Effects of major histocompatibility complex on antibody response in F1 and F2 crosses of chicken lines

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Submitted on 1 Jan 1993

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Effects of major histocompatibility complex on antibody

response in F1 and F2 crosses of chicken lines

Mh Pinard, Aj van der Zijpp

To cite this version:

Original

article

Effects of

_{major histocompatibility}

complex

on

antibody

_response

in

F

1

and

F

2

crosses

of

chicken lines

MH Pinard

AJ

Van

der

_Zijpp

1

Wageningen Agricultural University,

Departement of

Animal

_{Hv,s6andry, Wageningen;}

2

DLO-Research Institute

_for

Animal Production

_{"Schoonoord",}

Zeist,

The Netherlands

(Received

12

_May

1992;

accepted

5

January

1993)

Summary - Lines of chickens selected for 9

_generations

for

_high

_(H)

and low

_(L)

_antibody

(Ab)

response to

sheep

red blood cells

(SRBC)

were crossed to

_produce

F

1

(n

=

761)

and

F

2

(n

=

1033)

populations.

All animals _were

typed

for

_major

histocompatibility complex

(MHC)

B-types.

Effects of MHC _genotypes and

_haplotypes

on the Ab titer to SRBC were estimated. The MHC _genotypes and

_remaining

_genotype

_explained

2.5% and 31% of the total variation of the Ab titer in the F2

respectively.

Estimates of MHC effects in the

F

2 were similar to estimates in the selected lines. The 119 and 121

_B-haplotypes

were associated with a

_{significantly higher}

_response than the 114 and 124

_{B-haplotypes.}

These results confirm the

_hypothesis

that

changes

in

_B-type

distribution observed in the selected lines could be related to a direct or

_closely

linked effect of MHC on the immune response. chicken

_/

humoral response

/

selection

/

cross

_/

_{major histocompatibility complex} Résumé - Effets du complexe majeur d’histocompatibilité sur la réponse en _anticorps

dans des croisements FI et F2de _lignées de _poules. Des

lignées

de

poules,

sélectionnées

pendant

9

générations

sur la

_réponse

humorale haute et basse à des

_globules

rouges de

mouton, ont été croisées

_afin

de

_produire

une _Fl

(n

=

761)

_{et une}

_F

₂

(n

=

10,!,!).

Tous

les animau! ont été

_analysés

_pour leurs types B du

_{complexe majeur d’histocompatibilité}

(CMH).

Les

_effets

des

_génotypes

et des

_haplotypes

du CMH sur la

_réponse

en _anticorps aux

_globules

_rouges de mouton ont été estimés. Le

_génotype

du CMH

explique 2,5%

de la

variation totale de la

réponse

en _anticorps dans la

F

2

,

alors _que l’héritabilité du caractère

*

On leave from the Institut National de la Recherche

_Agronomique,

Laboratoire de

est de

0,,!1.

Les estimations des

effets

du CMH dans la

_F

₂

sont semblables à celles obtenues dans les

_lignées

sélectionnées. Les

_haplotypes

B 119 et B 121 sont associés à une

_réponse

immunitaire

_{significativement plus}

élevée _que les

_haplotypes

B 114 et

_124.

Ces résultats

confirment l’hypothèse

que les

changements de fréquence

des _types du CMH observés dans les

_lignées

sélectionnées

_pouvaient

être dus à un

_effet

direct ou

_{génétiquement}

lié du CMH

sur la

réponse

immunitaire.

poule

/

réponse immunitaire

_/

sélection

_/

croisement

_/

complexe majeur

d’histo-compatibilité

INTRODUCTION

There is

_accumulating

evidence that disease resistance and immune _response are

under

_genetic

control in most

_species,

_providing

the bases for an

_improvement

by

direct selection for the trait of

_interest;

_moreover, the use of markers

_might

add to the

_efficiency

of selection

_(Shook,

_1989;

Weller and

_Fernando,

_1991).

But in the latter

_option,

_{relationships}

between marker _genes and the trait of

interest have to be

_clearly

established. Studies on

relationships

between

_major

histocompatibility

complex

(MHC)

types

and immune traits or disease resistance have shown

_variability

in

_strength

and nature of association

_(Schierman

and

Collins,

1987;

Van der

_Zijpp

and

_Egberts,

_1989).

Inconsistencies

_might

be due to several

reasons:

_a)

the MHC does not

_directly

affect the trait and some

_crossing

over

has occurred between the MHC and immune _{response genes,} so that the

_apparent

effect of 1VIHC on the immune trait

_depends

on the

linkage phase

between MHC genes and immune response genes;

b)

the MHC is

directly

involved but there

are

_epistatic

effects with other

_background

genes

and/or

significant

genotype-environment

_{interactions;}

_c)

_only

a few MHC

_types

are

_present

_per

_study,

so

that the same

_haplotypes

differ in relative

_performance

_(good

or

poor)

in different

populations;

d)

different and even

_{inappropriate}

statistical methods

_might

have been

_used,

_especially

when animals are related.

High

(H)

and low

_(L)

lines of chickens have been

_{produced by divergent}

selective

breeding

for

_primary

_antibody

_response to

_sheep

red blood cells

_{(SRBC) (Van}

der

Zijpp

et

_{al, 1988;}

Pinard et

_al,

_1992).

After 10

_generations,

the H and L lines revealed a

diverging

distribution in MHC

_types,

_compared

to the random control

line;

moreover, MHC

types

were

_responsible

for a

_significant

_part

of variation of the immune _response

_(Pinard

et

_al,

_1993).

_However,

MHC

_genotypes

were not know in

early generations

so that estimates of the MHC effect

_might

be

_biased,

even when

using

all

_family

information

_(Kennedy

et

_al,

_1992).

_Moreover,

the number of animals for some

_genotypes

was limited.

Therefore,

a

_study

_involving

crosses between the H and L lines was

_required

to confirm the MHC association.

The

_objectives

of this

_experiment

were to

_produce

_F

_I

and

_F

₂

crosses from lines

of chickens selected for

_high

and low

_antibody

_response to

_SRBC,

and to estimate the MHC

_genotype

and

_haplotype

effects on the immune _response

_against

a random

MATERIALS AND METHODS

Crossing

of selected lines

Chickens were selected from an ISA Warren cross base

_population,

for

_high

_(H)

or

low

_(L)

total

_antibody

_(Ab)

titer 5 d

_postprimary

immunization with 1 ml

25%

sheep

red blood cells

_(SRBC)

at 37 d _{of age}

_(Van

der

_Zijpp

et

_{al, 1988;}

Pinard

et

_al,

_1992).

From the 9th

_generation,

26 males and 55 females of the H line were

mated with 53 females and 31 males of the L

line,

respectively,

to

_produce

761

_F

_i

animals. From the

_F

₁

_population,

243 females and 202 males were used to

produce

1 033

F

Z

chicks. Parents of the

F

1

and

F

Z

populations

were

chosen from as _many

different families as

_possible,

and were mated at

_random,

_providing

in

_{F2 !}

100

chicks for each of the 10 MHC

_genotypes

_{(see below).}

Immunization with

SRBC

was

_performed

on

_F

_I

and

F

2

animals

_identically

as in the selected

lines,

and Ab

titers

_against

SRBC 5 d

_postprimary

immunization were recorded. The vaccination

schedule

_applied

to

_F

_I

and

_F

₂

chicks was identical to the one used

_during

the

selection.

However,

the

_housing

_system

and environment differed: birds from the H and L lines were reared _{in cages} of 50 _{per 100}

em

2

with 10 chicks _{maximum per}

cage on one

farm;

F

1

and

F

Z

birds were housed free on the floor on 2 different

farms,

respectively.

Typing

for MHC

_haplotype

Major

histocompatibility complex

haplotypes

were determined

by

direct

haemag-glutination,

using

alloantisera obtained from the lines. Four

_serotypes,

_{provisionally}

called

_B

_1l4

_,

_B1l

₉

_,

_,

₁₂₁

_B

and

B

124

were identified

_previously

in the selected lines. As

_compared

to known reference

_B-types,

none of the serotypes identified in the lines was identical for both B-F and B-G.

Only

B1

l4

and

B11

9

showed similarities

for B-G with

B

14

and

_B

₁₉

_,

_{respectively,}

whereas

B

121

showed similarities for B-F with

B

21

_(Pinard

et

_al,

_1991;

Pinard and

_Hepkema,

_1992).

A MHC

_genotype

was

defined as the combination of 2

_{haplotypes. Serological}

_typing

was

performed

on all

the

F

1

and

F

2

chicks and

_segregation

of the

_haplotypes

was checked for

_consistency

within

_families;

inconsistent data

_(3%

of the

_data)

were removed from the

analysis.

Statistical

_analysis

Effects of MHC

_genotype

on the Ab _response were estimated in the

F

I

and

F

2

populations, using

the

_following

mixed model:

Where :

Ab

ijk

= the Ab titer of the kth

chick,

p = a _constant,

sex

i = the fixed effect of the ith _sex of the

chick,

MHC!

= the fixed effect of the

jth

MHC

_genotype,

U2!!

= the random additive

_genetic

effect _on the Ab titer in the kth chick and

The sex effect corrected for a

_higher

Ab _response to SRBC in females than in

males. All

_{relationships}

from the base

_population

until the

F

I

and

F

2

crosses were

used in the

_analysis

of the

_F

₁

and

_F

₂

_data,

_{respectively.}

The mixed model was

applied

assuming

a

heritability

of

_0.31,

as estimated

previously

from data of all

lines

_(Pinard

et

_al,

_1992).

Solutions for the model were obtained

_using

the

PEST-program

(Groeneveld,

1990;

Groeneveld and

_Kovac,

_1990),

which is a

_generalized

procedure

to set up and solve

_systems

of mixed model

_{equations containing genetic}

covariances between observations.

Differences between

_genotypes

within lines were tested as

orthogonal

contrasts

_by

an F-value calculated

by PEST,

which allows use of all relations between animals.

The overall effect of

_genotypes

was estimated

by

testing,

jointly,

n-1

independent

differences between

_genotypes,

with n

_being

the number of

_genotypes.

Heterozygote

superiority

was estimated for each available combination

by

test-ing

the difference between the

_heterozygote

genotypes

and the average of their

homozygous

counterparts.

The overall

_heterozygote

_superiority

was estimated

by

testing

the difference between all the

_heterozygote

_genotypes

and the _average of

their

_homozygous

_conterparts.

The

_haplotype

effect was estimated

_by

3 methods. In method

I,

the effect of

haplotype

i was estimated

_by

testing

the difference between

_genotype

_{combinations,}

comprised

of the

_haplotype

i and their

_{counterparts,}

_comprised

of a reference

. ,,

E,(GeTtOt,—G’eTtOr,)

, ! , ! , ..

ha

p

lo

typ

e

r, as follows:

E! (Geno2! - Geno,.! )

with

Geno2!

and

_Geno

_rj

_being

the estimated effects of MHC

_genotypes

_comprised

of

_haplotypes

i and

_j,

and r and

_j,

respectively,

and p

being

the number of

pairwise

combinations. Methods II and III

were

applied

in the

following haplotype

models,

as

adapted

from

0stergard

(1989):

where

₍

₃

_j

is the linear

_regression

coefficient on

_Haplo!,

which is the number of the

jth

MHC

_haplotype

₍₂

=

homozygous,

1 =

heterozygous

or 0 =

absent)

in the lth

chick,

r

k

is the linear

_regression

coefficient on

Comb

k

,

which is the kth

heterozygous

combination,

and all the other terms are as

previously

described.

In the

_F

_I

cross,

only

Method I was

_applied,

whereas all 3 methods were

_compared

in the

_F

₂

_population,

which

_provided

all

_{possible haplotype}

combinations in similar

numbers of animals.

RESULTS

Antibody

titer distribution in the

_F

_i

and

_F

₂

_populations

Antibody

titer distributions in the H and L lines of the 9th

_generation

and in the

F

1

and

_F

₂

crosses are shown in

figure

_1,

and mean titers are

_given

in table I. The

_F

_i

cross did not show any

positive

heterosis

effect,

and the titer of the cross between

L line females and H line males was even lower

(5.85)

than the mean

_parent

value

crosses than in the selected

lines,

but the

F

2

population

did not show a

_greater

variation of titers than the

_F

₁

cross.

MHC distribution in the

F

i

and

F

2

populations

Numbers of animals _per MHC

_genotype

in the

F,

and

F

2

crosses are

_given

in

table II. Sexes were

_{equally represented}

in each class. It was not

_possible

to obtain

homozygous

121-121 animals in the

_F,

cross because the 121

_B-haplotype

was not

present

in the L line of the 9th

_generation

_(Pinard

et

_al,

_1993).

Estimation of MHC

_genotype

effects on the

antibody

_response

Estimates of MHC

_genotype

on the Ab _response to SRBC in

_F

_i

and

F

2

animals

are

_given

in table III. The overall effect of MHC

genotypes

was

_greater

in the

_F

₂

than in the

_F

₁

_population.

_{The range of} estimates was

_higher

in the

F

1

than in

the

F

2

population,

but the SE of differences between

_genotypes

were half as

_large

in the

F

2

as

they

were in the

F

I

cross. The

ranking

of

_genotypes

according

to

their Ab titer estimates did not differ

_greatly

between the 2

_{populations; only}

the 124-124 and the 114-121

_B-genotypes

_{showed.relatively}

low

_estimates,

and the 119-119

_B-genotype

a

_{relatively high}

estimate in the

_F

_I

_compared

to those in the

F

2

animals. No

_{significant changes}

in the estimate were observed when

taking

other

input

heritability

values between 0.2 and 0.4

_(data

not

_shown).

In the

F

2

,

the distributions of Ab titers within

_genotypes

were normal and

_ranged

between those

Comparisons

of

_genotype

effects on the Ab _response to SRBC estimated in the

F

2

with their effects estimated in the

_H,

C and L lines

_(Pinard

et

_al,

₁₉₉₃₎

are

shown in

_figure

3. Results obtained from the

F

2

were more in

_agreement

with those

of obtained from the selected lines than from the C line.

The relative

_importance

of the MHC

_genotype

and the

_remaining

_genotype

on

the variation of the Ab titer in the

F

2

were calculated

by

_comparing

the coefficients

of determination

_using

different models

_{(table IV).}

When

used alone in the

model,

the MHC

_genotype

_{explained only}

4.4%

of the total

_variation,

which could still be the result of

_{partial confounding}

effects between MHC

_genotype

and the effects of the sex and of

_U!.

It

_is,

therefore,

better to look at the difference in

R

z

between a

31.1 when

_putting

_only

U

k

as an effect was close to the

_input

_heritability

_(0.31)

as

expected.

Estimation

_{of heterozygote superiority}

In the

_F

_I

_population,

no

significant

effect of

_heterozygote

_superiority,

overall or

for _any available

_combination,

was found

(data

not

_shown).

No

_significant

effect of overall

_heterozygote

_superiority

was shown in

F

2

animals either

(table V);

however,

the 114-124 and 119-121

_B-genotypes

demonstrated a

significant heterozygous

disadvantage

and

_{advantage, respectively.}

Estimation of MHC

_haplotype

effects on the

_antibody

_response

Results of the estimation of MHC

_haplotype

effect in the Ab titer in the

F

I

and

_F

₂

populations,

using

Method

_I,

are

_given

in table VI. In the

F

I

population,

the 119

B-haplotype

was

_{significantly}

associated with the

_highest

_estimate,

whereas in

the

_F

₂

_animals,

the estimated Ab titers of the 119 and 121

_B-haplotypes

were

significantly higher

than for the 114 and 124

_{B-haplotypes.}

As

_compared

to the results obtained with Method

_{I, using}

Method II in the

_F

₂

_population

did not

by

Method III were in fact

equivalent

to the additive effects of

_haplotypes,

which

could be obtained from the estimated effects of the

_{corresponding homozygous}

_genotype

combinations;

and the

_{specific heterozygous}

combination effects

_(Comb

_k

₎

DISCUSSION

When

_parental

lines are

_crossed,

the amount of heterosis shown

_by

the

_F

₁

_may

be defined as its deviation from the

_mid-parent

value

_{(Falconer, 1989).}

Crossing

effects are due to differences in the allelic

frequencies

between the 2

_parental

lines. In this

_experiment,

the 2 lines that were crossed came from the same base

population.

However,

after 9

_generations

of

selection,

they

differed

_greatly

for MHC

haplotype frequency

and

_probably

for other _{immune response genes} associated with

the _response to SRBC

_(Pinard

et

_al,

_1993).

No heterosis was demonstrated here.

Nevertheless,

the

_reciprocal

crosses showed similar Ab titer values

_although

their

respective

mid-parent

values

differed,

indicating

maternal or sex-linked effects.

When

_crossing

lines of mice at their selection limit for Ab _response to

_SRBC,

positive

heterosis was shown and was

_interpreted

as

_partial

dominance of the

character

_high

_responder

_(Biozzi

et

_al,

_1979).

In a similar

_experiment

with White

to

_SRBC,

showed a

_positive

heterosis

effect after 3

_generations

of selection

(Siegel

and

_Gross,

_1980),

but no heterosis effect was shown after 9

generations

(Ubosi

et

al,

1985).

In our

_lines,

environmental effects were

_responsible

for more than 2 titer

points

of variation in Ab titer

_during

the selection

_(Pinard

et

_al,

_1992).

Therefore,

selected lines and

_F

_I

should not be

_compared

on their

_phenotypic

values because

they

were

_kept

in 2

_separate

environments.

Because of a

_possible

bias in estimates of

_genotype

effects from selected lines

(Kennedy

et

_{al, 1992;}

Pinard et

al,

1993),

an

F

2

was

produced.

In

fact,

results

of estimation of

_genotype

effects in the

_F

₂

were more similar to the estimated effects in the selected lines than in the C line

_{(fig 3),}

_giving

_credibility

to the

analysis performed

in _{the selected lines. The average}

_genetic

value of the C

line,

as

measured

_by

the mean estimated

breeding value,

did not

_{change during}

the selection

(Pinard

et

_al,

₁₉₉₂₎

and the C line

_displayed,

as the

_F

₂

_,

a random

background.

However,

the

F

2

background

had a

_relatively

_great

_frequency

of

_high

and low

immune _response genes, whereas the C

background

had

low,

average, and

high

genes from the base

population.

Thus,

besides the fact that estimation of

genotype

effects in the C line could be

_{hampered by}

low numbers of

animals,

differences of effects between the

_F

₂

and the C line _may be

_interpreted

as interaction between

MHC and other immune response genes.

Moreover,

linkage disequilibrium

created

in the selected lines between MHC genes and linked immune response genes may

not have

disappeared

completely

in the

_F

₂

_.

How do the results of the

_F

₂

contribute to the

_{understanding}

of the role

_played

by

MHC

_{haplotypes during}

selection? In the Biozzi lines of mice at their selection

limit, analysis

of the

F

2

cross showed that MHC

haplotypes

found in the H and the L

lines

_segregated,

_{respectively,}

with a

_higher

and a lower _{immune response}

(Mouton

et

_al,

_1979).

In our

_experiment,

a selection limit was not reached.

Nevertheless,

the MHC

_haplotypes

most

_frequent

in the L line

₍₁₁₄

and

₁₂₄₎

and in the H line

(119

and

₁₂₁₎

were associated in the

_F

₂

with the lowest and

highest

Ab

titer,

respectively.

These results confirm the

_previous

_assumptions

_(Pinard

et

al,

1993)

that the

_changes

of MHC

_type

_frequency

observed in the selected lines were not the result of

chance,

but could be

_{explained by}

a direct or

_closely

linked effect of MHC

types

on the selected Ab _response.

However,

the

magnitude

of MHC effects

(2.5%

of the total

_variation)

could not

_{fully explain}

the interline difference.

Associations between MHC genes and the Ab response to SRBC have

_already

been shown in chickens

_(Scott

et

_al,

_1988;

Loudovaris et

_al,

_1990),

mice

_(Mouton

et

_al,

₁₉₇₉₎

and miniature

_pigs

_(Mallard

et

al,

1989).

Immunological knowledge

of

MHC can

_support

the

_hypothesis

of a direct involvement: when

injected,

the

T-dependent

SRBC

_antigens

are

_phagocytized

and

_{processed by macrophages,}

and

finally presented

to

_{T-helper cells, inducing,}

in collaboration with

_B-cells,

the

production

of Ab

_against

SRBC

_(Biozzi

et

al,

1984).

The T - B cell interaction has been shown in

_chickens,

as in mammalian

_species,

to be MHC class II

_(B-L)

restricted as is the

_presentation

of

processed

peptides

to T-cells

_(Vainio

et

_al,

_1987).

Efficiency

of the _{response may} be related to the varied

_ability

of MHC molecules

to bind and

_present

_antigens

to T-cell

_receptors

_(Watts

and Me

_{Connell, 1987;}

Buus et

_al,

_1987),

as combined to the T-cell

repertoire

(Grey

et

al,

1989).

Finally,

Kaufman and Salomonsen

₍₁₉₉₂₎

_proposed

some models for a

_possible

role of class

in these different

_paths

could

_{explain, respectively,}

the

_heterozygous

_advantage

and

disadvantage

observed for the combinations of the 2 best

₍₁₁₉

and

₁₂₁₎

and the 2

worst

₍₁₁₄

and

₁₂₄₎

_{B-haplotypes, regarding}

their effect on

antibody

_response to

SRBC.

In the case

of non-additivity

of some MHC-linked _genes, a

_genotype

model should

be

_preferred

because it is the most

_complete

and allows

_parallel

estimations of

the

_general

and

_{specific heterozygous}

effects. In the

_F

₂

_,

all

_possible

_haplotype

combinations were

_present

in a balanced

_design.

This is often not the case; a

genotype

model should

be, then,

also used to avoid the risk of

_{having haplotype}

effects

_completely

dominated

_by

one

_genotype.

_However,

it can be of

practical

interest to search for favorable

alleles,

for

_example

in cattle

_breeding

where

_only

sires are

_MHC-typed

and

extensively

used,

by

_using

haplotype

models such as

_type

II or

adapted

from this method

(Batra

et

al, 1989;

Lunden et

al,

1990).

Bentsen and

Klemetsdal

₍₁₉₉₁₎

_proposed

a

_haplotype

model

including

a

general heterozygous

effect but it is obvious that this

_hypothesis

should be tested before

_{being applied.}

In the case of

additivity,

all 3

haplotype

models would

_give

the same

_estimate;

otherwise,

the differences between models I and II will

depend

on the relative value

of

_heterozygous

genotypes.

In

_conclusion,

_selecting

for

_higher

immune _{response may} be achieved

_by

_choosing

the best

_{specific haplotype}

combination in a

particular

genetic

stock or line crosses.

In _many

_species,

it is not _easy to utilize the non-additive

genetic

variation in

practice.

The

_typical

_{multiple-line}

cross, which is used in commercial

poultry

breeding

may,

however,

provide

the necessary tool.

ACKNOWLEDGMENTS

The authors are

_grateful

to M Nieuwland for his excellent technical

help

and thank J van Arendonk for his useful comments on the manuscript.

REFERENCES

Batra

_TR,

Lee

_AJ,

Gavora

_JS,

Stear MJ

₍₁₉₈₉₎

Class I alleles of the bovine

_major

histocompatibility

system

and their association with economic traits. J

_Dairy

Sci

72,

2115-2124

Bentsen

HB,

Klemetsdal G

₍₁₉₉₁₎

The use of fixed effects models and mixed models

to estimate

_single

_gene associated effects on

polygenic

traits. Genet Sel Evol

23,

407-419

Biozzi

_G,

Mouton

D,

Heumann

_Am,

Bouthillier

_Y,

Stiffel

_C,

Mevel JC

₍₁₉₇₉₎

.Genetic

_analysis

of

_antibody

_{responsiveness}

to

_{sheep erythrocytes}

in crosses between lines of mice selected for

_high

or low

_antibody

synthesis. Immunology

_36,

427-438

Biozzi

_G,

Mouton

D,

Stiffel

_C,

Bouthillier Y

₍₁₉₈₄₎

A

_major

role of the

_macrophage

in

_{quantitative genetic}

_regulation

of

_{immunoresponsiveness}

and antiinfectious

im-munity.

Adv Immvnol

_36,

189-234

Buus

_S,

Sette

_A,

Colon

_SM,

Miles

C,

Grey

HM

₍₁₉₈₇₎

The relation between

major

histocompatibility complex

(MHC)

restriction and the

_capacity

of Ia to bind

Falconer DS

₍₁₉₈₉₎

Introduction to

_Quantitative

Genetics.

_Longman

Scientific and

Technical,

New

York,

3rd edn

Grey

HM,

Sette

A,

Buus S

₍₁₉₈₉₎

How T cells see

_antigen.

Sci Am

_Nov,

38-46

Groeneveld E

₍₁₉₉₀₎

PEST User’s Manual. Illinois

_{Univ, Urbana,}

IL

Groeneveld

_E,

Kovac

M

₍₁₉₉₀₎

A

_generalised

_computing

_procedure

for

_setting

_up and

_solving

mixed linear models. J

_Dairy

Sci

_73,

513-531

Kaufman

J,

Salomonsen J

₍₁₉₉₂₎

B-G: We know what it

_is,

but what does it do? Immunol

_Today

_13,

1-3

Kennedy

BW,

Quinton

M,

van Arendonk JAM

(1992)

Estimation of effects of

single

genes on

_quantitative

traits J Anim Sci

_70,

2000-2012

Loudovaris

_T,

Brandon

_MR,

_Fahey

KJ

₍₁₉₉₀₎

The

_major

_{histocompatibility}

com-plex

and

_genetic

control of

_antibody

_response to

_sheep

red blood cells in chickens. Avian Pathol

_19,

89-99

Lunden

_A,

_{Sigurdard6ttir, Edfors-Lilja}

_I,

Danell

B,

Rendel

J,

Andersson L

₍₁₉₉₀₎

The

_relationship

between bovine

_major

_{histocompatibility complex}

class II

poly-morphism

and disease studied

by

use of bull

_breeding

values. Anim Genet

_21,

221-232

Mallard

BA,

Wilkie

BN,

Kennedy

BW

₍₁₉₈₉₎

Genetic and other effects on

_antibody

cell mediated immune _{response in swine}

_leucocyte

_antigen

_{(SLA)-defined}

miniature

pigs.

Anim Genet

_20,

167-178

Mouton

_D,

Heumann

_AM,

Bouthillier

_Y,

Mevel

JC,

Biozzi G

₍₁₉₇₉₎

Interaction of

H-2 and non H-2 linked _{genes in} the

antibody

_response to a threshold dose of

sheep

erythrocytes.

Immunogenetics

8,

475-486

0stergard

H,

Kristensen

B,

Andersen S

₍₁₉₈₉₎

_{Investigation}

in farm animals of associations between the MHC

_system

and disease resistance and

_fertility.

Liv Prod Sci

_22,

49-67

Pinard

_M-H,

_Hepkema

BG

₍₁₉₉₂₎

Biochemical and

_serological

identification of

ma-jor

histocompatibility

antigens

in outbred chickens. In: Selection for

immunorespon-siveness in chickens: effects of the

_major

_{histocompatibility complex}

and resistance

to Marek’s disease. Ph D

_diss,

Univ

_Wageningen,

The

Netherlands,

43-59

Pinard

_M-H;

_Hepkema

BG,

van der Meulen

_MA,

Nieuwland

_MGB,

van der

_Zijpp

AJ

₍₁₉₉₁₎

_{Major histocompatibility complex haplotypes}

in chickens selected for

high

and low

_{antibody production.}

Anim Genet 22

_{(suppl 1),}

117-118

Pinard

M-H,

van Arendonk

JAM,

Nieuwland

MGB,

van der

_Zijpp

AJ

(1992)

Divergent

selection for immune

_{responsiveness}

in chicken: estimation of realized

heritability

with an animal model. J Anim Sci

_70,

2986-2993

Pinard

_M-H,

van Arendonk

_JAM,

Nieuwland

_MGB,

van der

_Zijpp

AJ

₍₁₉₉₃₎

Divergent

selection for humoral immune

_{responsiveness}

in chickens: distribution

and effects of

_major

_{histocompatibility complex}

_types.

Genet Sel Evol

_25,

191-203

Schierman

LW,

Collins

WM

₍₁₉₈₇₎

Influence of the

_major

_{histocompatibility}

complex

on tumor

_regression

and

_immunity

in chickens. Poult Sci

_66,

812-818

Scott

_TR,

Oduho

_GM,

Glick

_B,

_Hagan

_F,

Briles

WE,

Yamamoto Y

₍₁₉₈₈₎

Erythrocyte

alloantigen diversity

and some

immunological

effects of the B

_system

in related New

_Hampshire

strains. Poult Sci

_67,

1210-1217

Shook GE

₍₁₉₈₉₎

Selection for disease resistance. J

_Dairy

Sci

_72,

1349-1362

Siegel

PB,

Gross WB

₍₁₉₈₀₎

Production and

_persistence

of antibodies in chickens

Ubosi

CO,

Siegel

PB,

Gross WB

₍₁₉₈₅₎

_Divergent

selection of chickens for

_antibody

production

to

_{sheep erythrocytes:}

age effect in

parental

lines and their crosses. Avian

Dis

29,

150-158

Vainio

0,

Toivanen

_P,

Toivanen A

₍₁₉₈₇₎

_{Major histocompatibility}

_complex

and cell

_cooperation.

Poult Sci

_66,

795-801

Van der

_Zijpp

AJ,

Egberts

E

₍₁₉₈₉₎

The

_major

_{histocompatibility complex}

and diseases in farm animals. Immunol

_Today

_10,

109-111 1

Van der

_{Zijpp AJ,}

Blankert

_JJ,

_Egberts

_E,

Tilanus MGJ

₍₁₉₈₈₎

Advances in

_genetic

disease resistance in

_poultry.

In: Advances in Animal

_Breeding

_(Korver

_S,

van der

Steen

_HAM,

van Arendonk

JAM,

Bakker

_H,

_Brascamp

_EW,

Dommerholt

J,

eds)

Pudoc,

Wageningen,

The

Netherlands,

131-138

Watts

_TH,

Me Connel HM

₍₁₉₈₇₎

_Biophysical

_aspects

of

_{antigen recognition}

_by

T cells. Annu Rev

_Immunol,

_5,

461-475

.

Weller

_JI,

Fernando RL

₍₁₉₉₁₎

_Strategies

for the

_improvement

of animal

_production

using

marker-assisted selection. In:

_{Gene-Mapping Techniques}

and

_Applications

(Schook

LB,

Lewin

HA,

McLaren

_DG,

_eds)

Marcel Dekker

_{Inc, NY,}

305-328 ERRATUM

Pinard

_MH,

Van Arendonk

_JAM,

Nieuwland

MGB,

Van der

Zijpp

AJ

₍₁₉₉₃₎

Divergent

selection for humoral immune

_{responsiveness}

in chickens: distribution and effects of

_major

_{histocompatibility}

complex

types.

Genet Sel Evol

_25(2),

191-203.