RESUMO
In mammals, the Y-linked SRY gene is normally responsible for testis induction, yet testis development can occur in the absence of Y-linked genes, including SRY. The canine model of SRY-negative XX sex reversal could lead to the discovery of novel genes in the mammalian sex determination pathway. The autosomal genes causing testis induction in this disorder in dogs, humans, pigs, and horses are presently unknown. In goats, a large deletion is responsible for sex reversal linked to the polled (hornless) phenotype. However, this region has been excluded as being causative of the canine disorder, as have WT1 and DMRT1 in more recent studies. The purpose of this study was to determine whether microsatellite marker alleles near or within five candidate genes (GATA4, FOG2, LHX1, SF1, SOX9) are associated with the affected phenotype in a pedigree of canine SRY-negative XX sex reversal. Primer sequences flanking nucleotide repeats were designed within genomic sequences of canine candidate gene homologues. Fluorescence-labeled polymorphic markers were used to screen a subset of the multigenerational pedigree, and marker alleles were determined by software. Our results indicate that the mutation causing canine SRY-negative XX sex reversal in this pedigree is unlikely to be located in regions containing these candidates.
Assuntos
Transtornos do Desenvolvimento Sexual , Repetições de Microssatélites/genética , Cromossomo X/genética , Animais , Cães , Fator de Transcrição GATA4/genética , Genes sry/genética , Proteínas de Grupo de Alta Mobilidade/genética , Proteínas de Homeodomínio/genética , Linhagem , Reação em Cadeia da Polimerase , Receptores Citoplasmáticos e Nucleares/genética , Fatores de Transcrição SOX9 , Fator Esteroidogênico 1 , Fatores de Transcrição/genéticaRESUMO
XX sex reversal is known in 17 breeds of dogs. In the American cocker spaniel, it segregates as an autosomal recessive trait, and the affected animals lack the testis determining Sry gene. In the search for an autosomal gene that causes this trait, we considered the possibility of Lhx9, a gene encoding LIM homeobox containing transcription factor 9, as a candidate gene. An American cocker spaniel pedigree showing Sry-negative XX sex reversal phenotype was genotyped with an intronic Lhx9 microsatellite marker. Segregation of the Lhx9 marker in the pedigree indicated that a mutation in canine Lhx9 is not likely to be the cause of Sry-negative XX sex reversal. In addition, using the recently available 7.6X canine genomic sequence, we report the location and genomic organization of canine Lhx9.