Linkage Analysis of the whirler Deafness Gene on Mouse Chromosome 4

Abstract

The whirler mouse harbors an autosomal recessive mutation on mouse chromosome 4 that causes deafness and vestibular dysfunction in the adult that is manifested as head-bobbing and circling behavior. Although there is no obvious human homologue for this mutation as yet, whirler is a potential mouse model for human autosomal recessive deafness. Many genetic markers for this region of mouse chromosome 4 are now available, and we have used these to construct genetic linkage maps in both inter- and intraspecific backcrosses as the first step toward the cloning of the whirler gene. A total of 19 loci were analyzed in these crosses, giving the following gene orders: interspecific cross, centromere- (D4Mit5, D4Mit38)-D4Mit6-(Lv, Tzn, D4Mit44)-wi-Hxb-(D4Mit25, D4Nds9)-(D4Mit7, D4Ler2)-b-D4Mit45-(D4Wsm1, D4Mit27b)-(D4Rck65, D4Mit15), and intraspecific cross, centromere- (Mup-1, wi, Hxb)-b-D4Wsm1. This analysis has positioned the wi locus in the interval between the genes for δ-aminolevulinate dehydratase ( Lv) and hexabrachion ( Hxb). The human homologues of these genes, ALAD and HXB, both lie on human chromosome 9q32-q34. We therefore predict that a human homologue of the wi gene, involved in autosomal recessive deafness, lies in this region of conserved homology on 9q32-q34.