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

• DOI: 10.1371/journal.pone.0140749
• Publication Date: 2015-10-16T14:16:09Z
• Authors: Mirjam Frischknecht; Vidhya Jagannathan; Philippe Plattet; Markus Neuditschko; Heidi Signer-Hasler; Iris Bachmann; Alicja Pacholewska; Cord Drögemüller; Elisabeth Dietschi; Christine Flury; Stefan Rieder; Tosso Leeb
• Keywords: Withers; Shetland; Genome-wide Association Study

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