CS 563

Lecture 6
October 15, 2018

Components of Variance
The basic premise of quantitative genetic analysis is that, although individual genes and their
effects can only be studied under special circumstances, the variance of the trait can be
partitioned into components due to variance of genotypic values, breeding values, dominance
deviations, etc.

The population variance = the mean of the squared deviations from the mean.

Σ( Χ i  X)
2  = the mean of the squared deviation from the population mean. From this
Ν
point, we will use V to represent variance (σ²).

In the same way the phenotypic value of an individual can be partitioned into components:

P=G+E

P=A+D+I+E

The variance of phenotypic values of the population can be partitioned into:

VP = VG + VE

VP = VA + VD + VI + VE

VP = phenotypic variance, or variance of phenotypic values

VG = genotypic variance, or variance of genotypic values
VA = additive genetic variance, or variance of breeding values
VD = dominance variance, variance of dominance deviations
VI = interaction variance of interaction deviation
VE = environmental variance, variance of environmental deviations

(Assuming that there is no correlation between genotypic values and environmental

deviations, and no interaction between genotypes and environments)

Genetic Components of Variance

Recall that, the mean genotypic values, breeding values and dominance deviations at a single locus
are given as deviations from the population mean

Genotype A1A1 A1A2 A2A2

Frequency p2 2pq q2
1
Value a d −a

Deviations from population mean:

G 2q(a−pd) a(q−p)+d(1−2pq) −2p(a+qd)
2q(α-qd) (q-p) α + 2pqd -2p(α+pd)

A 2q[a + d(q−p)] (q−p) [a + d(q−p)] −2p[a + d(q−p)]

D −2q2d 2pqd −2p2d

Therefore to determine the expected variance of these, all that needs to be done is to square
the values on the table, multiply by the genotype frequency, and sum over all genotypes.

VA = 4p2q2α2 + 2pq(q-p)2α2 + 4p2q2α2 remember α=[a+d(q-p)]2

=4p2q2[a+d(q-p)]2 +2pq(q-p)2[a+d(q-p)]2 +4p2q2[a+d(q-p)]2
=[4p2q2 +2pq(q-p)2 +4p2q2][a+d(q-p)]2
=2pq[2pq +(q-p)2 +2pq][a+d(q-p)]2
=2pq[2pq +q2-2pq+p2 +2pq][a+d(q-p)]2
=2pq[q2+p2 +2pq][a-d(q-p)]2
=2pq[a+d(q-p)]2

VD = 4p2q4d2 + 8p3q3d2 +4p4q2d2

=4p2q2d2(q2+2pq+p2)
=(2pqd)2

VG = VA + VD

Note:
- Additive and dominance variance depend on gene frequency. They are thus maximal
when gene frequencies are intermediate (i.e., p=q=0.5), and become smaller as gene
frequencies approach 0 and 1. Recessive alleles at low frequency contribute little
variance. If one allele is fixed, VA = VD = 0 and all individuals have the same genotype,
so there is no genetic variance.
- VA and VD of a given trait will be different in populations with different gene frequencies,
and evolutionary factors that change gene frequency will change genetic variance
- VA and VD of a given trait may also be different in different populations with the same
gene frequencies if a and d, which can depend on the environment vary between the
populations
- If d =0, (strictly additive), VA =2pqa2
- If d = a (complete dominance) VA =8pq3a2, where q is the frequency of the recessive
allele
- For the special case of p = q = 0.5, as in a cross between inbred lines, VA= ½ a2 and VD
= ¼d2

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 (A) a = d; A1 dominant (B) d = 0 (additive)

(C) −a = d; A2 dominant (D) a = 0, d = 0.14 pure overdominance)

Example
Compute the total genetic variance, variance of breeding values (additive genetic variance)
and dominance variance for neck girth at the mh locus in whippets in two populations where
the frequency of the mh allele is

(a) q=0.8
(b) q=0.2

Note that, we can use two methods – formula of variances, or frequency × (value)2

Genotype mh/mh mh/+ +/+

Frequency of population (a) 0.64 0.32 0.04
Frequency of population (b) 0.04 0.32 0.64

G 4.61 −3.24 −4.61

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a) q(mh) =0.8
 2pq[a + d(q−p)]2
2
A=
= 0.32[4.61 −3.24(0.2−0.8)]2= 13.7456
 D2 = (2pqd)2= [0.32(−3.24)]2= 1.0750
 G2 =  A2 +  D2 = 14.8206

(b) p(mh) = 0.2

 A2 = 2pq[a + d(q-p)]2
= 0.32[4.61 -3.24(0.8-0.2)]2 = 2.2744

 D2 = (2pqd)2
= [0.32(-3.24)]2
= 1.0750

 G2 =  A2 +  D2 = 3.3494

Second, we can use the values of G, A and D we computed previously (all as deviations from
the population mean) and estimate the variances directly by multiplying the frequency by the
square of these values:

(a) p(mh) = 0.8

mh/mh mh/+ +/+
G 2.8808 -4.9692 -6.3392
A 2.6216 -3.9324 -10.4864
D 0.2592 -1.0368 4.1474

 G2 = 0.64(2.8808)2 + 0.32(-4.9692)2 + 0.04(-6.3392)2

= 14.8205
 = 0.64(2.6216)2 + 0.32(-3.9324)2 + 0.04(-10.4864)2
2
A
= 13.7456
 D = 0.64(0.2592)2 + 0.32(-1.0368)2 + 0.04(4.1474)2
2

= 1.0750
Check:  G =  A +  D (with rounding error in the last decimal)
2 2 2

(b) p(mh) = 0.2

mh/mh mh/+ +/+
G 8.4128 0.5628 -0.8072
A 4.2656 1.5996 -1.0664
D 4.1474 -1.0368 0.2592

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 G2 = 0.04(8.4128)2 + 0.32(0.5628)2 + 0.64(-0.8072)2
= 3.3494
 0.04(4.2656)2 + 0.32(1.5996)2 + 0.64(-10.4864)2
2
A=
= 2.2744
 D = 0.04(4.1474)2 + 0.32(-1.0368)2 + 0.64(0.2592)2
2

= 1.0750
Check:  G =  A +  D
2 2 2

Happily, the two methods are in agreement. Note the large difference in the amount of additive
genetic variance, and the relative contributions of additive and dominance variance between
the two populations.

Epistasis

With multiple loci, we must consider the additive effects and dominance deviations of all loci,
as well as additive and non-additive interactions between loci. Recall that epistasis refers to
non-additive interactions between loci, such that allelic variation at a second locus changes the
genotypic values at the first. For two loci we can decompose the genotypic value of an
individual as:

G  AA  AB  DA  DB  AA AB  AA DB  DA AB  DA DB

Here AAAB refers to epistasis between breeding values at locus A and B; AADB and DAAB refer
to the two possible ways there can be epistasis between breeding values and dominance
deviations at the two loci; and DADB refers to interactions between dominance deviations at the
two loci. It becomes difficult to specify all possible two-way, three-way and higher order
interactions for three or more loci. However, we can represent all possible interactions by
adding an interaction deviation, I, to the decomposition of the genotypic value: G = A + D + I

Like breeding values and dominance deviations, the interaction deviation is a property of the
specific interacting genotypes and their frequencies in the population. If I = 0, genes are said to
act additively between loci, so additive can be used in two different contexts. Referring to one
locus, D = 0 means additive (no dominance); referring to many loci, I = 0 = additive (no
epistasis). As we noted in a previous lecture, non-additive interactions within loci and between
loci are independent. There can be complete dominance yet no epistasis, and lots of epistasis
without any dominance.

The interaction deviation can be calculated for pairs of loci when genotypes and frequencies
are known for each locus; calculation of three-locus and higher order interactions becomes
very difficult. For two locus interactions, the interaction deviation is the deviation of the
observed genotypic value from the genotypic value of the average genetic background, where
the ‘average’ is weighted by gene frequency.

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A full partitioning of epistasis would entail knowing the variance contributed by all two-way,
three-way and higher order interactions, and the nature of those interactions. If there are
epistatic interactions among loci, they will give rise to epistatic variance. However, it is
commonly thought that three-way and higher order interactions contribute vanishingly small
amounts of variance, and can be ignored. For two-way interactions, the interaction variance is
partitioned into the variance attributable to interactions of breeding values at both loci,
interactions of breeding values at one locus with dominance deviations at another, and
interactions of dominance deviations at both loci:
 I2   AA
2
  AD
2
  DD
2

In practice, the use of generation means analysis allows the researcher to estimate additive,
dominance and all epistatic effects. The notation of Mather and Jinks represent the interaction
effects, AA, AD, and DD by i, j, and l, respectively.

Example of epistasis and interaction deviation

Worked example: F&M Problem 7.9

An example of additive, non-additive gene effect is observed in pigmentation (color genes) in

mice. Two loci exhibit a metric character which reflects in the color intensity of the
pigmentation in the coat, measured as size of the pigment granules (Russel, 1949). The two
genes are ‘brown’ (b) and ‘extreme dilution” (ce), an allele of the albino series. Measurements
were made on the mean size (diameter) of the granules in each of the four genotypes shown
below. The measurements represent the values.

Values
B- bb
C- 1.44 0.77
cece 0.94 0.77

If the effects of the same two genes on size of the pigment granules are not additive, work out
the interaction deviations of the genotypes in a population in which the bb homozygote has a
frequency of 0.4 and the cece homozygote has a frequency of 0.2.

Solution
We first have to calculate the population mean because we need to express genotypic means
and interaction deviations as deviation from the population mean. The rest of the allele
frequencies are shown below:

Freq. B- bb
0.6 0.4
C- 0.8 0.48 0.32
cece 0.2 0.12 0.08

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For b locus, the genotypes are BB, Bb, and bb. A genotype frequency of bb= 0.4 means, BB
plus Bb frequency is 1- 0.4 = 0.6. Note that p2 +q2 +2pq = 1
For ce locus, the genotypes are CC, Cce, and cece. A genotype frequency of cece = 0.2 means,
CC plus Cce frequency is 1- 0.2 = 0.8

Value B- bb Freq. B- bb
C- 1.44 0.77 0.6 0.4
cece 0.94 0.77 C- 0.8 0.48 0.32
cece 0.2 0.12 0.08

Population mean
Multiply the value of each genotype by its frequency and add to give the population mean
Pop. Mean = (0.48 × 1.44) + (0.32 × 0.77) +(0.12 × 0.94) + (0.08 × 0.77) = 1.112

Convert the values to deviations from the mean to get observed deviations from the population
mean to give genotypic values at the two loci

Freq. B- bb Mean
0.6 0.4
C- 0.8 1.44-1.112 =0.328 0.77-1.112= -0.342 0.06
cece 0.2 0.94 – 1.112= -0.172 0.77-1.112= -0.342 -0.24
Mean 0.228 -0.342

These deviations from the mean will now be referred to as simply values. Next, we have to
look at each locus separately and find the mean value (frequency × value) of each of its
genotypes in the population.

Mean value of each locus:

1. The mean value of C- genotype = (0.6 × 0.328)+ (0.4 × -0.342) = 0.06

2. The mean value of cece genotype = (0.6 × -0.172) +(0.4 × -0.342) = -0.24
3. The mean value of B- genotype = (0.8 × 0.328) + (0.2 × -0.172) = 0.228
4. The mean value of bb genotype = (0.8 × -0.342) + (0.2 × -0.342) = -0.342

Now we get the additive expectations of the combined genotypes. These are the values the
combined genotypes will have if the values of the single-locus genotypes were added together.
1. Additive expectation for B-C- genotype = 0.228 + 0.06 = 0.288
2. Additive expectation for B-cece genotype = 0.228 + (-0.24) = -0.012
3. Additive expectation for bbC- genotype = -0.342 + 0.06 = -0.282
4. Additive expectation for bb-cece genotype = -0.342 + (-0.24) = -0.582

Additive expectations in a table form

B- bb
C- 0.288 -0.282
cece -0.012 -0.582

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Finally, the interaction deviation of each genotype is the difference between the observed
deviations (i.e., genotypic value corrected for population mean) from the mean and the additive
expectation
1. Interaction deviation for B-C- genotype = 0.328 – 0.288 = 0.04
2. Interaction deviation for B-cece genotype = -0.172 – (-0.012) = -0.16
3. Interaction deviation for bbC- genotype = -0.342 – (-0.282) = -0.06
4. Interaction deviation for bb-cece genotype = -0.342 – (-0.582) = 0.24

Interaction deviation
B- bb
C- 0.04 -0.06
e e
c c -0.16 0.24

Environmental Components of Variance

Environmental variance is by definition all non-genetic variation. The list below shows some
obvious sources of variation in the environment that can give rise to differences in phenotypes
between individuals.

1. Differences in nutrition and temperature

2. Differences in social context
3. In mammals, differences in pre-natal and post-natal maternal nutritional influences
(maternal effects) can give rise to differences between individuals, especially infants.
4. Finally some phenotypes, particularly physiological and behavioral phenotypes, can be
difficult to measure with precision.

In humans, psychological traits are assessed by a series of questions, where the answer to
one question determines the next question to be answered, so all individuals being evaluated
do not even receive the same test! Blood pressure in humans can vary from minute to minute,
depending on stress level and posture. Many behavioral and physiological traits also vary
according to the circadian clock, making time of day the measurement is taken a factor
contributing to variation. Finally, most traits are affected by ‘intangible’ changes in the
environment. For example, if we measure the longevity of fruit flies of the same sex and
genotype, all housed together in the same culture vials, in a chamber in which temperature
and humidity is constant, there will be substantial variation in life span among the individuals.
This environmental variation stemming from unknown causes is called intangible variation,
and symbolized  EW
2
. (E=environment; W=within)

Falconer further partitions intangible environmental variation into two sources, general
environmental variance, (  EG ), and special environmental variance (  ES ) so
2 2

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that  EW   EG   ES .  EG
2 2 2 2
refers to variation caused by environmental circumstances
external to the organism and their nature is unknown. These environmental circumstances
cause permanent differences between individuals.  ES
2
refers to variation that gives rise to
differences within individuals in trait values. Such differences could arise from variation during
development that causes differences between spatially repeated anatomical structures (e.g.,
the difference in maximum digit span of the left and right hands of humans, differences
between number of bristles on the left and right sides of Drosophila). In this context the
magnitude of  ES
2
measures the extent of developmental homeostasis for the trait. In addition,
 ES
2
refers to differences in measurements of the same trait in the same individual taken at
different times (e.g., milk yield in different lactations of dairy cattle, blood pressure
measurements taken on successive days).

In addition, we need to take account of environmental variation due to rearing individuals in the
same, or common, environment. Common environmental variance (  EC ) is defined as the
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variance attributable to environmental conditions that cause phenotypes of individuals reared

in that environment to be more similar to each other than to individuals reared in different
common environments. The concept can be clarified by considering the main sources of
common environment. Examples of common spatial environments are fruit flies that are reared
in the same vial, mice that are housed in the same cage, or humans in the same household.
There will be differences in the environment between vials, cages and households, and these
differences in environments can affect quantitative traits. Such differences give rise to common
spatial environmental variance (  EC ( S ) ). Similarly, examples of common temporal
2

environments are measurements taken for one group of individuals at one time of day (week,
or year), and another group with measurements taken at a different time of day (week, or
year). Differences in circadian cycle, temperature or season between these different
measurement times can affect quantitative traits, and give rise to common temporal
environmental variance (  EC (T ) ).
2

Finally, mammalian siblings share a common maternal environment. Differences between

mothers in pre- and post natal nutrition can cause differences between quantitative traits of
their offspring, and thus give rise to common maternal environmental variance (  EC (T ) ). In
2

mammals, common intra-uterine maternal effects can be estimated directly by embryo

transplants, and common post-natal maternal effects can be estimated by cross-fostering
experiments.

These effects can be quite striking, as the following example illustrates. Reading (1966, J.
Comp. Physiol. Psychol. 62: 437-330) compared the behavior of C57BL/6 and BALB/c mouse
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pups that were either reared by mothers of their own strain or by mothers of the other strain, in
a number of tests of activity. The tests were, (1) open field activity, (2) a hole-in-the wall
emergence test, (3) a water-escape test, (4) and a barrier climbing test. There were
differences between strains in all tests except for the barrier climbing task. C57BL/6 mice were
more active in the open field, took longer to emerge from the hole-in-the wall, and required
longer time to escape from the water than BALB/c mice, regardless of mode of rearing. BALB/c
mice showed significant effects of cross-fostering in the open-field and hole-in-the-wall tests, in
the direction of the C57BL/6 performance. C57BL/6 mice showed significant effects of cross-
fostering in the water-escape test, in the direction of the BALB/c performance.

Fig. 6.1. Comparison in behavior of C57BL/6 and BALB/c mouse pups that were either reared by mothers of their
own strain or by mothers of the other strain, in a number of tests of activity.

Genotype-Environment Correlation and Interaction

A correlation between genotype and environment occurs if genotypic values are not
independent of environmental deviations. For example, if better phenotypes are given better
environments. Since P= G + E and VP = VG + VE, an additional term accounting for the
correlation between G and E must be introduced. From statistics,

Var (X + Y) = VarX + VarY + 2covXY;

therefore, with genotype-environment correlation:
VP= VG + VE + 2covGE

G×E correlation can occur in natural settings. Examples are dairy husbandry, where cows are
typically fed according to their milk yield, such that milk yield is correlated to feeding. Elite
young racehorses sell for huge amounts of money, based on their pedigree and performance

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of their parents. They consequently go to top trainers and are ridden by top jockeys. In
experimental quantitative genetics covGE is avoided because correct experimental design
stipulates that environments are randomized across genotypes. If covariance of GE exists and
we do not know about it, the practical consequence is that it is considered part of the
genotype, where it is increased by 2covGE

We have already noted that independence of genotype and environment means that a specific
difference in environment has the same effect on different genotypes. If this assumption is
violated, there is an interaction between genotype and environment and
 p2   G2   E2   GE
2

Genotype environment interaction (GEI) can arise if specific differences in the environment
have greater effects on some genotypes than others (changes in variance) and/or there is a
change in order of merit of a series of genotypes measured under different environment
(changes in rank).

We can estimate  GE
2
if the environmental differences are large (macroenvironments),
otherwise,  GE
2
is considered part of the environmental variance.

Partitioning Phenotypic Variance

A full partitioning of phenotypic variance would be:
σ 2p =σG2 + σ 2E
σ 2p =σ 2A +σ 2D +σ 2I +2covGE + σ2EC(S) +σ2EC(T) +σ2EC(M) +σ2EG +σ2ES +σGE
2

Nature Nurture

The partitioning of phenotypic variance is usually expressed as the ratio of one component to
the total phenotypic variance ( σ 2p ).

Controlling and Estimating Environmental Components of Variation

In organisms amenable to rearing and crossing under standardized conditions, some
environmental components of variance can be eliminated by correct experimental design. For
example, covGE, σ 2EC(S) and σ 2EC(T) can be eliminated if one can assure genotypes are
randomized with respect to environments. Alternatively, σ 2EC(S) and σ 2EC(T) can be estimated if
replicate measures are taken across different spatial and temporal environments (i.e., the
same genotype is measured in at least two different vials or cages; or two different time
periods).

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The statistical technique of analysis of variance (ANOVA) can be used to partition
environmental variation. For example, if one rears a single inbred line of Drosophila in multiple
vials (V), and measures a quantitative trait for several individuals from each vial, the ANOVA
model Y=μ +V + E is use to analyze the data, where V refers to the variance between vials and
E refers to variance within vials, i.e., experimental error. The ANOVA results in estimates of
components of variance among/ between vials and within vials. The variance among vials is
due to differences in mean phenotype between vials, due to common spatial environment. This
component is an estimate of σ 2EC(S) . The variance within vials arises from ‘intangible’ variation.
This component thus estimates σ 2EW .

ANOVA models can also be used to account for temporal environmental variation. If one
repeats the same experiment as above, but at two or more different times, the model Y = µ + T
+ V(T) + E is used to analyze the data. Here, T = time, V(T) is vial within time. The ANOVA
gives estimates of the components of variance among times, among vials, among vials nested
within time, and within vials (error). The variance among times is due to differences in mean
phenotype between time periods, due to common temporal environment. This component thus
estimates σ 2EC(T) . As before, the variance among vials estimates σ 2EC(S) and the variance within
vials estimates σ 2EW .

In the discussion that follows, we will assume (unless otherwise specified) that variance due to
genotype-environment correlation is eliminated by randomizing genotypes across
environments, and that common spatial and temporal environmental variance is either
eliminated by randomizing across environments, or accounted for by replication. However, pre-
and post-natal maternal common environment will be assumed to be present, due to the
difficulty of eliminating this component experimentally.

The plot of phenotypic values across an environmental gradient is the reaction norm of a
genotype. This is also called the environmental sensitivity of a genotype. In panel (a) the two
genotypes show environment sensitivity, but not GEI. Panel (b) shows GEI attributable to
crossing of reaction norms of two genotypes, while panel (c) shows GEI attributable to a
change in the variance between two genotypes.

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