A nonsense mutation in TFEC is the likely cause of the recessive piebald phenotype in ball pythons (Python regius)

Abstract

Captive-bred ball pythons (Python regius) represent a powerful model system for studying the genetic basis of colour variation and Mendelian phenotypes in vertebrates. Although hundreds of Mendelian phenotypes (colour morphs) affecting colouration and patterning have been described for ball pythons, the genes causing these colour morphs remain unknown. Here, we used crowdsourcing of samples from commercial ball python breeders to investigate the genetic basis of a classic phenotype found in the pet trade, the piebald [characterized by dorsolateral patches of unpigmented (white) skin]. We used whole-genome sequencing of pooled samples followed by population genetic methods to delineate the genomic region containing the causal gene. We identified TFEC of the MIT-family of transcription factors as a candidate gene. Functional annotation of SNPs identified a nonsense mutation in TFEC, which we conclude is the likely causal variant for the piebald phenotype. Our work shows that ball python colour morphs have the potential to be an excellent model system for studying the genetic basis of pigment variation in vertebrates, and highlights how collaborations with commercial breeders can accelerate discoveries.