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PLoS One. 2017 Jun 28;12(6):e0180170. doi: 10.1371/journal.pone.0180170. eCollection 2017.

A structural variant in the 5'-flanking region of the TWIST2 gene affects melanocyte development in belted cattle.

Author information

1
Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
2
DermFocus, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
3
Swiss Competence Center of Animal Breeding and Genetics, University of Bern, Bern University of Applied Sciences HAFL & Agroscope, Bern, Switzerland.
4
Department of Clinical Research, University of Bern, Bern, Switzerland.
5
Swiss Institute of Bioinformatics, Bern, Switzerland.
6
Interfaculty Bioinformatics Unit, University of Bern, Bern, Switzerland.
7
Chronix Biomedical, Göttingen, Germany.
8
Institute of Veterinary Medicine, University of Goettingen, Göttingen, Germany.
9
Bern University of Applied Sciences, School of Agricultural, Forest and Food Sciences, Zollikofen, Switzerland.
10
Clinic for Reproductive Medicine, University of Zurich, Zurich, Switzerland.
11
Institute of Anatomy, University of Bern, Bern, Switzerland.
12
Dutch Belted Cattle Association, EM Eefde, The Netherlands.
13
Agroscope, Swiss National Stud Farm, Avenches, Switzerland.
14
Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, United Kingdom.

Abstract

Belted cattle have a circular belt of unpigmented hair and skin around their midsection. The belt is inherited as a monogenic autosomal dominant trait. We mapped the causative variant to a 37 kb segment on bovine chromosome 3. Whole genome sequence data of 2 belted and 130 control cattle yielded only one private genetic variant in the critical interval in the two belted animals. The belt-associated variant was a copy number variant (CNV) involving the quadruplication of a 6 kb non-coding sequence located approximately 16 kb upstream of the TWIST2 gene. Increased copy numbers at this CNV were strongly associated with the belt phenotype in a cohort of 333 cases and 1322 controls. We hypothesized that the CNV causes aberrant expression of TWIST2 during neural crest development, which might negatively affect melanoblasts. Functional studies showed that ectopic expression of bovine TWIST2 in neural crest in transgenic zebrafish led to a decrease in melanocyte numbers. Our results thus implicate an unsuspected involvement of TWIST2 in regulating pigmentation and reveal a non-coding CNV underlying a captivating Mendelian character.

PMID:
28658273
PMCID:
PMC5489250
DOI:
10.1371/journal.pone.0180170
[Indexed for MEDLINE]
Free PMC Article

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