International Journal/or Parasilology, Vol. 26. No. I, pp. 7-17, 1996 Australian Society for Parasitology Elsevier Science Ltd Pergamon 0020-7519(95)00109-3 Printed in Great Britain 002&7519/96 $15.00 + 0.00 INVITED REVIEW Finding Genetic Markers for Complex Phenotypic Traits in Parasites A. J. LYMBERY Western Australian Department of Agriculture, P.O. Box 1231, Bunbury, W.A. 6231, Australia (Received 31 August 1995; accepted 18 September 1995) Abstract-Lymbery A. J. 1996. Finding genetic markers for complex phenotypic traits in parasites. Internuzional Journal for Parusi~ology 26: 7-17. The identification, mapping and eventual cloning of genes which determine or influence important epidemiological traits in parasites can have great benefits for the control of parasitic disease. In this review, strategies are outlined for identifying genetic markers for complex, quantitative traits. A genetic marker is a variable DNA sequence which co-occurs with a variable quantitative trait. Candidate markers are chosen because they are thought to directly influence the trait, whereas random markers are expected to be linked to another DNA sequence which influences the trait. Association studies compare the value of a quantitative trait between different marker genotype classes in a population, without regard to family structure. Linkage studies compare the value of a quantitative trait between marker genotype classes within families or within a population (usually derived from a cross between inbred lines) which is segregating for both marker and quantitative trait loci. The most commonly used analytical methods for determining the significance of association or linkage between marker and quantitative trait loci, and for estimating parameters such as recombination rate and quantitative gene action, are leasst-squares and maximum likelihood. Roth methods may be used to test either single markers or the interval between flanking markers, and both suffer from the need to minimize type I and type Il error rates with multiple tests. Key words: genetic markers; gene mapping; quantitative traits; QTL; linkage; association. INTRODUCTION The identification, and mapping to chromosomal location, of genes which determine phenotypic traits has a long history in a small number of plant and animal species amenable to genetic manipulation in the laboratory (Sturtevent, 1913; Sax, 1923). The explosion of interest in this field in recent years has been fuelled by the advent of recombinant DNA technology. By exploiting the DNA sequence varia- tion to which this technology provides access, pri- mary linkage maps have now been produced for the genomes of many different species (Goodfellow, Sefton & Farr, 1993; Beattie, 1994). Linkage and physical genome mapping projects have been initiated for the parasite species Plasmodium falci- parum, Schistosoma mansoni and Brugia malayi (Craig & Langsley, 1993; Unnasch, 1994; Tanaka et al., 1995) and for the mosquito vectors Aedes aegypti and Anopheles gambiae (Severson, 1994). Genome maps provide a resource for identifying the genetic determinants of phenotypes. I will define a genetic marker as a variable DNA sequence which co-occurs with a variable phenotypic trait, either because it determines the trait or because it is linked to another DNA sequence which determines the trait. Genetic markers for traits such as virulence, host preference, vector competence, development rate, antigenicity and drug resistance provide pre- dictive diagnostic tools which can greatly contribute to the epidemiological understanding of parasitic disease and to the efficient application of control measures (Blackwell, 1992; Dye, 1992). In addition, by providing information on the genetic architecture of such traits and by facilitating the cloning of genes