Lec 22

• Haplotype


  A set of closely linked genetic markers present on one chromosome that tend to be inherited together
• Linkage Disequilibrium


  Non-random association between alleles at different loci

  
• The ovine MHC or Ovar-MHC ('Ovar' representing Ovis aries) was discovered from serological studies on sheep lymphocyte antigen
• Ovar-MHC


  • Located on the long arm of ovine chromosome 20
  • Mainly partitioned into three distinct regions: classes I, II and III
  • The Ovar-MHC class II region is the best-characterized region and associated with the development of the specific immune response to parasites
  • A distinct feature of the sheep class II compared with other species is that class II splits into two clusters
• MHC is the most diverse region of the genome and influences the specificity of the immune response

  
• Consequences of sheep being classified as resistant to nematodes

  • Parasites unable to establish infection
  • Parasites incapable of completing their life cycle
  • Parasites rejected from host
• The general principle applied is an increase in host resistance associated with a better immune resistance against parasite
• Breeding of genetically resistant sheep

  • Permanent solution demanding no extra resources and inexpensive method
  • Able to slow down the development of anthelmintic resistance
  • Meeting the demand for drug free residues in meat for customers
  • Enhances resistance to other gastrointestinal nematodes (GIN)
  • Strong favourable genetic correlation between resistance (FEC) and growth rate
  • The heritability of nematode resistance is one-third suggesting that the breeding of nematode resistance is feasible
  • The ultimate 'instrument' for controlling parasites in the long term
• Resistance


  Ability of the host to prevent establishment of infection or to reject the parasite
• Resilience


  Ability of the host to withstand the effects of the parasite without necessarily preventing infection
• There was evidence that there is negative genetic correlation between resistance and resilience
• The main benefit of resistance compared with resilience is to reduce contamination of larvae in the field, thus other non-resilient sheep have a lower risk of parasite challenge
• Evidence of genetic variation in nematode resistance among breeds is well documented in different continents
• Differences in susceptibility among breeds have been observed especially towards the blood feeder, H. contortus
• Faecal Egg Count (FEC)


  A parameter used to measure nematode resistance, where low FEC is usually regarded as a sign of a nematode resistant animal
• Advantages of using FEC as a parameter of nematode resistance


  • Simple to measure and highly repeatable
  • Heritability of the single FEC ranging from 0.2 to 0.4, and this value is similar to heritability of milk production in dairy cattle
  • Selection of low FEC is a part of breeding programmes and has been proven to be successful in Australia and New Zealand, without any adverse genetic correlation with important economical traits
  • Computer simulation model has shown that selection of resistance based on FEC is promising
• Disadvantages of using FEC as a parameter of nematode resistance

  • Time-consuming and labour intensive processes
  • Animal needs to have encountered the parasitic challenge, compromises health and welfare of the animal
  • Less fecund gastrointestinal nematodes such as T. circumcincta, the number of eggs and worm burden are poorly correlated
  • Density-dependent relationship contributes to a low FEC even though the animal is heavily infected
• The study involved 1000 lambs and parents from a commercial flock in Southwest Strathclyde, central Scotland, with 5 cohorts of 200 lambs at three or four months of age after weaning
• Analysis methods

  1. DNA extraction

  2. PCR

  3. Purification

  4. Direct sequencing

  5. Alignment

  6. Translation

  7. Comparison

  8. Frequency alleles

  9. Linkage disequilibrium

  10. Association with FEC
• The study found that DQA1 is less diverse than DRB1 and DQB1, and DQA1 is associated with low FEC but it could be a secondary effect
• There is strong linkage disequilibrium between DR and DQ genes in the sheep MHC