Developmental duplications

Phene ID

4022

Name

Developmental duplications

Phene Name

N/A

OMIA ID

2103

Species ID

9913

Characterised

Yes

Characterised Year

2014

Much useful information on this disorder, including a video, is available from http://www.angus.org/pub/DD/DDInfo.aspx

A GWAS conducted by Prof. Beever showed clear evidence of a recessive mutation in a single autosomal gene. However, the likely causal variant shows incomplete penetrance and variable expressivity: not all homozygotes for the likely causal variant show signs of polymelia (at least externally) or any other NTD-related lesion, and the extent and location of supernumerary limbs varies considerably. In effect, this evidence points to DD being a polygenic/multifactorial developmental disorder with one (known) gene of large effect contributing to the phenotypic variation. (Text provided jointly by FN and Laurence Denholm)

Starting with a GWAS on genetically related polymelia affected and normal Angus calves under an assumption of recessive inheritance, Prof. Beever identified a likely causal mutation for this disorder in August 2013. The mutation was disclosed by Beever et al. (2014): a "non-synonymous substitution was identified within exon 5 of the bovine NHL repeat containing 2 (NHLRC2) gene causing a valine to alanine substitution at residue 311 (V311A) of the encoded protein. Comparative analysis using the protein sequence from diverse taxa indicates the amino acid valine is invariable among the 53 species with sequence available.” (Text provided jointly by FN and Laurence Denholm)

A DNA test for the causal allele is available from the Animal Genetics Laboratory in the School of Veterinary Science at the University of Queensland; from Neogen Corporation (GeneSeek), Lincoln, Nebraska; and from Zoetis Inc. (Text provided jointly by FN and Laurence Denholm)