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Introductory Genetics 1B
Heritability and Complex Traits
Greg Gibson
Department of Genetics
North Carolina State University
Course Outline
1A.
1B.
2A.
2B.
3A.
3B.
4A.
4B.
5A.
5B.
Mendelian Genetics (JA)
Heritability and Complex Traits (GG)
The Central Dogma and Gene Structure (JA)
Gene Regulation (GG)
Linkage Mapping (GG)
QTL Mapping (JA)
Genome Sequencing (JA)
Genome Annotation (GG)
Microarrays (GG)
Association Studies (JA)
Introduction
• Genetic analysis of common human diseases, animal and plant
breeding, and evolutionary biology all require the tools of
quantitative genetics.
• Quantitative genetics is the study of the variation in continuous
traits.
• Small effects of many individual genes add together and interact
with the environment, to produce natural variation
• Modern molecular quantitative genetics is focused on identifying
the underlying genes and describing how variation at the DNA
level translates into phenotypic variation
Oligogenic effects
1 Locus
Frequency
Frequency
2 Loci
1
2
-
+
-
1
+
+
1
4
- - -
+ - -
Frequency
3 Loci
1
- - - - -
6
15 20 15
+
+ - - - - - +
+
+ - - +
- - +
- - +
-
+
+ - +
- - +
+ + +
- -
6
1
+ + +
+ +
- - + + + + + +
+ - + + + -
6
+
+
+
+
-
4
+ +
+ -
1
+ +
+ +
Types of Complex Trait
• Continuous traits (eg height, IQ)
• Meristic traits (eg number of petals, whiskers)
• Discrete traits (eg disease status, color)
• Threshold-dependent traits
Heritability
• Heritability is the proportion of phenotypic
variation in a population that is due to genotypic
variation.
• Heritability describes the relative contributions of
genotype and environment to phenotypic variation.
• Heritability is a measure of a population, not an
individual, and does not say anything about the
genetic difference between populations.
• There are three common approaches to measuring
heritability.
Parent-Offspring Regression
Offspring Phenotype
6
5
4
3
2
1
1
2
3
4
Parental Phenotype
5
6
Variance among Lines
High heritability
6
6
5
5
4
4
Phenotype
Phenotype
Low heritability
3
3
2
2
1
1
1
2
3
Line Number
4
1
2
3
Line Number
4
Realized heritability
Frequency
Initial
population
Selected
sample
O
R
S
R
Progeny of
selected
sample
Phenotype
S
Polygenes
• The number of genes that affect a trait can be
estimated from the variance segregating in an F2
generation.
• There is a wide range in the number of genes that
affect traits.
• As the number of genes influencing a trait
increases, the relative number of individuals with
extreme phenotypes decreases.
• Transgressive segregation occurs when
grandchildren have more extreme phenotypes than
either grandparent.
Simple additive model
¼
AA (0)
½
Aa (1)
¼
aa (2)
¼ BB (0)
1/16 (0)
1/8 (1)
1/16 (2)
½ Bb (1)
1/8 (1)
1/4 (2)
1/8 (3)
¼ Bb (2)
1/16 (2)
1/8 (3)
1/16 (4)
Polygenic effects
Frequency
Parental samples
Frequency
F2 samples
Frequency
F1 sample
Phenotype
Transgressive segregation
Parental samples
Frequency
A.
-
;
+
+
; -- ;
-
+
+
;
-
; ++ ;
+
+
B.
F2
F1
F2 samples
Frequency
P2
Frequency
P1
25 35 45 55 65 75 85 95 105 115
Plant height (cm)
-
;
-
; -- ;
-
+
+
Phenotype
;
+
+
; ++ ;
+
+
VP = VA + VD + VI + VGxE + VE
• Loci are said to have Additive effects if the
contributions of each individual allele can simply
be added algebraically to arrive at a prediction of a
phenotype given a genotype.
• Dominance refers to the observation that
heterozygotes resemble one class of homozygotes
more than the other.
• Epistasis refers to a locus-by-locus Interaction,
such as when alleles at two loci antagonize or
synergize with one another.
• VE is the environmental variance
Growth Rate (mg/h)
Norm of Reaction
2
1
0
11
17
23
29
Growth Temperature (oC)
35
43
Mean phenotype
Dominance ratio
20
18
16
14
12
10
8
6
4
2
0
bb
Bb
a
d
d = 16-10
= 6
a = 18-10
= 8
0
Expected mid-value
= (18+2)/2 = 10
BB
-a
0
1
Number of “b” alleles
2
Epistasis
OBSERVED
38
37
36
35
34
33
32
31
EXPECTED
38
37
36
35
34
33
32
31
BB
Bb
bb
AA
Aa
BB
Bb
bb
aa
AA
EPISTATIC DEVIATIONS
1.00
0.75
0.50
0.25
0.00
- 0.25
- 0.50
- 0.75
- 1.00
Bb
bb
BB
AA
Aa
aa
Aa
aa