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Animal studies/molecular genetics/Munafò: The basic experimental design is the analysis of association between genotypic and phenotypic variation in a cross between two inbred strains of rodents (usually, but not necessarily, with contrasting temperament phenotypes).
Molecular genetic markers are then used to determine which chromosomal segments segregate with the trait (that is, which chromosomal regions are shared by animals that are phenotypically similar for the trait of interest). Over the past ten years, QTL (quantitative trait loci) putatively related to temperament have been identified on a number of chromosomes, although the molecular nature of these remains unclear.
(1) Genetic mapping identifies a potential functional variant, rather than a gene, and functionally-important variants that affect gene expression may lie some distance away from a gene, or even in the location of an unrelated gene.
(2) Experimental design offers only a limited number of recombinants in a single generation (typically, between one and two), so that the resolution to map a specific locus is limited, and may identify regions which can still contain hundreds or perhaps thousands of genes.
(3) One potential difficulty in animal studies lies in whether genes identified in animal studies have an orthologue in man (i.e., are functionally related to a human gene, with extensive sequence similarity), although the conservation of much of the genome in rodents and man is one reason for the extensive use of rodents as an animal model of human traits.
Solution: one can map in genetically heterogeneous stocks of rodents which are generated from multiple (usually eight) inbred strains which have been successively intercrossed for maximal diversity and maintained over multiple generations through a programme of pseudo-random mating. Since these animals are several generations removed from the original progenitor strains, this offers the potential of mapping a QTL to a limited number of genes, although this requires a substantial increase in marker density, and the analysis is considerably more complex in this case.
Marcus R. Munafò,“Behavioural genetics: from variance to DNA“, in: Corr, Ph. J. & Matthews, G. (eds.)2009. The Cambridge handbook of Personality Psychology. New York: Cambridge University Press_____________Explanation of symbols: Roman numerals indicate the source, arabic numerals indicate the page number. The corresponding books are indicated on the right hand side. ((s)…): Comment by the sender of the contribution. The note [Author1]Vs[Author2] or [Author]Vs[term] is an addition from the Dictionary of Arguments. If a German edition is specified, the page numbers refer to this edition.
Philip J. Corr
The Cambridge Handbook of Personality Psychology New York 2009