Deciphering the genetic control of flowering and ripening periods in apple is essential for breeding cultivars adapted to their growing environments. We implemented a large Genome-Wide Association Study (GWAS) at the European level using an association panel of 1,168 different apple genotypes distributed over six locations and phenotyped for these phenological traits. The panel was genotyped at a high-density of SNPs using the Axiom®Apple 480 K SNP array. We ran GWAS with a multi-locus mixed model (MLMM), which handles the putatively confounding effect of significant SNPs elsewhere on the genome. Genomic regions were further investigated to reveal candidate genes responsible for the phenotypic variation. At the whole population level, GWAS retained two SNPs as cofactors on chromosome 9 for flowering period, and six for ripening period (four on chromosome 3, one on chromosome 10 and one on chromosome 16) which, together accounted for 8.9 and 17.2% of the phenotypic variance, respectively. For both traits, SNPs in weak linkage disequilibrium were detected nearby, thus suggesting the existence of allelic heterogeneity. The geographic origins and relationships of apple cultivars accounted for large parts of the phenotypic variation. Variation in genotypic frequency of the SNPs associated with the two traits was connected to the geographic origin of the genotypes (grouped as North+East, West and South Europe), and indicated differential selection in different growing environments. Genes encoding transcription factors containing either NAC or MADS domains were identified as major candidates within the small confidence intervals computed for the associated genomic regions. A strong microsynteny between apple and peach was revealed in all the four confidence interval regions. This study shows how association genetics can unravel the genetic control of important horticultural traits in apple, as well as reduce the confidence intervals of the associated regions identified by linkage mapping approaches. Our findings can be used for the improvement of apple through marker-assisted breeding strategies that take advantage of the accumulating additive effects of the identified SNPs.

Apple Research Station Institute of Fruit Tree and Tea Science National Agriculture and Food Research Organization Morioka Japan

Department of Agricultural Sciences Public University of Navarre Pamplona Spain

Department of Agricultural Sciences University of Bologna Bologna Italy

Department of Plant Breeding Swedish University of Agricultural Sciences Alnarp Sweden

Department of Plant Breeding Swedish University of Agricultural Sciences Kristianstad Sweden

Fondazione Edmund Mach San Michele all'Adige Italy

Hendrix Genetics Boxmeer Netherlands

Institut de Recherche en Horticulture et Semences UMR 1345 INRA SFR 4207 QUASAV Beaucouzé France

Plant Breeding and Biodiversity Centre Wallon de Recherches Agronomiques Gembloux Belgium

Plateforme Gentyane INRA UMR 1095 Genetics Diversity and Ecophysiology of Cereals Clermont Ferrand France

Research and Breeding Institute of Pomology Holovousy Ltd Horice Czechia

School of Agriculture Policy and Development University of Reading Reading United Kingdom

Wageningen UR Biometris Wageningen Netherlands

Zobrazit více v PubMed

Abbott A. G., Zhebentyayeva T., Barakat A., Liu Z. (2015). The genetic control of bud-break in trees, in Advances in Botanical Research, Vol. 74, eds Christophe P., Anne-Françoise A. B. (San Diego, CA: Academic Press; ), 201–228.

Allard A., Legave J. M., Martinez S., Kelner J. J., Bink M. C. A. M., Di Guardo M., et al. . (2016). Detecting QTLs and putative candidate genes involved in budbreak and flowering time in an apple multiparental population. J. Exp. Bot. 67, 2875–2888. 10.1093/jxb/erw130 PubMed DOI PMC

Amasino R. M. (2005). Vernalization and flowering time. Curr. Opin. Biotechnol. 16, 154–158. 10.1016/j.copbio.2005.02.004 PubMed DOI

Amasino R. M., Michaels S. D. (2010). The timing of flowering. Plant Physiol. 154, 516–520. 10.1104/pp.110.161653 PubMed DOI PMC

An X. H., Hao Y. J., Li E. M., Xu K., Cheng C. G. (2016). Functional identification of apple MdJAZ2 in Arabidopsis with reduced JA-sensitivity and increased stress tolerance. Plant Cell Rep. 36, 255–265. 10.1007/s00299-016-2077-9 PubMed DOI

Aranzana M. J., Kim S., Zhao K., Bakker E., Horton M., Jakob K., et al. . (2005). Genome-wide association mapping in Arabidopsis identifies previously known flowering time and pathogen resistance genes. PLoS Genet. 1:e60. 10.1371/journal.pgen.0010060 PubMed DOI PMC

Atwell S., Huang Y. S., Vilhjálmsson B. J., Willems G., Horton M., Li Y., et al. . (2010). Genome-wide association study of 107 phenotypes in Arabidopsis thaliana inbred lines. Nature 465, 627–631. 10.1038/nature08800 PubMed DOI PMC

Balding D. J. (2006). A tutorial on statistical methods for population association studies. Nat. Rev. Genet. 7, 781–791. 10.1038/nrg1916 PubMed DOI

Bates D. M., Sarkar D. (2007). lme4: Linear Mixed-effects Models using S4 Classes. R package version 0.99875–99876.

Bianco L., Cestaro A., Linsmith G., Muranty H., Denancé C., Théron A., et al. (2016). Development and validation of the Axiom®Apple 480 K SNP genotyping array. Plant J. 86, 62–74. 10.1111/tpj.13145 PubMed DOI

Bianco L., Cestaro A., Sargent D. J., Banchi E., Derdak S., Di Guardo M., et al. . (2014). Development and validation of a 20K single nucleotide polymorphism (SNP) whole genome genotyping array for apple (Malus × domestica Borkh). PLoS ONE 9:e110377. 10.1371/journal.pone.0110377 PubMed DOI PMC

Bielenberg D. G., Wang Y., Li Z., Zhebentyayeva T., Fan S., Reighard G. L., et al. (2008). Sequencing and annotation of the evergrowing locus in peach (Prunus Persica [L.] Batsch) reveals a cluster of six MADS-box transcription factors as candidate genes for regulation of terminal bud formation. Tree Genet. Genomes 4, 495–507. 10.1007/s11295-007-0126-9 DOI

Boss P. K., Bastow R. M., Mylne J. S., Dean C. (2004). Multiple pathways in the decision to flower: enabling, promoting, and resetting. Plant Cell 16, S18–S31. 10.1105/tpc.015958 PubMed DOI PMC

Brachi B., Morris G. P., Borevitz J. O. (2011). Genome-wide association studies in plants: the missing heritability is in the field. Genome Biol. 12:232. 10.1186/gb-2011-12-10-232 PubMed DOI PMC

Busov V. B., Brunner A. M., Meilan R., Filichkin S., Ganio L., Gandhi S., et al. . (2005). Genetic transformation: a powerful tool for dissection of adaptive traits in trees. New Phytol. 167, 9–74. 10.1111/j.1469-8137.2005.01412.x PubMed DOI

Campoy J. A., Ruiz D., Egea J. (2011). Dormancy in temperate fruit trees in a global warming context: a review. Sci. Hortic. 130, 357–372. 10.1016/j.scienta.2011.07.011 DOI

Cannell M. G. R., Smith R. I. (1986). Climate warming, spring budburst and frost damage on trees. J. Appl. Ecol. 23, 177–191. 10.2307/2403090 DOI

Castède S., Campoy J. A., Quero-García J., Le Dantec L., Lafargue M., Barreneche T., et al. . (2014). Genetic determinism of phenological traits highly affected by climate change in Prunus avium: flowering date dissected into chilling and heat requirements. New Phytol. 202, 703–715. 10.1111/nph.12658 PubMed DOI

Celton J. M., Martinez S., Jammes M. J., Bechti A., Salvi S., Legave J. M., et al. . (2011). Deciphering the genetic determinism of bud phenology in apple progenies: a new insight into chilling and heat requirement effects on flowering dates and positional candidate genes. New Phytol. 192, 378–392. 10.1111/j.1469-8137.2011.03823.x PubMed DOI

Chagné D., Crowhurst R. N., Troggio M., Davey M. W., Gilmore B., Lawley C., et al. . (2012). Genome-wide SNP detection, validation, and development of an 8K SNP array for apple. PLoS ONE 7:e31745. 10.1371/journal.pone.0031745 PubMed DOI PMC

Chagné D., Dayatilake D., Diack R., Oliver M., Ireland H., Watson A., et al. . (2014). Genetic and environmental control of fruit maturation, dry matter and firmness in apple (Malus × domestica Borkh.). Hortic. Res. 1:14046. 10.1038/hortres.2014.46 PubMed DOI PMC

Chen J., Chen Z. (2008). Extended Bayesian information criteria for model selection with large model space. Biometrika 95, 759–771. 10.1093/biomet/asn034 DOI

Chen M., Tan Q., Sun M., Li D., Fu X., Chen X., et al. . (2016). Genome-wide identification of WRKY family genes in peach and analysis of WRKY expression during bud dormancy. Mol. Genet. Genomics 291, 1319–1332. 10.1007/s00438-016-1171-6 PubMed DOI PMC

Cook B. I., Wolkovich E. M., Parmesan C. (2012). Divergent responses to spring and winter warming drive community level flowering trends. Proc. Natl. Acad. Sci. U.S.A. 109, 9000–9005. 10.1073/pnas.1118364109 PubMed DOI PMC

Daccord N., Celton J. M., Linsmith G., Becker C., Choisne N., Schijlen E., et al. . (2017). High-quality de novo assembly of the apple genome and methylome dynamics of early fruit development. Nat. Genet. 49, 1099–1106. 10.1038/ng.3886 PubMed DOI

Dickson S. P., Wang K., Krantz I., Hakonarson H., Goldstein D. B. (2010). Rare variants create synthetic genome-wide associations. PLoS Biol. 8:e1000294. 10.1371/journal.pbio.1000294 PubMed DOI PMC

Di Guardo M., Bink M. C. A. M., Guerra W., Letschka T., Lozano L., Busatto N., et al. . (2017). Deciphering the genetic control of fruit texture in apple by multiple family-based analysis and genome-wide association. J. Exp. Bot. 68, 1451–1466. 10.1093/jxb/erx017 PubMed DOI PMC

Dirlewanger E., Quero-Garcia J., Le Dantec L., Lambert P., Ruiz D., Dondini L., et al. . (2012). Comparison of the genetic determinism of two key phenological traits, flowering and maturity dates, in three Prunus species: peach, apricot and sweet cherry. Heredity 109, 280–292. 10.1038/hdy.2012.38 PubMed DOI PMC

Ensminger I., Schmidt L., Lloyd J. (2008). Soil temperature and intermittent frost modulate the rate of recovery of photosynthesis in Scots pine under simulated spring conditions. New Phytol. 177, 428–442. 10.1111/j.1469-8137.2007.02273.x PubMed DOI

Erez A. (2000). Bud dormancy; phenomenon, problems and solutions in the tropics and subtropics, in Temperate Fruit Crops in Warm Climates, ed Erez A. (Dordrecht: Kluwer Academic Publishers; ), 17–48. 10.1007/978-94-017-3215-4_2 DOI

Farneti B., Di Guardo M., Khomenko I., Cappellin L., Biasioli F., Velasco R., et al. . (2017). Genome-wide association study unravels the genetic control of the apple volatilome and its interplay with fruit texture. J. Exp. Bot. 68, 1467–1478. 10.1093/jxb/erx018 PubMed DOI PMC

Fleckinger J. (1964). Phénologie et arboriculture fruitière, in Le bon jardinier, (Tome I, 2éme partie), eds Grisvard P., Chaudun V. C. (La Maison Rustique: ), 362–372.

Flint-Garcia S. A., Thuillet A., Yu J., Pressoir G., Romero S. M., Mitchell S. E., et al. . (2005). Maize association population: a high-resolution platform for quantitative trait locus dissection. Plant J. 44, 1054–1064. 10.1111/j.1365-313X.2005.02591.x PubMed DOI

Fox J. (2003). Effect displays in R for generalised linear models. J. Stat. Soft. 8, 1–27. 10.18637/jss.v008.i15 DOI

Gardner K. M., Brown P., Cooke T. F., Cann S., Costa F., Bustamante C., et al. . (2014). Fast and cost-effective genetic mapping in apple using next-generation sequencing. G3 4, 1681–1687. 10.1534/g3.114.011023 PubMed DOI PMC

Gibson G. (2011). Rare and common variants: twenty arguments. Nat. Rev. Genet. 13, 135–145. 10.1038/nrg3118 PubMed DOI PMC

Hänninen H., Tanino K. (2011). Tree seasonality in a warming climate. Trends Plant Sci. 16, 412–416. 10.1016/j.tplants.2011.05.001 PubMed DOI

Hayes B. (2013). Overview of statistical methods for Genome-Wide Association Studies (GWAS). Methods Mol. Biol. 1019, 149–169. 10.1007/978-1-62703-447-0_6 PubMed DOI

Hedley P. E., Russell J. R., Jorgensen L., Gordon S., Morris J. A., Hackett C. A., et al. . (2010). Candidate genes associated with bud dormancy release in blackcurrant (Ribes nigrum L.). BMC Plant Biol. 10:202. 10.1186/1471-2229-10-202 PubMed DOI PMC

Horvath D. P., Chao W. S., Suttle J. C., Thimmapuram J., Anderson J. V. (2008). Transcriptome analysis identifies novel responses and potential regulatory genes involved in seasonal dormancy transitions of leafy spurge (Euphorbia esula L.). BMC Genomics 9:536. 10.1186/1471-2164-9-536 PubMed DOI PMC

Horvath D. P., Sung S., Kim D., Chao W., Anderson J. (2010). Characterization, expression and function of DORMANCY ASSOCIATED MADS-BOX genes from leafy spurge. Plant Mol. Biol. 73, 169–179. 10.1007/s11103-009-9596-5 PubMed DOI

Ingvarsson P. K., Street N. R. (2011). Association genetics of complex traits in plants. New Phytol. 189, 909–922. 10.1111/j.1469-8137.2010.03593.x PubMed DOI

Ionescu I. A., Moller B. L., Sánchez-Pérez R. (2017). Chemical control of flowering time. J. Exp. Bot. 68, 369–382. 10.1093/jxb/erw427 PubMed DOI

Jansen R. C., Jannink J. L., Beavis W. D. (2003). Mapping quantitative trait loci in plant breeding populations: use of parental haplotype sharing. Crop Sci. 43, 829–834. 10.2135/cropsci2003.8290 DOI

Jerzmanowski A. (2007). SWI/SNF chromatin remodeling and linker histones in plants. Biochim. Biophys. Acta 1769, 330–345. 10.1016/j.bbaexp.2006.12.003 PubMed DOI

Johnston J. W., Gunaseelan K., Pidakala P., Wang M., Schaffer R. J. (2009). Co-ordination of early and late ripening events in apples is regulated through differential sensitivities to ethylene. J. Exp. Bot. 60, 2689–2699. 10.1093/jxb/erp122 PubMed DOI PMC

Jung C., Pillen K., Staiger D., Coupland G., von Korff M. (2017). Editorial: recent advances in flowering time control. Front. Plant Sci. 7:2011. 10.3389/fpls.2016.02011 PubMed DOI PMC

Karlova R., Chapman N., David K., Angenent G. C., Seymour G. B., de Maagd R. A. (2014). Transcriptional control of fleshy fruit development and ripening. J. Exp. Bot. 65, 4527–4541. 10.1093/jxb/eru316 PubMed DOI

Kenis K., Keulemans J., Davey M. W. (2008). Identification and stability of QTLs for fruit quality traits in apple. Tree Genet. Genomes 4, 647–661. 10.1007/s11295-008-0140-6 DOI

Korte A., Farlow A. (2013). The advantages and limitations of trait analysis with GWAS: a review. Plant Methods 9:29. 10.1186/1746-4811-9-29 PubMed DOI PMC

Kou X., Liu C., Han L., Wang S., Xue Z. (2016). NAC transcription factors play an important role in ethylene biosynthesis, reception and signaling of tomato fruit ripening. Mol. Genet. Genomics 291, 1205–1217. 10.1007/s00438-016-1177-0 PubMed DOI

Kunihisa M., Moriya S., Abe K., Okada K., Haji T., Hayashi T., et al. . (2014). Identification of QTLs for fruit quality traits in Japanese apples: QTLs for early ripening are tightly related to preharvest fruit drop. Breed. Sci. 64, 240–251. 10.1270/jsbbs.64.240 PubMed DOI PMC

Lasky J. R., Upadhyaya H. D., Ramu P., Deshpande S., Hash C. T., Bonnette J., et al. . (2015). Genome-environment associations in sorghum landraces predict adaptive traits. Sci. Adv. 1, 1–13. 10.1126/sciadv.1400218 PubMed DOI PMC

Laurens F., Aranzana M. J., Arús P., Bassi D., Bonany J., Corelli L., et al. (2012). Review of fruit genetics and breeding programmes and a new European initiative to increase fruit breeding efficiency. Acta Hortic. 929, 95–102. 10.17660/ActaHortic.2012.929.12 DOI

Leforestier D., Ravon E., Muranty H., Cornille A., Lemaire C., Giraud T., et al. . (2015). Genomic basis of the differences between cider and dessert apple varieties. Evol. Appl. 8, 650–661. 10.1111/eva.12270 PubMed DOI PMC

Lê S., Josse J., Husson F. (2008). FactoMineR: an R package for multivariate analysis. J. Stat. Soft. 25, 1–18. 10.18637/jss.v025.i01 DOI

Li X., Yin X., Wang H., Li J., Guo C., Gao H., et al. (2015). Genome-wide identification and analysis of the apple (Malus × domestica Borkh.) TIFY gene family. Tree Genet. Genomes 11, 1–13. 10.1007/s11295-014-0808-z DOI

Licausi F., Giorgi F. M., Zenoni S., Ost F., Pezzotti M., Perata P. (2010). Genomic and transcriptomic analysis of the AP2/ERF superfamily in Vitis vinifera. BMC Genomics 11:719. 10.1186/1471-2164-11-719 PubMed DOI PMC

Liebhard R., Kellerhals M., Pfammatter W., Jertmini M., Gessler C. (2003). Mapping quantitative physiological traits in apple (Malus × domestica Borkh.). Plant Mol. Biol. 52, 511–526. 10.1023/A:1024886500979 PubMed DOI

Lv J., Rao J., Johnson F., Shin S., Zhu Y. (2015). Genome-wide identification of jasmonate biosynthetic genes and characterization of their expression profiles during apple (Malus × domestica) fruit maturation. Plant Growth Reg. 75, 355–364. 10.1007/s10725-014-9958-0 DOI

Maher B. (2008). Personal genomes: the case of the missing heritability. Nature 456, 18–21. 10.1038/456018a PubMed DOI

Mangin B., Siberchicot A., Nicolas S., Doligez A., This P., Cierco-Ayrolles C. (2012). Novel measures of linkage disequilibrium that correct the bias due to population structure and relatedness. Heredity 108, 285–291. 10.1038/hdy.2011.73 PubMed DOI PMC

Manolio T. A., Collins F. S., Cox N. J., Goldstein D. B., Hindorff L. A., Hunter D. J., et al. . (2009). Finding the missing heritability of complex diseases. Nature 461, 747–753. 10.1038/nature08494 PubMed DOI PMC

Mariette S., Tai F. W. J., Roch G., Barre A., Chague A., Decroocq S., et al. . (2016). Genome-wide association links candidate genes to resistance to Plum pox virus in apricot (Prunus armeniaca). New Phytol. 209, 773–784. 10.1111/nph.13627 PubMed DOI

Mazzitelli L., Hancock R. D., Haupt S., Walker P. G., Pont S. D., McNicol J., et al. . (2007). Co-ordinated gene expression during phases of dormancy release in raspberry (Rubus idaeus L.) buds. J. Exp. Bot. 58, 1035–1045. 10.1093/jxb/erl266 PubMed DOI

Meuwissen T., Hayes B., Goddard M. (2001). Prediction of total genetic value using genome-wide dense marker maps. Genetics 157, 1819–1829. PubMed PMC

Micheletti D., Dettori M. T., Micali S., Aramini V., Pacheco I., Linge C. D. S., et al. . (2015). Whole-genome analysis of diversity and SNP-major gene association in peach germplasm. PLoS ONE 10:e0136803. 10.1371/journal.pone.0136803 PubMed DOI PMC

Migicovsky Z., Gardner K. M., Sawler J., Money D., Bloom J. S., Zhong G. Y., et al. . (2016). Genome to phenome mapping in apple using historical data. Plant Genome 9, 1–15. 10.3835/plantgenome2015.11.0113 PubMed DOI

Muranty H., Troggio M., Sadok I. B., Rifaï M. A., Auwerkerken A., Banchi E., et al. . (2015). Accuracy and responses of genomic selection on key traits in apple breeding. Hortic. Res. 2:15060. 10.1038/hortres.2015.60 PubMed DOI PMC

Myles S., Peiffer J., Brown P. J., Ersoz E. S., Zhang Z., Costich D. E., et al. . (2009). Association mapping: critical considerations shift from genotyping to experimental design. Plant Cell 21, 2194–2202. 10.1105/tpc.109.068437 PubMed DOI PMC

Neale D. B., Savolainen O. (2004). Association genetics of complex traits in conifers. Trends Plant Sci. 9, 325–330. 10.1016/j.tplants.2004.05.006 PubMed DOI

Nicolas S. D., Péros J. P., Lacombe T., Launay A., Le Paslier M. C., Bérard A., et al. . (2016). Genetic diversity, linkage disequilibrium and power of a large grapevine (Vitis vinifera L) diversity panel newly designed for association studies. BMC Plant Biol. 16:74. 10.1186/s12870-016-0754-z PubMed DOI PMC

Nieuwenhuizen N. J., Chen X., Wang M. Y., Matich A. J., Perez R. L., Allan A. C., et al. . (2015). Natural variation in monoterpene synthesis in kiwifruit: transcriptional regulation of terpene synthases by NAC and ETHYLENE-INSENSITIVE3-like transcription factors. Plant Physiol. 167, 1243–1258. 10.1104/pp.114.254367 PubMed DOI PMC

Ning Y. Q., Ma Z. Y., Huang H. W., Mo H., Zhao T. T., Li L., et al. . (2015). Two novel NAC transcription factors regulate gene expression and flowering time by associating with the histone demethylase JMJ14. Nucleid Acids Res. 43, 1469–1484. 10.1093/nar/gku1382 PubMed DOI PMC

Nishitani C., Hirai N., Komori S., Wada M., Okada K., Osakabe K., et al. . (2016). Efficient genome editing in apple using a CRISPR/Cas9 system. Sci. Rep. 6:31481. 10.1038/srep31481 PubMed DOI PMC

Pascual L., Albert E., Sauvage C., Duangjit J., Bouchet J. P., Bitton F., et al. . (2016). Dissecting quantitative trait variation in the resequencing era: complementarity of bi-parental, multi-parental and association panels. Plant Sci. 242, 120–130. 10.1016/j.plantsci.2015.06.017 PubMed DOI

Pirona R., Eduardo I., Pacheco I., Da Silva L. C., Miculan M., Verde I., et al. . (2013). Fine mapping and identification of a candidate gene for a major locus controlling maturity date in peach. BMC Plant Biol. 13:166. 10.1186/1471-2229-13-166 PubMed DOI PMC

Porto D. D., Bruneau M., Perini P., Anzanello R., Renou J. P., Pessoa dos Santos H., et al. . (2015). Transcription profiling of the chilling requirement for bud break in apples: a putative role for FLC-like genes. J. Exp. Bot. 66, 2659–2672. 10.1093/jxb/erv061 PubMed DOI

Purcell S., Neale B., Todd-Brown K., Thomas L., Ferreira M. A. R., Bender D., et al. . (2007). PLINK: A tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559–575. 10.1086/519795 PubMed DOI PMC

R Core Team A. (2014). R: A Language and Environment for Statistical Computing. [Internet].Vienna: R Foundation for Statistical Computing; Available online at: http://www.Rproject.org/

Ríos G., Leida C., Conejero A., Badenes M. L. (2014). Epigenetic regulation of bud dormancy events in perennial plants. Front. Plant Sci. 5:247. 10.3389/fpls.2014.00247 PubMed DOI PMC

Saito T., Bai S., Ito A., Sakamoto D., Saito T., Ubi B. E., et al. . (2013). Expression and genomic structure of the dormancy-associated MADS box genes MADS13 in Japanese pears (Pyrus pyrifolia Nakai) that differ in their chilling requirement for endodormancy release. Tree Physiol. 33, 654–667. 10.1093/treephys/tpt037 PubMed DOI

Sánchez-Pérez R., Del Cueto J., Dicenta F., Martínez-Gómez P. (2014). Recent advancements to study flowering time in almond and other Prunus species. Front. Plant Sci. 5:334. 10.3389/fpls.2014.00334 PubMed DOI PMC

Sauvage C., Segura V., Bauchet G., Stevens R., Do P. T., Nikoloski Z., et al. . (2014). Genome-Wide Association in tomato reveals 44 candidate loci for fruit metabolic traits. Plant Physiol. 165, 1120–1132. 10.1104/pp.114.241521 PubMed DOI PMC

Segura V., Vilhjálmsson B. J., Platt A., Korte A., Seren Ü., Long Q., et al. . (2012). An efficient multi-locus mixed-model approach for genome-wide association studies in structured populations. Nat. Genet. 44, 825–830. 10.1038/ng.2314 PubMed DOI PMC

Stranger B. E., Stahl E. A., Raj T. (2011). Progress and promise of genome-wide association studies for human complex trait genetics. Genetics 187, 367–383. 10.1534/genetics.110.120907 PubMed DOI PMC

Tadiello A., Longhi S., Moretto M., Ferrarini A., Tononi P., Farneti B., et al. . (2016). Interference with ethylene perception at receptor level sheds light on auxin and transcriptional circuits associated with the climacteric ripening of apple fruit (Malus x domestica Borkh.). Plant J. 88, 963–975. 10.1111/tpj.13306 PubMed DOI

Trainin T., Zohar M., Shimoni-Shor E., Doron-Faigenboim A., Bar-Ya'akov I., Hatib K., et al. (2016). A unique haplotype found in apple accessions exhibiting early bud-break could serve as a marker for breeding apples with low chilling requirements. Mol. Breed. 36:158 10.1007/s11032-016-0575-7 DOI

Ubi B. E., Sakamoto D., Ban Y., Shimada T., Ito A., Nakajima I., et al. (2010). Molecular cloning of dormancy associated MADS-box gene homologs and their characterization during seasonal endodormancy transitional phases of Japanese pear. J. Am. Soc. Hort. Sci. 135, 174–182.

Urrestarazu J., Denancé C., Ravon E., Guyader A., Guisnel R., Feugey L., et al. . (2016). Analysis of the genetic diversity and structure across a wide range of germplasm reveals prominent gene flow in apple at the European level. BMC Plant Biol. 16:130. 10.1186/s12870-016-0818-0 PubMed DOI PMC

Verde I., Bassil N., Scalabrin S., Gilmore B., Lawley C. T., Gasic K., et al. . (2012). Development and evaluation of a 9K SNP array for peach by internationally coordinated SNP detection and validation in breeding germplasm. PLoS ONE 7:e35668. 10.1371/journal.pone.0035668 PubMed DOI PMC

Verde I., Jenkins J., Dondini L., Micali S., Pagliarani G., Vendramin E., et al. . (2017). The Peach v2.0 release: high-resolution linkage mapping and deep resequencing improve chromosome-scale assembly and contiguity. BMC Genomics 18:225. 10.1186/s12864-017-3606-9 PubMed DOI PMC

Visscher P. M., Yang J., Goddard M. E. (2010). A commentary on ‘common SNPs explain a large proportion of the heritability for human height' by Yang et al. (2010). Twin Res. Hum. Genet. 13, 517–524. 10.1375/twin.13.6.517 PubMed DOI

Vitasse Y., Lenz A., Körner C. (2014). The interaction between freezing tolerance and phenology in temperate deciduous trees. Front. Plant Sci. 5:541. 10.3389/fpls.2014.00541 PubMed DOI PMC

Wegrzyn J. L., Eckert A. J., Choi M., Lee J. M., Stanton B. J., Sykes R., et al. . (2010). Association genetics of traits controlling lignin and cellulose biosynthesis in black cottonwood (Populus trichocarpa, Salicaceae) secondary xylem. New Phytol. 188, 15–32. 10.1111/j.1469-8137.2010.03415.x PubMed DOI

Wilczek A. M., Roe J. L., Knapp M. C., Cooper M. D., Lopez-Gallego C., Martin L. J., et al. . (2009). Effects of genetic perturbation on seasonal life history plasticity. Science 323, 930–934. 10.1126/science.1165826 PubMed DOI

Wood A. R., Hernandez D. G., Nalls M. A., Yaghootkar H., Gibbs J. R., Harries L. W., et al. . (2011). Allelic heterogeneity and more detailed analyses of known loci explain additional phenotypic variation and reveal complex patterns of association. Hum. Mol. Genet. 20, 4082–4092. 10.1093/hmg/ddr328 PubMed DOI PMC

Wu R. M., Walton E. F., Richardson A. C., Wood M., Hellens R. P., Varkonyi-Gasic E. (2012). Conservation and divergence of four kiwifruit SVP-like MADSbox genes suggest distinct roles in kiwifruit bud dormancy and flowering. J. Exp. Bot. 63, 797–807. 10.1093/jxb/err304 PubMed DOI PMC

Xie X. I., Yin X. R., Chen K. S. (2016). Roles of APETALA2/Ethylene-Response factors in regulation of fruit quality. Crit. Rev. Plant Sci. 35, 120–130. 10.1080/07352689.2016.1213119 DOI

Xu H., Guan Y. (2014). Detecting local haplotype sharing and haplotype association. Genetics 197, 823–838. 10.1534/genetics.114.164814 PubMed DOI PMC

Yamane H., Ooka T., Jotatsu H., Hosaka Y., Sasaki R., Tao R. (2011). Expressional regulation of PpDAM5 and PpDAM6, peach (Prunus persica) dormancy-associated MADS-box genes, by low temperature and dormancy breaking reagent treatment. J. Exp. Bot. 62, 3481–3488. 10.1093/jxb/err028 PubMed DOI PMC

Yang J., Benyamin B., McEvoy B. P., Gordon S., Henders A. K., Nyholt D. R., et al. . (2010). Common SNPs explain a large proportion of the heritability for human height. Nat. Genet. 42, 565–571. 10.1038/ng.608 PubMed DOI PMC

Yano K., Yamamoto E., Aya K., Takeuchi H., Lo P. C., Hu L., et al. . (2016). Genome-wide association study using whole-genome sequencing rapidly identifies new genes influencing agronomic traits in rice. Nat. Genet. 48, 927–934. 10.1038/ng.3596 PubMed DOI

Yoo S. Y., Kim Y., Kim S. Y., Lee J. S., Ahn J. H. (2007). Control of flowering time and cold response by a NAC-domain protein in Arabidopsis. PLoS ONE 2:e642. 10.1371/journal.pone.0000642 PubMed DOI PMC

Zhebentyayeva T. N., Fan S., Chandra A., Bielenberg D. G., Reighard G. L., Okie W. R., et al. (2014). Dissection of chilling requirement and bloom date QTLs in peach using a whole genome sequencing of sibling trees from an F2 mapping population. Tree Genet. Genomes 10, 35–51. 10.1007/s11295-013-0660-6 DOI

Zhou X., Stephens M. (2012). Genome-wide efficient mixed-model analysis for association studies. Nat. Genet. 44, 821–824. 10.1038/ng.2310 PubMed DOI PMC

Zhu C. S., Gore M., Buckler E. S., Yu J. M. (2008). Status and prospects of association mapping in plants. Plant Genome 2, 121–133. 10.3835/plantgenome2008.02.0089 DOI

Zhu M., Chen G., Zhou S., Tu Y., Wang Y., Dong T., et al. . (2014). A new tomato NAC (NAM/ATAF1/2/CUC2) transcription factor, SlNAC4, functions as a positive regulator of fruit ripening and carotenoid accumulation. Plant Cell Physiol. 55, 119–135. 10.1093/pcp/pct162 PubMed DOI

Zuk O., Hechter E., Sunyaev S. R., Lander E. S. (2012). The mystery of missing heritability: genetic interactions create phantom heritability. Proc. Natl. Acad. Sci. U.S.A. 109, 1193–1198. 10.1073/pnas.1119675109 PubMed DOI PMC

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