A Mutation in Hairless Dogs Implicates FOXI3 in Ectodermal Development

Abstract

Mexican and Peruvian hairless dogs and Chinese crested dogs are characterized by missing hair and teeth, a phenotype termed canine ectodermal dysplasia (CED). CED is inherited as a monogenic autosomal semidominant trait. With genomewide association analysis we mapped the CED mutation to a 102-kilo-base pair interval on chromosome 17. The associated interval contains a previously uncharacterized member of the forkhead box transcription factor family (FOXI3), which is specifically expressed in developing hair and teeth. Mutation analysis revealed a frameshift mutation within the FOXI3 coding sequence in hairless dogs. Thus, we have identified FOXI3 as a regulator of ectodermal development.

Rethinking dog domestication by integrating genetics, archeology, and biogeography

“…Chinese and Mexican breeds both possess the same hairless gene (26), sub-Saharan African and Thai breeds possess a ridged line of hair on their backs caused by the same genetic mutation (27)…”

Disease: A Hitherto Unexplored Constraint on the Spread of Dogs (Canis lupus familiaris) in Pre-Columbian South America

“…AD 600) in the Antilles also indicates a connection to these hairless breeds because this condition is known to be associated with an allele linked to hairlessness in a phenotype known as canine ectodermal dysplasia (Grouard et al 2013). Given that hairlessness is inherited as a monogenic autosomal semidominant trait caused by a mutation of the FOX13 gene, with heterozygous dogs being hairless but homozygous ones dying in embryo (Drögemuller et al 2008), 'these dogs must have been viewed as valuable' (Schwartz 1997, p. 133) for the phenotype to survive. Might this condition, which is also shared by Argentine pila dogs and the khala of Bolivia's Andes, therefore survive not just by human selection, but because it provides a degree of immunity against disease?…”

Le chien dans la pathologie et la génétique comparée: exemples de maladies et de gènes partagés entre l'homme et le chien

“…Concernant les maladies à composantes génétiques « simples » ou supposées simples, de nombreux travaux font actuellement état de l'identification de gènes responsables d'affections partagées entre l'homme et le chien, comme, par exemple, des rétinopa-thies (Wilk et al 2008), la sclérose amyothrophique latérale (Awano et al 2009), des maladies cardiaques (Meurs et al 2010), les lipofuscinoses neuronales canines (Abitbol et al 2010 ;Katz et al 2011), les épilepsies (Lohi et al 2005 ;Sepalla et al 2011), des maladies dermatologiques telle que l'ichtyose (Grall et al 2012), ou encore des anomalies comme le phénotype sans poil des chiens nus (Drogemuller et al, 2008).…”