared, we found significant divergence in genomic regions using population genomics methods that contained metal transport and stress response gene ontologies. Several of these genomic regions show high linkage disequilibrium (LD) among candidate genes suggesting they have evolved together. Minor allele frequency (MAF) and effect size of the most significant SNPs was negatively correlated with large effect alleles being most rare. This is consistent with purifying selection against alleles that increase toxicity and abiotic stress. Conversely, the alleles with large affect that had higher frequencies that were associated with the exclusion of Cd and Hg. Overall, macroevolutionary conservation of heavy metal and stress response genes is important for improvement of forage crops by harnessing wild genetic variants in gene banks such as the Medicago HapMap collection.« less

Authors:
 [1];  [2];  [3];  [1];  [3];  [3]
  1. Brookhaven National Lab. (BNL), Upton, NY (United States)
  2. Univ. of Zurich (Switzerland)
  3. Inst. of Agricultural Sciences, ICA-CSIC, Madrid (Spain)
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
OSTI Identifier:
1844563
Report Number(s):
BNL-222704-2022-JAAM
Journal ID: ISSN 1664-462X
Grant/Contract Number:  
SC0012704
Resource Type:
Accepted Manuscript
Journal Name:
Frontiers in Plant Science
Additional Journal Information:
Journal Volume: 12; Journal ID: ISSN 1664-462X
Publisher:
Frontiers Research Foundation
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; cadmium; mercury; polygenic; standing variation; genetic architecture; Medicago truncatula

Citation Formats

Paape, Timothy, Heiniger, Benjamin, Domingo, Miguel Santo, Clear, Michael R., Lucas, M. Mercedes, and Pueyo, José J. Genome-Wide Association Study Reveals Complex Genetic Architecture of Cadmium and Mercury Accumulation and Tolerance Traits in Medicago truncatula. United States: N. p., 2022. Web. doi:10.3389/fpls.2021.806949.
Paape, Timothy, Heiniger, Benjamin, Domingo, Miguel Santo, Clear, Michael R., Lucas, M. Mercedes, & Pueyo, José J. Genome-Wide Association Study Reveals Complex Genetic Architecture of Cadmium and Mercury Accumulation and Tolerance Traits in Medicago truncatula. United States. https://doi.org/10.3389/fpls.2021.806949
Paape, Timothy, Heiniger, Benjamin, Domingo, Miguel Santo, Clear, Michael R., Lucas, M. Mercedes, and Pueyo, José J. Fri . "Genome-Wide Association Study Reveals Complex Genetic Architecture of Cadmium and Mercury Accumulation and Tolerance Traits in Medicago truncatula". United States. https://doi.org/10.3389/fpls.2021.806949. https://www.osti.gov/servlets/purl/1844563.
@article{osti_1844563,
title = {Genome-Wide Association Study Reveals Complex Genetic Architecture of Cadmium and Mercury Accumulation and Tolerance Traits in Medicago truncatula},
author = {Paape, Timothy and Heiniger, Benjamin and Domingo, Miguel Santo and Clear, Michael R. and Lucas, M. Mercedes and Pueyo, José J.},
abstractNote = {Heavy metals are an increasing problem due to contamination from human sources that and can enter the food chain by being taken up by plants. Understanding the genetic basis of accumulation and tolerance in plants is important for reducing the uptake of toxic metals in crops and crop relatives, as well as for removing heavy metals from soils by means of phytoremediation. Following exposure of Medicago truncatula seedlings to cadmium (Cd) and mercury (Hg), we conducted a genome-wide association study using relative root growth (RRG) and leaf accumulation measurements. Cd and Hg accumulation and RRG had heritability ranging 0.44 – 0.72 indicating high genetic diversity for these traits. The Cd and Hg trait associations were broadly distributed throughout the genome, indicated the traits are polygenic and involve several quantitative loci. For all traits, candidate genes included several membrane associated ATP-binding cassette transporters, P-type ATPase transporters, oxidative stress response genes, and stress related UDP-glycosyltransferases. The P-type ATPase transporters and ATP-binding cassette protein-families have roles in vacuole transport of heavy metals, and our findings support their wide use in physiological plant responses to heavy metals and abiotic stresses. We also found associations between Cd RRG with the genes CAX3 and PDR3, two linked adjacent genes, and leaf accumulation of Hg associated with the genes NRAMP6 and CAX9. When plant genotypes with the most extreme phenotypes were compared, we found significant divergence in genomic regions using population genomics methods that contained metal transport and stress response gene ontologies. Several of these genomic regions show high linkage disequilibrium (LD) among candidate genes suggesting they have evolved together. Minor allele frequency (MAF) and effect size of the most significant SNPs was negatively correlated with large effect alleles being most rare. This is consistent with purifying selection against alleles that increase toxicity and abiotic stress. Conversely, the alleles with large affect that had higher frequencies that were associated with the exclusion of Cd and Hg. Overall, macroevolutionary conservation of heavy metal and stress response genes is important for improvement of forage crops by harnessing wild genetic variants in gene banks such as the Medicago HapMap collection.},
doi = {10.3389/fpls.2021.806949},
journal = {Frontiers in Plant Science},
number = ,
volume = 12,
place = {United States},
year = {Fri Jan 28 00:00:00 EST 2022},
month = {Fri Jan 28 00:00:00 EST 2022}
}

Works referenced in this record:

Evolution of metal hyperaccumulation required cis-regulatory changes and triplication of HMA4
journal, April 2008

  • Hanikenne, Marc; Talke, Ina N.; Haydon, Michael J.
  • Nature, Vol. 453, Issue 7193
  • DOI: 10.1038/nature06877

Plant Peptides Govern Terminal Differentiation of Bacteria in Symbiosis
journal, February 2010


MtMTP2-Facilitated Zinc Transport Into Intracellular Compartments Is Essential for Nodule Development in Medicago truncatula
journal, July 2018

  • León-Mediavilla, Javier; Senovilla, Marta; Montiel, Jesús
  • Frontiers in Plant Science, Vol. 9
  • DOI: 10.3389/fpls.2018.00990

VariScan: Analysis of evolutionary patterns from large-scale DNA sequence polymorphism data
journal, April 2005


The NRAMP6 metal transporter contributes to cadmium toxicity
journal, August 2009

  • Cailliatte, Rémy; Lapeyre, Bruno; Briat, Jean-François
  • Biochemical Journal, Vol. 422, Issue 2
  • DOI: 10.1042/BJ20090655

The distribution of fitness effects of new mutations
journal, August 2007

  • Eyre-Walker, Adam; Keightley, Peter D.
  • Nature Reviews Genetics, Vol. 8, Issue 8
  • DOI: 10.1038/nrg2146

Fast model-based estimation of ancestry in unrelated individuals
journal, July 2009


The ABC transporter AtPDR8 is a cadmium extrusion pump conferring heavy metal resistance: Role of AtPDR8 in cadmium resistance
journal, March 2007


Heavy Metal Toxicity and the Environment
book, January 2012


Biochemical Effects of Mercury, Cadmium, and Lead
journal, June 1972


WhoGEM: an admixture-based prediction machine accurately predicts quantitative functional traits in plants
journal, May 2019


Nramp5 Is a Major Transporter Responsible for Manganese and Cadmium Uptake in Rice
journal, May 2012


The NRAMP family of metal-ion transporters
journal, July 2006

  • Nevo, Yaniv; Nelson, Nathan
  • Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1763, Issue 7
  • DOI: 10.1016/j.bbamcr.2006.05.007

The Medicago genome provides insight into the evolution of rhizobial symbioses
journal, November 2011

  • Young, Nevin D.; Debellé, Frédéric; Oldroyd, Giles E. D.
  • Nature, Vol. 480, Issue 7378
  • DOI: 10.1038/nature10625

GAPIT: genome association and prediction integrated tool
journal, July 2012


Cadmium-Tolerant and -Sensitive Cultivars Identified by Screening of Medicago truncatula Germplasm Display Contrasting Responses to Cadmium Stress
journal, March 2021

  • García de la Torre, Vanesa S.; Coba de la Peña, Teodoro; Pueyo, José J.
  • Frontiers in Plant Science, Vol. 12
  • DOI: 10.3389/fpls.2021.595001

Genome‐wide association mapping of cadmium accumulation in different organs of barley
journal, June 2015

  • Wu, Dezhi; Sato, Kazuhiro; Ma, Jian Feng
  • New Phytologist, Vol. 208, Issue 3
  • DOI: 10.1111/nph.13512

Integrative genomics viewer
journal, January 2011

  • Robinson, James T.; Thorvaldsdóttir, Helga; Winckler, Wendy
  • Nature Biotechnology, Vol. 29, Issue 1
  • DOI: 10.1038/nbt.1754

Divalent Metal Ions in Plant Mitochondria and Their Role in Interactions with Proteins and Oxidative Stress-Induced Damage to Respiratory Function
journal, December 2009

  • Tan, Yew-Foon; O'Toole, Nicholas; Taylor, Nicolas L.
  • Plant Physiology, Vol. 152, Issue 2
  • DOI: 10.1104/pp.109.147942

An inventory of heavy metals inputs to agricultural soils in England and Wales
journal, July 2003


Selection, genome-wide fitness effects and evolutionary rates in the model legume Medicago truncatula
journal, June 2013

  • Paape, Timothy; Bataillon, Thomas; Zhou, Peng
  • Molecular Ecology, Vol. 22, Issue 13
  • DOI: 10.1111/mec.12329

Soft Sweeps: Molecular Population Genetics of Adaptation From Standing Genetic Variation
journal, February 2005


Phytoremediation: A Promising Approach for Revegetation of Heavy Metal-Polluted Land
journal, April 2020


Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration
journal, April 2012

  • Thorvaldsdottir, H.; Robinson, J. T.; Mesirov, J. P.
  • Briefings in Bioinformatics, Vol. 14, Issue 2, p. 178-192
  • DOI: 10.1093/bib/bbs017

TASSEL: software for association mapping of complex traits in diverse samples
journal, June 2007


Combining population genomics and quantitative genetics: finding the genes underlying ecologically important traits
journal, February 2007


Fine-Scale Population Recombination Rates, Hotspots, and Correlates of Recombination in the Medicago truncatula Genome
journal, January 2012

  • Paape, Timothy; Zhou, Peng; Branca, Antoine
  • Genome Biology and Evolution, Vol. 4, Issue 5
  • DOI: 10.1093/gbe/evs046

Quantitative Trait Loci for Mercury Tolerance in Rice Seedlings
journal, May 2013


Current status of cadmium as an environmental health problem
journal, August 2009


MTGD: The Medicago truncatula Genome Database
journal, November 2014

  • Krishnakumar, Vivek; Kim, Maria; Rosen, Benjamin D.
  • Plant and Cell Physiology, Vol. 56, Issue 1
  • DOI: 10.1093/pcp/pcu179

The role of heavy-metal ATPases, HMAs, in zinc and cadmium transport in rice
journal, December 2012

  • Takahashi, Ryuichi; Bashir, Khurram; Ishimaru, Yasuhiro
  • Plant Signaling & Behavior, Vol. 7, Issue 12
  • DOI: 10.4161/psb.22454

Genotype Imputation with Millions of Reference Samples
journal, January 2016

  • Browning, Brian L.; Browning, Sharon R.
  • The American Journal of Human Genetics, Vol. 98, Issue 1
  • DOI: 10.1016/j.ajhg.2015.11.020

The phytochelatin transporters AtABCC1 and AtABCC2 mediate tolerance to cadmium and mercury
journal, October 2011


Evolution and diversity of the 2-oxoglutarate-dependent dioxygenase superfamily in plants
journal, April 2014

  • Kawai, Yosuke; Ono, Eiichiro; Mizutani, Masaharu
  • The Plant Journal, Vol. 78, Issue 2
  • DOI: 10.1111/tpj.12479

Heavy metal-associated isoprenylated plant protein (HIPP): characterization of a family of proteins exclusive to plants
journal, February 2013

  • de Abreu-Neto, João Braga; Turchetto-Zolet, Andreia C.; de Oliveira, Luiz Felipe Valter
  • FEBS Journal, Vol. 280, Issue 7
  • DOI: 10.1111/febs.12159

Validating Genome-Wide Association Candidates Controlling Quantitative Variation in Nodulation
journal, January 2017

  • Curtin, Shaun J.; Tiffin, Peter; Guhlin, Joseph
  • Plant Physiology, Vol. 173, Issue 2
  • DOI: 10.1104/pp.16.01923

Rapid screening of Medicago truncatula germplasm for mercury tolerance at the seedling stage
journal, July 2013

  • García de la Torre, Vanesa S.; Coba de la Peña, Teodoro; Lucas, M. Mercedes
  • Environmental and Experimental Botany, Vol. 91
  • DOI: 10.1016/j.envexpbot.2013.03.004

The variant call format and VCFtools
journal, June 2011


Association mapping reveals the role of purifying selection in the maintenance of genomic variation in gene expression
journal, November 2015

  • Josephs, Emily B.; Lee, Young Wha; Stinchcombe, John R.
  • Proceedings of the National Academy of Sciences, Vol. 112, Issue 50
  • DOI: 10.1073/pnas.1503027112

Comparisons of heavy metal input inventory in agricultural soils in North and South China: A review
journal, April 2019


The biochemistry of environmental heavy metal uptake by plants: Implications for the food chain
journal, August 2009

  • Peralta-Videa, Jose R.; Lopez, Martha Laura; Narayan, Mahesh
  • The International Journal of Biochemistry & Cell Biology, Vol. 41, Issue 8-9
  • DOI: 10.1016/j.biocel.2009.03.005

agriGO: a GO analysis toolkit for the agricultural community
journal, April 2010

  • Du, Zhou; Zhou, Xin; Ling, Yi
  • Nucleic Acids Research, Vol. 38, Issue suppl_2
  • DOI: 10.1093/nar/gkq310

Metal Hyperaccumulation in Plants
journal, June 2010


The Role of CAX1 and CAX3 in Elemental Distribution and Abundance in Arabidopsis Seed
journal, November 2011

  • Punshon, Tracy; Hirschi, Kendal; Yang, Jian
  • Plant Physiology, Vol. 158, Issue 1
  • DOI: 10.1104/pp.111.184812

The Five AhMTP1 Zinc Transporters Undergo Different Evolutionary Fates towards Adaptive Evolution to Zinc Tolerance in Arabidopsis halleri
journal, April 2010


Experimental and Field Data Support Range Expansion in an Allopolyploid Arabidopsis Owing to Parental Legacy of Heavy Metal Hyperaccumulation
journal, September 2020


Modeling of Dolichol Mass Spectra Isotopic Envelopes as a Tool to Monitor Isoprenoid Biosynthesis
journal, April 2017

  • Jozwiak, Adam; Lipko, Agata; Kania, Magdalena
  • Plant Physiology, Vol. 174, Issue 2
  • DOI: 10.1104/pp.17.00036

Whole-genome nucleotide diversity, recombination, and linkage disequilibrium in the model legume Medicago truncatula
journal, September 2011

  • Branca, A.; Paape, T. D.; Zhou, P.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 42
  • DOI: 10.1073/pnas.1104032108

Genome-wide efficient mixed-model analysis for association studies
journal, June 2012

  • Zhou, Xiang; Stephens, Matthew
  • Nature Genetics, Vol. 44, Issue 7
  • DOI: 10.1038/ng.2310

Understanding quantitative genetic variation
journal, January 2002

  • Barton, Nicholas H.; Keightley, Peter D.
  • Nature Reviews Genetics, Vol. 3, Issue 1
  • DOI: 10.1038/nrg700

AtHMA3, a P 1B -ATPase Allowing Cd/Zn/Co/Pb Vacuolar Storage in Arabidopsis
journal, November 2008

  • Morel, Mélanie; Crouzet, Jérôme; Gravot, Antoine
  • Plant Physiology, Vol. 149, Issue 2
  • DOI: 10.1104/pp.108.130294

Glycine-Rich Proteins Encoded by a Nodule-Specific Gene Family Are Implicated in Different Stages of Symbiotic Nodule Development in Medicago Spp.
journal, September 2002

  • Kevei, Zoltán; Vinardell, José María; Kiss, György B.
  • Molecular Plant-Microbe Interactions®, Vol. 15, Issue 9
  • DOI: 10.1094/MPMI.2002.15.9.922

Massive genomic variation and strong selection in Arabidopsis thaliana lines from Sweden
journal, June 2013

  • Long, Quan; Rabanal, Fernando A.; Meng, Dazhe
  • Nature Genetics, Vol. 45, Issue 8
  • DOI: 10.1038/ng.2678

A functional genomics approach to (iso)flavonoid glycosylation in the model legume Medicago truncatula
journal, April 2007

  • Modolo, Luzia V.; Blount, Jack W.; Achnine, Lahoucine
  • Plant Molecular Biology, Vol. 64, Issue 5
  • DOI: 10.1007/s11103-007-9167-6

Plant-lead interactions: Transport, toxicity, tolerance, and detoxification mechanisms
journal, December 2018


Overexpression of PtABCC1 contributes to mercury tolerance and accumulation in Arabidopsis and poplar
journal, March 2018

  • Sun, Liping; Ma, Yifeng; Wang, Huihong
  • Biochemical and Biophysical Research Communications, Vol. 497, Issue 4
  • DOI: 10.1016/j.bbrc.2018.02.133

What can genome‐wide association studies tell us about the evolutionary forces maintaining genetic variation for quantitative traits?
journal, February 2017

  • Josephs, Emily B.; Stinchcombe, John R.; Wright, Stephen I.
  • New Phytologist, Vol. 214, Issue 1
  • DOI: 10.1111/nph.14410

Heavy Metal Detoxification in Plants: Phytochelatin Biosynthesis and Function
journal, March 2001

  • Cobbett, Christopher S.
  • IUBMB Life (International Union of Biochemistry and Molecular Biology: Life), Vol. 51, Issue 3
  • DOI: 10.1080/152165401753544250

Cadmium-inducible expression of the ABC-type transporter AtABCC3 increases phytochelatin-mediated cadmium tolerance in Arabidopsis
journal, April 2015

  • Brunetti, Patrizia; Zanella, Letizia; De Paolis, Angelo
  • Journal of Experimental Botany, Vol. 66, Issue 13
  • DOI: 10.1093/jxb/erv185

Identification of novel rice (Oryza sativa) HPP and HIPP genes tolerant to heavy metal toxicity
journal, July 2019

  • khan, Irfan ullah; Rono, Justice Kipkoir; Zhang, Bai Qing
  • Ecotoxicology and Environmental Safety, Vol. 175
  • DOI: 10.1016/j.ecoenv.2019.03.040

The Multifaceted Roles of Plant Vacuoles
journal, June 2018

  • Martinoia, Enrico; Mimura, Tetsuro; Hara-Nishimura, Ikuko
  • Plant and Cell Physiology
  • DOI: 10.1093/pcp/pcy113

Functional Association of Arabidopsis CAX1 and CAX3 Is Required for Normal Growth and Ion Homeostasis
journal, July 2005

  • Cheng, Ning-Hui; Pittman, Jon K.; Shigaki, Toshiro
  • Plant Physiology, Vol. 138, Issue 4
  • DOI: 10.1104/pp.105.061218

Genome-wide association analysis identifies loci governing mercury accumulation in maize
journal, March 2017


High‐density genome‐wide association mapping implicates an F ‐box encoding gene in M edicago truncatula resistance to A phanomyces euteiches
journal, November 2013

  • Bonhomme, Maxime; André, Olivier; Badis, Yacine
  • New Phytologist, Vol. 201, Issue 4
  • DOI: 10.1111/nph.12611

Adaptation from standing genetic variation
journal, January 2008


Legumes in the reclamation of marginal soils, from cultivar and inoculant selection to transgenic approaches
journal, March 2011

  • Coba de la Peña, Teodoro; Pueyo, José J.
  • Agronomy for Sustainable Development, Vol. 32, Issue 1
  • DOI: 10.1007/s13593-011-0024-2

Second-generation PLINK: rising to the challenge of larger and richer datasets
journal, February 2015


Metallochaperone-like genes in Arabidopsis thaliana
journal, January 2010

  • Tehseen, Muhammad; Cairns, Narelle; Sherson, Sarah
  • Metallomics, Vol. 2, Issue 8
  • DOI: 10.1039/c003484c

Genome-Wide Association Study of Cadmium Accumulation at the Seedling Stage in Rapeseed (Brassica napus L.)
journal, April 2018


Toxic Heavy Metal and Metalloid Accumulation in Crop Plants and Foods
journal, April 2016


High-Affinity Manganese Uptake by the Metal Transporter NRAMP1 Is Essential for Arabidopsis Growth in Low Manganese Conditions
journal, March 2010

  • Cailliatte, Rémy; Schikora, Adam; Briat, Jean-François
  • The Plant Cell, Vol. 22, Issue 3
  • DOI: 10.1105/tpc.109.073023

BLAST+: architecture and applications
journal, January 2009

  • Camacho, Christiam; Coulouris, George; Avagyan, Vahram
  • BMC Bioinformatics, Vol. 10, Issue 1
  • DOI: 10.1186/1471-2105-10-421

Oxidative injury and antioxidant genes regulation in cadmium-exposed radicles of six contrasted Medicago truncatula genotypes
journal, March 2014

  • Rahoui, Sondès; Ben, Cécile; Chaoui, Abdelilah
  • Environmental Science and Pollution Research, Vol. 21, Issue 13
  • DOI: 10.1007/s11356-014-2718-x

Population differentiation as a test for selective sweeps
journal, January 2010


Arabidopsis thaliana acyl‐CoA‐binding protein ACBP2 interacts with heavy‐metal‐binding farnesylated protein AtFP6
journal, December 2008


Genome‐wide association analysis of salinity responsive traits in Medicago truncatula
journal, January 2019

  • Kang, Yun; Torres‐Jerez, Ivone; An, Zewei
  • Plant, Cell & Environment, Vol. 42, Issue 5
  • DOI: 10.1111/pce.13508

An improved genome release (version Mt4.0) for the model legume Medicago truncatula
journal, January 2014


LDheatmap : An R Function for Graphical Display of Pairwise Linkage Disequilibria Between Single Nucleotide Polymorphisms
journal, January 2006

  • Shin, Ji-Hyung; Blay, Sigal; Graham, Jinko
  • Journal of Statistical Software, Vol. 16, Issue Code Snippet 3
  • DOI: 10.18637/jss.v016.c03

Mercury Toxicity and Treatment: A Review of the Literature
journal, January 2012

  • Bernhoft, Robin A.
  • Journal of Environmental and Public Health, Vol. 2012
  • DOI: 10.1155/2012/460508

Genetics in geographically structured populations: defining, estimating and interpreting FST
journal, September 2009

  • Holsinger, Kent E.; Weir, Bruce S.
  • Nature Reviews Genetics, Vol. 10, Issue 9
  • DOI: 10.1038/nrg2611

Plasma membrane-localized transporter for aluminum in rice
journal, October 2010

  • Xia, J.; Yamaji, N.; Kasai, T.
  • Proceedings of the National Academy of Sciences, Vol. 107, Issue 43
  • DOI: 10.1073/pnas.1004949107

GAPIT Version 2: An Enhanced Integrated Tool for Genomic Association and Prediction
journal, January 2016