GE McClearn, LM Tarantino, LA Rodriguez, BC Jones, DA Blizard, R Plomin Department of Behavioral Health, Pennsylvania State University, University Park, PA, USA
For decades, available methods have permitted only aggregated descriptions of the effects of the many genes that collectively influence complex diseases or disorders. The dramatic recent advances in mapping the genomes of several species have made it possible now to identify some of these genes, thereby opening possibilities of discovering the mechanisms through which their influence is exerted.
The methods by which these "quantitative trait loci" or QTLs are located have in common the necessity of setting the criteria for evidence so that both the number of false claims and the number of overlooked loci is reduced to a low level. The decision is a delicate one, because as one of these types of error is reduced, the other necessarily rises. An increasingly popular resolution is to make initial observations on one group of animals with a liberal criterion that gives a good chance to find the relevant genes, but with follow-up observations on a different group with a more stringent criterion to sort out the false claims that inevitably will be generated.
The present study demonstrates the utility of genotypic selection as the second, confirmatory, stage in such a research program. In this procedure, animals with known QTLs are mated to provide numerous offspring of differing genetic constitution. The confirmation test is a statistically simple comparison of the offspring of parents of the different types and is more economical and effective than most other currently available methods.
Another valuable aspect of this demonstration of genotypic selection is the prospect offered by selecting for different QTLs in succeeding generations, thus building the genetic structure of a complex characteristic systematically and to specification. Animals derived from this tandem selection should constitute powerful analytical methods for determining genetic susceptibility to alcoholism.
For further information, please contact the corresponding author, Dr. Gerald E. McClearn, Department of Behavioral Health, Pennsylvania State University, University Park, PA, USA FAX: +1 814 863-4768; Tel: +1 814 865 1717; e-mail: gm1@psu.edu reference: Molecular Psychiatry 1997; 2 (October-November): [in press]
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