Genetics of Mastitis Susceptibility

1. Genetics of Mastitis Susceptibility By Riyashna Rampersadh

2. Introduction • Most expensive and common disease. • Affects approximately one-third of all dairy cows. • Occurrences of mastitis cost dairy producers - $200/cow/year • Unlikely that in any dairy herd, the animals are free of this disease. • Defined as an inflammatory reaction occurring in the mammary gland. • Can be non-infectious but may be an infectious disease. • The majority of infections are caused by a few types of bacteria. • Common pathogens fall into two main categories i.e. contagious & environmental bacteria • NB: distinction between the abovementioned.

3. Introduction cont… • Clinical mastitis - visible abnormalities in the udder or the milk, can vary in the degree of severity depending on the type of microorganism causing the infection. • Subclinical mastitis - far more subtle and one cannot detect it by visual observation, can only be identified when tests are conducted in order to identify the type of microorganism or the products of inflammation e.g. somatic cells. • Somatic cells are normal constituents of milk and only result in a problem when their numbers become excessive. • NB: milk is a safe, wholesome and nutritious product. • Cannot be eradicated but one can control the disease.

4. Mastitis Susceptibility • Breeding for resistance to udder pathogens is an important tool. • Cellular/hormonal and DNA levels - monitoring the cows susceptibility to pathogens. • Despite rigorous management practices - remains a problem in high producing dairy cows during periparturition. • Periparturient mastitis susceptibility is related to the generalized immune suppression taking place from approximately 1 week prepartum to approximately 1 week postpartum. • Discover what genes result in this condition. • Genetic selection against periparturient mastitis susceptibility may be the best long-term approach

5. Mastitis Susceptibility cont… • Dairy cattle breeders have focused on the improvement of milk output as well as the quality at the expense of disease resistance. • Research in this field has a long history and has been concentrated mainly on determining appropriate markers or traits for genetic selection. • Immune response traits measured in vivo and in vitro generally possess higher heritabilities than mastitis itself • However, researchers still have no knowledge of the genes which regulate normal immune resistance against mastitis-causing pathogens

6. Mastitis Susceptibility cont… • NB: significantly change our experimental approaches to these problems. • Allow leukocytes to tell their own story about those genes involved in normal immunocompetence and in the suppression of immunocompetence that takes place around parturition. • Burton et al (2003) focused on cDNA microarray analysis of global gene expression changes occurring in bovine blood leukocytes around parturition. • However, it has not been determined which population of leukocytes are affected or what factors of parturition cause the repression of the 18 leukocyte genes that were found. • Preliminary studies link neutrophils as the main leukocyte targets of parturition-induced changes in gene expression. • Additional studies need to be carried out.

7. Mastitis Susceptibility cont… • A microarray experiment - identified 18 genes normally expressed in blood leukocytes • A majority of them showed high DNA sequence homology to genes that are needed for normal cell functions. • Observed changes in gene expression relating to fluctuating hormone concentrations and nutrient status of periparturient cows. • New knowledge generated about gene expression changes in leukocytes of parturient dairy cows - useful for the development of novel management strategies. • Major future goals - to determine which leukocyte genes participate in the regulation of mammary immunity and study them as possible candidate markers for genetic selection.

8. New Findings • Patent application on a cloned gene that promises to treat or prevent bacterial infections that result in mastitis in dairy cows. • The gene produces a protein that is naturally present in cows' milk and blood plasma, but in amounts too small to have any therapeutic effect. • The recombinant protein, named CD14, binds to and neutralizes toxins that are made by bacteria causing mastitis. • Max Paape, a dairy scientist, and Dante Zarlenga, a molecular biologist, along with cell biologist Yan Wang, cloned the gene and confirmed the effectiveness of the protein against mastitis infections. • CD14 brings about sensitivity in the lining of a cow's mammary glands to the very low levels of the bacterial toxin known as endotoxin. Once sensitized, these mammary cells recruit white blood cells which attack and kill infiltrating bacteria before they can establish an infection. • Scientists now are conducting tests to support the new hypothesis that cows genetically engineered to produce higher than normal amounts of CD14 could enjoy CD14's protection from infection as well.

9. Role of Genetics in Reduction of Mastitis + Cell Counts • It is important to note that antibiotic treatment to prevent mastitis requires stringent measures. • Nearly all udder infections are brought about by bacteria that enter the quarter through the end of the teat. • Factors affecting the balance of infection and defence are influenced significantly by the cow's environment. • In general, the greatest impact on udder health is achieved by activities to do with managing cows before, during and after the milking process. • It has been found that there is a slight tendency for higher production bulls to leave daughters with higher mastitis levels, so selection for production may be slowly leading to a small increase in genetic susceptibility to mastitis. • udder health from a genetic point of view plays a small role.

10. Role of Genetics cont… • Use of genetics to reduce the occurrence of cases of clinical mastitis - measure the occurrence rate of cases for every progeny test daughter of each bull. • Cell counts should be taken into account as well. • Different countries use different formulae to calculate their scores. In practice this means that you can't directly compare the SCS in one country with the SCS in another just like bull proofs. • As it turns out, the simpler methods for doing these calculations may not be too much different from the fancier methods. • The ideal way to evaluate bulls would involve using both cell count information and combining it with any records where a cow had been treated for mastitis.

11. A step forward… • Numerous experiments that have identified different QTL regions in cattle • QTLs envelop large chromosomal regions on average spreading from 10 to 40 cM which involve hundreds or thousands of genes. • The ultimate goal of the QTL analysis is identification of causal gene itself • Beside QTLs, a large number of genetic polymorphisms within the causal gene regions or genetic markers associated with mastitis traits have been identified in cattle. • Technologies e.g. microarray analysis offers the possibility to study changes in expression profiles of thousands of genes at the same time as a response to infection with the pathogen.