Lecture 5

Inbreeding and
Crossbreeding
Bruce Walsh lecture notes
Introduction to Quantitative Genetics
SISG, Seattle
16 – 18 July 2018

Inbreeding
• Inbreeding = mating of related individuals
• Often results in a change in the mean of a trait
• Inbreeding is intentionally practiced to:
– create genetic uniformity of laboratory stocks
– produce stocks for crossing (animal and plant
breeding)
• Inbreeding is unintentionally generated:
– by keeping small populations (such as is found
at zoos)
– during selection

2
 Genotype frequencies under inbreeding

• The inbreeding coefficient, F

• F = Prob(the two alleles within an individual
are IBD) -- identical by descent
• Hence, with probability F both alleles in an
individual are identical, and hence a
homozygote
• With probability 1-F, the alleles are
combined at random

Alleles IBD

1-F
Random mating
1-F

Alleles IBD

Genotype Alleles IBD Alleles not IBD frequency

A1A1 Fp (1-F)p2 p2 + Fpq

A2A1 0 (1-F)2pq (1-F)2pq
A2A2 Fq (1-F)q2 q2 + Fpq
4
 Changes in the mean under inbreeding
Genotypes A1A1 A1A2 A2A2
0 a+d 2a

freq(A1) = p, freq(A2) = q

Using the genotypic frequencies under inbreeding, the

population mean µF under a level of inbreeding F is
related to the mean µ0 under random mating by

µF = µ0 - 2Fpqd

• There will be a change of mean value if dominance is present (d not 0)

• For a single locus, if d > 0, inbreeding will decrease the mean value of
the trait. If d < 0, inbreeding will increase the mean

• For multiple loci, a decrease (inbreeding depression) requires

directional dominance --- dominance effects di tending to be positive.

• The magnitude of the change of mean on inbreeding depends on gene

frequency, and is greatest when p = q = 0.5
6
Inbreeding Depression and Fitness
traits

Inbred Outbred
7

Inbreeding depression

F2 F3 F4 F5 F6
Example for maize height
8
 Fitness traits and inbreeding depression

• Often seen that inbreeding depression is

strongest on fitness-relative traits such as
yield, height, etc.
• Traits less associated with fitness often show
less inbreeding depression
• Selection on fitness-related traits may
generate directional dominance

Why do traits associated with fitness

show inbreeding depression?
• Two competing hypotheses:
– Overdominance Hypothesis: Genetic variance for fitness is
caused by loci at which heterozygotes are more fit than both
homozygotes. Inbreeding decreases the frequency of
heterozygotes, increases the frequency of homozygotes, so
fitness is reduced.
– Dominance Hypothesis: Genetic variance for fitness is caused
by rare deleterious alleles that are recessive or partly recessive;
such alleles persist in populations because of recurrent mutation.
Most copies of deleterious alleles in the base population are in
heterozygotes. Inbreeding increases the frequency of
homozygotes for deleterious alleles, so fitness is reduced.

10
 Inbred depression in largely
selfing lineages
• Inbreeding depression is common in outcrossing
species
• However, generally fairly uncommon in species with
a high rate of selfing
• One idea is that the constant selfing have purged
many of the deleterious alleles thought to cause
inbreeding depression
• However, lack of inbreeding depression also means
a lack of heterosis (a point returned to shortly)
– Counterexample is Rice: Lots of heterosis but
little inbreeding depression

11

Evolution of the Selfing Rate

• Automatic selection (the cost of
outcrossing)
– An allele that increases the selfing rate has
a 50% advantage
– Pollen discounting
• Selection for reproductive assurance
– When population density is low, or
pollinators rare, failure to outcross may
occur
– Baker’s law: Colonizing species generally
have the ability to self. 12
What stops all plants from being selfers?

Inbreeding depression. If fitness of selfed-

produced offspring is less than 50% of that
from outcrossed-produced

13

Lande and Schemske (1985)

• As selfing rate increases, inbreeding
load can decrease
– If inbreeding largely due to recessive or
partially recessive deleterious alleles, the
mutation-selection equilibrium frequency
decreases in selfers
– As inbreeding load decreases, alleles that
increase outcrossing rate are not favored
– Hence, once largely selfing, very hard to
revert
14
Variance Changes Under Inbreeding
Inbreeding reduces variation within each population

Inbreeding increases the variation between populations

(i.e., variation in the means of the populations)

F=0
15

Between-group variance increases with F

F = 1/4

F = 3/4

F=1

16
Within-group variance decreases with F
 Implications for traits
• A series of inbred lines from an F2 population
are expected to show
– more within-line uniformity (variance about the
mean within a line)
• Less within-family genetic variation for
selection
– more between-line divergence (variation in the
mean value between lines)
• More between-family genetic variation for
selection

17

Variance Changes Under Inbreeding

General F=1 F=0

Between lines 2FVA 2VA 0

Within Lines (1-F) VA 0 VA
Total (1+F) VA 2VA VA

The above results assume ONLY additive variance

i.e., no dominance/epistasis. When nonadditive
variance present, results very complex (see WL Chpt 11).
18
 Line Crosses: Heterosis
When inbred lines are crossed, the progeny show an increase in mean
for characters that previously suffered a reduction from inbreeding.

This increase in the mean over the average value of the

parents is called hybrid vigor or heterosis

A cross is said to show heterosis if H > 0, so that the

F1 mean is larger than the average of both parents.
19

Expected levels of heterosis

If pi denotes the frequency of Qi in line 1, let pi + dpi denote
the frequency of Qi in line 2.

The expected amount of heterosis becomes

Xn
H F1 = ( pi ) 2 di
i= 1
• Heterosis depends on dominance: d = 0 = no inbreeding depression and no
Heterosis. As with inbreeding depression, directional dominance is required for heterosis.

•H is proportional to the square of the difference in allele frequencies

between populations. H is greatest when alleles are fixed in one population and
lost in the other (so that |dpi| = 1). H = 0 if dp = 0.

• H is specific to each particular cross. H must be determined empirically,

since we do not know the relevant loci nor their gene frequencies. 20
 Heterosis declines in the F2
In the F1, all offspring are heterozygotes. In the F2,
random mating has occurred, reducing the frequency
of heterozygotes.

As a result, there is a reduction of the amount of

heterosis in the F2 relative to the F1,

Since random mating occurs in the F2 and subsequent

generations, the level of heterosis stays at the F2 level.

Agricultural importance of heterosis

Crosses often show high-parent heterosis, wherein the
F1 not only beats the average of the two parents
(mid-parent heterosis), it exceeds the best parent.

Crop % planted % yield Annual Annual Annual land

as hybrids advantage added added savings
yield: % yield: tons
Maize 65 15 10 55 x 106 13 x 106 ha

Sorghum 48 40 19 13 x 106 9 x 106 ha

Sunflower 60 50 30 7 x 106 6 x 106 ha

Rice 12 30 4 15 x 106 6 x 106 ha

22
 Hybrid Corn in the US
Shull (1908) suggested objective of corn breeders
should be to find and maintain the best parental
lines for crosses

Initial problem: early inbred lines had low seed set

Solution (Jones 1918): use a hybrid line as the seed

parent, as it should show heterosis for seed set

1930’s - 1960’s: most corn produced by double crosses

Since 1970’s most from single crosses

23

A Cautionary Tale
1970-1971 the great Southern Corn Leaf Blight almost
destroyed the whole US corn crop

Much larger (in terms of food energy) than the great potato
blight of the 1840’s

Cause: Corn can self-fertilize, so to make hybrids either have to

manually detassle the pollen structures or use genetic tricks that
cause male sterility.

Almost 85% of US corn in 1970 had Texas cytoplasm Tcms, a

mtDNA encoded male sterility gene

Tcms turned out to be hyper-sensitive to the fungus

Helminthosporium maydis. Resulted in over a billion dollars
of crop loss

24
 Crossing Schemes to Reduce the
Loss of Heterosis: Synthetics
Take n lines and construct an F1 population by
making all pairwise crosses

Synthetics
• Major trade-off
– As more lines are added, the F2 loss of
heterosis declines
– However, as more lines are added, the
mean of the F1 also declines, as less elite
lines are used
– Bottom line: For some value of n, F1 - H/n
reaches a maximum value and then starts
to decline with n

26
 Types of crosses
• The F1 from a cross of lines A x B (typically
inbreds) is called a single cross
• A three-way cross (also called a modified
single cross) refers to the offspring of an A
individual crossed to the F1 offspring of B x
C.
– Denoted A x (B x C)
• A double (or four-way) cross is (A x B) x (C x
D), the offspring from crossing an A x B F1
with a C x D F1.

27

Predicting cross performance

• While single cross (offspring of A x B) hard to
predict, three- and four-way crosses can be
predicted if we know the means for single
crosses involving these parents
• The three-way cross mean is the average mean
of the two single crosses:
– mean(A x {B x C}) = [mean(A x B) + mean(A x C)]/2
• The mean of a double (or four-way) cross is the
average of all the single crosses,
– mean({A x B} x {C x D}) = [mean(AxC) + mean(AxD) +
mean(BxC) + mean(BxD)]/4

28
 Individual vs. Maternal Heterosis
• Individual heterosis
– enhanced performance in a hybrid individual
• Maternal heterosis
– enhanced maternal performance (such as
increased litter size and higher survival rates of
offspring)
– Use of crossbred dams
– Maternal heterosis is often comparable, and can
be greater than, individual heterosis

Individual vs. Maternal Heterosis in Sheep traits

Trait Individual H Maternal H total

Birth weight 3.2% 5.1% 8.3%

Weaning weight 5.0% 6.3% 11.3%

Birth-weaning 9.8% 2.7% 12.5%

survival
Lambs reared 15.2% 14.7% 29.9%
per ewe
Total weight 17.8% 18.0% 35.8%
lambs/ewe
Prolificacy 2.5% 3.2% 5.7%
 Estimating the Amount of
Heterosis in Maternal Effects
Contributions to mean value of line A

0
zA = z + gAI + gM
A + gM
A

Individual Maternal Grandmaternal

genetic genetic effect genetic effect (BV)
effect (BV) (BV)

Consider the offspring of an A sire and a B dam

Individual genetic
value is the Contribution
average of both from (individual)
parental lines heterosis

gAI + gIB M0
z AB =z + + gB + gB + h IA B
M
2
Maternal and
grandmaternal effects
from the B mothers
 gAI + gIB M0
z AB =z + + gB + gB + h IA B
M
2
Now consider the offspring of an B sire and a A dam

gAI + gIB M0
zBA =z + + gA + gA + h IA B
M
2
Maternal and grandmaternal
genetic effects for B line

Difference between the two line means estimates

difference in maternal + grandmaternal effects
in A vs. B

Hence, an estimate of individual heteroic effects is

z AB + z B A z AA + z B B
= h IA B
2 2
 The mean of offspring from a sire in line C crossed to
a dam from a A X B cross (B = granddam, AB = dam)

Genetic maternal effect

Average individual genetic value (average of maternal BV for both
(average of the line BV’s) lines)
Grandmaternal
genetic effect

2gIC + gAI + gBI h IC A + h IC B gAM + gBM M M0 r aI b

zC AB = + + + h AB + gB +
4 2 2 2

New individual Maternal genetic

heterosis of C x AB heteroic effect
cross “Recombinational loss” ---
decay of the F1 heterosis
in the F2
One estimate (confounded) of maternal heterosis

zCA + zCB M r Ia b
zC AB = = hAB +
2 2