Repeat polymorphism in the dopamine receptor gene of dog

Abstract

In human and primate, the 48 base pair repeat polymorphism in the third cytoplasmic loop of the type 4 dopamine receptor (DRD4) has been reported, whereas no repeat-like sequence is present in more primitive rodent DRD4. Previous study had discovered a novel repeat polymorphism consisting of three modular varieties of 27, 39, and 51 base pair sizes in various species of Canidae (unpublished). Various sequential combinations of such modules as well as distinct sequence conservations are found in wolf-like Canidae. In the evolutionary divergent organisms, the repeat region (repeat core) has also been found, and evolutionarily distinct hierarchy of structure in DRD4 repeat core has been found. An in vivo simulation of repeat core pattern generation in a model system has been performed, and a highly recombinogenic activities are mainly distributed over the variable region of the repeat core, but constant region had fewer crossover junction points, implying a certain constraint to retain a specific pattern, e.g. the constant region. This simulation could generate virtually identical one found in dog breed from the two other dog alleles. Moreover, the repeat polymorphism can be generated by recA-independent recombination mechanism as well as unequal, homologous recombination similar to tri-nucleotide repeat expansion/deletion mechanism in such as Huntington’s disease, since the crossover event and subsequent changes in repeat module structure can be generated also in recA-deficient strain as well as recA+ strain at significant numbers. It is suggested that these highly organism (breed)-specific or individual-specific polymorphism within this region may serve as differences in DRD4 function in vivo.