Systems genetics, bioinformatics and eQTL mapping

Genetica

Volumn 138, Issue 9, 2010, Pages 915-924

  Li, Hong ^a   Deng, Hongwen ^b  

^a CHONGQING TECHNOLOGY AND BUSINESS UNIVERSITY   (China)

^b CREIGHTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Bioinformatics; Expression quantitative trait loci (eQTL); Gene expression patterns; Genomic marker data; Microarray

Indexed keywords

BIOLOGY; CHROMOSOME MAP; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETIC ASSOCIATION; GENOMICS; METHODOLOGY; QUANTITATIVE TRAIT LOCUS; REVIEW;

CHROMOSOME MAPPING; COMPUTATIONAL BIOLOGY; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENOME-WIDE ASSOCIATION STUDY; GENOMICS; QUANTITATIVE TRAIT LOCI;

EID: 77957374321     PISSN: 00166707     EISSN: None     Source Type: Journal    
DOI: 10.1007/s10709-010-9480-x     Document Type: Review

References (95)

1. Abraham AP, Miguel V, Rathi S, Helen MK, Cheryl LR, Li Na, Sue BK, Carrie SM, John KB, Conrad TG, Tamara JP (2005) Gene expression differences in mice divergently selected for methamphetamine sensitivity. Mamm Genome 16: 291-305. doi: 10. 1007/s00335-004-2451-8.
2. Adam R, Fernando PMV, Wang W, Leonard M, David WT (2007) The polymorphism architecture of mouse genetic resources elucidated using genome-wide resequencing data: implications for QTL discovery and systems genetics. Mamm Genome 18: 473-481. doi: 10. 1007/s00335-007-9045-1.
3. Andersson L (2001) Genetic dissection of phenotypic diversity in farm animals. Nat Rev Genet 2: 130-138. doi: 10. 1038/35052563.
4. Andrew RW, Nicolas D, Sean MR, Jérôme SC, Jérôme L, Aurélie L, Arne N, Sébastien R, Julie J, Louis B (2008) The phenomics and expression quantitative trait locus mapping of brain trans-criptomes regulating adaptive divergence in lake whitefish species pairs (Coregonus sp.). Genetics 180: 147-164. doi: 10. 1534/genetics. 108. 089938.
5. Aylor DL, Zeng ZB (2008) From classical genetics to quantitative genetics to systems biology: modeling epistasis. PLoS Genet 4(3): e1000029. doi: 10. 1371/journal. pgen. 1000029.
6. Bao L, Wei L, Peirce JL, Homayouni R, Li HQ, Zhou M, Chen H, Lu L, Williams RW, Pfeffer LM, Goldowitz D, Cui Y (2006) Combining gene expression QTL mapping and phenotypic spectrum analysis to uncover gene regulatory relationships. Mamm Genome 17: 575-583. doi: 10. 1007/s00335-005-0172-2.
7. Brem RB, Kruglyak L (2005) The landscape of genetic complexity across 5, 700 gene expression traits in yeast. PNAS 102(5): 1572-1577. doi: 10. 1073/pnas. 0408709102.
8. Brem RB, Yvert G, Clinton R, Kruglyak L (2002) Genetic dissection of transcriptional regulation in budding yeast. Science 296: 752-755. doi: 10. 1126/science. 1069516.
9. Broman KW (2005) The genomes of recombinant inbred lines. Genetics 169(2): 1133-1146. doi: 10. 1534/genetics. 104. 035212.
10. Bystrykh L, Weersing E, Dontje B, Sutton S, Pletcher MT, Wiltshire T, Su AI, Vellenga E, Wang JT, Manly KF, Lu L, Chesler EJ, Alberts R, Jansen RC, Williams RW, Cooke MP, de Haan G (2005) Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics'. Nat Genet 37: 225-232. doi: 10. 1038/ng1497.
11. Chen M, Kendziorski C (2007) A statistical framework for expression quantitative trait loci mapping. Genetics 177: 761-771. doi: 10. 1534/genetics. 107. 071407.
12. Chen L, Tong TJ, Zhao HY (2008) Considering dependence among genes and markers for false discovery control in eQTL mapping. Bioinformatics 24(18): 2015-2022. doi: 10. 1093/bioinformatics/btn373.
13. Chesler EJ, Lu L, Shou S, Qu Y, Gu J, Wang J, Hsu HC, Mountz JD, Baldwin NE, Langston MA, Threadgill DW, Manly KF, Williams RW (2005) Complex trait analysis of gene expression uncovers polygenic and pleiotropic networks that modulate nervous system function. Nat Genet 37: 233-242. doi: 10. 1038/ng1518.
14. Chesler EJ, Miller DR, Branstetter LR, Galloway LD, Jackson BL, Vivek MP, Voy BH, Culiat CT, Threadgill DW, Williams RW, Churchill GA, Johnson DK, Manly KF (2008) The Collabora-tive Cross at Oak Ridge National Laboratory: developing a powerful resource for systems genetics. Mamm Genome 19: 382-389. doi: 10. 1007/s00335-008-9135-8.
15. Churchill GA, Airey DC, Allayee H, Angel JM, Attie AD, Beatty J, Beavis WD, Belknap JK, Bennett B, Berrettini W, Bleich A, Bogue M, Broman KW, Buck KJ, Buckler E, Burmeister M, Chesler EJ, Cheverud JM, Clapcote S, Cook MN, Cox RD, Crabbe JC, Crusio WE, Darvasi A, Deschepper CF, Doerge RW, Farber CR, Forejt J, Gaile D, Garlow SJ, Geiger H, Gershenfeld H, Gordon T, Gu J, Gu W, de Haan G, Hayes NL, Heller C, Himmelbauer H, Hitzemann R, Hunter K, Hsu HC, Iraqi FA, Ivandic B, Jacob HJ, Jansen RC, Jepsen KJ, Johnson DK, Johnson TE, Kempermann G, Kendziorski C, Kotb M, Kooy RF, Llamas B, Lammert F, Lassalle JM, Lowenstein PR, Lu L, Lusis A, Manly KF, Marcucio R, Matthews D, Medrano JF, Miller DR, Mittleman G, Mock BA, Mogil JS, Montagutelli X, Morahan G, Morris DG, Mott R, Nadeau JH, Nagase H, Nowakowski RS, O'Hara BF, Osadchuk AV, Page GP, Paigen B, Paigen K, Palmer AA, Pan HJ, Peltonen-Palotie L, Peirce J, Pomp D, Pravenec M, Prows DR, Qi Z, Reeves RH, Roder J, Rosen GD, Schadt EE, Schalkwyk LC, Seltzer Z, Shimomura K, Shou S, Sillanpää MJ, Siracusa LD, Snoeck HW, Spearow JL, Svenson K, Tarantino LM, Threadgill D, Toth LA, Valdar W, de Villena FPM, Warden C, Whatley S, Williams RW, Tim Wiltshire T, Yi N, Zhang D, Zhang M, Zou F (2004) The collaborative cross, a community resource for the genetic analysis of complex traits. Nat Genet 36: 1133-1137. doi: 10. 1038/ng1104-1133.
16. Comai L, Young K, Till BJ, Reynolds SH, Greene EA, Codomo CA, Enns LC, Johnson JE, Burtner C, Odden AR, Heniloff S (2004) Efficient discovery of DNA polymorphisms in natural populations by Ecotilling. Plant J 37: 778-786. doi: 10. 1111/j. 0960-7412. 2003. 01999. x.
17. Daniel MG, Alison HH, Fred AW, David WT, Ivan R (2009a) Replication and narrowing of gene expression quantitative trait loci using inbred mice. Mamm Genome 20: 437-446. doi: 10. 1007/s00335-009-9199-0.
18. Daniel MG, Andrey AS, Tieu-Chong L, Fred AW, Ivan R, Andrew BN (2009b) FastMap: fast eQTL mapping in homozygous populations. Bioinformatics 25(4): 482-489. doi: 10. 1093/bioinformatics/btn648.
19. Daniel CC, Lu L, Khyobeni M, Xusheng W, Manjunatha J, John AM, William LT, Klaus D, Perikles S, Robert WW (2010) Detection, validation, and downstream analysis of allelic variation in gene expression. Genetics 184: 119-128. doi: 10. 1534/genetics. 109. 107474.
20. David WT (2006) Meeting report for the 4th annual complex trait consortium meeting: from QTLs to systems genetics. Mamm Genome 17: 2-4. doi: 10. 1007/s00335-005-0153-5.
21. de Koning DJ, Haley CS (2005) Genetical genomics in humans and model organisms. Trends Genet 21(7): 377-381.
22. Derome N, Bougas B, Rogers SM, Whiteley AR, Labbe A, Laroche J, Bernatchez L (2008) Pervasive sex-linked effects on transcription regulation as revealed by expression quantitative trait loci mapping in lake whitefish species pairs (Coregonus sp., salmonidae). Genetics 179: 1903-1917. doi: 10. 1534/genetics. 107. 086306.
23. Dinanath S, Alex R, Mark D, Michael W, Veronika N, Ian F, Natalia M (2005) GNARE: automated system for high- throughput genome analysis with Grid computational backend. J Clin Monit Comput 19: 361-369. doi: 10. 1007/s10877-005-3463-y.
24. Doerge RW (2002) Mapping and analysis of quantitative trait loci in experimental populations. Nat Rev Genet 3: 43-52. doi: 10. 1038/nrg703.
25. Doss S, Schadt EE, Drake TA, Lusis AJ (2005) Cis-acting expres-sion quantitative trait loci in mice. Genome Res 15: 681-691. doi: 10. 1101/gr. 3216905.
26. Farrall M (2004) Quantitative genetic variation: a post-modern view. Hum Mol Genet 13(1): 1R-R7. doi: 10. 1093/hmg/ddh084.
27. Flint J, Valdar W, Shifman S, Mott R (2005) Strategies for mapping and cloning quantitative trait genes in rodents. Nat Rev Genet 6: 271-285. doi: 10. 1038/nrg1576.
28. Gelfond J, Ibrahim J, Zou F (2007) Proximity model for expression quantitative trait loci (eQTL) detection. Biometrics 63: 1108-1116. doi: 10. 1111/j. 1541-0420. 2007. 00778. x.
29. Gilad Y, Rifkin SA, Pritchard JK (2008) Revealing the architecture of gene regulation: the promise of eQTL studies. Trends Genet 24: 408-415. doi: 10. 1016/j. tig. 2008. 06. 001.
30. Gowda M, Venu RC, Roopalakshmi K, Sreerekha MV, Kulkarni RS (2003) Advances in rice breeding, genetics and genomics. Mol Breeding 11: 337-352.
31. Hao K, Schadt EE, Storey JD (2008) Calibrating the performance of SNP arrays for whole-genome association studies. PLoS Genet 4(6): e1000109. doi: 10. 1371/journal. pgen. 1000109.
32. Hill AE, Lander ES, Nadeau JH (2006) Chromosome substitution strains: a new way to study genetically complex traits. Methods Mol Med 128: 153-172.
33. Hitzemann B, Dains K, Kanes S, Hitzemann R (1994) Further studies on the relationship between dopamine cell density and haloperidol-induced catalepsy. J Pharmacol Exp Ther 271: 969-976.
34. Hu XX, Gao Y, Feng CG QY, Wang XB, Du Z, Wang QS, Li N (2009) Advanced technologies for genomic analysis in farm animals and its application for QTL mapping. Genetica 136: 371-386. doi: 10. 1007/s10709-008-9338-7.
35. Hubner N, Wallace CA, Zimdahl H, Petretto E, Schulz H, Maciver F, Mueller M, Hummel O, Monti J, Zidek V, Musilova A, Kren V, Causton H, Game L, Born G, Schmidt S, Müller A, Cook SA, Kurtz TW, Whittaker J, Pravenec M, Aitman TJ (2005) Integrated transcriptional profiling and linkage analysis for identification of genes underlying disease. Nat Genet 37: 243-253. doi: 10. 1038/ng1522.
36. Hudgins CC, Steinberg RT, Klinman DM, Reeves MJ, Steinberg AD (1985) Studies of Consomic mice bearing the Y chromosome of the BXSB mouse. J Immunol 134(6): 3849-3854.
37. Hyonho C, Sündüz K (2009) Expression quantitative trait loci map- ping with multivariate sparse partial least squares regression. Genetics 182: 79-90. doi: 10. 1534/genetics. 109. 100362.
38. Iakoubova OA, Olsson CL, Dains KM, Ross DA, Andalibi A, Lau K, Choi J, Kalcheva I, Cunanan M, Louie J, Nimon V, Machrus M, Bentley LG, Beauheim C, Silvery S, Cavalcoli J, Lusis AJ, West DB (2001) Genome-tagged mice (GTM): two sets of genome-wide congenic strains. Genomics 74: 89-104. doi: 10. 1006/geno. 2000. 6497.
39. Ideker T, Winslow LR, Lauffenburger AD (2006) Bioengineering and systems biology. Ann Biomed Eng 34(2): 257-264. doi: 10. 1007/s10439-005-9047-7.
40. Jansen RC (2003) Studying complex biological systems using multifactorial perturbation. Nat Rev Genet 4: 145-151. doi: 10. 1038/nrg996.
41. Jansen RC, Nap JP (2001) Genetical genomics: the added value from segregation. Trends Genet 17(7): 388-391. doi: 10. 1016/S0168-9525(01)02310-1.
42. Jia ZY, Xu SZ (2007) Mapping quantitative trait loci for expression abundance. Genetics 176: 611-623. doi: 10. 1534/genetics. 106. 065599.
43. Kendziorski C, Wang P (2006) A review of statistical methods for expression quantitative trait loci mapping. Mamm Genome 17: 509-517. doi: 10. 1007/s00335-005-0189-6.
44. Kendziorski C, Newton M, Lan H, Gould M (2003) On parametric empirical bayes methods for comparing multiple groups using replicated gene expression profiles. Stat Med 22: 3899-3914. doi: 10. 1002/sim. 1548.
45. Kendziorski CM, Chen M, Yuan M, Lan H, Attie AD (2006) Statistical methods for expression quantitative trait loci (eQTL) mapping. Biometrics 62: 19-27. doi: 10. 1111/j. 1541-0420. 2005. 00437. x.
46. Keurentjes JJB, Fu JY, Terpstra IR, Garcia JM, van den Ackerveken G, Snoek LB, Peeters AJM, Vreugdenhil D, Koornneef M, Jansen RC (2007) Regulatory network construction in Arabidopsis by using genome-wide gene expression quantitative trait loci. PNAS 104(5): 1708-1713. doi: 10. 1073/pnas. 0610429104.
47. Khlestkina EK, Salina EA (2006) SNP Markers: methods of analysis, ways of development, and comparison on an example of common wheat. Russ J Genet 42(6): 585-594. doi: 10. 1134/S1022795406060019.
48. Lee SI, Dudley AM, Drubin D, Silver PA, Krogan NJ, Pe'er D, Koller D (2009) Learning a prior on regulatory potential from eQTL data. PLoS Genet 5(1): e1000358. doi: 10. 1371/journal. pgen. 1000358.
49. Li J, Burmeister M (2005) Genetical genomics: combining genetics with gene expression analysis. Hum Mol Genet 14: R163-R169. doi: 10. 1093/hmg/ddi267.
50. Liu B, de la Fuente A, Hoeschele I (2008) Gene network inference via structural equation modeling in genetical genomics experiments. Genetics 178: 1763-1776. doi: 10. 1534/genetics. 107. 080069.
51. Marilyn ALW, Kyunga K, Daniel JK, van Hans L, Richard WM, Doerge RW, Dina ASC (2007) Global eQTL mapping reveals the complex genetic architecture of transcript-level variation in arabidopsis. Genetics 175: 1441-1450. doi: 10. 1534/genetics. 106. 064972.
52. Martin H, Hans PM, Albrecht EM, Matthias F (2008) The Plabsoft database: a comprehensive database management system for integrating phenotypic and genomic data in academic and commercial plant breeding programs. Euphytica 161: 173-179. doi: 10. 1007/s10681-007-9478-3.
53. Matias K, Christopher JB, Alexander AM, Zhao-Bang Z, Ronald RS (2005) Genetic architecture of transcript-level variation in differentiating xylem of a eucalyptus hybrid. Genetics 169: 2295-2303. doi: 10. 1534/genetics. 104. 039198.
54. Meng H, Vera I, Che N, Wang X, Wang SS, Ingram-Drake L, Schadt EE, Drake TA, Lusis AJ (2007) Identification of Abcc6 as the major causal gene for dystrophic cardiac calcification in mice through integrative genomics. PNAS 104(11): 4530-4535. doi: 10. 1073/pnas. 0607620104.
55. Monks SA, Leonardson A, Zhu H, Cundiff P, Pietrusiak P, Edwards S, Phillips JW, Sachs A, Schadt EE (2004) Genetic inheritance of gene expression in human cell lines. Am J Hum Genet 75: 1094-1105. doi: 10. 1086/426461.
56. Morley M, Molony CM, Weber TM, Devlin JL, Ewens KG, Spielman RS, Cheung VG (2004) Genetic analysis of genome-wide variation in human gene expression. Nature 430: 743-747. doi: 10. 1038/nature02797.
57. Nadeau JH, Singer JB, Matin A, Lander ES (2000) Analysing complex genetic traits with chromosome substitution strains. Nat Genet 24(3): 221-225. doi: 10. 1038/73427.
58. Nan B, Ina H (2005) Genetical genomics analysis of a yeast segregant population for transcription network inference. Genetics 170: 533-542. doi: 10. 1534/genetics. 105. 041103.
59. Newton M, Kendziorski C, Richmond C, Blattner F, Tsui K (2001) On differential variability of expression ratios: improving statistical inference about gene expression changes from microarray data. J Comput Biol 8: 37-52. doi: 10. 1089/106652701300099074.
60. Noble D (2002) Modeling the heart-from genes to cells to the whole organ. Science 295: 1678-1682. doi: 10. 1126/science. 1069881.
61. Paigen K, Eppig JT (2000) A mouse phenome project. Mamm Genome 11(9): 715-717. doi: 10. 1007/s003350010152.
62. Paul S (2008) Statistical power of expression quantitative trait loci for mapping of complex trait loci in natural populations. Genetics 178: 2201-2216. doi: 10. 1534/genetics. 107. 076687.
63. Peters LL, Robledo RF, Bult CJ, Churchill GA, Paigen BJ, Svenson KL (2007) The mouse as a model for human biology: a resource guide for complex trait analysis. Nat Rev Genet 8: 58-59. doi: 10. 1038/nrg2025.
64. Phillip M, Jeff J, Chunlei W, David LD, John RW, Serge B, Joseph ST, Kazuhiro S, Akira K, Joseph B, Tim W, Andrew IS (2007) Genomewide association analysis in diverse inbred mice: power and population structure. Genetics 176: 675-683. doi: 10. 1534/genetics. 106. 066241.
65. Potokina EK, Druka A, Luo Z, Waugh R, Kearsey MJ (2009) The transcriptome analysis of barley (Hordeum vulgare L.) using the Affymetrix Barley1 GeneChip. Russ J Genet 45(11): 1317-1328. doi: 10. 1134/S1022795409110064.
66. Prem N (2010) Quantitative genetics: past and present. Mol Breeding 26(2): 135-146. doi: 10. 1007/s11032-010-9406-4.
67. Rhonda DC, Sonia L, Dan N, Stephen HH (2006) Genetic regulation of gene expression during shoot development in arabidopsis. Genetics 172: 1155-1164. doi: 10. 1534/genetics. 105. 042275.
68. Rockman MV, Kruglyak L (2006) Genetics of global gene expression. Nat Rev Genet 7: 862-872. doi: 10. 1038/nrg1964.
69. Rudi B (2007) From mouse genetics to systems biology. Mamm Genome 18: 383-388. doi: 10. 1007/s00335-007-9044-2.
70. Sasaki T, Antonio B (2005) Where does the accurate rice genome sequence lead us? Plant Mol Biol 59: 27-32. doi: 10. 1007/s11103-005-1224-4.
71. Satoshi Y, Kuniko W, Tomoko N, Yoshimi T, Takashi K, Toshikazu U (2005) Expression quantitative trait loci analysis of 13 genes in the rat prostate. Genetics 171: 1231-1238. doi: 10. 1534/genetics. 104. 038174.
72. Schadt EE, Lum PY (2006) Thematic review series: systems biology approaches to metabolic and cardiovascular disorders. reverse engineering gene networks to identify key drivers of complex disease phenotypes. J Lipid Res 47: 2601-2613. doi: 10. 1194/jlr. R600026-JLR200.
73. Schadt EE, Monks SA, Drake TA, Lusis AJ, Che N, Colinayo V, Ruff TG, Milligan SB, Lamb JR, Cavet G, Linsley PS, Mao M, Stoughton RB, Friend SH (2003) Genetics of gene expression surveyed in maize, mouse and man. Nature 422: 297-302. doi: 10. 1038/nature01434.
74. Schadt EE, Molony C, Chudin E, Hao K, Yang X, Lum PY, Kasarskis A, Zhang B, Wang S, Suver C, Zhu J, Millstein J, Sieberts S, Lamb J, GuhaThakurta D, Derry J, Storey JD, Avila-Campillo I, Kruger MJ, Johnson JM, Rohl CA, van Nas A, Mehrabian M, Drake TA, Lusis AJ, Smith RC, Guengerich FP, Strom SC, Schuetz E, Rushmore TH, Ulrich R (2008) Mapping the genetic architecture of gene expression in human liver. PLoS Biol 6(5): 1020-1032. doi: 10. 1371/journal. pbio. 0060107.
75. Schadt EE, Zhang B, Zhu J (2009) Advances in systems biology are enhancing our understanding of disease and moving us closer to novel disease treatments. Genetica 136: 259-269. doi: 10. 1007/s10709-009-9359-x.
76. Shi C, Uzarowska A, Ouzunova M, Landbeck M, Wenzel G, Lübberstedt T (2007) Identification of candidate genes associated with cell wall digestibility and eQTL (expression quantitative trait loci)analysis in a Flint X Flint maize recombinant inbred line population. BMC Genomics 8: 22. doi: 10. 1186/1471-2164-8-22.
77. Sieberts SK, Schadt EE (2007) Moving toward a system genetics view of disease. Mamm Genome 18: 389-401. doi: 10. 1007/s00335-007-9040-6.
78. Silpa S, Andreas B, Richard MK, Yonina E, Trey I (2008) eQED: an efficient method for interpreting eQTL associations using protein networks. Mol Sys Biol 4: 162. doi: 10. 1038/msb. 2008. 4.
79. Storey JD, Akey JM, Kruglyak L (2005) Multiple locus linkage analysis of genome-wide expression in yeast. PLoS Biol 3(8): 1380-1390. doi: 10. 1371/journal. pbio. 0030267.
80. Su WL, Sieberts SK, Kleinhanz RR, Lux K, Millstein J, Molony C, Schadt EE (2010) Assessing the prospects of genome-wide association studies performed in inbred mice. Mamm Genome 21: 143-152. doi: 10. 1007/s00335-010-9249-7.
81. Sun W, Yu TW, Li KC (2007) Detection of eQTL modules mediated by activity levels of transcription factors. Bioinformatics 23(17): 2290-2297. doi: 10. 1093/bioinformatics/btm327.
82. Sun W, Yuan SS, Li KC (2008) Trait-trait dynamic interaction: 2D-trait eQTL mapping for genetic variation study. BMC Genomics 9: 242. doi: 10. 1186/1471-2164-9-242.
83. Todd ES, Kwang-Youn AK, Ruth ES, Alisdair RP, Terry AB, Kevin LK, Anne MD, Gerald FD, Jian H, Thomas LC, Val CS, Edwin MS (2006) Regulation of gene expression in the mammalian eye and its relevance to eye disease. PNAS 103(39): 14429-14434. doi: 10. 1073/pnas. 0602562103.
84. Tusher V, Tibshirani R, Chu G (2001) Significance analysis of microarrays applied to the ionizing radiation response. PNAS 98: 5116-5121. doi: 10. 1073/pnas. 091062498.
85. Valdar W, Solberg LC, Gauguier D, Burnett S, Klenerman P, Cookson WO, Taylor MS, Rawlins JNP, Mott R, Flint J (2006) Genome-wide genetic association of complex traits in heterogeneous stock mice. Nat Genet 38(8): 879-887. doi: 10. 1038/ng1840.
86. Wan XY, Wan JM, Jiang L, Wang JK, Zhai HQ, Weng JF, Wang HL, Lei CL, Wang JL, Zhang X, Cheng ZJ, Guo XP (2006) QTL analysis for rice grain length and fine mapping of an identified QTL with stable and major effects. Theor Appl Genet 112: 1258-1270. doi: 10. 1007/s00122-006-0227-0.
87. Wang S, Yehya N, Schadt EE, Wang H, Drake TA, Lusis AJ (2006) Genetic and genomic analysis of a fat mass trait with complex inheritance reveals marked sex specificity. PLoS Genet 2(2): 0148-0159. doi: 10. 1371/journal. pgen. 0020015.
88. Wittkopp PJ (2005) Genomic sources of regulatory variation in cis and in trans. Cell Mol Life Sci 62: 1779-1783. doi: 10. 1007/s00018-005-5064-9.
89. Wu CL, Delano DL, Mitro N, Su SV, Janes J, McClurg P, Batalov S, Welch GL, Zhang J, Orth AP, Walker JR, Glynne RJ, Cooke MP, Takahashi JS, Shimomura K, Kohsaka A, Bass J, Saez E, Wiltshire T, Su AI (2008) Gene set enrichment in eQTL data identifies novel annotations and pathway regulators. PLoS Genet 4(5): e1000070. doi: 10. 1371/journal. pgen. 1000070.
90. Xu YB, McCouch SR, Zhang QF (2005) How can we use genomics to improve cereals with rice as a reference genome? Plant Mol Biol 59: 7-26. doi: 10. 1007/s11103-004-4681-2.
91. Yan F, Tsui-Jung W, Yefim IR, Hsin DC, Ling G, David IM, Hsin DC, Ling G, David IM, Yongjie Y, Michael L, Abraham BK, Daniel AA, Patrick SS (2006) Genetic dissection of intermated recombinant inbred lines using a new genetic map of maize. Genetics 174: 1671-1683. doi: 10. 1534/genetics. 106. 060376.
92. Yvert G, Brem RB, Whittle J, Akey JM, Foss E, Smith EN, Mackelprang R, Kruglyak L (2003) Trans-acting regulatory variation in Saccharomyces cerevisiae and the role of transcription factors. Nat Genet 35(1): 57-64. doi: 10. 1038/ng1222.
93. Zou W, Zeng ZB (2009) Multiple interval mapping for gene expression QTL analysis. Genetica 137: 125-134. doi: 10. 1007/s10709-009-9365-z.
94. Zou F, Gelfond JA, Airey DC, Lu L, Manly KF, Robert W, Williams RW, Threadgill DW (2005) Quantitative trait locus analysis using recombinant inbred intercrosses: theoretical and empirical considerations. Genetics 170: 1299-1311. doi: 10. 1534/genetics. 104. 035709.
95. Zou W, Aylor DL, Zeng ZB (2007) eQTL Viewer: visualizing how sequence variation affects genome-wide transcription. BMC Bioinformatics 8: 7. doi: 10. 1186/1471-2105-8-7.