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Equine trait mapping

from disease loci to the discovery of a major gene controlling vertebrate locomotion

Andersson, Lisa S. (2012). Equine trait mapping. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis Agriculturae Sueciae, 1652-6880 ; 2012:65
ISBN 978-91-576-7712-9
[Doctoral thesis]

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Assigning function to genes is essential for a better understanding of biological
systems. To date, approximately half of the genes in the vertebrate genome have known
function. Domestic animals are a rich source for trait mapping and in this thesis we
have mapped three distinct equine phenotypes. The result provides increased
knowledge regarding gene function and importantly, practical implications for horse
welfare. In paper I and IV, we confirm that Equine Multiple Congenital Ocular
Anomalies (MCOA) syndrome is inherited as an incompletely dominant trait (p=
2.2x10-16). By first identifying a 208 kb identity-by decent (IBD) region and
subsequently excluding polymorphic sites identified through Illumina sequencing, we
conclude that the gene PMEL causes these defects in horse. Our findings, together with
functional analyses recently published, support that the cause of MCOA syndrome is a
missense mutation (Arg625Cys) near the transmembrane region of PMEL that results
in altered biochemical properties. In paper II we show that variants in the MHC-II
region influence the susceptibility to equine Insect Bite Hypersensitivity with the same
marker risk allele identified in two distinct populations, OR 4.19 (p= 2.3x10-5) and 1.48
(p= 0.04) for Icelandic horses and Exmoor ponies respectively. In addition,
homozygosity across the MHC-II region confers a higher risk of developing disease,
OR= 2.67 (p= 1.3x10-3). Finally, in paper III we utilize the EquineSNP50 BeadChip to
identify the first Gait locus in horse. A highly significant SNP (EMP2= 2.0x10-4) was
identified to be consistent with a recessive mode of inheritance for the lateral gait pace
in Icelandic horses, and confirmed in an independent sample set (p= 2.4x10-14).
Illumina sequencing of an established IBD region identified a nonsense mutation in the
gene DMRT3. A clearly dichotomous distribution in a panel of gaited and non-gaited
breeds revealed that the DMRT3 mutation is permissive for a variety of alternate gaits.
The mutation also has a favorable effect in harness racing horses. Functional
characterization of the truncated protein demonstrated correct localization and an intact
DNA binding profile. mRNA expression in a small population of commissural neurons
from the spinal cord was confirmed in mutant and wild type horses. Further, a DMRT3
null mouse displayed a change in spinal cord circuit signaling and locomotion. These
findings reveal a new molecule involved in the regulation of limb movement.

Authors/Creators:Andersson, Lisa S.
Title:Equine trait mapping
Subtitle:from disease loci to the discovery of a major gene controlling vertebrate locomotion
Series Name/Journal:Acta Universitatis Agriculturae Sueciae
Year of publishing :7 September 2012
Number of Pages:64
I.Andersson LS, Lyberg K, Cothran G, Ramsey DT, Juras R, Mikko S, Ekesten B, Ewart S, Lindgren G (2011). Targeted analysis of four breeds narrows equine Multiple Congenital Ocular Anomalies locus to 208 kilobases. Mammalian genome 22 (5-6):353-360.
II.Andersson LS, Swinburne JE, Meadows JR, Brostrom H, Eriksson S, Fikse WF, Frey R, Sundquist M, Tseng CT, Mikko S, Lindgren G (2011). The same ELA class II risk factors confer equine insect bite hypersensitivity in two distinct populations. Immunogenetics 64(3), 201- 208.
III.Andersson LS, Larhammar M, Memic F, Wootz H, Schwochow D, Rubin CJ, Patra K, Arnason T, Wellbring L, Hjälm G, Imsland F, Petersen JL, McCue ME, Mickelson JR, Cothran G, Ahituv N, Roepstorff L, Mikko S, Vallstedt A, Lindgren G, Andersson L, Kullander K (2012). Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice. Accepted in Nature.
IV.Lisa S Andersson, Maria Wilbe, Agnese Viluma, Gus Cothran, Björn Ekesten, Susan Ewart, Gabriella Lindgren. Next Generation Sequencing Establishes Equine Multiple Congenital Ocular Anomalies (MCOA) is Caused by Mutant PMEL (manuscript).
Place of Publication:Uppsala
Publisher:Dept. of Animal Breeding and Genetics, Swedish University of Agricultural Sciences
ISBN for printed version:978-91-576-7712-9
Publication Type:Doctoral thesis
Full Text Status:Public
Agris subject categories.:L Animal production > L10 Animal genetics and breeding
L Animal production > L73 Animal diseases
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Genetics (medical genetics to be 30107 and agricultural genetics to be 40402)
(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Medical Bioscience
Agrovoc terms:horses, breeds (animals), animal diseases, hypersensitivity, locomotion, animal performance, genetic inheritance, genetic maps, quantitative trait loci, genes
Keywords:horse, association mapping, GWA, MCOA, IBH, Insect bite hypersensitivity, Multiple congenital ocular anomalies, pace, locomotion, athletic performance
Permanent URL:
ID Code:9031
Department:(VH) > Dept. of Animal Breeding and Genetics
External funders:FORMAS and Stiftelsen Hästforskning
Deposited By: Lisa S Andersson
Deposited On:07 Sep 2012 12:05
Metadata Last Modified:02 Dec 2014 10:51

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