A consensus framework map of durum wheat (Triticum durum Desf.) suitable for linkage disequilibrium analysis and genome-wide association mapping

BMC Genomics

Roberto Tuberosa¹  Gyula Vida⁵  Ildikó Karsai⁵  Karim Ammar⁸  Steven Xu^1,10  Jorge Dubcovsky²  Tzion Fahima⁹  John M Clarke⁶  Curtis J Pozniak⁶  Ron Knox⁷  Fran Clarke⁷  Andrea Massi⁴  Maria C Colalongo¹  Silvio Salvi¹  Maria C Sanguineti¹  Maria Angela Cane’¹  Marco Maccaferri³ 

[1] Department of Agricultural Sciences (DipSA), Viale Fanin 44, University of Bologna, 40127 Bologna, Italy;Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA;Department of Plant Sciences, University of California, Davis, CA 95616, USA;Società Produttori Sementi Bologna (PSB), 40050 Argelato (BO), Italy;Center for Agricultural Research, Hungarian Academy of Sciences (ARI-HAS), Brunszvik U. 2, H-2462, Martonvasar, Hungary;Crop Development Centre and Department of Plant Sciences, University of Saskatchewan, 51 Campus Drive, Saskatoon, SK S7N 5A8, Canada;Semiarid Prairie Agricultural Research Centre, Agriculture and Agri-Food Canada, P.O. Box 1030, Swift Current, SK S9H 3X2, Canada;International Maize and Wheat Improvement Center (CIMMYT), Apartado Postal 6-641, 06600, Mexico D.F., Mexico. Carretera Mexico-Veracruz KM. 45, 56130 Texcoco, Mexico;Department of Evolutionary and Environmental Biology, Institute of Evolution, Faculty of Science and Science Education, University of Haifa, Mt. Carmel, Haifa 31905, Israel;USDA/ARS Cereal Crops Research Unit, NCSL 1605 Albrecht Blvd. N., Fargo, ND 58102, USA

关键词: QTL;    Heading date;    Genome-wide association mapping;    Linkage disequilibrium;    Consensus map;    Triticum durum Desf;   

Others  :  1128502
DOI  :  10.1186/1471-2164-15-873

 received in 2014-05-25, accepted in 2014-09-23,  发布年份 2014

【 摘 要 】

Background

Durum wheat (Triticum durum Desf.) is a tetraploid cereal grown in the medium to low-precipitation areas of the Mediterranean Basin, North America and South-West Asia. Genomics applications in durum wheat have the potential to boost exploitation of genetic resources and to advance understanding of the genetics of important complex traits (e.g. resilience to environmental and biotic stresses). A dense and accurate consensus map specific for T. durum will greatly facilitate genetic mapping, functional genomics and marker-assisted improvement.

Results

High quality genotypic data from six core recombinant inbred line populations were used to obtain a consensus framework map of 598 simple sequence repeats (SSR) and Diversity Array Technology^® (DArT) anchor markers (common across populations). Interpolation of unique markers from 14 maps allowed us to position a total of 2,575 markers in a consensus map of 2,463 cM. The T. durum A and B genomes were covered in their near totality based on the reference SSR hexaploid wheat map. The consensus locus order compared to those of the single component maps showed good correspondence, (average Spearman’s rank correlation rho ρ value of 0.96). Differences in marker order and local recombination rate were observed between the durum and hexaploid wheat consensus maps. The consensus map was used to carry out a whole-genome search for genetic differentiation signatures and association to heading date in a panel of 183 accessions adapted to the Mediterranean areas. Linkage disequilibrium was found to decay below the r² threshold = 0.3 within 2.20 cM, on average. Strong molecular differentiations among sub-populations were mapped to 87 chromosome regions. A genome-wide association scan for heading date from 27 field trials in the Mediterranean Basin and in Mexico yielded 50 chromosome regions with evidences of association in multiple environments.

Conclusions

The consensus map presented here was used as a reference for genetic diversity and mapping analyses in T. durum, providing nearly complete genome coverage and even marker density. Markers previously mapped in hexaploid wheat constitute a strong link between the two species. The consensus map provides the basis for high-density single nucleotide polymorphic (SNP) marker implementation in durum wheat.

【 授权许可】

   
2014 Maccaferri et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 4.

【 参考文献 】

• [1]Dubcovsky J, Dvorak J: Genome plasticity a key factor in the success of polyploid wheat under domestication. Science 2007, 316:1862-1866.
• [2]Feuillet C, Stein N, Rossini L, Praud S, Mayer K, Schulman A, Eversole K, Appels R: Integrating cereal genomics to support innovation in the Triticeae. Funct Integr Genomics 2012, 12:573-583.
• [3]Gupta PK, Mir RR, Mohan A, Kumar J: Wheat genomics: present status and future prospects. Int J Plant Genomics 2008, 2008:896451.
• [4]Röder MS, Korzun V, Wendehake K, Plaschke J, Tixier MH, Leroy P, Ganal MW: A microsatellite map of wheat. Genetics 1998, 149:2007-2023.
• [5]Varshney RK, Langridge P, Graner A: Application of genomics to molecular breeding of wheat and barley. Adv Genet 2007, 58:121-155. Review
• [6]Blanco A, Bellomo MP, Cenci A, De Giovanni C, D’Ovidio R, Iacono E, Laddomada B, Pagnotta MA, Porceddu E, Sciancalepore A, Simeone R, Tanzarella OA: A genetic linkage map of durum wheat. Theor Appl Genet 1998, 97:721-728.
• [7]Korzun V, Röder MP, Wendehake K, Pasqualone A, Lotti C, Ganal MW, Blanco A: Integration of dinucleotide microsatellites from hexaploid bread wheat into a genetic linkage map of durum wheat. Theor Appl Genet 1999, 98:1202-1207.
• [8]Lotti C, Salvi S, Pasqualone A, Tuberosa R, Blanco A: Integration of AFLP markers into an RFLP-based map of durum wheat. Plant Breed 2000, 119:393-401.
• [9]Eujail ME, Sorrells M, Baum P, Wolters W, Powell W: Isolation of EST-derived microsatellite markers for genotyping the A and B genomes of wheat. Theor Appl Genet 2002, 10:399-407.
• [10]Maccaferri M, Sanguineti MC, Donini P, Tuberosa R: Microsatellite analysis reveals a progressive widening of the genetic basis in the elite durum wheat germplasm. Theor Appl Genet 2003, 107:783-797.
• [11]Nachit MM, Elouafi I, Pagnotta MA, El Saleh A, Iacono E, Labhilili M, Asbati A, Azrak M, Hazzam H, Benscher D, Khairallah M, Ribaut JM, Tanzarella OA, Porceddu E, Sorrells ME: Molecular linkage map for an intraspecific recombinant inbred population of durum wheat (Triticum turgidum L. var. durum). Theor Appl Genet 2001, 102:177-186.
• [12]Maccaferri M, Mantovani P, Tuberosa R, Deambrogio E, Giuliani S, Demontis A, Massi A, Sanguineti MC: A major QTL for durable leaf rust resistance widely exploited in durum wheat breeding programs maps on the distal region of chromosome arm 7BL. Theor Appl Genet 2008, 117:1225-1240.
• [13]Mantovani P, Maccaferri M, Sanguineti MC, Tuberosa R, Catizone I, Wenzl P, Thompson B, Carling J, Huttner E, DeAmbrogio E, Kilian A: An integrated DArT-SSR linkage map of durum wheat. Mol Breeding 2008, 22:629-648.
• [14]Marone D, Del Olmo AI, Laido G, Sillero JC, Emeran AA, Russo MA, Ferragonio P, Giovanniello V, Mazzucotelli E, De Leonardis AM: Genetic analysis of durable resistance against leaf rust in durum wheat. Mol Breed 2009, 24:25-39.
• [15]Peleg Z, Saranga Y, Suprunova T, Ronin Y, Röder MS, Kilian A, Korol AB, Fahima T: High-density genetic map of durum wheat × wild emmer wheat based on SSR and DArT markers. Theor Appl Genet 2008, 117:103-115.
• [16]Somers DJ, Isaac P, Edwards K: A high-density microsatellite consensus map for bread wheat (Triticum aestivum L.). Theor Appl Genet 2004, 109:1105-1114.
• [17]Crossa J, Burgueño J, Dreisigacker S, Vargas M, Herrera-Foessel SA, Lillemo M, Singh RP, Trethowan R, Warburton M, Franco J, Reynolds M, Crouch JH, Ortiz R: Association analysis of historical bread wheat germplasm using additive genetic covariance of relatives and population structure. Genetics 2007, 177:1889-1913.
• [18]Trebbi D, Maccaferri M, de Heer P, Sørensen A, Giuliani S, Salvi S, Sanguineti MC, Massi A, van der Vossen EA, Tuberosa R: High-throughput SNP discovery and genotyping in durum wheat (Triticum durum Desf.). Theor Appl Genet 2011, 123:555-569.
• [19]Marone D, Laidò G, Gadaleta A, Colasuonno P, Ficco DB, Giancaspro A, Giove S, Panio G, Russo MA, De Vita P, Cattivelli L, Papa R, Blanco A, Mastrangelo AM: A high-density consensus map of A and B wheat genomes. Theor Appl Genet 2012, 125:1619-1638.
• [20]Letta T, Maccaferri M, Badebo A, Ammar K, Ricci A, Crossa J, Tuberosa R: Searching for novel sources of field resistance to Ug99 and Ethiopian stem rust races in durum wheat via association mapping. Theor Appl Genet 2013, 126:1237-1256.
• [21]Buerstmayr H, Ban T, Anderson JA: QTL mapping and marker-assisted selection for Fusarium head blight resistance in wheat: a review. Plant Breed 2009, 128:1-26.
• [22]Miedaner T, Korzun V: Marker-assisted selection for disease resistance in wheat and barley breeding. Phytopathology 2012, 102:560-566.
• [23]Paux E, Sourdille P, Mackay I, Feuillet C: Sequence-based marker development in wheat: advances and applications to breeding. Biotechnol Adv 2012, 30:1071-1088.
• [24]Maccaferri M, Sanguineti MC, Corneti S, Ortega JL, Salem MB, Bort J, DeAmbrogio E, del Moral LF, Demontis A, El-Ahmed A, Maalouf F, Machlab H, Martos V, Moragues M, Motawaj J, Nachit M, Nserallah N, Ouabbou H, Royo C, Slama A, Tuberosa R: Quantitative trait loci for grain yield and adaptation of durum wheat (Triticum durum Desf.) across a wide range of water availability. Genetics 2008, 178:489-511.
• [25]Maccaferri M, Sanguineti MC, Mantovani P, Demontis A, Massi A, Ammar K, Kolmer J, Czembor J, Breiman A, Tuberosa R: Association mapping of leaf rust response in durum wheat. Mol Breed 2010, 26:189-228.
• [26]Marone D, Russo MA, Laidò G, De Vita P, Papa R, Blanco A, Gadaleta A, Rubiales D, Mastrangelo AM: Genetic basis of qualitative and quantitative resistance to powdery mildew in wheat: from consensus regions to candidate genes. BMC Genomics 2013, 14:562. BioMed Central Full Text
• [27]Reimer S, Pozniak CJ, Clarke FR, Clarke JM, Somers DJ, Knox RE, Singh AK: Association mapping of yellow pigment in an elite collection of durum wheat cultivars and breeding lines. Genome 2008, 51:1016-1025.
• [28]Bauer E, Falque M, Walter H, Bauland C, Camisan C, Campo L, Meyer N, Ranc N, Rincent R, Schipprack W, Altmann T, Flament P, Melchinger AE, Menz M, Moreno-González J, Ouzunova M, Revilla P, Charcosset A, Martin OC, Schön CC: Intraspecific variation of recombination rate in maize. Genome Biol 2013, 14:R103. BioMed Central Full Text
• [29]Saintenac C, Faure S, Remay A, Choulet F, Ravel C, Paux E, Balfourier F, Feuillet C, Sourdille P: Variation in crossover rates across a 3-Mb contig of bread wheat (Triticum aestivum) reveals the presence of a meiotic recombination hotspot. Chromosoma 2011, 120:185-198.
• [30]Maccaferri M, Stefanelli S, Rotondo F, Tuberosa R, Sanguineti MC: Relationships among durum wheat accessions. I. Comparative analysis of SSR, AFLP, and phenotypic data. Genome 2007, 50:373-384.
• [31]Ooijen V: JoinMap® 4, Software for the calculation of genetic linkage maps in experimental populations. Wageningen: Kyazma B.V; 2006.
• [32]de Givry S, Bouchez M, Chabrier P, Milan D, Schiex T: CARHTA GENE: multipopulation integrated genetic and radiation hybrid mapping. Bioinformatics 2005, 21:1703-1704.
• [33]Wu Y, Close TJ, Lonardi S: Accurate construction of consensus genetic maps via integer linear programming. IEEE/ACM Trans Comput Biol Bioinform 2011, 8:381-394.
• [34]Ronin Y, Mester D, Minkov D, Belotserkovski R, Jackson BN, Schnable PS, Aluru S, Korol A: Two-phase analysis in consensus genetic mapping. G3 Genes, Genomes, Genetics 2012, 2:537-549.
• [35]Blanco A, Colasuonno P, Gadaleta A, Mangini G, Schiavulli A, Simeone R, Digesù AM, De Vita P, Mastrangelo AM, Cattivelli L: Quantitative trait loci for yellow pigment concentration and individual carotenoid compounds in durum wheat. J Cereal Sci 2011, 54:255-264.
• [36]Patil RM, Oak MD, Tamhankar SA, Sourdille P, Rao VS: Mapping and validation of a major QTL for yellow pigment content on 7AL in durum wheat (Triticumturgidum L. ssp. durum). Mol Breeding 2008, 21:485-496.
• [37]Paux E, Sourdille P, Salse J, Saintenac C, Choulet F, Leroy P, Korol A, Michalak M, Kianian S, Spielmeyer W, Lagudah E, Somers D, Kilian A, Alaux M, Vautrin S, Bergès H, Eversole K, Appels R, Safar J, Simkova H, Dolezel J, Bernard M, Feuillet C: A physical map of the 1-gigabase bread wheat chromosome 3B. Science 2008, 322:101-104.
• [38]Maccaferri M, Sanguineti MC, Demontis A, El-Ahmed A, del Moral Garcia L, Maalouf F, Nachit M, Nserallah N, Ouabbou H, Rhouma S, Royo C, Villegas D, Tuberosa R: Association mapping in durum wheat grown across a broad range of water regimes. J Exp Bot 2011, 62:409-438.
• [39]Sved JA: Linkage disequilibrium and homozygosity of chromosome segments in finite populations. Theor Popul Biol 1971, 2:125-141.
• [40]Wilhelm EP, Turner AS, Laurie DA: Photoperiod insensitive Ppd-A1a mutations in tetraploid wheat (Triticum durum Desf.). Theor Appl Genet 2009, 118:285-294.
• [41]Griffiths S, Simmonds J, Leverington M, Wang Y, Fish L, Sayers L, Alibert L, Orford S, Wingen L, Herry L, Faure S, Laurie D, Bilham L, Snape J: Meta-QTL analysis of the genetic control of ear emergence in elite European winter wheat germplasm. Theor Appl Genet 2009, 119:383-395.
• [42]Hanocq E, Laperche A, Jaminon O, Lainé AL, Le Gouis J: Most significant genome regions involved in the control of earliness traits in bread wheat, as revealed by QTL meta-analysis. Theor Appl Genet 2007, 114:569-584.
• [43]Hanocq E, Niarquin M, Heumez E, Rousset M, Le Gouis J: Detection and mapping of QTL for earliness components in a bread wheat recombinant inbred lines population. Theor Appl Genet 2004, 110:106-115.
• [44]Bennett D, Izanloo A, Edwards J, Kuchel H, Chalmers K, Tester M, Reynolds M, Schnurbusch T, Langridge P: Identification of novel quantitative trait loci for days to ear emergence and flag leaf glaucousness in a bread wheat (Triticum aestivum L.) population adapted to southern Australian conditions. Theor Appl Genet 2012, 124:697-711.
• [45]Le Gouis J, Bordes J, Ravel C, Heumez E, Faure S, Praud S, Galic N, Remoué C, Balfourier F, Allard V, Rousset M: Genome-wide association analysis to identify chromosomal regions determining components of earliness in wheat. Theor Appl Genet 2012, 124:597-611.
• [46]Bonnin I, Rousset M, Madur D, Sourdille P, Dupuits C, Brunel D, Goldringer I: FT genome A and D polymorphisms are associated with the variation of earliness components in hexaploid wheat. Theor Appl Genet 2008, 116:383-394.
• [47]Yan L, Fu D, Li C, Blechl A, Tranquilli G, Bonafede M, Sanchez A, Valarik M, Yasuda S, Dubcovsky J: The wheat and barley vernalization gene VRN3 is an orthologue of FT. Proc Natl Acad Sci U S A 2006, 103:19581-19586.
• [48]Hudson CJ, Freeman JS, Kullan AR, Petroli CD, Sansaloni CP, Kilian A, Detering F, Grattapaglia D, Potts BM, Myburg AA, Vaillancourt RE: A reference linkage map for eucalyptus. BMC Genomics 2012, 13:240. BioMed Central Full Text
• [49]Khan MA, Han Y, Zhao YF, Troggio M, Korban SS: A multi-population consensus genetic map reveals inconsistent marker order among maps likely attributed to structural variations in the apple genome. PLoS One 2012, 7:e47864.
• [50]Maccaferri M, Sanguineti MC, Noli E, Tuberosa R: Population structure and long-range linkage disequilibrium in a durum wheat elite collection. Mol Breed 2005, 15:271-290.
• [51]Peng J, Korol AB, Fahima T, Röder MS, Ronin YI, Li YC, Nevo E: Molecular genetic maps in wild emmer wheat, Triticum dicoccoides: genome-wide coverage, massive negative interference, and putative quasi-linkage. Genome Res 2000, 10:1509-1531.
• [52]Haudry A, Cenci A, Ravel C, Bataillon T, Brunel D, Poncet C, Hochu I, Poirier S, Santoni S, Glémin S, David J: Grinding up wheat: a massive loss of nucleotide diversity since domestication. Mol Biol Evol 2007, 24:1506-1517.
• [53]Ardlie KG, Kruglyak L, Seielstad M: Patterns of linkage disequilibrium in the human genome. Nat Rev Genet 2002, 3:299-309.
• [54]Carlson CS, Eberle MA, Rieder MJ, Yi Q, Kruglyak L, Nickerson DA: Selecting a maximally informative set of single-nucleotide polymorphisms for association analyses using linkage disequilibrium. Am J Hum Genet 2004, 74:106-120.
• [55]Somers DJ, Banks T, DePauw R, Fox S, Clarke J, Pozniak C, McCartney C: Genome-wide linkage disequilibrium analysis in bread wheat and durum wheat. Genome 2007, 50:557-567.
• [56]Chao S, Dubcovsky J, Dvorak J, Ming-Cheng L, Baenziger SP, Matnyazov R, Clark DR, Talbert LE, Anderson JA, Dreisigacker S, Glover K, Chen J, Campbell K, Bruckner PL, Rudd JC, Haley S, Carver BF, Perry S, Sorrells ME, Akhunov ED: Population-and genome-specific patterns of linkage disequilibrium and SNP variation in spring and winter wheat (Triticum aestivum L.). BMC Genomics 2010, 11:727. BioMed Central Full Text
• [57]Cavanagh CR, Chao S, Wang S, Huang BE, Stephen S, Kiani S, Forrest K, Saintenac C, Brown-Guedira GL, Akhunova A, See D, Bai G, Pumphrey M, Tomar L, Wong D, Kong S, Reynolds M, da Silva Lopez M, Bockelman H, Talbert L, Anderson JA, Dreisigacker S, Baenziger S, Carter A, Korzun V, Morrell PL, Dubcovsky J, Morell MK, Sorrells ME, Hayden MJ, et al.: Genome-wide comparative diversity uncovers multiple targets of selection for improvement in hexaploid wheat landraces and cultivars. Proc Natl Acad Sci U S A 2013, 110:8057-8062.
• [58]Pasam RK, Sharma R, Malosetti M, van Eeuwijk FA, Haseneyer G, Kilian B, Graner A: Genome-wide association studies for agronomical traits in a world wide spring barley collection. BMC Plant Biol 2012, 12:16. BioMed Central Full Text
• [59]Bost B, de Vienne D, Moreau L, Dillmann C: Genetic and nongenetic bases for the L-shaped distribution of quantitative trait loci effects. Genetics 2001, 157:1773-1787.
• [60]Brachi B, Faure N, Horton M, Flahauw E, Vazquez A, Nordborg M, Bergelson J, Cuguen J, Roux F: Linkage and association mapping of Arabidopsis thaliana flowering time in nature. PLoS Genet 2010, 6:e1000940.
• [61]Reif JC, Gowda M, Maurer HP, Longin CFH, Korzun V, Ebmeyer E, Bothe R, Pietsch C, Würschum T: Association mapping for quality traits in soft winter wheat. Theor Appl Genet 2011, 122:961-970.
• [62]Salvi S, Castelletti S, Tuberosa R: An updated consensus map for flowering time QTLs in maize. Maydica 2009, 54:501-512.
• [63]Wang WY, Barratt BJ, Clayton DG, Todd JA: Genome-wide association studies: theoretical and practical concerns. Nat Rev Genet 2005, 6:109-118.
• [64]van Poecke RM, Maccaferri M, Tang J, Truong HT, Janssen A, van Orsouw NJ, Salvi S, Sanguineti MC, Tuberosa R, van der Vossen EA: Sequence‒based SNP genotyping in durum wheat. Plant Biotechnol J 2013, 11:809-817.
• [65]Salvi S, Corneti S, Bellotti M, Carraro N, Sanguineti MC, Castelletti S, Tuberosa R: Genetic dissection of maize phenology using an intraspecific introgression library. BMC Plant Biol 2011, 11:4. BioMed Central Full Text
• [66]Graziani M, Maccaferri M, Royo C, Salvatorelli F, Tuberosa R: QTL dissection of yield components and morpho-physiological traits in a durum wheat elite population tested in contrasting thermo-pluviometric conditions. Crop and Pasture Science 2014, 65:80-95.
• [67]Maccaferri M, Francia R, Ratti C, Rubies-Autonell C, Colalongo C, Ferrazzano G, Tuberosa R, Sanguineti MC: Genetic analysis of Soil-borne cereal mosaic virus response in durum wheat: evidence for the role of the major quantitative trait locus QSbm.ubo-2BS and of minor quantitative trait loci. Mol Breed 2012, 29:973-988.
• [68]Zhang W, Chao S, Manthey F, Chicaiza O, Brevis JC, Echenique V, Dubcovsky J: QTL analysis of pasta quality using a composite microsatellite and SNP map of durum wheat. Theor Appl Genet 2008, 117:1361-1377.
• [69]Somers DJ, Fedak G, Clarke J, Cao W: Mapping of FHB resistance QTLs in tetraploid wheat. Genome 2006, 49:1586-1593.
• [70]Chu C-G, Friesen TL, Chao S, Faris JD, Zhong SB, Xu SS: Novel tan spot resistance QTLs detected using an SSR-based linkage map of tetraploid wheat. Mol Breed 2010, 25:327-338.
• [71]Gadaleta A, Giancaspro A, Giove SL, Zacheo S, Mangini G, Simeone R, Signorile A, Blanco A: Genetic and physical mapping of new EST-derived SSRs on the A and B genome chromosomes of wheat. Theor Appl Genet 2009, 118:1015-1025.
• [72]Cone KC, McMullen MD, Bi IV, Davis GL, Yim Y-S, Gardiner JM, Pol-acco ML, Sanchez-Villeda H, Fang Z, Schroeder SG, Havermann SA, Bowers JE, Paterson AH, Soderlund CA, Engler FW, Wing RA, Coe EH: Genetic, physical and informatics resources for maize: on the road to an integrated map. Plant Physiol 2002, 130:1598-1605.
• [73]Yu J, Pressoir G, Briggs WH, Vroh Bi I, Yamasaki M, Doebley JF, McMullen MD, Gaut BS, Nielsen DM, Holland JB, Kresovich S, Buckler ES: A unified mixed-model method for association mapping that accounts for multiple levels of relatedness. Nat Genet 2006, 38:203-208.
• [74]Rexroad CE III, Vallejo RL: Estimates of linkage disequilibrium and effective population size in rainbow trout. BMC Genet 2009, 10:83.
• [75]Breseghello F, Sorrells ME: Association mapping of kernel size and milling quality in wheat (Triticum aestivum L.) cultivars. Genetics 2006, 172:1165-1177.
• [76]Excoffier L, Laval G, Schneider S: Arlequin (version 3.0): an integrated software package for population genetics data analysis. Evol Bioinform Online 2007, 1:47-50.
• [77]Kang HM, Zaitlen NA, Wade CM, Kirby A, Heckerman D, Daly MJ, Eskin E: Efficient control of population structure in model organism association mapping. Genetics 2008, 178:1709-1723.
• [78]Pritchard JK, Przeworski M: Linkage disequilibrium in humans: Models and data. Am J Hum Genet 2001, 69:1-14.
• [79]Lawrence R, Day-Williams AG, Mott R, Broxholme J, Cardon LR, Zeggini E: GLIDERS–a web-based search engine for genome-wide linkage disequilibrium between HapMap SNPs. BMC Bioinformatics 2009, 10:367. BioMed Central Full Text