Aristaless-Like Homeobox protein 1 (ALX1) variant associated with craniofacial structure and frontonasal dysplasia in Burmese cats

Dev Biol. 2016 Jan 15;409(2):451-8. doi: 10.1016/j.ydbio.2015.11.015. Epub 2015 Dec 2.

Abstract

Frontonasal dysplasia (FND) can have severe presentations that are medically and socially debilitating. Several genes are implicated in FND conditions, including Aristaless-Like Homeobox 1 (ALX1), which is associated with FND3. Breeds of cats are selected and bred for extremes in craniofacial morphologies. In particular, a lineage of Burmese cats with severe brachycephyla is extremely popular and is termed Contemporary Burmese. Genetic studies demonstrated that the brachycephyla of the Contemporary Burmese is a simple co-dominant trait, however, the homozygous cats have a severe craniofacial defect that is incompatible with life. The craniofacial defect of the Burmese was genetically analyzed over a 20 year period, using various genetic analysis techniques. Family-based linkage analysis localized the trait to cat chromosome B4. Genome-wide association studies and other genetic analyses of SNP data refined a critical region. Sequence analysis identified a 12bp in frame deletion in ALX1, c.496delCTCTCAGGACTG, which is 100% concordant with the craniofacial defect and not found in cats not related to the Contemporary Burmese.

Keywords: CART1; Cartilage homeo protein 1; Domestic cat; FND; Facial development; Felis silvestris catus; Frontonasal dysplasia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breeding
  • Cats
  • Craniofacial Abnormalities / genetics*
  • Face / abnormalities*
  • Genetic Association Studies*
  • Genetic Linkage
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotyping Techniques
  • Homeodomain Proteins / genetics*
  • Polymorphism, Single Nucleotide / genetics*

Substances

  • Homeodomain Proteins

Supplementary concepts

  • Frontonasal dysplasia