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Lecture 14 - Complex Traits and QTL Maping Doerge (2001) Nature Genetics Reviews 3:43-52 Neale, chapter 18 Liu, chapters 13-14

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Figures from Lander and Schork, Science, 265-September 1994-pp2037

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QTL Mapping Mapping population Markers and a map Phenotypes (trait measurements) QTL mapping software

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Distribution of Phenotypic Values Continuous Catagorical Binary

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Pitch Canker Phenotypes Fusiform Rust Phenotypes SusceptibleResistant SmallRoughLarge

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QTL Mapping - Basic Approaches Single-factor mapping Interval mapping

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X A1 Q1 B1 A1 Q1 B1 A2 Q2 B2 A2 Q2 B2 Genotypic value= 20 Genotypic value= 4 A1 Q1 B1 A2 Q2 B2 A2 Q2 B2 A2 Q2 B2 X A1 Q1 B1 A2 Q2 B2 A2 Q2 B2 A2 Q2 B2 A1 Q1 B2 A2 Q2 B2 A2 Q2 B1 A2 Q2 B2 Genotypic value= 12 Genotypic value= A1-A2 = (12+12) -(4+4) = 16 B1-B2 = (12+4) -(12+4) = 0 Genotypic Value Q1= 10 Q2 =2 Q = additive

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Edwards et al. 1987, Genetics, Single factor QTL mapping

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Advantages of Single Factor QTL Mapping No map needed Standard stat packages, SAS

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Disdvantages of Single Factor QTL Mapping Map position not precisely determined Biased estimates of a and d Phenotypic effect overestimated Multiple testing

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Interval Mapping Fig 21.1 from Falconer and Mackay. Pg 364 Recombination frequencies between two marker loci, M and N, and a QTL, A M1 N1A1 M2 N2A2 c2 c1 c

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Table Falconer and Mackay

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Advantages of Interval QTL Mapping More precise location of QTL Better estimates of %PVE

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Disdvantages of Interval QTL Mapping Computationally demanding Custom software

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ewsg lwsg vol% emfa lmfa ecwc lcwc DETECTION VERIFICATION RELATED UNRELATED Aco_1 0.0 PtIFG_3012_ PtIFG_2150_A PtIFG_2885_B 20.1 estPtIFG_8569_a 29.5 PtIFG_2538_B 30.2 PtIFG_2564_A 40.3 PtIFG_1A7_A 42.6 estPtIFG_9022_a 43.1 PtIFG_2536_ PtIFG_1A7_D 46.8 estPtIFG_48_a 58.3 estPaINRA_PAXY13_a 59.5 estPtIFG_464_a 62.2 PtIFG_1633_a 66.0 PtIFG_48_ estPtIFG_8939_a PtIFG_3006_ PtIFG_1918_h PtIFG_1623_A 90.9 estPtIFG_66_a PtIFG_1626_a 95.4 PtIFG_2986_A PtIFG_1D11_A PtIFG_1165_a Pgd_ estPpaINRA_AS01C10-1_a LG 2 PtIFG_2006_C 0.0 estPtIFG_1934_a 0.3 PtIFG_2145_1 3.4 PtIFG_2068_A 7.8 PtIFG_2897_d 10.4 PtIFG_975_ estPtIFG_8500_a 18.8 PtIFG_138_B 24.1 estPtNCS_22C5_a 30.1 PtIFG_2588_ estPtNCS_C612F_a 33.8 PtIFG_2718_ PtIFG_2745_ PtIFG_1918_ estPtIFG_8612_a 64.2 PtIFG_2090_ PtIFG_1636_ PtIFG_2988_ PtIFG_2718_ estPtIFG_2889_a 95.7 PtIFG_2889_ estPtIFG_8781_a PtIFG_2145_ PtIFG_2145_ PtIFG_1D9_ LG 3 C4H-1 Pta14A 9 SAMS-1 DETECTION VERIFICATION RELATED UNRELATED DETECTION VERIFICATION RELATED UNRELATED PtIFG_2819_12 PtIFG_653_d PtIFG_2086_13 PtIFG_1626_c PtIFG_2697_A PtIFG_2006_A estPtINCS_20G2_a estPtIFG_9053_a estPtIFG_8843_a PtUME_Ps3_A estPtIFG_8537_a estPtIFG_2253_a estPpINR_AS01G01_a estPtIFG_1576_a PtIFG_2253_A PtIFG_2782_31 PtIFG_1457_b estPtIFG_9198_a estPtIFG_8496_a PtIFG_2146_31 PtIFG_2441_1 estPtIFG_107_a PtIFG_2931_b estPtNCS_6N3E_a PtIFG_2393_1 PtIFG_2931_A PtIFG_851_1 LG 1 LAC GlyHMT PtNCS_CAD-08_b SCALE 0 cM 10 cM Brown et al Genetics164:

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What can be learned from a QTL mapping experiment Estimate of number of genes controlling complex trait Location of genes in the genome Estimates of a and d Estimate of %PVE

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