A Non-Synonymous HMGA2 Variant Decreases Height in Shetland Ponies and Other Small Horses

Frischknecht, Mirjam; Jagannathan, Vidhya; Plattet, Philippe; Neuditschko, Markus; Signer-Hasler, Heidi; Bachmann, Iris; Pacholewska, Alicja Elzbieta; Drögemüller, Cord; Dietschi, Elisabeth; Flury, Christine; Rieder, Stefan; Leeb, Tosso (2015). A Non-Synonymous HMGA2 Variant Decreases Height in Shetland Ponies and Other Small Horses. PLoS ONE, 10(10), e0140749. Public Library of Science 10.1371/journal.pone.0140749

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The identification of quantitative trait loci (QTL) such as height and their underlying causative variants is still challenging and often requires large sample sizes. In humans hundreds of loci with small effects control the heritable portion of height variability. In domestic animals, typically only a few loci with comparatively large effects explain a major fraction of the heritability. We investigated height at withers in Shetland ponies and mapped a QTL to ECA 6 by genome-wide association (GWAS) using a small cohort of only 48 animals and the Illumina equine SNP70 BeadChip. Fine-mapping revealed a shared haplotype block of 793 kb in small Shetland ponies. The HMGA2 gene, known to be associated with height in horses and many other species, was located in the associated haplotype. After closing a gap in the equine reference genome we identified a non-synonymous variant in the first exon of HMGA2 in small Shetland ponies. The variant was predicted to affect the functionally important first AT-hook DNA binding domain of the HMGA2 protein (c.83G>A; p.G28E). We assessed the functional impact and found impaired DNA binding of a peptide with the mutant sequence in an electrophoretic mobility shift assay. This suggests that the HMGA2 variant also affects DNA binding in vivo and thus leads to reduced growth and a smaller stature in Shetland ponies. The identified HMGA2 variant also segregates in several other pony breeds but was not found in regular-sized horse breeds. We therefore conclude that we identified a quantitative trait nucleotide for height in horses.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) > Equine Clinic
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV)
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Experimental Clinical Research
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)

UniBE Contributor:

Frischknecht, Mirjam; Jagannathan, Vidya; Plattet, Philippe; Pacholewska, Alicja Elzbieta; Drögemüller, Cord; Dietschi, Elisabeth and Leeb, Tosso

Subjects:

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

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Tosso Leeb

Date Deposited:

04 Nov 2015 08:56

Last Modified:

22 Oct 2016 00:25

Publisher DOI:

10.1371/journal.pone.0140749

PubMed ID:

26474182

BORIS DOI:

10.7892/boris.72460

URI:

https://boris.unibe.ch/id/eprint/72460

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