关联分析及其在植物遗传学研究中的应用

doi:10.3724/SP.J.1259.2011.00108

摘要/Abstract

摘要： 植物的很多重要经济性状均属于复杂性状。基于连锁分析的QTL作图是研究复杂性状的有效手段, 但其尚存在一定的局限性。随着现代生物学的发展, 一种基于连锁不平衡的新剖分复杂性状方法——关联分析法, 开始应用于植物遗传学研究。与QTL作图法相比, 应用关联分析法具有不需要构建特殊的群体, 可同时对多个等位基因进行分析, 定位QTL精度可达到单基因水平等优势。该文介绍了关联分析方法学的基础和特性, 简述了其在植物遗传学研究中的进展情况, 并对其未来发展和在植物遗传学研究中的应用进行了展望。

Abstract: Most of the important economic traits in plant genetics are attributed to complex traits. Quantitative trait loci (QTL) mapping is an important tool for studying complex traits. However, because of its limitations, QTL mapping is used only in certain cases. Association analysis, a new approach for dissecting complex traits based on linkage disequilibrium, can overcome the limitations of QTL mapping for use in plant genetic studies. As compared with QTL mapping and other methods used to dissect complex traits, association analysis does not need specific population construction, multiple alleles can be analyzed synchronously, and mapping resolution is higher. Here, we introduce the methodology and properties of association analysis, outline the progress with such analysis in plant genetics research, and discuss future applications and potential development of association analysis in plant genetics research.

谭贤杰吴子恺程伟东王天宇黎裕. 关联分析及其在植物遗传学研究中的应用. 植物学报, 2011, 46(1): 108-118.

Xianjie Tan, Zikai Wu, Weidong Cheng, Tianyu Wang, Yu Li. Association analysis and its application in plant genetic research. Chinese Bulletin of Botany, 2011, 46(1): 108-118.

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参考文献

Agrama HA, Eizenga GC, Yan W (2007). Association mapping of yield and its components in rice cultivars. Molecular Breeding 19,341-356.
Andersen JR, Schrag T, Melchinger AE, Zein I, Lübberstedt T (2005). Validation of Dwarf8 polymorphisms associated with flowering time in elite European inbred lines of maize (Zea mays L.). Theor Appl Genet 111, 206-217.
Aranzana MJ, Kim S, Zhao K, Bakker E, Horton M, Jakob K, Lister C, Molitor J, Shindo C, Tang C, Toomajian C, Traw B, Zheng H, Bergelson J, Dean C, Marjoram P, Nordborg M (2005). Genome-wide association mapping in arabidopsis identifies previously known flowering time and pathogen resistance genes. PLoS Genetics 1,e60 .
Ashikari M, Sakakibara H, Lin S Y, Yamamoto T, Takashi T, Nishimura A, Angeles E R, Qian Q, Kitano H, Matsuoka M (2005). Cytokinin oxidase regulates rice grain production. Science 309, 741-745.
Atwell S, Huang YS, Vilhjálmsson BJ, Willems G, Horton M, Li Y, Meng D, Platt A, Tarone AM, Hu TT, Jiang R, Muliyati NW, Zhang X, Amer MA, Baxter I, Brachi B, Chory J, Dean C, Debieu M, de Meaux J, Ecker JR, Faure N, Kniskern JM, Jones JD, Michael T, Nemri A, Roux F, Salt DE, Tang C, Todesco M, Traw MB, Weigel D, Marjoram P, Borevitz JO, Bergelson J, Nordborg M (2010). Genome-wide association study of 107 phenotypes in Arabidopsis thaliana inbred lines. doi:10.1038/nature08800(Epub ahead of print).
Bao JS, Corke H,Sun M (2006). Nucleotide diversity in starch synthase lla and validation of single nucleotide polymorphisms in relation to starch gelatinization temperature and other physicochemical properties in rice (Oryza sativa L.). Theor Appl Gen 113, 1171-1183.
Belo A,Zheng PZ,Luck S,Shen B,Meyer DJ,Li BL,Tingey S,Rafalski A (2008). Whole genome scan detects an allelic variant of fod2 associated with increased oleic acid levels in maize. Molecular Genetics and Genomics 279, 1-10.
Breseghello F,Sorrells ME (2006). Association mapping of kernel size and milling quality in wheat (Triticum aestivum L.). Cultivars. Genetics 172, 1165-117.
Briggs W, Mcmullen MD, Gaut BS, Doebley J (2007). Linkage mapping of domestication loci in a large maize-teosinte backcross resource. Genetics 177, 1915-1928.
Camus-Kulandaivelu L, Veyrieras JB, Madur D, Combes V, Fourmann M, Barraud S, Dubreuil P, Gouesnard B, Manicacci D, Charcosset A (2006). Maize adaptation to temperate climate: relationship with population structure and polymorphism in the Dwarf8 gene. Genetics 10, 1534-1572.
Cardon L R,Palmer JL (2003). Population stratification and spurious allelic association. Lancet 361, 598-604.
Casa AM,Pressoira G,Brown PJ,Mitchell SE,Rooney WL,Tuinstrac MR,Franks CD,Kresovicha S (2008). Community resources and strategies for association mapping in sorghum. Crop Science 48, 30-40.
Cockram J, White J, Leigh FJ, Lea VJ, Chiapparino E, Laurie DA, Mackay IJ, Powell W, O'Sullivan DM (2008). Association mapping of partitioning loci in barley. BMC Genet 18, 9-16.
Delvin B, Risch N (1995). A comparison of linkage disequilibrium measures for fine mapping. Genomics 29, 311-322.
Devlin B, Roeder K (1999). Genomic control for association studies. Biometrics 55, 997-1004.
Doerge, RW (2002). Mapping and analysis of quantitative trait loci in experimental populations. Nat Rev Genet 3, 43-52.
Ehrenreich IM,Hanzawa Y, Chou L,Roe J,Kover P,Purugganan M (2009). Candidate Gene Association Mapping of Arabidopsis Flowering Time. Genetics 183, 325-335.
Ehrenreich IM,Stafford PA,Purugganan MD (2007). The genetic architecture of shoot branching in Arobidopsis thaliana:a comparative assessment of candidate gene associations vs.quantitative trait locus mapping. Genetics 176, 1223-1236.
Epstein MP, Allen AS,Satten GA (2007). A simple and improved correction for population stratification in case-control studies. Am J Hum Genet 80,912-930.
Flint-Garcia SA, Thornsberry JM, Buckler ES (2003). Structure of linkage disequilibrium in plants. Annu Rev Plant Biol 54, 357-374.
Flint-Garcia SA, Thuillet A, Yu J, Pressoir G, Romero SM, Mitchell SE, Doebley J, Kresovich S, Goodman MM, Buckler ES (2005). Maize association population: a high resolution platform for quantitative trait locus dissection. Plant Journal 44, 1054-1064.
Frary A, Nesbitt TC, Grandillo S, Knaap E, Cong B, Liu J, Meller J, Elber R, Alpert KB, Tanksley SD.(2000) fw2.2：a quantitative trait locus key to the evolution of tomato fruit size. Science 289, 85-88.
Frisse L,Hudson RR,Bartoszewicz A,Wall JD,Donfack J, Di Rienao A (2001). Gene conversion and different population histories may explain the contrast between polymorphism and linkage disequilibrium levels．Am J Hum Genet 69,831-843．
Gaut BS,Long AD (2003). The Lowdown on Linkage Disequilibrium. Plant Cell 15, 1502-1506.
Gebhardt C,Ballvora A,Walkemeier B,Oberhagemann P,Schuler K (2004). Assessing genetic potential in germplasm collections of crop plants by marker-trait association:a case study for potatoes with quantitative variation of resistance to late blight.Molecular Breeding 13, 93-102.
Gonzalez-Martinez SC,Ersoz E,Brown GR,Wheeler NC,Neale DB (2006). DNA sequence variation and selection of tag singlenucleotide polymorphisms at candidate genes for drought-stress response in Pinus taeda L. Genetics 172, 1915-1926.
Gonzalez-Martinez SC,Wheeler NC,Ersoz E,Nelson CD,Neale DB (2007). Association genetics in Pinus taeda L.I.Wood property traits. Genetics 175, 399-409.
Hamblin MT ,Close TJ,Bhat PR,Chao S, Kling JG,Abraham KJ,Black T,Brooks WS,Cooper B,Griffey CA,Hayes Hole DJ,Horsley RD,Obert DE,Smith KP,Ullrich SE,Muehlbauer GJ,Jannink JL (2010). Population Structure and Linkage Disequilibrium in U.S. Barley Germplasm: Implications for Association Mapping. Crop Sci 50,556-566.
Hansen M, Kraft T, Ganestam S,S?ll T, Nilsson N (2001). Linkage disequilibrium mapping of the bolting gene in sea beet using AFLP markers. Genet Res 77, 61-66.
Harjes CE, Rocheford TR, Bai L, Brutnell TP, Kandianis CB, Sowinski SG, Stapleton AE, Vallabhaneni R, Williams M, Wurtzel ET, Yan J, Buckler ES (2008). Natural genetic variation in lycopene epsilon cyclase tapped for maize biofortification. Science 319,330-333.
Hastbacka J, de la Chapelle A, Kaitila I,Sistonen P, Weaver A, Lander E (1992). Linkage disequilibrium mapping in isolated founder populations: diastrophic dysplasia in Finland. Nat Genet 2, 204-211.
Hey J,Machado CA (2003). The study of structured populations-new hope for a difficult and divided science. Nat Rev Genet 4, 535-543.
Holland JB (2007). Genetic architecture of complex traits in plants. Curr Opin Plant Biol 10, 156-161.
http://www.ncbi.nlm.nih.gov/genomes/PLANTS/PlantList.html
Iwata H,Ebana K,Uga Y,Hayashi T, Jannink J-L (2010). Genome-wide association study of grain shape variation among Oryza sativa L. germplasms based on elliptic Fourier analysis. Mol Breeding 25, 203-215.
Jorde JB (2000). Linkage disequilibrium and the search for complex disease gene. Genome Res 10, 1435-1444.
Jun T-H, Van K, Kim M-Y, Lee S-H,Walker DR (2008). Association analysis using SSR markers to find QTL for seed protein content in soybean. Euphytica 162, 179-191.
Kang HM, Zaitlen NA, Wade CM, Kirby A, Heckerman D, Daly MJ ,Eskin E (2008). Efficient control of population structure in model organism association mapping. Genetics 178, 1709-1723.
Kover PX, Valdar W, Trakalo J, Scarcelli N, Ehrenreich I M, Purugganan M D,Durrant C, Richard M (2009). A Multiparent Advanced Generation Inter-Cross to Fine-Map Quantitative Traits inArabidopsis thaliana. PLoS Genet 57, e1000551.
Kraakman ATW,Niks RE,van den Berg PMMM,Stam P,van Eeuwijk FA (2004). Linkage disequilibrium mapping of yield and yield stability in modern spring barley cultivars. Genetics 168, 435-446.
Krill AM, Kirst M, Kochian LV, Buckler ES, Hoekenga OA (2010). Association and Linkage Analysis of Aluminum Tolerance Genes in Maize. PLoS ONE 5,e9958.
Lander ES, Schork NJ (1994). Genetic dissection of complex traits. Science 265, 2037-2048.
Li Q,Yu K (2008). Improved correction for population stratification in genome-wide association studies by identifying hidden population structures. Genetic Epidemiology 32, 215-226.
Lubberstedt T,Zein I,Andersen JR,Wenzel G,Krutzfeldt B,Eder J,Ouzunova M, Chun S (2005). Development and application of functional markers in maize. Euphytica 146,101-108.
Malosetti M,van der Linden CG,Vosman B,van Eeuwijk FA (2007). A mixed-model approach to association mapping using pedigree information with an illustration of resistance to Phytophthora infestans in potato. Genetics 175, 879-889.
Mardis ER (2008). Next-generation sequencing methods.Annu Rev Genomics Hum Genet 9, 387-402.
McVean G, Awadalla P, Fearnhead P (2002). A coalescent-based method for detecting and estimating recombination from gene sequences. Genetics 160, 1231-1241.
Meuwissen THE, Goddard ME (2000). Fine mapping of quantitative trait loci using linkage disequilibria with closely linked marker loci. Genetics 155,421-430.
Myles S, Chia J-M, Hurwitz B, Simon C, Zhong G-Y, Buckler ES Ware D (2010). Rapid Genomic Characterization of the Genus Vitis. PLoS ONE 5,e8219.
Nordborg M, Borevitz, JO, Bergelson J, Berry CC, Chory J, Hagenblad J,Kreitman M, Maloof JN, Noyes T,Oefner PJ, Stahl EA,Weigel D (2002). The extent of linkage disequilibrium in Arabidopsis thaliana. Nat Genet 30, 190-193.
Olsen KM,Purugganan MD(2002). Molecular evidence on the origin and evolution of glutinous rice.Genetics 162,941-950.
Olsen KM,Halldorsdottir SS,Stinchcombe JR,Weinig C,Schmitt J,Purugganan MD (2004). Linkage disequilibrium mapping of A rabidopsis CRY2 flowering time alleles. Genetics 167, 1361-1369.
Palaisa KA, Morgante M, Tingey S,Rafalski A (2004). Long-range patterns of diversity and linkage disequilibrium surrounding the maize Y1 geneareindicative of ana sym-metric selective sweep. PNAS 101, 9885-9890.
Palaisa KA, Morgante M, Williams M Rafalski A (2003). Contrasting effects of selection on sequence diversity and linkage disequilibrium at two phytoene synthase loci. Plant Cell 15, 795-1806.
Patterson N, Price AL, Reich D (2007). Population structure and eigenanalysis. PLoS Genet 2, e90.
Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D (2006). Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38, 904-909.
Pritchard JK, Rosenberg NA (1999). Use of unlinked genetic markers to detect population stratification in association studies. Am J Hum Genet 65, 220-228.
Pritchard JK, Stephens M, Rosenberg NA, Donnelly P (2000). Association mapping in structured populations. Am J Hum Genet 67, 170-181.
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007).PLINK: a toolset for whole-genome association and population-based linkage analyses. Am J Hum Genet 81,559-575.
Rafalski A (2002). Applications of single nucleotide polymorphisms in crop genetics. Curr Opin Plant Biol 5, 94-100.
Remington DL, Thornsberry JM, Matsuoka Y, Wilson LM, Whitt SR, Doebley J, Kresovich S, Goodman MM, Buckler ES (2001). Structure of linkage disequilibrium and phenotypic associations in the maize genome. PNAS 98, 11479-11484.
Rosenberg NA, Pritchard JK, Weber JL, Cann HM, Kidd K k,Zhivotovsky LA, Feldman MW (2002). Genetic structure of human populations. Science 298, 2381-2385.
Rostoks N, Ramsay L, MacKenzie K, Cardle L, Svensson JT, Bhat P, Roose ML, Stein N, Varshney RK, Marshall D, Graner A, Close TJ, Waugh R (2006). A recent history of artificial outcrossing facilitates whole genome association mapping in elite inbred crop varieties. PNAS 103, 18656-18661.
Sa?dou A-A, Mariac C, Luong V,Pham J-L,Bezancon G, Yigouroux Y (2009). Association Studies Identify Natural Variation at PHYC Linked to Flowering Time and Morphological Variation in Pearl Millet. Genetics 182, 899-910.
Salvi S, Sponza G, Morgante M, Tomes D, Niu X, Fengler KA, Meeley R, Ananiev EV, Svitashev S, Bruggemann E, Li B, Hainey CF, Radovic S, Zaina G, Rafalski J A,Tingey S V, Miao G H,Phillips R L, Tuberosa R (2007). Conserved noncoding genomic sequences associated with a flowering-time quantitative trait locus in maize. PNAS 104, 11376-11381.
Sharbel TF, Haubold B, Mitchell-Olds T (2000). Genetic isolation by distance in Arabidopsis thaliana: biogeography and postglacial colonization of Europe. Mol Ecol 9, 2109-2118.
Shehzad T, Iwata H, Okuno K (2009). Genome-wide association mapping of quantitative traits in sorghum (Sorghum bicolor (L.) Moench) by using multiple models. Breed Sci 59, 217-227.
Sk?t L,Humphreys J,Humphreys MO,Thorogood D,Gallagher J,Sanderson R,Armstead IP,Thomas ID (2007). Association of candidate genes with flowering time and water-soluble carbohydrate content in Loliurn perenne(L.). Genetics 177, 535-547.
Sk?t L,Humphreys MO,Armstead I,Heywood S,Sk?t KP,Sanderson R,Thomas ID,Chorlton KH,Hamilton NRS (2005). An association mapping approach to identify flowering time genes in natural populations of Lolium perenne (L.). Molecular Breeding 15,233-245.
Spielman RS, McGinnis RE, Ewens WJ (1993). Transmission test for linkage disequilibrium: The insulin gene region and insulin-dependent diabetes mellitus. Am J Hum Genet 52, 506-516.
Stich B, Melchinger AE, Heckenberger M, M?hring J, Schechert A, Piepho HP (2008). Association mapping in multiple segregating populations of sugar beet (Beta vulgaris L.). Theor Appl Genet 117,1167-79.
Stich B (2009). Comparison of Mating Designs for Establishing Nested Association Mapping Populations in Maize and Arabidopsis thaliana. Genetics 183,1525-1534.
Stitch B, Melchinger AE (2009). Comparison of mixed-model approaches for association mapping in rapeseed, potato, sugar beet, maize, and Arabidopsis. BMC Genomics 10, 94.
Szalma SJ, Buckler ES, Snook ME, McMullen MD (2005). Association analysis of candidate genes for maysin and chlorogenic acid accumulation in maize silks. Theor Appl Genet 110, 1324-1333.
Thornsberry JM, Goodman MM, Doebley J, Kresovich S, Nielsen D, Buckler ES (2001). Dwarf8 polymorphisms associate with variation in flowering time. Nat Genet 28, 286-289.
Thumma BR,Nolan MF,Evans R,and Moran GF (2005). Polymorphisms in cinnamoyl CoA reductase (CCR) are associated with variation in microfibril angle in Eucalyptus spp. Genetics 171, 1257-1265.
Tian Z,Qian Q,Liu Q,Yan M,Liu X,Yan C,Liu G,Gao Z,Tang S,Zeng D,Wang Y,Yu J,Gu M,Li J (2009). Allelic diversities in rice starch biosynthesis lead to a diverse array of rice eating and cooking qualities. PNAS 106,21760-21765.
Tommasini U,Schnurbusch T,Fossati D,Mascher F,Keller B (2007). Association mapping of Stagonospora nodorum blotch resistance in modern European winter wheat varieties. Theor Appl Genet 115,697-708.
Tracy WF,Whitt SR,Buckler ES (2006). Recurrent mutation and genome evolution:Example of Sugaryl and the origin of sweet maize. Crop Science 46, S49-S54.
Wang H, Nussbaum-Wagler T, Li B, Zhao Q, Vigouroux Y, Faller M, Bomblies K , Lukens L, Doebley J F (2005). The origin of the naked grains of maize. Nature 436, 714-719.
Weber AL,Briggs WH, Rucker J,Baltazar BM,Sanchez-Gonzalez JJ,Feng P,Buckler ES,Doebley J (2008). The Genetic Architecture of Complex Traits in Teosinte (Zea mays ssp. parviglumis):New Evidence From Association Mapping. Genetics 180, 1221-1232.
Wei XM,Jackson PA,McIntyre CL,Aitken KS,Croft B (2006). Associations between DNA markers and resistance to diseases in sugarcane and effects of population substructure. Theor Appl Genet 114,155-164.
Wen W,Mei H,Feng F,Yu S,Huang ZC,Wu JH,Chen L,Xu XY,Luo LJ (2009). Population structure and association mapping on chromosome 7 using a diverse panel of Chinese germplasm office (Oryza sativa L.). Theor Appl Genet 119,459-470.
Wilson LM, Whitt SR, Ibanez AM, Rocheford TR, Goodman MM, Buckler ES (2004). Dissection of maize kernel composition and starch production by candidate gene associations. Plant Cell 16, 2719-2733.
Xu Y, Skinner DJ, Wu H, Palacios-Rojas N, Araus JL, Yan J, Gao S, Warburton ML, Crouch JH (2009). Advances in maize genomics and their value for enhancing genetic gains from breeding. Int J Plant Genomics 2009, 957602.
Yan J, Shah T, Warburton ML, Buckler ES, McMullen MD, Crouch J (2009). Genetic Characterization and Linkage Disequilibrium Estimation of a Global Maize Collection Using SNP Markers. PLoS ONE 4, e8451.
Yan WG,Li Y,Agrama HA,Luo D,Gao FY,Lu XJ,Ren GJ (2009). Association mapping of stigma and spikelet characteristicsin rice (Oryza sativa L.). Molecular Breeding 24,277-292.
Yano M, Katayosea Y, Ashikarib M, Yamanouchi U, Monnac L, Fuseb T, Babac T, Yamamotoc K, Umeharaa Y, Nagamuraa Y, Sasakia T (2000). Hd1, a Major. Photoperiod Sensitivity Quantitative Trait Locus in Rice, is Closely Related to the Arabidopsis Flowering Time. Gene CONSTANS, Plant Cell 12, 2473-2483.
Yu J,Holland JB,McMullen MD,Buckler ES (2008). Genetic design and statistical power of nested association mapping in maize. Genetics 178, 539-551.
Yu JM, Pressoir G, Briggs WH, Bi IV, Yamasaki M, Doebley JF,McMullen MD, Gaut BS, Nielsen DM, Holland JB Kresovich S, Buckler ES(2006).A unified mixed-model method for association mapping that accounts for multiple levels of relatedness. Nat Genet 38,203-208.
Zhang L-B, Zhu Q, Wu Z-Q, Ross-Ibarra J, Gaut B S, Ge S, Sang T(2009). Fast fixation of non-shattering allele but slow domestication of rice. New Phytologist 184,708-720.
Zhao HH, Fernando RL, Dekkers JCM (2007). A Power and precision of alternate methods for linkage disequilibrium mapping of quantitative trait loci. Genetics 175, 1975-1986.
Zhu C, Yu J (2009). Nonmetric multidimensional scaling corrects for population structure in whole genome association studies. Genetics 182, 875-888.
莫惠栋，顾世梁（2000）. 基因组长度的估算方法. 中国科学通报 45,122-125.