”8 In allele-sharing methods of analysis, one checks whether or not the inheritance pattern of a chromosomal region is consistent with random mendelian segregation. If not, patients and their affected relatives will inherit identical copies of DNA markers within that chromosomal region more often than expected by chance. Since allele-sharing methods are nonparamctric (that is, they assume no model for the inheritance of the trait), they tend to be more robust than linkage analysis, particularly for complex disorders, Inhibitors,research,lifescience,medical for which the inheritance

pattern is not clear. Association studies are case-control studies based on a comparison of unrelated affected and unaffected individuals from a population. An allele of a gene of interest is said to be associated with the trait if it occurs at a significantly higher frequency among affected compared with control individuals. Familial inheritance patterns are irrelevant to the method, however, the choice of the control group and its match to the patient group Inhibitors,research,lifescience,medical is

vital to the study. Population associations between a genetic marker and a phenotypic trait can arise either from population stratification (ie, ethnic differences, and hence different allele Inhibitors,research,lifescience,medical frequencies between populations) or genetic transmission. A refinement of association studies is to use family trios (a patient and his or her parents) or sibling pairs, in an attempt to eliminate problems of population stratification. Association studies have most been applied to genes or DNA markers linked to genes proposed as candidates for a particular trait. Experimental crosses of mice and rats Inhibitors,research,lifescience,medical offer an ideal setting for the genetic dissection of mammalian physiology. With the LY335979 opportunity to Inhibitors,research,lifescience,medical study hundreds of meioses from a single set of parents, the problem of genetic heterogeneity disappears, and far more complex genetic interactions can be probed than would be possible in human families. Animal studies relating to anxiety will be described in more detail in the final section of this review. One way to undertake genetic studies of psychiatric illness is to find a classification that might relate more unless directly

to the inheritance pattern. The ideal would be to find pedigrees in which the disorder segregates in a strictly mendelian fashion, as a recessive or dominant. Although these families may not be phenotypically typical of the disorder, there would be good chance of finding genetic linkage and the first step towards isolating an abnormal gene. This gene and its product may provide a clue as to the type of pathway or mechanism causing the disorder. Unfortunately, such families are not abundant. An alternative is to find other genetically determined features that predispose to psychiatric illness, for example, the deletion of chromosomal region 22qll has been shown to be associated with an increased risk of developing a psychotic illness.