Lecture 7:

Inbreeding and
Crossbreeding
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
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
Genotype Alleles IBD Alleles not IBD frequency
A
1
A
1
Fp (1-F)p
2
p
2
+ Fpq
A
2
A
1
0 (1-F)2pq (1-F)2pq
A
2
A
2
Fq (1-F)q
2
q
2
+ Fpq
p
A
1
A
2
q
F
F
A
1
A
1
A
2
A
2
1-F
1-F
p
p A
1
A
1
A
2
A
1
q
A
2
A
1
q
A
2
A
2
Alleles IBD Random mating
Changes in the mean under inbreeding
m
F
= m
0
- 2Fpqd
Using the genotypic frequencies under inbreeding, the
population mean m
F
under a level of inbreeding F is
related to the mean m
0
under random mating by
Genotypes A
1
A
1
A
1
A
2
A
2
A
2

0 a+d 2a
freq(A
1
) = p, freq(A
2
) = q

F
=
0
2F
k
X
i
= 1
p
i
q
i
d
i
=
0
B F
For k loci, the change in mean is
B = 2
X
p
i
q
i
d
i
Here B is the reduction in mean under
complete inbreeding (F=1) , where
There will be a change of mean value dominance is present (d not zero)
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 d
i
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
Break for Problem 1
Inbreeding Depression and Fitness
traits
Inbred Outbred
Define ID = 1-m
F
/m
0
= 1-(m
0
-B)/m
0
= B/m
0

Drosophila Trait Lab-measured ID = B/m
0

Viability 0.442 (0.66, 0.57, 0.48, 0.44, 0.06)
Female fertility 0.417 (0.81, 0.35, 0.18)
Female reproductive rate 0.603 (0.96, 0.57, 0.56, 0.32)
Male mating ability 0.773 (0.92, 0.76, 0.52)
Competitive ability 0.905 (0.97, 0.84)
Male fertility 0.11 (0.22, 0)
Male longevity 0.18
Male weight 0.085 (0.1, 0.07)
Female weight -0.10
Abdominal bristles 0.077 (0.06, 0.05, 0)
Sternopleural bristles -.005 (-0.001, 0)
Wing length 0.02 (0.03, 0.01)
Thorax length 0.02
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.






Estimating B
In many cases, lines cannot be completely inbred due to
either time constraints and/or because in many species
lines near complete inbreeding are nonviable
In such cases, estimate B from the regression of m
F
on F,
m
F
= m
0
- BF
0
m
0
1
m
0
- B
If epistasis is present, this regression is non-linear,
with C
k
F
k
for k-th order epistasis
m
F
F
Minimizing the Rate of Inbreeding
Avoid mating of relatives
Maximum effective population size N
e
Ne maximized with equal representation
Contribution (number of sibs) from each parent as
equal as possible
Sex ratio as close to 1:1 as possible
When sex ratio skewed (r dams/sires ), every male
should contribute (exactly) one son and r daughters,
while every female should leave one daughter and
also with probability 1/r contribute a son
Variance Changes Under Inbreeding
F = 0 F = 1/4 F = 3/4 F = 1
Inbreeding reduces variation within each population Inbreeding increases the variation between populations
(i.e., variation in the means of the populations)
Variance Changes Under Inbreeding
General F = 1 F = 0
Between lines
2FV
A
2V
A
0
Within Lines
(1-F) V
A
0 V
A
Total
(1+F) V
A
2V
A
V
A
Line Crosses: Heterosis
P
1
P
2
F
1
x
F
2
H
F
1
=
F
1


P
1
+
P
2
2
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
F
1
mean is average than the average of both parents.
Expected levels of heterosis
If p
i
denotes the frequency of Q
i
in line 1, let p
i
+ d
i
denote
the frequency of Q
i
in line 2.
H
F
1
=
n
X
i
= 1
(p
i
)
2
d
i
The expected amount of heterosis becomes
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 gene frequency
Between populations. H is greatest when alleles are fixed in one population and
lost in the other (so that | d
i
| = 1). H = 0 if d = 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.
Heterosis declines in the F
2

H
F
2
=
F
2


P
1
+
P
2
2
=
(p)
2
d
2
=
H
F
1
2
In the F
1
, all offspring are heterozygotes. In the F
2
,
Random mating has occurred, reducing the frequency
of heterozygotes.
As a result, there is a reduction of the amount of
heterosis in the F
2
relative to the F
1
,
Since random mating occurs in the F
2
and subsequent
generations, the level of heterosis stays at the F
2
level.
Agricultural importance of heterosis
Crop % planted
as hybrids
% yield
advantage
Annual
added
yield: %
Annual
added
yield: tons
Annual land
savings
Maize 65 15 10 55 x 10
6
13 x 10
6
ha
Sorghum 48 40 19 13 x 10
6
9 x 10
6
ha
Sunflower 60 50 30 7 x 10
6
6 x 10
6
ha
Rice 12 30 4 15 x 10
6
6 x 10
6
ha
Crosses often show high-parent heterosis, wherein the
F
1
not only beats the average of the two parents
(mid-parent heterosis), it exceeds the best parent.
Break for Problem 2
Crossbreeding in Animals
Individual heterosis:
Enhanced performance in a hybrid individual
Maternal heterosis:
Enhanced maternal performance, e.g.,
increased litter size and higher survival
rates of offspring
Maternal heterosis is often comparable,
and can be greater than, individual heterosis
h
I
n h
M
n
Birth weight
3.2% 42 5.1% 12
Weaning weight
5.0% 56 6.3% 27
Preweaning growth rate
5.3% 19
Postweaning growth rate
6.6% 10
Yearling weight
5.2% 18
Ovulation rate
-2.0% 4
Fertility
2.6% 20 8.7% 30
Prolificacy
2.8% 20 3.2% 31
Birth-weaning survival
9.8% 29 2.7% 25
Lambs per ewe
5.3% 20 11.5% 25
Lambs reared per ewe
15.2% 20 14.7% 25
Total weight lambs/ewe
17.8% 24 18.0% 25
Carcass traits
0% 7 25







Maternal and individual heterosis effects can be combined by
using crossbred (hybrid) dams.
For example, for total weight of lambs rear per
mated ewe has an 18% individual heterotic advantage
in a crossbred offspring and an addition 18% advantage
(from maternal heterosis) when crossbred
ewes are used in place of purebred ewes.
This combining of maternal and individual heterotic effects
is one reason why three-way crosses are common in animal
breeding, generally by crossing a male from line A with
a hybrid female (from a B x C cross).
This strategy exploits maternal heterosis in the female,
with the sire line often chosen for its contribution to
some production trait.
Synthetics and Rotational
Crossbreeding
To maximally exploit heterosis, we ideally would use only
F
1
individuals, as the heterotic advantage decreases
in the F
2

Problem: In (most) large farm animals, the number of
offspring is on order of the number of dams. Thus, to
produce n triple cross hybrid offspring requires on the
order of 2n dams (the granddam to produce the
B x C dam, and the dam herself in the A X (B X C) cross).
One partial solution around this problem:
Synthetics: n parental lines are chosen and a
random-mating population formed by first making all
n(n-1)/2 pairwise intercrosses between the lines
F
2
= F
1

F
1

P
n
H
F
2
= H

1
1
n

( )
Average of the founding lines
Mean of the F1 from all pairwise crosses
The larger n (number of founding lines), smaller decrease
in H
This is equivalent to
Second Solution: Rotational Crossbreeding
A x B
(A x B) x A
dam
dam
cross dam back to A sire
cross dam back to B sire
((A x B) x A) x B
dam
cross dam back to A sire
And so on .
R
2
= z
AB

z
AB
P
2
3
; where P
2
=
z
A
+ z
B
2
b
R
3
= SC
3

z
AB
P
3
7
; where SC
3
=
z
AB
+ z
AC
+ z
B C
3
The expected mean value under a two-way rotation:
The expected mean value under a three-way rotation: Key: Heterosis advantage divided by 3, not by
2 as in F
2

Under a 4-way rotation, the order matters:

1/7th of heterosis is lost
1/15 of heterosis is lost
Mean of all six pair-wise crosses
Mean of crosses of nonadjacent lines
b
R
(
A;B ; C; D
)
4
= SC
4

SC
n a
P
4
15
; where SC
n a
=
z
AC
+ z
B D
2
Trait
P F
1
R S BC
Weaning weight 154.2 180.5 178.3 170.1 181.4
12-month weight 210.5 246.8 232.2 212.3 233.6
18-month weight 274.9 315.7 296.6 276.6 295.3
12-18 m weight gain 64.4 68.9 64.4 64.6 61.7
Note that F
1
> R > S > P
b
R
2
= F
1

F
1
P
2
3
For a 2-way rotation:
For the 2-breed synthetic,
b
S
2
= 180:5
180:5 154:2
2
= 167:4
For weaning weight
b
R
2
= 180:5
180:5 154:2
3
= 171:7
Break for Problem 3
Estimating the Amount of
Heterosis in Maternal Effects

A
= + g
I
A
+ g
M
A
+ g
M
0
A
Contributions to mean value of line A
Individual genetic effect (BV) Maternal genetic effect (BV)
Grandmaternal genetic effect (BV)

AB
= +
g
I
A
+ g
I
B
2
+ g
M
B
+ g
M
0
B
+ h
I
AB

B A
= +
g
I
A
+ g
I
B
2
+ g
M
A
+ g
M
0
A
+ h
I
AB
Consider the offspring of an A sire and a B dam
Individual genetic value is the average of both parental lines
Maternal and grandmaternal effects
from the B mothers
Contribution from (individual)
heterosis
Now consider the offspring of an B sire and a A dam
Individual genetic and heterotic effects as in A x B cross
Maternal and grandmaternal genetic effects for B line

AB
+
B A
2

AA
+
B B
2
= h
I
AB
Hence, an estimate of individual heteroic effects is

B A

AB
=

g
M
A
+ g
M
0
A

g
M
B
+ g
M
0
B

( ( ) )
Likewise, an estimate of maternal/grandmaternal
effects is given by
How about estimation of maternal heteroic effects?

C AB
=
2g
I
C
+ g
I
A
+ g
I
B
4
+
h
I
C A
+ h
I
C B
2
+
g
M
A
+ g
M
B
2
+ h
M
AB
+ g
M
0
B
+
r
I
a b
2

CAB


C A
+
C B
2
= h
M
AB
+
r
I
a b
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)
Average individual genetic value
(average of the line BVs)
New individual heterosis of C x AB cross Genetic maternal effect
(average of maternal BV for both lines)
Grandmaternal genetic effect
Maternal genetic heteroic effect
Recombinational loss --- decay of the F
1
heterosis in
The F
2

One estimate (confounded) of maternal heterosis