Identification of a Missense Variant in MFSD12 Involved in Dilution of Phaeomelanin Leading to White or Cream Coat Color in Dogs
, Edouard Cadieu 1, Nadine Botherel 1, Caroline Dufaure de Citres 2, Anna Letko 3, Maud Rimbault 1, Cord Drögemüller 3, Vidhya Jagannathan 3, Thomas Derrien 1, Sheila Schmutz 4, Tosso Leeb 3 and Catherine André 1
Round 1
Reviewer 1 Report
The manuscript describes the use of a large number of dog breeds to identify the locus responsible for solid white coat color. Two rounds of GWAS allowed to detect a locus on chromosome 20. The authors identified a same variant for all breeds in the MFSD12 gene. The variant segregates in all breeds with fixed phaeomelanin dilution, reflecting strong linkage disequilibrium. No other MFSD12 variant was found. Homozygosity for the variant is however not sufficient in all breeds to produce fixed white coat color. This suggests the presence of other modifier genes.
MFSD12 was previously detected as a pigmentation locus is man, mouse and horses.
The data are convincing.
Author Response
We would like to thank the reviewers for taking the time to review this article and for their positive answer.
Reviewer 2 Report
This manuscript described a missense variant in MFSD12 involved in dilution of phaeomelanin leading to white or cream coat color in dogs. Using several genome‐wide association studies, authors identified the I locus on chromosome 20 and a missense variant linked to phaeomelanin dilution in dogs. In addition to genome‐wide association studies, long read sequences were produced, and sequencing of DNA canine samples and qPCR were performed. They detected two significant associations with solid white: one on chromosome 5, 28 kb upstream from the MC1R gene (CanFam3.1 position 64 Mb) and a novel locus on chromosome 20 (position 55 Mb). After confirming that solid white dogs do not express eumelanin but only phaeomelanin, they identified a coding MFSD12 variant linked to phaeomelanin dilution. The variant perfectly segregated with breeds presenting diluted phaeomelanin but not with breeds presenting the red coat color. They concluded that the role of this variant in phaeomelanin dilution of numerous canine breeds, and the conserved role of MFSD12 in mammalian pigmentation. The manuscript was written clearly and the results support the conclusion.
Author Response
We would like to thank the reviewers for taking the time to review this article and for their positive answer.
