A gene duplication affecting expression of the ovine ASIP gene is responsible for white and black sheep

Agouti signaling protein (ASIP) functions to regulate pigmentation in mice, while its role in many other animals and in humans has not been fully determined. In this study, we identify a 190-kb tandem duplication encompassing the ovine ASIP and AHCY coding regions and the ITCH promoter region as the...

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Bibliographic Details
Published in:Genome Research 2008-08, Vol.18 (8), p.1282-1293
Main Authors: Norris, Belinda J, Whan, Vicki A
Format: Article
Language:English
Subjects:
Agouti Signaling Protein - biosynthesis
Agouti Signaling Protein - genetics
Alleles
Alternative Splicing
Animals
Base Sequence
Exons
Gene Dosage
Gene Duplication
Gene Expression
Haplotypes
Introns
Letter
Molecular Sequence Data
Mutation
Phenotype
Pigmentation - genetics
Promoter Regions, Genetic
RNA, Messenger - metabolism
Sequence Deletion
Sheep - anatomy & histology
Sheep - genetics
Sheep - metabolism
Ubiquitin-Protein Ligases - genetics
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Summary:Agouti signaling protein (ASIP) functions to regulate pigmentation in mice, while its role in many other animals and in humans has not been fully determined. In this study, we identify a 190-kb tandem duplication encompassing the ovine ASIP and AHCY coding regions and the ITCH promoter region as the genetic cause of white coat color of dominant white/tan (A(Wt)) agouti sheep. The duplication 5' breakpoint is located upstream of the ASIP coding sequence. Ubiquitous expression of a second copy of the ASIP coding sequence regulated by a duplicated copy of the nearby ITCH promoter causes the white sheep phenotype. A single copy ASIP gene with a silenced ASIP promoter occurs in recessive black sheep. In contrast, a single copy functional wild-type (A(+)) ASIP is responsible for the ancient Barbary sheep coat color phenotype. The gene duplication was facilitated by homologous recombination between two non-LTR SINE sequences flanking the duplicated segment. This is the first sheep trait attributable to gene duplication and shows nonallelic homologous recombination and gene conversion events at the ovine ASIP locus could have an important role in the evolution of sheep pigmentation.
ISSN:1088-9051
1549-5469
1549-5477
DOI:10.1101/gr.072090.107