Linkage analysis of the whirler deafness gene on mouse chromosome 4.
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 delta-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.
Fleming
J
J
MRC Institute of Hearing Research, Nottingham, United Kingdom.
Rogers
M J
MJ
Brown
S D
SD
Steel
K P
KP
D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D003638:Deafness / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000235:genetics*; D009115:Muridae / Q000235:genetics; D013045:Species Specificity; D015837:Vestibular Diseases / Q000235:genetics*