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
 A1 A1
p A1 A1
F
q
A1 1-F A1 A2
p
Random
Alleles IBDmating
p A2 A1
q A2 1-F
q
F A2 A2
A2 A2

Genotype Alleles IBD Alleles not IBD frequency

A1A1 Fp (1-F)p2 p2 + Fpq

A 2A 1 0 (1-F)2pq (1-F)2pq

A 2A 2 Fq (1-F)q2 q2 + Fpq
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 F under a level of inbreeding F is
related to the mean 0 under random mating by

F = 0 - 2Fpqd
 For k loci, the change in mean is
Xk
š F = š 0 ° 2F pi qi di = š 0 ° B F
i= 1

Here B is the reduction in mean under X

complete inbreeding (F=1) , where B = 2 p i qi d i

• 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 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
Break for Problem 1
Inbreeding Depression and Fitness
traits

Inbred Outbred
Define ID = 1-F/0 = 1-(0-B)/0 = B/0
Drosophila Trait Lab-measured ID = B/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 F on F,

F = 0 - BF
0
F
0 - B

0 F 1

If epistasis is present, this regression is non-linear,

with CkFk for k-th order epistasis
 Minimizing the Rate of Inbreeding
• Avoid mating of relatives
• Maximum effective population size Ne
• 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
reduces variation
Inbreeding increases withinbetween
the variation each population
populations
(i.e., variation in the means of the populations)

F = 1/4
0
3/4
1
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
 Line Crosses: Heterosis
When inbred lines are crossed, the progeny show an increase in mean
for characters that previously suffered a reduction from inbreeding.

P1over
This increase in the mean P2 average value of the
x the
parents is called hybrid vigor or heterosis
F1
š P1 + š P 2
H F1 = š F 1 F°2
2
A cross is said to show heterosis if H > 0, so that the
F1 mean is average than the average of both parents.
 Expected levels of heterosis
If pi denotes the frequency of Qi in line 1, let pi + i denote
the frequency of Qi in line 2.

The expected amount of heterosis becomes

Xn
H F1 = (±pi ) 2 d i
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 gene frequency

Between populations. H is greatest when alleles are fixed in one population and
lost in the other (so that | i| = 1). H = 0 if  = 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 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,

š P 1 + š P2 (±p) 2 d HF 1
HF 2 = š F 2 ° = =
2 2 2

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

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
 hI n hM 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
F1 individuals, as the heterotic advantage decreases
in the F2

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

F1 ° P
F2 = F 1 °
n Average of the founding lines
Mean of the F1 from all pairwise crosses
This is equivalent to
 
1
HF 2 = H 1°(n )
The larger n (number of founding lines), smaller decrease
in H
Second Solution: Rotational Crossbreeding
AxB
cross dam back to A sire
dam

(A x B) x A
cross dam back to B sire
dam

((A x B) x A) x B cross dam back to A sire

dam
And so on ….
 The expected mean value under a two-way rotation:

zA B ° P 2 zA + z B
R 2 = zA B ° ; where P2 =
3 2
Key:mean
The expected Heterosis advantage
value under dividedrotation:
a three-way by 3, not by

b3 = SC 3 °z 2 as
° in
ABP F2 3 z + z + z
AB AC BC
R ; where S C3 =
7 3
Under a 4-way
1/7th rotation,isthe
of heterosis lostorder matters:

b ( A ;B ; C ; D ) SCna ° P4 zA C + zB D
R4 = S C4 ° ; where S C n a =
15 2
Mean of 1/15all of
sixheterosis
pair-wiseiscrosses
Mean oflostcrosses of nonadjacent lines
Trait P F1 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 F1 > R > S > P

For a 2-way rotation:
For weaning weight
b F1 ° P 2
R 2 = F1 °
3 Rb 2 = 180:5 °
180:5 ° 154:2
= 171:7
3
For the 2-breed synthetic,

b 180:5 ° 154:2
S 2 = 180:5 ° = 167:4
2
Break for Problem 3
 Estimating the Amount of
Heterosis in Maternal Effects
Contributions to mean value of line A
0
I M M
šA = š + gA + gA + gA
Grandmaternal
IndividualMaternal
genetic effect
genetic(BV) genetic
effect (BV) effect (BV)
Consider the offspring of an A sire and a B dam

I I
gA + gB M M 0
I
š AB = š + + gB + gB + hAB
2
Maternal and grandmaternal effects
Individual genetic value is the Contribution
average from (individual)
from the an B sire and a A dam lines
B of
mothers
Now consider the offspring ofheterosis both parental

gAI + g IB M M0 I
šBA = š + + gA + gA + h A B
2
Individual genetic and heterotic effects as in A x B cross
Maternal and grandmaternal genetic effects for B line
Hence, an estimate of individual heteroic effects is

š AB + š B A š AA + š B B I
= hAB
2 2
Likewise, an estimate of maternal/grandmaternal
effects is given by

 ¥  ¥
( ) ( )
0 0
š B A ° š AB = gAM + gAM ° gM B
+ gB
M

How about estimation of maternal heteroic effects?

 The mean of offspring from a sire in line C crossed to
a dam from a A X B cross (B = granddam, AB = dam)

2gIC + gAI + gBI h IC A + h IC B gAM + gBM M M 0 r aI b

š C ¢A B = + + + h A B + gB +
4 2 2 2
Average individual genetic value
New individual
Genetic
“Recombinational Maternal
heterosis
loss” maternal
--- genetic
Grandmaternal
of C
decayx
effect
AB
of heteroic
cross
the genetic
F effect
effect
heterosis in
(average of the line BV’s) 1
The F2 (average of maternal BV for both lines)

One estimate (confounded) of maternal heterosis

I
š CA + š CB r
š C .¢A B ° = hM
AB + ab
2 2