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In the name of God
Genetic Selection for Disease Resistance: Challenges and Opportunities
Supervisor: Professor G. Rahimi Mianji
By: M. Ghaderzadeh
November, 2014
1
The objectives of this presentation
1. Importance of animal health
2. Animal health symptoms and animal welfare
3. Introduction Livestock diseases
4. Challenges of selecting for disease resistance
5. Genetic selection for disease resistance
6. Future prospects and conclusion
2
Importance of animal health
Whether it is a herd of cattle, a flock of sheep or goats, a pen of chickens or a group of
weaned pigs, poor animal health decreases the performance of the animals leading to
lower production and financial losses.
Inputs such as feed, water, proper housing and good management practices and record
keeping are essential to your outputs and financial gain. Without proper animal health
practices there will be reduce efficiency and optimal profits.
only healthy animals are delivered for anti-mortem inspection and meat production
ensuring safe and wholesome meat for public consumption. (1)
3
Importance of animal health
In order to have a successful farm operation, livestock farmers should seek to do the
following:
1.Seek good genetically sound animals with good reproductive ability.
2. Provide adequate land space for farm operation in order to reduce overcrowding.
3. Provide proper housing with adequate temperature control for the newborn and young
animals.
4. Ensure adequate feed supply in order to provide proper nutrition for the animals.
5. Potable and clean water should be provided at all times for the animals.
6. Have proper animal identification records and include financial and inventory records on
the animals and the farm.
7. Have sufficient pastures for your cattle, sheep and goats and practice proper pasture
rotation to prevent parasite build up and reduce pasture destruction ( 2).
4
Animal health symptoms and animal welfare
Healthy Livestock:
Alertness
Chewing of cud
Sleek coat
Bright eyes
Normal feces and urine
Normal temperature
Normal pulse rate
Normal respiration
Unhealthy Livestock:
Loss of appetite
Rough hair coat
Abnormal feces
Dull eyes
High temperature
Discolored urine
Ruminants not chewing their cud (2).
5
What Is Animal Welfare?
‘The physical and
psychological state of an
animal’
Is it fit?
Is it healthy?
Is it free from suffering?
(4, 5)
6
7
Animal welfare is the well-being of animals.
The standards of "good" animal welfare vary
considerably between different contexts.
These standards are under constant review
and are debated, created and revised by
animal welfare groups, legislators and
academics worldwide (3) (4). Animal welfare
science uses measures such as longevity,
disease, immunosuppression, behavior,
physiology, and reproduction although there
is debate about which of these indicators
provide the best information (5).
Animal welfare
Introduction Livestock diseases
8
Mastitis in dairy cattle is the
persistent, inflammatory reaction of
the udder tissue. This potentially fatal
mammary gland infection is the most
common disease in dairy cattle in the
United States. It is also the most
costly to the dairy industry (6).
Mastitis
9
Bovine spongiform encephalopathy (BSE),
commonly known as mad cow disease, is a
fatal neurodegenerative disease
(encephalopathy) in cattle that causes a spongy
degeneration in the brain and spinal cord. BSE
has a long incubation period, about 30 months
to 8 years, usually affecting adult cattle at a
peak age onset of four to five years, all breeds
being equally susceptible (7). In the United
Kingdom, the country worst affected, more
than 180,000 cattle have been infected and 4.4
million slaughtered during the eradication
program (8).
BSE
Introduction Livestock diseases
Introduction Livestock diseases
Pinkeye in Cattle
Infectious bovine keratoconjunctivitis, more
commonly known as pinkeye, is a contagious
bacterial infection of the eye in cattle. The
infection causes inflammation of the tissue
lining of the eyelid and the eyeball itself.
Ultimately, the cornea may become ulcerated,
resulting in pain and possible blindness. A
1997 report by the National Animal Health
Monitoring System (NAHMS) found pinkeye
to be the second most prevalent infection in
nursing calves more than three weeks old (9).
10
11
Introduction Livestock diseases
Foot-and-mouth disease
is an infectious and sometimes fatal viral
disease that affects cloven-hoofed animals,
including domestic and wild bovids.(10)
(11). The virus causes a high fever for two
or three days, followed by blisters inside
the mouth and on the feet that may rupture
and cause lameness. Foot-and-mouth
disease (FMD) has severe implications for
animal farming, since it is highly
infectious and can be spread by infected
animals through aerosols, through contact
with contaminated farming equipment,
vehicles, clothing, or feed, and by
domestic and wild predators (13).
Introduction Livestock diseases
Avian influenza
12
Bird flu" is a phrase similar to "swine
flu," "dog flu," "horse flu," or "human
flu" in that it refers to an illness caused
by any of many different strains of
influenza viruses that have adapted to a
specific host. While its most highly
pathogenic strain (H5N1) had been
spreading throughout Asia since 2003,
avian influenza reached Europe in 2005,
and the Middle East, as well as Africa,
the following year (13). On January 22,
2012, China reported its second human
death due to bird flu in a month
following other fatalities in Vietnam
and Cambodia (14).
Introduction Livestock diseases
Avian infectious bronchitis is an
acute and highly contagious
respiratory disease of chickens.
The disease is caused by avian
infectious bronchitis virus, a
coronavirus, and characterized by
respiratory signs including
gasping, coughing, sneezing,
tracheal rales, and nasal discharge
(15 ,16).
Avian infectious bronchitis
13
Introduction Livestock diseases
Newcastle disease is a contagious viral
disease of birds and considered one of
the most important poultry diseases
worldwide. The disease can vary from
mild to severe. A highly contagious
and severe form of the disease, called
exotic Newcastle disease (END), is so
deadly that many birds die suddenly
without showing any signs of disease.
Signs of severe illness include swelling
of the tissues of the head, muscle
tremors, drooping wings, twisted head,
circling, paralysis or sudden death
(17).
14
Newcastle Disease
Introduction Livestock diseases
The disease is characterized by the presence of T cell
lymphoma as well as infiltration of nerves and organs by
lymphocytes (18). Viruses related to MDV appear to be
benign and can be used as vaccine strains to prevent
Marek's disease. For example, the related Herpesvirus of
Turkeys (HVT), causes no apparent disease in turkeys
and continues to be used as a vaccine strain for
prevention of Marek's disease. Birds infected with
GaHV-2 can be carriers and shedders of the virus for life.
Newborn chicks are protected by maternal antibodies for
a few weeks. After infection, microscopic lesions are
present after one to two weeks, and gross lesions are
present after three to four weeks. The virus is spread in
dander from feather follicles and transmitted by
inhalation (19).
Marek's disease
15
Challenges of selecting for disease resistance
For below reasons, new approaches or alternatives to addressing animal diseases are
needed:
Animal health and important issues for animal producers and consumers.
Animal diseases causing morbidity and mortality significantly decrease profitability
of animal production.
consumer fears of residual drugs in meat products and microbial resistance to
commonly used antibiotics.
Current fear of a worldwide human influenza pandemic caused by transmission of
avian.
influenza virus to humans has increased public awareness of a need to control
animal diseases.
Therapeutic treatment costs for sick animals have continued to increase.
Breeding for improved disease resistance has become perhaps the
major challenge facing animal geneticists.
16
17
Challenges of selecting for disease resistance
One approach for these problems is genetic selection for animals resistant to disease.
Animal health is influenced by many factors including:
Genetics
Nutrition
Age
Stress
Management system
Season
Pathogen dosage
Immunological background
Epidemiology
Animal biological status
Many other variables and interact these factors
Challenges of selecting for disease resistance
What is Disease Resistance?
Animal disease resistance protects animals from pathogens in two ways: by preformed
mechanisms and by infection-induced responses of the immune system.
Disease resistance is the reduction of pathogen growth on or in the animal, while the term
disease tolerance describes animals that exhibit little disease damage despite substantial
pathogen levels (21).
18
19
Challenges of selecting for disease resistance
Resistance and Tolerance
Resistance is best understood from an ecological Consideration of
the interaction between the host and the Pathogen species may be
defined as the ability of the host to exert some degree of control
over the pathogen life cycle (22).
This broad definition encompasses the many ways a host species
may be more resistant (e.g., less likely to become infected, reduced
pathogen proliferation once infected, reduced shedding or
transmission of infection), and it also inherently recognises that
resistance is usually relative rather than absolute .(22)
Challenges of selecting for disease resistance
Resistance and Tolerance
20
Tolerance may be defined as the net impact on performance of a given
level of infection, i.e. the regression of performance on (a function of)
pathogen load. A related concept, resilience, may be defined as the
productivity of an animal in the face of infection. Whereas resistance
implies a host exerting a deleterious influence on the fitness of the
pathogen, hosts with a greater tolerance are those able to maintain a
greater fitness as pathogen load increases. Definitions are presented
diagrammatically in Fig. 1.(22).
Challenges of selecting for disease resistance
Resistance and Tolerance
Fig. 1. Definitions used in the paper are: Resistance is the ability of the host
animal to exert control over the parasite or pathogen life cycle; Tolerance is the
net impact on performance of a given level of infection; Resilience is the
productivity of an animal in the face of infection.The figure (from Bishop, 2012)
show saschematic representation of perfor mance and level of infection(or some
function that linearises the relationship between level of infection and
performance).The regression slope represents Tolerance, point A indicates
Resistance and point B represents Resilience (22).
21
22
Challenges of selecting for disease resistance :
 Identifying the phenotype for disease resistance is difficult.
 It is a false assumption that in a population of sick and healthy animals all healthy
animals are disease resistant.
 Some susceptible animals may not have been sufficiently exposed to the disease
organism to get sick.
 Animals that appear healthy may have sub-clinical infections and represent pathogen
reservoirs.
 Often the clinical expression of a disease can be confounded with a similar disease.
 Accurate disease diagnosis is costly and time consuming.
Challenges of selecting for disease resistance :
The success of selection for disease resistance is dependent on correctly
identifying the phenotype for disease resistance.
Selection for disease resistance is much more complicated than selecting for
production traits which can be measured directly or indirectly on each animal.
Before breeding schemes for disease resistance can be developed,
consideration of many different scientific areas such as microbiology,
epidemiology, immunology, host-pathogen interaction, host biology, livestock
production systems, etc., must be understood (23).
23
Challenges of selecting for disease resistance :
Keeping the host’s immune defense system in homeostasis may be
difficult.
Also, selection for immunity without leading to autoimmunity may be a
difficult balance to achieve.
Justification for including disease resistance in breeding programs can be
challenging to establish. Most importantly, the economical cost of the disease
must be sufficiently high to rationalize selecting for resistance (23).
24
25
Challenges of selecting for disease resistance :
When genetic selection is helpful?
 If antibiotics and other drugs have become inefficient because of
microbial resistance, selection for disease resistance may be logical.
 Genetic selection for disease resistance may be useful against diseases
for which neither vaccines nor therapeutics have been found.
 Selection may also be of interest for diseases due to a variety of
pathogens infecting the host in a similar manner or pathway.
 Organic meat production systems that cannot use vaccines or therapeutics may
also find it economically important to select for disease resistance (23).
26
Challenges of selecting for disease resistance :
When Genetic Selection is undesirable?
If the genetic factors that improve disease resistance reduce production traits such as
growth or feed efficiency then selection for disease resistance will decrease production.
Examples:
Milk yield in dairy cattle has a positive correlation with many disease traits (24).
Selection for growth rate in turkeys increased their susceptibility to Newcastle disease
(25).
In beef cattle, the genetic correlations of disease resistance with growth
and feed efficiency traits are unknown.!!!!???
27
Challenges of selecting for disease resistance :
However, with all these conflicts, what is the solution ?
If these genetic correlations are unfavorable, then a selection index for total merit
may be feasible to maintain production levels while selecting for disease
resistance (23).
I = b1x1 + b2x2 + …+ b m x m
(Hazel 1943)
Definition selection Index:
28
Challenges of selecting for disease resistance :
Biggest challenge
The biggest challenge of selecting for disease resistance is to accurately
identify the phenotype for disease resistance and/or to have reliable
genetic markers with high predictive values for a disease phenotype. For
some diseases, disease resistance may include sub clinical and clinical
infection while for other diseases only the clinical expression may be
considered (23).
29
Challenges of selecting for disease resistance :
Understanding the Immune System
The pathogen must penetrate host cell barriers in sufficient numbers, attack
target cells and replicate (23).
Immune defenses animal
Natural
Innate
Acquired
immunity
30
Understanding the Immune System
Natural immunity: is the first barrier and is comprised of skin, hair,
mucous membranes, secretions (tears, urine, stomach, saliva, mucous,
skin secretions, etc.), grooming behavior (licking, dust rolling, tail
swishing, etc.) and favorable microorganisms that compete directly or
indirectly against pathogens (23).
Innate immunity: refers to the immune system one is born with and is the initial
response by the body to eliminate microbes and prevent infection. It commonly
involves white blood cells (natural killer cells, neutrophils, eosinophils, monocytes,
and macrophages), complement proteins (C1 - C4) that adhere to pathogens, and
cytokines(interferons and chemokines) that attract immune cells to the site of
infection. The innate immune system constantly searches for antigens(bacteria,
fungi, and viruses). When an antigen is discovered, the innate system can attack it or
illicit inflammation to attract immune cells (23).
31
Understanding the Immune System
Acquired immunity: occurs in two forms: passive and active. Passive or
maternal immunity is passed from the cow to the calf via colostrum
containing high levels of antibodies. Passive immunity is temporary.
Disease resistance of very young calves is highly dependent on passive
immunity.
The acquired immune system is comprised of T and B cells, which are
specialized white blood cells. The T cells destroy pathogen-infected cells. The
B cells develop into specific antibody producing cells (23).
32
Genetic Selection for Disease Resistance
From a genetic perspective, understanding the natural, innate, and acquired immune
systems is crucial in developing selection programs for disease resistance. For example,
if the breeding goal is to reduce bacterial diarrhea in young calves, then selection traits
might include the dam’s genetic potential for producing specific colostrum antibodies
(passive immunity) and the calf’s genetic potential for developing an innate and
acquired immune system early in life that responds to the diarrhea causing pathogen.
There may be further problems because negative genetic correlations
between the dam and calf resistance to some diseases have been estimated.
Selection for disease resistance is costly. Potential costs associated with
measuring disease resistance include reduced production, mortality,
decreased longevity, diagnostic costs, and therapeutic expenses.
 
33
Genetic Selection for Disease Resistance
Direct selection
Direct selection for disease resistance can occur in three different scenarios:
a) First, animals may be observed in a given production system or environment
for lack of clinical expression of a disease. Under this selection approach, it is
assumed that the disease pathogen is constantly present.
Animals with clinical expression of the disease may be identified with relative
accuracy but not all healthy animals may be exposed to the pathogen or
challenged equally. Diseases often occur in clusters of time (years, seasons,
production cycles, etc.) and space (herd, pasture, farm, region, etc.). In years
when the disease incidence is high, there can be an increase in the accuracy of
identifying animals with a high probability of being disease resistant but in
years of low incidence the accuracy will be diminished (23).
Genetic Selection for Disease Resistance
Direct selection
b) The second direct approach is to uniformly challenge all
breeding stock with infection. This approach can be costly
depending upon the pathogen’s virulence and clinical expression
of the disease but is a reliable measure of disease resistance. This
may require isolation of the population to prevent transmission
to non-breeding stock (23).
34
Genetic Selection for Disease Resistance
Direct selection
c) A third approach is to challenge relatives or clones of the breeding
stock, especially if the disease has a high mortality rate. This latter
approach is also a reliable method of determining genetic resistance.
The latter two approaches are not without error because
immunological background (previous exposure to the pathogen) may
vary among animals (23).
35
Genetic Selection for Disease Resistance
Direct selection
Researchers will have to determine the significance of immunological
background for biasing the observed animal response to a disease
challenge. In cattle, direct selection for reducing brucellosis had a
favorable response. Templeton et al., (1990) increased natural
resistance to brucellosis in calves from 20% to59% after breeding cows
to a naturally resistant bull.
36
Genetic Selection for Disease Resistance
Indirect selection
Indirect selection for disease resistance can also be achieved by selecting
for indicators of disease resistance. Indicators of disease resistance include
pathogen products (i.e., pathogen reproductive rates, pathogen by products),
and biological or immunological responses of the host.
Examples:
One of the most successful approaches of indirect selection for disease
resistance has been reported in sheep by selecting for low fecal internal
parasite egg count. In dairy cattle, somatic cell count has been used as a
selection criteria for reducing mastitis (23).
37
Genetic Selection for Disease Resistance
Indirect selection
Hernandez et al. (2003) suggested that immune responsiveness would be a
useful indicator of disease resistance in cattle. Selection for immune response
is generally beneficial when a single disease is targeted. However, studies in
swine have indicated that selection for immune responsiveness can improve
disease resistance to other diseases while, at the same time, increasing
susceptibility to others ( Wilkie and Mallard, 1998) (23).
38
Genetic Selection for Disease Resistance
Indirect selection
39
 For effective selection, indicator traits must be heritable, highly genetically
correlated with resistance to the disease or diseases of interest, accurate to
measure, and affordable.
 Interactions between the genetics of the animal and the environment commonly
exist. If the genetic by environmental interaction is significant, animals selected
for improved disease resistance in one environment may be more susceptible to
the same disease in a different environment. Therefore, selection programs may
have to be environment specific with the selection environment matching the
commercial production environment.
Important Notice
Genetic Selection for Disease Resistance
40
Gene Mapping
Most genes related to disease resistance have been discovered using
inbred strains of mice.
Only a few genes have been linked to disease resistance in cattle. The
Nramp1 gene (natural resistance-associated macrophage protein) is
associated with the innate immune system. Nramp1 has been linked
with resistance to brucellosis (Harmon et al., 1989), tuberculosis, and
salmonellosis (Qureshi et al. 1996).
The major histocompatibility complex (MHC) genes are linked to
specific immunological responses. MHC genes were some of the first
mapped and sequenced genes related to disease resistance (23).
Genetic Selection for Disease Resistance
Gene Mapping
In dairy cattle, the bovine MHC complex has been linked to disease
resistance of economically important traits (Batra et al., 1989). In
chickens, MHC has been linked to resistance to Marek’s disease
and fowl cholera (Lamont, 1989).
Other examples of recently discovered single genes influencing
disease resistance in livestock include the fimbriae F4 (K88) gene
in swine for reducing e. coli intestinal infection (Moon et al., 1999),
the prion protein (PrP) gene related to scrapie susceptibility in
sheep (Bossers et al., 1996), and the TNC gene related to
salmonellosis in chickens (Hu et al., 1997).
41
Genetic Selection for Disease Resistance
42
Polygenic Effects
The complexity of the immune system clearly infers that many genes are involved in
disease resistance. It is highly doubtful that many single genes will be discovered
and associated with major diseases. Chromosome mapping may lead to quantitative
trait loci or regions related to disease resistance.  Most recently, a region on
chromosome 1 was associated with infectious keratoconjunctivitis (pinkeye) in cattle
(Casas et al., 2006).
As the human and mice genomes are further investigated for disease related genes, it
ishighly plausible that quantitative trait loci(QTL) associated with disease resistant
inlivestock may also be identified in the near future (23).
Genetic Selection for Disease Resistance
Polygenic Effects
Micro array technology is advancing rapidly to enable association of
livestock DNA with human ( Chitko- McKown et al., 2004) and mice
DNA. Comparative genomics may make the identification of disease
loci easier and more affordable. It may be possible to identify similar
genes associated with disease susceptibility/resistance among human,
mice, and livestock (23).
 
43
Genetic Selection for Disease Resistance
44
Using genetic tools
Gene transfer technologies
Current major advances in gene transfer technologies, in parallel with the significant new
genetic information provided by genomic technologies, have made it possible to
investigate the host-pathogen interaction in more detail than ever before. Major advances
in our understanding of disease are likely to be achieved within the next few years. These
technologies will lead to new opportunities for diagnosis, intervention and the selective
breeding of animals for resistance. The combination of advanced gene transfer
technologies and traditional disease control measures, should allow for more effective and
sustainable disease control (26).
Genetic Selection for Disease Resistance
Using genetic tools
Gene transfer technologies
Genetic modification offers alternative strategies to traditional animal breeding. This
technology is likely to have specific application where genetic variation does not exist in
a given population or species and where novel genetic improvements can be engineered.
With either approach, the intention would be to enhance the ability of the animals to
mount an appropriate immune response against the pathogen (which could require
dampening down the immune system at strategic stages) or to generate an effective
system that would directly block pathogen entry or directly destroy the pathogen.
Indeed, a combination of strategies may prove to be the most successful approach (26).
45
Genetic Selection for Disease Resistance
46
Using genetic tools
Marker-assisted selection (Candidate gene)
The strategy of improving the immune response (a new strategy for which
experimental examples are only now being tested) could be used in instances
where specific gene alleles that confer resistance are present in a species but
have been lost from commercial populations. The Mx genes of vertebrates were
first discovered in mice because of the ability of functional alleles to induce a
potent antiviral state in response to infection by specific groups of viruses,
including influenza. Chickens also have an Mx gene, but the allele present in
most commercial lines is apparently not functional, due to a single amino acid
substitution (26).
Genetic Selection for Disease Resistance
47
Genetically modified technology
a)Dominant-negative proteins: the introduction of mutant versions of key factors in
pathogen infection, such as cell surface receptors, can block disease progression.
b) Ribonucleic acid interference (RNAi): this strategy relies on the ability of
specific short RNA sequences to anneal with the RNA of the pathogen, causing
destruction of the foreign RNA. RNAi requires access to the target RNA, which may
limit this approach to viruses (26).
 
Genetic Selection for Disease Resistance
Ribonucleic acid interference (RNAi):
48
Genetic Selection for Disease Resistance
Genetically modified technology
49
c) Ribonucleic acid decoys: expression of RNA sequences that mimic specific
sequences within a pathogen can disrupt the activity of the pathogen’s replication
machinery. Again, this approach is probably restricted to specific viruses, with
influenza being a good candidate (26).
d) Antibodies: the transgenic production of antibodies in the host animal may act
in an analogous manner to vaccination (26).
 
50
Future prospects and conclusion
Other, less prominent diseases of livestock are also of concern because of their
effect on human health, animal welfare and/or the economics of livestock
production. There is a need to reexamine the best ways of controlling disease
outbreaks in farm animals, not just in the case of the diseases that have captured the
headlines but across the board. Perhaps the most important targets are those
endemic diseases that blight the economy and society of developing countries.
Diseases in farm animals can be controlled by vaccination, the use of drugs,
improved husbandry and by breeding animals for improved resistance. Successful
management of disease is likely to include a combination of approaches.
 
Future prospects and conclusion
51
The researchers propose that the use of GM animals will complement these more
traditional tactics, and provide novel intervention strategies that are not possible
through the established approaches. They do not anticipate that GM will be the
primary tool in the fight against disease, but rather that its use will be restricted to
specific diseases. More cooperation is required, and the decision making bodies
have to find the confidence to support what is both an exciting scientific frontier
and one that may bring huge benefit to animals and humans through combating
disease.
Future prospects and conclusion
52
We do not know at this time to predict whether or not selection for disease resistance can
be effective in livestock. Basic research into the complexities underlying diseases will
likely reveal effective approaches for many disease problems. It may be possible to select
directly against the disease, select for indicator traits(indirect selection), to select directly
for the gene(s) that confer resistance or some combination of these approaches
Certainly, genetic selection will not solve all of our livestock disease problems.
Therefore, management, nutrition, vaccination, culling, therapeutic treatment, stress
reduction practices and other measures must accompany genetic approaches to reduce
the impact of livestock disease on profitability and animal well being.
53
My offers for be effective Disease Resistance
 Management, feeding, herd health and hygienics
 Write Records all animals and direct selection
 Definition economic selection index for all animal triats
 Considering interaction effects between different phenotyps and
environments in different areas
‫ییییی‬ ‫یییی‬ ‫ییی‬ ‫یی‬
‫ییی‬ ‫یییی‬ ‫ییییی‬
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Rev. sci. tech. Off. int. Epiz., 2005, 24 (1), 275-283
57
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Mahabad city
58

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Genetic selection for disease resistance (animal breeding). اصلاح دام

  • 1. In the name of God Genetic Selection for Disease Resistance: Challenges and Opportunities Supervisor: Professor G. Rahimi Mianji By: M. Ghaderzadeh November, 2014 1
  • 2. The objectives of this presentation 1. Importance of animal health 2. Animal health symptoms and animal welfare 3. Introduction Livestock diseases 4. Challenges of selecting for disease resistance 5. Genetic selection for disease resistance 6. Future prospects and conclusion 2
  • 3. Importance of animal health Whether it is a herd of cattle, a flock of sheep or goats, a pen of chickens or a group of weaned pigs, poor animal health decreases the performance of the animals leading to lower production and financial losses. Inputs such as feed, water, proper housing and good management practices and record keeping are essential to your outputs and financial gain. Without proper animal health practices there will be reduce efficiency and optimal profits. only healthy animals are delivered for anti-mortem inspection and meat production ensuring safe and wholesome meat for public consumption. (1) 3
  • 4. Importance of animal health In order to have a successful farm operation, livestock farmers should seek to do the following: 1.Seek good genetically sound animals with good reproductive ability. 2. Provide adequate land space for farm operation in order to reduce overcrowding. 3. Provide proper housing with adequate temperature control for the newborn and young animals. 4. Ensure adequate feed supply in order to provide proper nutrition for the animals. 5. Potable and clean water should be provided at all times for the animals. 6. Have proper animal identification records and include financial and inventory records on the animals and the farm. 7. Have sufficient pastures for your cattle, sheep and goats and practice proper pasture rotation to prevent parasite build up and reduce pasture destruction ( 2). 4
  • 5. Animal health symptoms and animal welfare Healthy Livestock: Alertness Chewing of cud Sleek coat Bright eyes Normal feces and urine Normal temperature Normal pulse rate Normal respiration Unhealthy Livestock: Loss of appetite Rough hair coat Abnormal feces Dull eyes High temperature Discolored urine Ruminants not chewing their cud (2). 5
  • 6. What Is Animal Welfare? ‘The physical and psychological state of an animal’ Is it fit? Is it healthy? Is it free from suffering? (4, 5) 6
  • 7. 7 Animal welfare is the well-being of animals. The standards of "good" animal welfare vary considerably between different contexts. These standards are under constant review and are debated, created and revised by animal welfare groups, legislators and academics worldwide (3) (4). Animal welfare science uses measures such as longevity, disease, immunosuppression, behavior, physiology, and reproduction although there is debate about which of these indicators provide the best information (5). Animal welfare
  • 8. Introduction Livestock diseases 8 Mastitis in dairy cattle is the persistent, inflammatory reaction of the udder tissue. This potentially fatal mammary gland infection is the most common disease in dairy cattle in the United States. It is also the most costly to the dairy industry (6). Mastitis
  • 9. 9 Bovine spongiform encephalopathy (BSE), commonly known as mad cow disease, is a fatal neurodegenerative disease (encephalopathy) in cattle that causes a spongy degeneration in the brain and spinal cord. BSE has a long incubation period, about 30 months to 8 years, usually affecting adult cattle at a peak age onset of four to five years, all breeds being equally susceptible (7). In the United Kingdom, the country worst affected, more than 180,000 cattle have been infected and 4.4 million slaughtered during the eradication program (8). BSE Introduction Livestock diseases
  • 10. Introduction Livestock diseases Pinkeye in Cattle Infectious bovine keratoconjunctivitis, more commonly known as pinkeye, is a contagious bacterial infection of the eye in cattle. The infection causes inflammation of the tissue lining of the eyelid and the eyeball itself. Ultimately, the cornea may become ulcerated, resulting in pain and possible blindness. A 1997 report by the National Animal Health Monitoring System (NAHMS) found pinkeye to be the second most prevalent infection in nursing calves more than three weeks old (9). 10
  • 11. 11 Introduction Livestock diseases Foot-and-mouth disease is an infectious and sometimes fatal viral disease that affects cloven-hoofed animals, including domestic and wild bovids.(10) (11). The virus causes a high fever for two or three days, followed by blisters inside the mouth and on the feet that may rupture and cause lameness. Foot-and-mouth disease (FMD) has severe implications for animal farming, since it is highly infectious and can be spread by infected animals through aerosols, through contact with contaminated farming equipment, vehicles, clothing, or feed, and by domestic and wild predators (13).
  • 12. Introduction Livestock diseases Avian influenza 12 Bird flu" is a phrase similar to "swine flu," "dog flu," "horse flu," or "human flu" in that it refers to an illness caused by any of many different strains of influenza viruses that have adapted to a specific host. While its most highly pathogenic strain (H5N1) had been spreading throughout Asia since 2003, avian influenza reached Europe in 2005, and the Middle East, as well as Africa, the following year (13). On January 22, 2012, China reported its second human death due to bird flu in a month following other fatalities in Vietnam and Cambodia (14).
  • 13. Introduction Livestock diseases Avian infectious bronchitis is an acute and highly contagious respiratory disease of chickens. The disease is caused by avian infectious bronchitis virus, a coronavirus, and characterized by respiratory signs including gasping, coughing, sneezing, tracheal rales, and nasal discharge (15 ,16). Avian infectious bronchitis 13
  • 14. Introduction Livestock diseases Newcastle disease is a contagious viral disease of birds and considered one of the most important poultry diseases worldwide. The disease can vary from mild to severe. A highly contagious and severe form of the disease, called exotic Newcastle disease (END), is so deadly that many birds die suddenly without showing any signs of disease. Signs of severe illness include swelling of the tissues of the head, muscle tremors, drooping wings, twisted head, circling, paralysis or sudden death (17). 14 Newcastle Disease
  • 15. Introduction Livestock diseases The disease is characterized by the presence of T cell lymphoma as well as infiltration of nerves and organs by lymphocytes (18). Viruses related to MDV appear to be benign and can be used as vaccine strains to prevent Marek's disease. For example, the related Herpesvirus of Turkeys (HVT), causes no apparent disease in turkeys and continues to be used as a vaccine strain for prevention of Marek's disease. Birds infected with GaHV-2 can be carriers and shedders of the virus for life. Newborn chicks are protected by maternal antibodies for a few weeks. After infection, microscopic lesions are present after one to two weeks, and gross lesions are present after three to four weeks. The virus is spread in dander from feather follicles and transmitted by inhalation (19). Marek's disease 15
  • 16. Challenges of selecting for disease resistance For below reasons, new approaches or alternatives to addressing animal diseases are needed: Animal health and important issues for animal producers and consumers. Animal diseases causing morbidity and mortality significantly decrease profitability of animal production. consumer fears of residual drugs in meat products and microbial resistance to commonly used antibiotics. Current fear of a worldwide human influenza pandemic caused by transmission of avian. influenza virus to humans has increased public awareness of a need to control animal diseases. Therapeutic treatment costs for sick animals have continued to increase. Breeding for improved disease resistance has become perhaps the major challenge facing animal geneticists. 16
  • 17. 17 Challenges of selecting for disease resistance One approach for these problems is genetic selection for animals resistant to disease. Animal health is influenced by many factors including: Genetics Nutrition Age Stress Management system Season Pathogen dosage Immunological background Epidemiology Animal biological status Many other variables and interact these factors
  • 18. Challenges of selecting for disease resistance What is Disease Resistance? Animal disease resistance protects animals from pathogens in two ways: by preformed mechanisms and by infection-induced responses of the immune system. Disease resistance is the reduction of pathogen growth on or in the animal, while the term disease tolerance describes animals that exhibit little disease damage despite substantial pathogen levels (21). 18
  • 19. 19 Challenges of selecting for disease resistance Resistance and Tolerance Resistance is best understood from an ecological Consideration of the interaction between the host and the Pathogen species may be defined as the ability of the host to exert some degree of control over the pathogen life cycle (22). This broad definition encompasses the many ways a host species may be more resistant (e.g., less likely to become infected, reduced pathogen proliferation once infected, reduced shedding or transmission of infection), and it also inherently recognises that resistance is usually relative rather than absolute .(22)
  • 20. Challenges of selecting for disease resistance Resistance and Tolerance 20 Tolerance may be defined as the net impact on performance of a given level of infection, i.e. the regression of performance on (a function of) pathogen load. A related concept, resilience, may be defined as the productivity of an animal in the face of infection. Whereas resistance implies a host exerting a deleterious influence on the fitness of the pathogen, hosts with a greater tolerance are those able to maintain a greater fitness as pathogen load increases. Definitions are presented diagrammatically in Fig. 1.(22).
  • 21. Challenges of selecting for disease resistance Resistance and Tolerance Fig. 1. Definitions used in the paper are: Resistance is the ability of the host animal to exert control over the parasite or pathogen life cycle; Tolerance is the net impact on performance of a given level of infection; Resilience is the productivity of an animal in the face of infection.The figure (from Bishop, 2012) show saschematic representation of perfor mance and level of infection(or some function that linearises the relationship between level of infection and performance).The regression slope represents Tolerance, point A indicates Resistance and point B represents Resilience (22). 21
  • 22. 22 Challenges of selecting for disease resistance :  Identifying the phenotype for disease resistance is difficult.  It is a false assumption that in a population of sick and healthy animals all healthy animals are disease resistant.  Some susceptible animals may not have been sufficiently exposed to the disease organism to get sick.  Animals that appear healthy may have sub-clinical infections and represent pathogen reservoirs.  Often the clinical expression of a disease can be confounded with a similar disease.  Accurate disease diagnosis is costly and time consuming.
  • 23. Challenges of selecting for disease resistance : The success of selection for disease resistance is dependent on correctly identifying the phenotype for disease resistance. Selection for disease resistance is much more complicated than selecting for production traits which can be measured directly or indirectly on each animal. Before breeding schemes for disease resistance can be developed, consideration of many different scientific areas such as microbiology, epidemiology, immunology, host-pathogen interaction, host biology, livestock production systems, etc., must be understood (23). 23
  • 24. Challenges of selecting for disease resistance : Keeping the host’s immune defense system in homeostasis may be difficult. Also, selection for immunity without leading to autoimmunity may be a difficult balance to achieve. Justification for including disease resistance in breeding programs can be challenging to establish. Most importantly, the economical cost of the disease must be sufficiently high to rationalize selecting for resistance (23). 24
  • 25. 25 Challenges of selecting for disease resistance : When genetic selection is helpful?  If antibiotics and other drugs have become inefficient because of microbial resistance, selection for disease resistance may be logical.  Genetic selection for disease resistance may be useful against diseases for which neither vaccines nor therapeutics have been found.  Selection may also be of interest for diseases due to a variety of pathogens infecting the host in a similar manner or pathway.  Organic meat production systems that cannot use vaccines or therapeutics may also find it economically important to select for disease resistance (23).
  • 26. 26 Challenges of selecting for disease resistance : When Genetic Selection is undesirable? If the genetic factors that improve disease resistance reduce production traits such as growth or feed efficiency then selection for disease resistance will decrease production. Examples: Milk yield in dairy cattle has a positive correlation with many disease traits (24). Selection for growth rate in turkeys increased their susceptibility to Newcastle disease (25). In beef cattle, the genetic correlations of disease resistance with growth and feed efficiency traits are unknown.!!!!???
  • 27. 27 Challenges of selecting for disease resistance : However, with all these conflicts, what is the solution ? If these genetic correlations are unfavorable, then a selection index for total merit may be feasible to maintain production levels while selecting for disease resistance (23). I = b1x1 + b2x2 + …+ b m x m (Hazel 1943) Definition selection Index:
  • 28. 28 Challenges of selecting for disease resistance : Biggest challenge The biggest challenge of selecting for disease resistance is to accurately identify the phenotype for disease resistance and/or to have reliable genetic markers with high predictive values for a disease phenotype. For some diseases, disease resistance may include sub clinical and clinical infection while for other diseases only the clinical expression may be considered (23).
  • 29. 29 Challenges of selecting for disease resistance : Understanding the Immune System The pathogen must penetrate host cell barriers in sufficient numbers, attack target cells and replicate (23). Immune defenses animal Natural Innate Acquired immunity
  • 30. 30 Understanding the Immune System Natural immunity: is the first barrier and is comprised of skin, hair, mucous membranes, secretions (tears, urine, stomach, saliva, mucous, skin secretions, etc.), grooming behavior (licking, dust rolling, tail swishing, etc.) and favorable microorganisms that compete directly or indirectly against pathogens (23). Innate immunity: refers to the immune system one is born with and is the initial response by the body to eliminate microbes and prevent infection. It commonly involves white blood cells (natural killer cells, neutrophils, eosinophils, monocytes, and macrophages), complement proteins (C1 - C4) that adhere to pathogens, and cytokines(interferons and chemokines) that attract immune cells to the site of infection. The innate immune system constantly searches for antigens(bacteria, fungi, and viruses). When an antigen is discovered, the innate system can attack it or illicit inflammation to attract immune cells (23).
  • 31. 31 Understanding the Immune System Acquired immunity: occurs in two forms: passive and active. Passive or maternal immunity is passed from the cow to the calf via colostrum containing high levels of antibodies. Passive immunity is temporary. Disease resistance of very young calves is highly dependent on passive immunity. The acquired immune system is comprised of T and B cells, which are specialized white blood cells. The T cells destroy pathogen-infected cells. The B cells develop into specific antibody producing cells (23).
  • 32. 32 Genetic Selection for Disease Resistance From a genetic perspective, understanding the natural, innate, and acquired immune systems is crucial in developing selection programs for disease resistance. For example, if the breeding goal is to reduce bacterial diarrhea in young calves, then selection traits might include the dam’s genetic potential for producing specific colostrum antibodies (passive immunity) and the calf’s genetic potential for developing an innate and acquired immune system early in life that responds to the diarrhea causing pathogen. There may be further problems because negative genetic correlations between the dam and calf resistance to some diseases have been estimated. Selection for disease resistance is costly. Potential costs associated with measuring disease resistance include reduced production, mortality, decreased longevity, diagnostic costs, and therapeutic expenses.  
  • 33. 33 Genetic Selection for Disease Resistance Direct selection Direct selection for disease resistance can occur in three different scenarios: a) First, animals may be observed in a given production system or environment for lack of clinical expression of a disease. Under this selection approach, it is assumed that the disease pathogen is constantly present. Animals with clinical expression of the disease may be identified with relative accuracy but not all healthy animals may be exposed to the pathogen or challenged equally. Diseases often occur in clusters of time (years, seasons, production cycles, etc.) and space (herd, pasture, farm, region, etc.). In years when the disease incidence is high, there can be an increase in the accuracy of identifying animals with a high probability of being disease resistant but in years of low incidence the accuracy will be diminished (23).
  • 34. Genetic Selection for Disease Resistance Direct selection b) The second direct approach is to uniformly challenge all breeding stock with infection. This approach can be costly depending upon the pathogen’s virulence and clinical expression of the disease but is a reliable measure of disease resistance. This may require isolation of the population to prevent transmission to non-breeding stock (23). 34
  • 35. Genetic Selection for Disease Resistance Direct selection c) A third approach is to challenge relatives or clones of the breeding stock, especially if the disease has a high mortality rate. This latter approach is also a reliable method of determining genetic resistance. The latter two approaches are not without error because immunological background (previous exposure to the pathogen) may vary among animals (23). 35
  • 36. Genetic Selection for Disease Resistance Direct selection Researchers will have to determine the significance of immunological background for biasing the observed animal response to a disease challenge. In cattle, direct selection for reducing brucellosis had a favorable response. Templeton et al., (1990) increased natural resistance to brucellosis in calves from 20% to59% after breeding cows to a naturally resistant bull. 36
  • 37. Genetic Selection for Disease Resistance Indirect selection Indirect selection for disease resistance can also be achieved by selecting for indicators of disease resistance. Indicators of disease resistance include pathogen products (i.e., pathogen reproductive rates, pathogen by products), and biological or immunological responses of the host. Examples: One of the most successful approaches of indirect selection for disease resistance has been reported in sheep by selecting for low fecal internal parasite egg count. In dairy cattle, somatic cell count has been used as a selection criteria for reducing mastitis (23). 37
  • 38. Genetic Selection for Disease Resistance Indirect selection Hernandez et al. (2003) suggested that immune responsiveness would be a useful indicator of disease resistance in cattle. Selection for immune response is generally beneficial when a single disease is targeted. However, studies in swine have indicated that selection for immune responsiveness can improve disease resistance to other diseases while, at the same time, increasing susceptibility to others ( Wilkie and Mallard, 1998) (23). 38
  • 39. Genetic Selection for Disease Resistance Indirect selection 39  For effective selection, indicator traits must be heritable, highly genetically correlated with resistance to the disease or diseases of interest, accurate to measure, and affordable.  Interactions between the genetics of the animal and the environment commonly exist. If the genetic by environmental interaction is significant, animals selected for improved disease resistance in one environment may be more susceptible to the same disease in a different environment. Therefore, selection programs may have to be environment specific with the selection environment matching the commercial production environment. Important Notice
  • 40. Genetic Selection for Disease Resistance 40 Gene Mapping Most genes related to disease resistance have been discovered using inbred strains of mice. Only a few genes have been linked to disease resistance in cattle. The Nramp1 gene (natural resistance-associated macrophage protein) is associated with the innate immune system. Nramp1 has been linked with resistance to brucellosis (Harmon et al., 1989), tuberculosis, and salmonellosis (Qureshi et al. 1996). The major histocompatibility complex (MHC) genes are linked to specific immunological responses. MHC genes were some of the first mapped and sequenced genes related to disease resistance (23).
  • 41. Genetic Selection for Disease Resistance Gene Mapping In dairy cattle, the bovine MHC complex has been linked to disease resistance of economically important traits (Batra et al., 1989). In chickens, MHC has been linked to resistance to Marek’s disease and fowl cholera (Lamont, 1989). Other examples of recently discovered single genes influencing disease resistance in livestock include the fimbriae F4 (K88) gene in swine for reducing e. coli intestinal infection (Moon et al., 1999), the prion protein (PrP) gene related to scrapie susceptibility in sheep (Bossers et al., 1996), and the TNC gene related to salmonellosis in chickens (Hu et al., 1997). 41
  • 42. Genetic Selection for Disease Resistance 42 Polygenic Effects The complexity of the immune system clearly infers that many genes are involved in disease resistance. It is highly doubtful that many single genes will be discovered and associated with major diseases. Chromosome mapping may lead to quantitative trait loci or regions related to disease resistance.  Most recently, a region on chromosome 1 was associated with infectious keratoconjunctivitis (pinkeye) in cattle (Casas et al., 2006). As the human and mice genomes are further investigated for disease related genes, it ishighly plausible that quantitative trait loci(QTL) associated with disease resistant inlivestock may also be identified in the near future (23).
  • 43. Genetic Selection for Disease Resistance Polygenic Effects Micro array technology is advancing rapidly to enable association of livestock DNA with human ( Chitko- McKown et al., 2004) and mice DNA. Comparative genomics may make the identification of disease loci easier and more affordable. It may be possible to identify similar genes associated with disease susceptibility/resistance among human, mice, and livestock (23).   43
  • 44. Genetic Selection for Disease Resistance 44 Using genetic tools Gene transfer technologies Current major advances in gene transfer technologies, in parallel with the significant new genetic information provided by genomic technologies, have made it possible to investigate the host-pathogen interaction in more detail than ever before. Major advances in our understanding of disease are likely to be achieved within the next few years. These technologies will lead to new opportunities for diagnosis, intervention and the selective breeding of animals for resistance. The combination of advanced gene transfer technologies and traditional disease control measures, should allow for more effective and sustainable disease control (26).
  • 45. Genetic Selection for Disease Resistance Using genetic tools Gene transfer technologies Genetic modification offers alternative strategies to traditional animal breeding. This technology is likely to have specific application where genetic variation does not exist in a given population or species and where novel genetic improvements can be engineered. With either approach, the intention would be to enhance the ability of the animals to mount an appropriate immune response against the pathogen (which could require dampening down the immune system at strategic stages) or to generate an effective system that would directly block pathogen entry or directly destroy the pathogen. Indeed, a combination of strategies may prove to be the most successful approach (26). 45
  • 46. Genetic Selection for Disease Resistance 46 Using genetic tools Marker-assisted selection (Candidate gene) The strategy of improving the immune response (a new strategy for which experimental examples are only now being tested) could be used in instances where specific gene alleles that confer resistance are present in a species but have been lost from commercial populations. The Mx genes of vertebrates were first discovered in mice because of the ability of functional alleles to induce a potent antiviral state in response to infection by specific groups of viruses, including influenza. Chickens also have an Mx gene, but the allele present in most commercial lines is apparently not functional, due to a single amino acid substitution (26).
  • 47. Genetic Selection for Disease Resistance 47 Genetically modified technology a)Dominant-negative proteins: the introduction of mutant versions of key factors in pathogen infection, such as cell surface receptors, can block disease progression. b) Ribonucleic acid interference (RNAi): this strategy relies on the ability of specific short RNA sequences to anneal with the RNA of the pathogen, causing destruction of the foreign RNA. RNAi requires access to the target RNA, which may limit this approach to viruses (26).  
  • 48. Genetic Selection for Disease Resistance Ribonucleic acid interference (RNAi): 48
  • 49. Genetic Selection for Disease Resistance Genetically modified technology 49 c) Ribonucleic acid decoys: expression of RNA sequences that mimic specific sequences within a pathogen can disrupt the activity of the pathogen’s replication machinery. Again, this approach is probably restricted to specific viruses, with influenza being a good candidate (26). d) Antibodies: the transgenic production of antibodies in the host animal may act in an analogous manner to vaccination (26).  
  • 50. 50 Future prospects and conclusion Other, less prominent diseases of livestock are also of concern because of their effect on human health, animal welfare and/or the economics of livestock production. There is a need to reexamine the best ways of controlling disease outbreaks in farm animals, not just in the case of the diseases that have captured the headlines but across the board. Perhaps the most important targets are those endemic diseases that blight the economy and society of developing countries. Diseases in farm animals can be controlled by vaccination, the use of drugs, improved husbandry and by breeding animals for improved resistance. Successful management of disease is likely to include a combination of approaches.  
  • 51. Future prospects and conclusion 51 The researchers propose that the use of GM animals will complement these more traditional tactics, and provide novel intervention strategies that are not possible through the established approaches. They do not anticipate that GM will be the primary tool in the fight against disease, but rather that its use will be restricted to specific diseases. More cooperation is required, and the decision making bodies have to find the confidence to support what is both an exciting scientific frontier and one that may bring huge benefit to animals and humans through combating disease.
  • 52. Future prospects and conclusion 52 We do not know at this time to predict whether or not selection for disease resistance can be effective in livestock. Basic research into the complexities underlying diseases will likely reveal effective approaches for many disease problems. It may be possible to select directly against the disease, select for indicator traits(indirect selection), to select directly for the gene(s) that confer resistance or some combination of these approaches Certainly, genetic selection will not solve all of our livestock disease problems. Therefore, management, nutrition, vaccination, culling, therapeutic treatment, stress reduction practices and other measures must accompany genetic approaches to reduce the impact of livestock disease on profitability and animal well being.
  • 53. 53 My offers for be effective Disease Resistance  Management, feeding, herd health and hygienics  Write Records all animals and direct selection  Definition economic selection index for all animal triats  Considering interaction effects between different phenotyps and environments in different areas ‫ییییی‬ ‫یییی‬ ‫ییی‬ ‫یی‬ ‫ییی‬ ‫یییی‬ ‫ییییی‬
  • 54. References: 1. The Importance of veterinary medicine to livestock health By Dr. Godfrey A. Springer, BSc, DVM. 2. www.google.com. 3. Grandin, Temple (2013). "Animals are not things: A view on animal welfare based on neurological complexity". Trans-Scripts 3: An Interdisciplinary Online Journal in Humanities And Social Sciences at UC Irvine. UC Irvine. Retrieved 20 December 2013. 4. Hewson, C.J. (2003). "What is animal welfare? Common definitions and their practical consequences". The Canadian Veterinary Journal 44 (6): 496–499. PMC 340178. PMID 12839246. 5. Broom, D.M. (1991). "Animal welfare: concepts and measurement". Journal of Animal Science 69 (10): 4167–75. PMID 1778832. 6. Department of Animal Science. "Mastitis in Dairy Cows". MacDonald Campus of McGill University. Retrieved 4 February 2010. 54
  • 55. References: 7."A Focus on Bovine Spongiform Encephalopathy". Pathogens and Contaminants. Food Safety Research Information Office. November 2007. Archived from the original on 3 March 2008. Retrieved 2008-04-07. 8. Brown, David (19 June 2001). "The 'recipe for disaster' that killed 80 and left a £5bn bill". The Daily Telegraph (London). Retrieved 2008-04-07 9. Pinkeye in Cattle, Infectious bovine keratocinjunctivitis Marie-Pierre Oury, Patricia Scharko, and John Johns. 10. http://onlinelibrary.wiley.com/doi/10.1111/j.1865-1682.2011.01204.x/abstract 11. http://onlinelibrary.wiley.com/doi/10.1111/j.1865-1682.2011.01236.x/abstract 12. Canadian Food Inspection Agency - Animal Products - Foot-and-Mouth Disease Hazard Specific Plan. 13. Monke, Jim. "Avian Influenza: Agricultural Issues." CRS Report for Congress. RS21747. August 29, 2006. 14. China reports second bird flu death in a month - Health - Cold and flu - msnbc.com. 55
  • 56. 15. "Infectious Bronchitis: Introduction". The Merck Veterinary Manual. 2006. Archived from the original on 22 June 2007. Retrieved 2007-06-17. 16. Cavanagh, D., and S. A. Naqi. Infectious bronchitis. In: Diseases of poultry, 11th ed. Y. M. Saif, ed. Iowa State University Press, Ames, IA. pp. 101–120. 2003. 17. Newcastle Disease, April 2008, CFSPH Technical Fact Sheets. Newcastle Disease at http://www.cfsph.iastate edu/DiseaseInfo/ 18. Hirai, K (Ed.), ed. (2001). Current Topics in Microbiology and Immunology: Marek's Disease (Current Topics in Microbiology and Immunology). Springer: Berlin. ISBN 3-540- 67798-4. 19. Fenner, Frank J.; Gibbs, E. Paul J.; Murphy, Frederick A.; Rott, Rudolph; Studdert, Michael J.; White, David O. (1993). Veterinary Virology (2nd ed.). Academic Press, Inc. ISBN 0-12-253056-X 20. Gary Snowder, USDA, ARS, MARC, Genetic Selection for Disease Resistance: Challenges and Opportunities. . References: 56
  • 57. References: 21. Breeding for disease resistance in farm animals,(2010) Edited by Stephen C. Bishop The Roslin Institute and Royal (Dick) School of Veterinary Studies University of Edinburgh Midlothian, UK, Roger F.E. Axford. 22. Genomics and disease resistance studies in livestock, (2014 ). StephenCBishop n, JohnAWoolliams. LivestockScience. 166(2014)190–198. 23. Genetic Selection for Disease Resistance: Challenges and Opportunities, Gary Snowder. 24. Simianer H., H. Solbu, and L. R. Schaeffer. 1991. Estimated genetic correlations between disease and yield traits in dairy cattle. J. Dairy Sci. 74:4358-4365. 25. Sacco, R. E., K. E. Nestor, Y. M. Saif, H. J. Tsai, and R. A. Patterson. 1994. Effects of genetic selection for increased body weight and sex of poults on antibody response of turkeys to Newcastle virus and Pasturella multocida vaccines. Avian Dis. 38:33-36. 26. C.B.A. Whitelaw & H.M. Sang, Disease-resistant genetically modified animals. Rev. sci. tech. Off. int. Epiz., 2005, 24 (1), 275-283 57