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Dr. Vicki-Meyers-Wallen is working to identify the genetic causes behind inherited disorders of sexual development, or DSDs, conditions that impair the normal development of reproductive organs in animals and humans alike. Inherited disorders of dogs have long plagued dog breeding because, in many cases, it is difficult to tell which dogs carry the mutations related to the condition and which do not, an ambiguity that enables the mutation to continue to be passed down through the generations.
This ambiguity is true of the particular form of DSD that Meyers-Wallen is currently studying, “XX DSD”, which causes infertility (impaired ability to reproduce) and sterility (the incapacity to reproduce) in 28 breeds of purebred dogs. And like other inherited conditions, XX DSD can’t be eliminated from a population unless all the dogs that carry the mutations for the condition are identified and are prevented from reproducing and carrying the condition to the next generation. Similar conditions also strike in humans, but the genetics and the mode of inheritance of these conditions are often difficult or impossible to tease apart.
Dogs that are affected with XX DSD have normal female chromosomes but instead of developing ovaries, they develop testicles or combination ovary-testes called ovotestes, which produce testosterone and promote male features in the remainder of internal and external genitalia. Genetically speaking, these dogs are female because they have two X chromosomes, but since they have some features of male external genitals, they can appear to be males or females. Early investigations of the disorder focused on a gene called SRY, which is responsible for initiating male sex determination in humans, but Meyers-Wallen’s lab put that possibility to rest by showing that SRY isn’t present in XX DSD-affected dogs.
In order to determine the real cause, Meyers-Wallen is applying whole genome sequencing, computational tools, and careful analysis to solve the riddle of XX DSD. The search has been narrowed down to a small region in the genome where affected dogs differ from dogs who definitely do not carry the mutation for the disorder. Further testing lies ahead to determine which mutation is responsible for testes development in XX DSD dogs.
Once Meyers-Wallen has identified the mutation responsible for XX DSD, a test can be developed to identify dogs that carry the mutation. Determining the genetic cause of XX DSD would not only help dogs. A better understanding of the normal pathways of sexual development may also help human families struggling with these disorders by pointing the way to genetic tests that can help with family planning decisions.
This ambiguity is true of the particular form of DSD that Meyers-Wallen is currently studying, “XX DSD”, which causes infertility (impaired ability to reproduce) and sterility (the incapacity to reproduce) in 28 breeds of purebred dogs. And like other inherited conditions, XX DSD can’t be eliminated from a population unless all the dogs that carry the mutations for the condition are identified and are prevented from reproducing and carrying the condition to the next generation. Similar conditions also strike in humans, but the genetics and the mode of inheritance of these conditions are often difficult or impossible to tease apart.
Dogs that are affected with XX DSD have normal female chromosomes but instead of developing ovaries, they develop testicles or combination ovary-testes called ovotestes, which produce testosterone and promote male features in the remainder of internal and external genitalia. Genetically speaking, these dogs are female because they have two X chromosomes, but since they have some features of male external genitals, they can appear to be males or females. Early investigations of the disorder focused on a gene called SRY, which is responsible for initiating male sex determination in humans, but Meyers-Wallen’s lab put that possibility to rest by showing that SRY isn’t present in XX DSD-affected dogs.
In order to determine the real cause, Meyers-Wallen is applying whole genome sequencing, computational tools, and careful analysis to solve the riddle of XX DSD. The search has been narrowed down to a small region in the genome where affected dogs differ from dogs who definitely do not carry the mutation for the disorder. Further testing lies ahead to determine which mutation is responsible for testes development in XX DSD dogs.
Once Meyers-Wallen has identified the mutation responsible for XX DSD, a test can be developed to identify dogs that carry the mutation. Determining the genetic cause of XX DSD would not only help dogs. A better understanding of the normal pathways of sexual development may also help human families struggling with these disorders by pointing the way to genetic tests that can help with family planning decisions.
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Katharina Freiberger,Shelby Hemker, Ryan McAnally, Rachel King,Vicki N Meyers-Wallen,Brian C Schutte,John C Fyfe
semanticscholar(2019)
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semanticscholar(2012)
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