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Mapping
Basics of QTL Mapping
Guoyou Ye
E-mail: g.ye@cigar.org
Biparental populations
F2
BC: backcross
Maximum Likelihood Method for
DH, doubled haploids Estimating Recombination Rate
RIL, recombination inbred lines
CSSL: chromosome segment substitution
lines
Natural population
r13 = r12 (1 − r23 ) + (1 − r12 )r23 = r12 + r23 − 2r12 r23 Morgan is defined as that distance along which one crossing over is
expected to occur per gamete per generation
when δ= 1 (Complete interference, crossover at on Mapping distance m is function of recombination rate:
interval completely prevent crossover event in the other m = f (r )
interval) f is called mapping function
r13 = r12 + r23
Common Mapping Functions
• Morgan 三种作图函数的比较
m =r ×100 (cM)
• Haldane: no interference
r = 12 (1 − e − 2 m )
1 + 2r 1e
m / 25
−1
m = 25 ln r=
1 − 2r 2 em / 25 + 1
(P2), 1 (F1)
LA
Genotype P2: A2A2 (0) F1: A1A2 (1) P1: A1A1 (2) LOD = log( ) = log( L A ) − log( L0 )
L0
mid-parent m
Genotypic G22 G12 G11 LRT LRT
value LOD = ≈ LRT ≈ 4.61LOD
2 ln(10) 4.61
23 24
:What Is QTL
Quiz 3:
?
Detection Power? :What is Power
Quiz 4:
Analysis ?
The power of a statistical test is the Quantify the power of a QTL mapping approach
probability that the test will reject a false Commonly used to compare different mapping
null hypothesis (i.e., it will not make a methods
Type II error). In most cases it requires the use of Monte
Carlos Simulation
Power= 1.0 - Type II error (the
Generating 100+ mapping populations using the
probability of correctly detecting the true same pre-specified inheritance (QTL) model
QTL) Conduct QTL detection
Compute the percentage of correctly detecting the
pre-specified QTL
25 26
Power (%)
Under LOD threshold 3.0, 180 200
24 60
LOD score
27 28
:How to Improve
Quiz 5:
Power: Population Size
?
Mapping Precision?
Probability The length of empirical 95% confidence intervals of QTL
PVE (%) 0.9 0.8 0.7 0.6 PVE (%) PS=200 PS=400
MD=5 MD=10 MD=20 MD=40 MD=5 MD=10 MD=20 MD=40
1 >600 540 cM cM cM cM cM cM cM cM
2 600 420 340 280 1 93.30 104.55 103.10 120.03 47.00 61.94 76.83 88.24
2 54.14 62.37 73.66 86.08 37.55 32.38 38.34 47.59
3 430 280 230 200 3 52.65 47.12 50.02 48.18 25.64 21.95 18.78 33.36
4 340 250 190 160 4 38.89 46.14 41.94 56.72 25.01 18.46 22.74 36.57
5 25.99 37.83 44.73 59.74 16.35 16.39 22.54 36.30
5 280 200 160 130
10 10.31 8.35 11.29 46.45 3.72 4.78 7.92 22.74
10 160 120 100 80 20 8.55 10.19 14.78 26.97 4.90 6.04 8.70 15.56
20 100 80 60 50 30 5.33 8.23 11.56 18.62 3.18 4.78 6.62 12.62
30 100 60 50 40 29 30
31 32
:Can We Add PVEs for
Quiz 7: :Can the Overall PVE Be
Quiz 8:
Each of the QTL Together? More Than 100%?
基因型 频率 基因型值
Z=X+Y, X and Y are random variables 1
AABB 2
(1 − r ) a1+a2
E(X+Y) = E(X) + E(Y)
AAbb 1
2
r a1-a2
V(X+Y) = V(X) + V(Y) +2Cov(X, Y)
aaBB 1
2
r -a1+a2
When all QTL are independent, Cov(X, Y)=0, aabb 1
2
(1 − r ) -a1-a2
PVEs can be added together to measure
In RIL,locus A, genetic variance is a12 while for locus B
totally how much varinace is accounted for. it is a22. the total genetic variance is a12 +a22+2(1-2r)a1a2
When QTL are linked, overall PVE does not Thus, when QTL are linked, total PVE can be higher than
equal to the sum of individual PVEs 100%; But, for unlinked QTL PVE cannot be higher than
100%
33 34
:What is Distorted
Quiz 9: Segregation Distortion in An
Segregation? Actual Rice F2 Population
Theoretical segregation ratio
RP129
P1 (AA) X P2 (aa) (no selection) 20
RM491
RP178
P2BC1: Aa:aa=1:1 RM143
12
RM304
F2: AA:Aa:aa=1:2:1
8
RM44
RM552
DH, RIL: AA:aa=1:1
4
Segregation Distortion
0
Random drift
1
1
1
1
2
2
2
2
3
3
3
3
4
4
5
5
5
5
6
6
6
6
7
7
8
8
9
9
10
10
11
11
11
12
12
Gamete/ zygote selection Markers on the 12 rice chromosomes
35
When Distorted Markers Are Not When Distorted Markers Are
Linked With QTL Linked With QTL
A
100 No distortion SDM1 SDM2 SDM3
A C 100
SDM4 SDM5 SDM6 SDM7 100 No distortion SDM1 SDM2 SDM3
A,QTL for 80 SDM8 SDM9
80
SDM4
SDM8
SDM5
SDM9
SDM6 SDM7
80
Power (%)
Power (%)
plant height,
Power (%)
60 60 60
40 40 40
population 20 20
20
size=180 0
0
qPH1-1 qPH1-2 qPH3-1 qPH3-2 qPH4 qPH5 qPH6 qPH7 qPH12
0
qHD1 qHD3 qHD4 qHD5 qHD8 qHD11
B 100 D 120
qPH1-1 qPH1-2 qPH3-1 qPH3-2 qPH4 qPH5 qPH6 qPH7 qPH12 FDR
100
80
B,QTL for B 80
Power (%)
Power (%)
100 60
60
heading 80 40
40
days, 60
20 20
Power (%)
0 0
population 40 qPH1-1 qPH1-2 qPH3-1 qPH3-2 qPH4 qPH5 qPH6 qPH7 qPH12 qHD1 qHD3 qHD4 qHD5 qHD8 qHD11
size=180 20
A,QTL for plant height, population size=180 C, QTL for heading days, population size=180
0 B,QTL for plant height, population size=500 D, QTL for heading days, population size=500
qHD1 qHD3 qHD4 qHD5 qHD8 qHD11 FDR
Power (%)
Power (%)
60
60
40
40
20 20
0 0
qPH1-1 qPH1-2 qPH3-1qPH3-2 qPH4 qPH5 qPH6 qPH7 qPH12 FDR qHD1 qHD3 qHD4 qHD5 qHD8 qHD11 FDR
B 100
D
100
10% missing 15% missing
80
Power (%)
80
Power (%)
60
60
40
40
20 20
0 0
qPH1-1qPH1-2qPH3-1qPH3-2 qPH4 qPH5 qPH6 qPH7 qPH12 FDR qHD1 qHD3 qHD4 qHD5 qHD8 qHD11 FDR
C
A,QTL for plant height, population size=180 C, QTL for heading days, population size=180
41 B,QTL for plant height, population size=500 D, QTL for heading days, population size=500
Power
140
50 160 6
1 marker per 10-20 cM
40
30
180
200
220
4 10 cM
20 2
240
Increase marker density increases the 10
0
260
280
0
20
80
140
200
260
320
380
440
500
560
300
chance to make QTL ‘isolated’ 1 2 3 4 5 10 20 30
Phenotypic variation explained (PVE) (%)
320
340 Population size
140
50
40
160
180
6 20 cM
4
Recombinants are needed between dense 30
20
200
220
240
2
10
markers 0
260
280
0
20
80
140
200
260
320
380
440
500
560
300
1 2 3 4 5 10 20 30 320
Depends on the mapping methods as well 43
Phenotypic variation explained (PVE) (%) 340 Population size
44
Power and FDR for Two Marker Densities
(10cM interval, QTL in the middle)
:What is QTL by E?
Quiz 12:
100 20 90 A. 互作模式1 B. 互作模式2
90 40 80
基因型值
基因型值
70 100 60
60 120 50
Power
140
50 40
40
160
180 30 10 cM
30 200 20
20
220
10 基因型1 基因型1
240
10 260 0 基因型2 基因型2
0 280
20
80
140
200
260
320
380
440
500
560
300
1 2 3 4 5 10 20 30 320
Phenotypic variation explained (PVE) (%) 340 Population size 环境1 环境2 环境1 环境2
100 20
40
90 C. 互作模式3 D. 互作模式4
90 80
基因型值
基因型值
60 120 50
Power
140
50 160 40 20 cM
40 180 30
30 200
220
20
20 240 10 基因型1 基因型1
10 260 0
0 280 基因型2 基因型2
20
80
140
200
260
320
380
440
500
560
300
1 2 3 4 5 10 20 30 320
Phenotypic variation explained (PVE) (%) 340 Population size 45 环境1 环境2 环境1 环境2 46
2
= 0 .0 0 h mg
2
= 0 .9 5 , h pg
2
= 0 .0 5 h mg
2
= 0 .8 9 , h pg
2
= 0 .1 1 h mg
2
= 0 .8 8 , h pg
2
= 0 .1 2
h = 1 .0 0
LODa E1 0.00 0.26 0.01 0.00 1.87 0.00 0.12 0.03 0.03 0.01 0.02 6.06 0.47 0.01 0.17 0.61 pg
E2 0.00 1.05 2.88 4.66 0.95 0.14 0.35 0.30 0.11 0.13 5.84 3.92 2.89 0.22 0.12 0.05
E3
E4
2.06
0.04
4.03
0.04
0.00
0.00
0.20
4.03
0.84
0.05
2.60
0.32
0.05
0.04
9.61
0.02
4.64
0.49
0.04
0.70
0.04
0.05
3.98
15.89
3.36
6.26
4.35
2.57
0.89
0.10
2.17
0.24
A single major gene and h mg
2
F2
= 0 .8 0 , h pg
2
= 0 .1 0 h
h
mg
B1
2
2
= 0 .0 0
= 0 .3 8
h mg
2
B2
= 0 .8 7 , h pg
2
= 0 .0 5 h
h
F 2 :3
mg
2
2
= 0 .8 2
= 0 .1 2
h mg
2
R IL
= 0 .8 4 , h pg
2
= 0 .1 3
pg pg
E5 0.35 0.66 0.41 3.13 0.40 0.00 4.09 12.51 16.53 2.04 3.18 5.56 9.04 0.31 0.42 0.15 many minor genes: the
E6 0.13 0.38 1.06 1.35 0.30 0.22 0.32 0.02 0.18 0.00 0.16 1.84 4.15 0.90 0.29 0.05
E7 0.08 5.07 0.22 0.21 0.04 0.26 1.47 0.33 0.07 0.03 5.52 6.33 4.07 1.66 4.04 0.01 distribution will be h mg
2
F2
= 0 .7 0 , h pg
2
= 0 .1 0 h
h
mg
pg
B1
2
2
= 0 .0 0
= 0 .2 3
h mg
2
B2
= 0 .7 8 , h pg
2
= 0 .0 5 h
h
F 2 :3
mg
pg
2
2
= 0 .7 4
= 0 .1 2
h mg
2
R IL
= 0 .7 8 , h pg
2
= 0 .1 3
E8 0.01 0.00 0.02 0.45 2.16 1.54 0.01 0.02 0.01 0.67 0.17 16.89 10.01 0.01 0.00 0.00
ADDb E1 -0.11 -0.72 -0.12 -0.08 -2.13 0.06 -0.36 -0.19 0.25 -0.13 0.17 4.13 1.27 0.08 -0.35 -1.99 normal.
E2 -0.07 2.21 -2.98 4.35 -2.11 0.78 -0.88 -0.89 -0.72 0.54 4.43 4.51 4.62 -0.72 -0.43 -0.78 h mg
2
F2
= 0 .6 0 , h pg
2
= 0 .1 0 h mg
B1
2
= 0 .0 0 h mg
2
B2
= 0 .6 9 , h pg
2
= 0 .0 5 h
F 2 :3
mg
2
= 0 .6 6 h mg
2
R IL
= 0 .7 2 , h pg
2
= 0 .1 4
2 2
h = 0 .1 7 h = 0 .1 2
E3 3.89 4.69 0.11 -0.84 -2.03 -3.66 0.32 -6.12 5.11 -0.32 0.35 4.62 5.16 3.57 -1.21 5.68 pg pg
E4 -0.24 -0.23 -0.04 2.05 -0.25 -0.61 -0.16 0.12 0.76 -0.67 -0.18 5.84 3.71 1.32 -0.20 -0.91
E5 1.06 1.22 -0.75 2.42 -0.94 0.07 2.30 -5.19 8.28 -1.59 2.20 3.86 6.40 0.60 -0.55 0.98 However, the residual h mg
2
F2
= 0 .5 0 , h pg
2
= 0 .1 0 h mg
B1
2
= 0 .0 0 h mg
2
B2
= 0 .5 9 , h pg
2
= 0 .0 5 h
F 2 :3
mg
2
= 0 .5 7 h mg
2
R IL
= 0 .6 5 , h pg
2
= 0 .1 6
2 2
E6 -1.22 1.73 -2.29 2.88 -1.53 -1.30 -1.11 -0.30 -1.14 0.13 0.86 3.79 -1.87 -0.85 1.04
needs to be normally
h = 0 .1 3 h = 0 .1 3
7.38 pg pg
E7 -0.52 3.74 -0.56 0.61 -0.31 -0.78 -1.37 -0.69 -0.41 -0.19 3.11 4.29 4.01 1.44 -1.91 -0.21
PVEc
E8
E1
-0.09
0.01
0.05
0.48
-0.11
0.02
0.63
0.01
-1.63
4.15
-1.31
0.00
-0.09
0.23
-0.12
0.06
0.09
0.06
-0.62
0.03
-0.33
0.04
5.94
15.60
4.95
1.00
-0.09
0.01
0.03
0.34
0.09
1.24
distributed. h mg
2
F2
= 0 .4 0 , h pg
2
= 0 .1 0 h
h
mg
pg
B1
2
2
= 0 .0 0
= 0 .1 1
h mg
2
B2
= 0 .4 9 , h pg
2
= 0 .0 5 h
h
F 2 :3
mg
pg
2
2
= 0 .4 7
= 0 .1 3
h mg
2
R IL
= 0 .5 7 , h pg
2
= 0 .1 7
E2 0.00 2.24 6.60 11.44 2.04 0.28 0.69 0.59 0.24 0.26 14.54 9.36 6.66 0.46 0.25 0.10
E3 3.61 7.76 0.01 0.33 1.45 4.73 0.07 21.28 9.19 0.07 0.07 7.54 6.35 8.53 1.53 3.91 F2 B1 B2 F 2 :3 R IL
E4
E5
0.04
0.35
0.05
0.68
0.00
0.41
5.62
3.51
0.06
0.41
0.38
0.00
0.05
4.61
0.03
19.86
0.59
31.26
0.86
2.18
0.05
3.57
34.66
6.79
9.49
12.65
3.35
0.31
0.11
0.41
0.29
0.15
There are methods that h mg
2
= 0 .3 0 , h pg
2
= 0 .1 0 h
h
mg
pg
2
2
= 0 .0 0
= 0 .0 9
h
h
mg
pg
2
2
= 0 .3 8
= 0 .0 6
h
h
mg
pg
2
2
= 0 .3 7
= 0 .1 4
h mg
2
= 0 .4 7 , h pg
2
= 0 .1 9
E6
E7
0.46
0.11
1.37
8.28
3.88
0.29
4.99
0.29
1.07
0.06
0.78
0.36
1.07
2.13
0.07
0.46
0.60
0.10
0.02
0.04
0.55
9.25
6.60
10.89
16.93
6.44
3.06
2.33
0.98
6.37
0.17
0.01
can handle non-normal F2
2
B1
2
B2
2
F 2 :3
2
R IL
2
h mg = 0 .2 0 h mg = 0 .0 0 h mg = 0 .2 6 h mg = 0 .2 6 h mg = 0 .3 4
E8 0.01 0.00 0.02 0.52 2.66 1.70 0.02 0.02 0.01 0.73 0.17 35.08 16.53 0.01 0.00 0.00
47 distribution of residual. h pg
2
= 0 .1 0 h pg
2
= 0 .0 8 h pg
2
= 0 .0 6 h pg
2
= 0 .1 5 h pg
2
= 0 .2 1
48
A simulation: A QTL accounted for 80% of :Do Mapping Component
Quiz 14:
the phenotypic variation with additive effect 1.0 Traits Help?
and located at 25 cM
50
40
Effect Trait I Trait II Addition Subtraction Multiplication Division
Frequency
30 Mean 25 20 45 5 500 1.2563
20
A1 1 0 1 1 20 0.0503
10
0
A2 1 0 1 1 20 0.0503
8.5 9 9.5 10 10.5
Phenotypic value
11 11.5 12 A3 0 1 1 -1 25 -0.0631
100 1.2
A4 0 1 1 -1 25 -0.0631
80 1 A12 0 0 0 0 0 0
Estimated effect
LOD score
-0.2
100
105
110
115
120
125
130
135
140
145
150
155
160
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
0
5
1D-scanning on one chromosome, step=1cM 1D-scanning on one chromosome, step=1cM A34 0 0 0 0 0 0.0063
A123 0 0 0 0 0 0
A124 0 0 0 0 0 0
A134 0 0 0 0 0 0.0003
A234 0 0 0 0 0 0.0003
49 A1234 0 0 0 0 0 0 50