Unit 4b. Genetics Flashcards
why consider gentic selection to improve animal health?
- Evidence suggests that it can be dnoe
- genetic improvement is permanent
- vaccines may not exist for all diseases, or cant be used because antibody levels are used to diagnose disease
- development of antimicrobial resistance requires that we improve animal health
- potential to reduce risk of zoonotic disease
- potential to reduce animal health costs
How do we carry out the genetic selection to enhance animal health?
selection based on phenotypic biomarkers
selection for resistance to a specific disease
Health Recording in Canadian Holsteins
genetic traits for health and fertility have not been achieved over the past 50 years for the following reasons:
- these phenotypes are more difficult to measure
- these phenotypes have low-to-moderate heritability
- these phenotypes are dependent on small interacting contributions from many genes
- these phenotypes are often inversely correlated with production traits
cows with high genetic merit for milk and protein yield are significantly more susceptible to mastitis, cystic ovaries and lameness
Example: Immunity plus
bovine antibody response to vaccination with novel antigens was used as a biomarker to identify immunity plus bulls
“whose daughters have less mastitis, metritis, Johnes disease, retianed placenta, increased longevity and improved response to vaccination
SNPs
make excellent genetic markers for health association studies because they frequently occur throughout the genome. also, most SNPs are bi-allelic, which makes them appealing for high throughput genotyping
SNP panels are now being used to perform genome-wide association studies to identify quantitative trait loci that harbour genes influencing complex triats, to replace traditional phenotypic selection practices with genomic selection; this was based on:
- Once QTL association with a trait of interest are identified, the SNPs within these QTLs can be used to predict the phenotype of a newborn animals, sperm or embryo long before the phenotype can be measured
- animals with preferred genotypes can be used in a selective breeding program to increase the frequency of the genotype within a population. using this approach, genetic gain can be achieved over a much shorter period of time because the generation interval is reduced
MHC class II receptor
the MHC class II-DQ molecules are heterodimers; the A and B chains are coded by BOLA-DQA and BOLA-DQB genes respectively
NCBI Map View
there are several BOLA genes in this region of chromosome 23 that code for different class II molecules including DRB3, DRA1, DQA and DQB; DRB3 being the most polymorphic of these BOLA genes. any of these genes, and/or the remaining genes found around the top 10 SNPs associated with AbMIR, could be putative genes contributing to the immunity plus phenotypes
SNPs found with BOLA-DRB3
these SNPs can affect the 3D structure of the MHC class II molecule, which can affect antigen binding affinity and therefore antigen presentation during microbial infection and vaccination
the SNPs in genes coding the MHC class I and class II receptors are inherited from parent to offspring and these genes rarely undergo somatic mutation. the genes coding the MHC class I and class I receptors are the most polymorphic genes found within the genome
Genetic Selection for Resistance to Specific Diseases EXAMPLE: BOLA-DRB3 and foot and mouth disease
foot and mouth disease is a highly communicable virus of cattle, pigs, sheep and goats. this disease is characterized by fever and blister like sores on the tongue, lips, in the mouth, on the teats and between the hooves
FMD is a reportable disease in Canada, people, animals, vehicles can spread FMD virus
Canada currently has a FMD free status
due to the economic impact of this disease, there is much interest in using genetic selection to enhance resistance to FMD
Example: Helminth Resistance Sheep
the co-evolution of livestofk with pathogens can lead to natural selection for disease resistance and/or resilience within a population
nematodes have co-evolved with sheep for millions of years. both parasite and host have developed strategies to ensure survival.
fecal egg shedding for example is greater during the peripartum period-(weeks before and after lambing) when the ewe experiences changes in her nutritional status that affect immune function. this increase in fecal shedding ensures parasite survival by transmission to offspring
at the same time, low-level parasite transmission is likely beneficial to the offspring in that it contributes to the neonatal immune system development and long-term immunity to subsequent infection
Resistance/ Resilience Definition
where resistance refers to the ability of an animal to resist microbial infection, resilience refers to the ability of an animal to tolerate microbial infection with minimal adverse effects but transmits the pathogen to herd mates. if the genetic goal is to prevent disease transmission within and across populations, then selection for disease resistance is preferred
from an evolutionary perspective, resilience is likely preferred since it will reduce selective pressure on the pathogens to undergo genetic change, and will contribute to immune system, development
Scrapie in Belgium
scrapie is a prion transmissible spongiform encephalopathy that manifests as a neurodegenerative disorder of sheep
susceptibility to scrapie is determined by host genetic variants in the PrP gene encoding the prion protein
these genetic variants alter amino acids codons making up the prion protein, and there are three codons that relate to disease susceptibility
- Codon 136
- Codon 154
- Codon 171
the combination of these three polymorphisms on the amino acid sequence is referred to as a haplotype
Change in Haplotype frequencies in PrP gene
in 1998 an “atypical” form of scrapie was identified in Norway and has since spread throughout the EU
interestingly, the ARR/ARR genotype was found to be susceptible to it ( they are resistant to the normal strain)
Mareks Disease (MD)
is a viral disease of chickens caused by a type 2 herpes virus. infected chicken exhibit weight loss, bursal and thymus atrophy and T cell tumours
vaccination prevents disease but not an infection or viral shedding
this disease shows that selection for disease resistance may also cause the pathogen to become more virulent
