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

Awasthi, Nivedita; Drögemüller, Cord; Jagannathan, Vidhya; Keller, Irene; Wüthrich, Daniel; Bruggmann, Rémy; Beck, Julia; Schütz, Ekkehard; Brenig, Bertram; Demmel, Steffi; Moser, Simon; Signer-Hasler, Heidi; Pieńkowska-Schelling, Aldona; Schelling, Claude; Sande Melon, Marcos; Rongen, Ronald; Rieder, Stefan; Kelsh, Robert N.; Mercader Huber, Nadia and Leeb, Tosso (2017). A structural variant in the 5’-flanking region of the TWIST2 gene affects melanocyte development in belted cattle. PLoS ONE, 12(6), e0180170. Public Library of Science 10.1371/journal.pone.0180170

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > DermFocus
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Services > Central Animal Facility
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)
08 Faculty of Science > Department of Biology > Bioinformatics

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Awasthi, Nivedita; Drögemüller, Cord; Jagannathan, Vidya; Keller, Irene; Wüthrich, Daniel; Bruggmann, Rémy; Demmel, Steffi; Pieńkowska-Schelling, Aldona; Sande Melon, Marcos; Mercader Huber, Nadia and Leeb, Tosso

Subjects:

500 Science > 590 Animals (Zoology)
600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Nadia Isabel Mercader Huber

Date Deposited:

10 Aug 2017 09:13

Last Modified:

10 Aug 2017 09:13

Publisher DOI:

10.1371/journal.pone.0180170

PubMed ID:

28658273

BORIS DOI:

10.7892/boris.101727

URI:

https://boris.unibe.ch/id/eprint/101727

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