ABSTRACT
Polymelia, the manifestation of extra limbs or parts of limbs, occurs when there is
a developmental duplication in the novel NHL repeat domain containing protein (NHLRC2) gene in Angus cattle. In Holstein cattle, little is known about the etiology of
polymelia. To determine the genetic etiology of polymelia in a Holstein calf, genotyping
and sequencing of the Angus developmental duplication locus, karyotyping, and a genome-wide
association analysis were performed. The genome-wide association analysis compared
the polymelia calf (case) to 2,650 control (normal) Holstein calves using EMMAX-GRM
(Efficient Mixed-Model Association eXpedited-Genomic Relationship Matrix) software.
In addition, homozygous loci within genes in the case that were never found in a control
were also evaluated as putative loci. The polymelia calf had a normal Angus developmental
duplication genotype that was confirmed by sequencing. Karyotyping revealed no evidence
of chromosomal breakage or gross chromosomal abnormalities in the polymelia calf.
The additive genome-wide association analysis identified loci associated with polymelia
on BTA13 (P < 1 × 10−281) and BTA10 (P < 2 × 10−110). Seventy-nine candidate genes were identified that contained homozygous genotypes
in the case that were never identified in 2,650 controls. Candidate genes include
MSH homeobox 2 (MSX2) on BTA20, which has been associated with limb development in mice, and GINS complex
subunit 1 (GINS1) on BTA13, which is involved in early embryogenesis in mice. In summary, these results
suggest that the etiology of polymelia differs by cattle breed and is the result of
genetic variants at more than one locus.
Key words
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Article info
Publication history
Accepted:
January 31,
2017
Received:
November 17,
2016
Identification
Copyright
Copyright © 2017, American Registry of Professional Animal Scientists. All rights reserved.
