Shades of gray: the world of quantitative disease resistance Jesse A. Poland 1 , Peter J. Balint-Kurti 2 , Randall J. Wisser 3, 4 , Richard C. Pratt 5 and Rebecca J. Nelson 1, 6 1 Department of Plant Breeding & Genetics, Cornell University, Ithaca, NY 14853, USA 2 USDA-ARS, Plant Science Research Unit, Department of Plant Pathology, North Carolina State University, Raleigh, NC 27695, USA 3 Department of Plant Pathology, North Carolina State University, Raleigh, NC 27695, USA 4 Current address: Department of Plant and Soil Sciences, University of Delaware, Newark, DE 19716, USA 5 Department of Horticulture and Crop Science, The Ohio State University, Wooster, OH 44691, USA 6 Department of Plant Pathology & Plant-Microbe Biology, Cornell University, Ithaca, NY 14853, USA A thorough understanding of quantitative disease resist- ance (QDR) would contribute to the design and deploy- ment of durably resistant crop cultivars. However, the molecular mechanisms that control QDR remain poorly understood, largely due to the incomplete and incon- sistent nature of the resistance phenotype, which is usually conditioned by many loci of small effect. Here, we discuss recent advances in research on QDR. Based on inferences from analyses of the defense response and from the few isolated QDR genes, we suggest several plausible hypotheses for a range of mechanisms under- lying QDR. We propose that a new generation of genetic resources, complemented by careful phenotypic analysis, will produce a deeper understanding of plant defense and more effective utilization of natural resist- ance alleles. The two worlds of disease resistance Two general categories of disease resistance have long been recognized in plants (e.g. Ref. [1]): (i) complete resist- ance conditioned by a single gene and (ii) incomplete resistance conditioned by multiple genes of partial effect. In their extreme forms, these types of resistance are clear and easily distinguished. A variety of terms have been used to refer to this perceived dichotomy, including horizontal versus vertical, complete versus incomplete, major-gene versus minor-gene and narrow-spectrum versus broad- spectrum. This diversity of terms reflects the range of interests and assumptions made by the respective authors, but it also adds an element of confusion to the literature because some terms are used in different ways by different authors. Here, we use the terms ‘qualitative disease resist- ance’ and ‘quantitative disease resistance’ (QDR; see Glos- sary) to refer to the respective phenomena. We use the term ‘R-genes’ (resistance genes) to refer to genes that confer qualitative effects and ‘QRLs’ (quantitative resist- ance loci; see Glossary) [2] to refer to loci or genes that confer QDR. Although the phenomena of qualitative and quantitative resistance can be considered different, there is a great deal of gray area between the extremes, suggesting that it might be useful to reexamine the concepts in light of emerging evidence on mechanisms of resistance. As we will discuss, several authors have ques- tioned whether the loci controlling the two types of resist- ance are distinct [3], suggesting that quantitative and qualitative resistance are conditioned by the same genetic mechanisms. There is substantial support for this hypothesis in some cases, as well as evidence that alternative mechanisms also underlie QDR (e.g. Refs [4,5]). Several credible hypotheses can be proposed, and it is likely that a diversity of mech- anisms will be implicated, some overlapping with qualita- tive resistance (e.g. specific recognition of pathogen effectors or their targets) and innate immunity (e.g. rela- tively non-specific recognition, such as recognition of broadly conserved pathogen features; also known as basal resistance). Other plausible mechanisms to explain QDR would include the detection and mitigation of infection- related damage, the modulation and transduction of defense signals and mechanisms of direct defense (e.g. establishment or reinforcement of defensive structures, Review Glossary Compatible interaction: a host–pathogen interaction that results in disease (the host is susceptible). Defeated R-gene: a resistance gene that has become ineffective. Incompatible interaction: a host–pathogen interaction that does not result in disease (the host is resistant). NB-LRR (nucleotide binding-leucine rich repeat): two amino acid sequence motifs commonly found in resistance genes. Near isogenic lines (NIL): inbred lines that differ at only a small genomic region. Pathosystem: the combination of a specific host species and pathogen species. Pattern-recognition receptors: proteins that identify molecules, such as flagellin or chitin components, that are associated with microbial pathogens. Quantitative disease resistance (QDR): resistance that is expressed as a reduction in disease, rather than as the absence of disease. Quantitative resistance locus (QRL): a locus with an effect on QDR. Quantitative trait locus (QTL): a locus with an effect on a quantitative trait (i.e. a trait showing continuous variation). Recombinant inbred line (RIL): an inbred line produced from an initial cross followed by continuous inbreeding; populations of RILs are often used for QTL- mapping studies. Resistance breakdown: the phenomenon of a resistant cultivar becoming susceptible owing to changes in the pathogen race. Resistance gene analogs: putative genes that share sequence similarity with known R-genes. R-gene breakdown: the phenomenon of a resistance gene becoming ineffective in a crop variety. Corresponding author: Nelson, R.J. (rjn7@cornell.edu). 1360-1385/$ – see front matter ß 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.tplants.2008.10.006 Available online 4 December 2008 21