Biomarkers diagnose, predict or assess the risk of disease, and studies of the effects of genetic variation on biomarker phenotypes in the general population complement studies on patients diagnosed with disease. This paper traces the evolution of studies on biomarker genetics over the past 40 years through examples drawn from the work of Professor Martin and his colleagues.

Observational studies of cattle production systems usually find that cattle from conventional dairies harbor a higher prevalence of antimicrobial resistant (AMR) enteric bacteria compared to organic dairies or beef-cow operations; given that dairies usually use more antimicrobials, this result is not unexpected. Experimental studies have usually verified that application of antimicrobials leads to at least a transient expansion of AMR bacterial populations in treated cattle. Nevertheless, on dairy farms the majority of antibiotics are used to treat mastitis and yet AMR remains relatively low in mastitis pathogens. Other studies have shown no correlation between antimicrobial use and prevalence of AMR bacteria including documented cases where the prevalence of AMR bacteria is non-responsive to antimicrobial applications or remains relatively high in the absence of antimicrobial use or any other obvious selective pressures. Thus, there are multi-factorial events and pressures that influence AMR bacterial populations in cattle production systems. We introduce a heuristic model that illustrates how repeated antimicrobial selection pressure can increase the probability of genetic linkage between AMR genes and niche- or growth-specific fitness traits. This linkage allows persistence of AMR bacteria at the herd level because subpopulations of AMR bacteria are able to reside long-term within the host animals even in the absence of antimicrobial selection pressure. This model highlights the need for multiple approaches to manage herd health so that the total amount of antimicrobials is limited in a manner that meets animal welfare and public health needs while reducing costs for producers and consumers over the long-term.

A key aim of anthelmintic resistance research is to identify molecular markers that could form the basis of sensitive and accurate diagnostic tests. These would provide powerful tools to study the origin and spread of anthelmintic resistance in the field and to monitor strategies aimed at preventing and managing resistance. Molecular markers could also form the basis of routine diagnostic tests for use in surveillance and clinical veterinary practice. Much of the research conducted to date has focused on the investigation of possible associations of particular candidate genes with the resistance phenotype. In the future, as full parasite genome sequences become available, there will be an opportunity to apply genome-wide approaches to identify the genetic loci that underlie anthelmintic resistance. Both the interpretation of candidate gene studies and the application of genome-wide approaches require a good understanding of the genetics and population biology of the relevant parasites as well as knowledge of how resistance mutations arise and are selected in populations. Unfortunately, much of this information is lacking for parasitic nematodes. This review deals with a number of aspects of genetics and population biology that are pertinent to these issues. We discuss the possible origins of resistance mutations and the likely effects of subsequent selection on the genetic variation at the resistance-conferring locus. We also review some of the experimental approaches that have been used to test associations between candidate genes and anthelmintic resistance phenotypes and highlight implications for future genome-wide studies.

Les récents progrès de la biologie moléculaire offrent l’espoir d’une meilleure compréhension de la composante génétique des maladies mentales, la dépression en particulier. L’accès à un nombre quasiment illimité de marqueurs génétiques polymorphes et couvrant le génome, accroît l’efficacité des techniques de liaison génétique (linkage) qui permettent l’étude de la cotransmission des marqueurs génétiques et du trait clinique dans des familles dont plusieurs membres sont malades. D’ores et déjà, en ce qui concerne les troubles de l’humeur, 2 pistes ont été mises en évidence: celle d’une liaison à l’extrémité distale du bras long du chromosome X (Mendlewicz et al., 1987) et celle d’une liaison à l’extrémité du bras court du chromosome 11 (Egeland et al., 1987). Toutefois, ces résultats n’ont pas été constamment répliqués, ce qui soulève le problème de l’hétérogénéité étiologique des troubles dépressifs.