Abstract

Two FGF4 retrogenes (FGF4L1 on chromosome 18 and FGF4L2 on chromosome 12) have been identified to cause dwarfism across many dog breeds. Some breeds are nearly homozygous for both retrogenes (e.g., Dachshunds) and others are homozygous for just one (e.g., Beagles and Scottish Terriers). Since most breeds do not segregate both of these retrogenes, it is challenging to evaluate their individual effects on long bone length and body size. We identified two dog breeds selected for hunting ability, the Alpine Dachsbracke and the Schweizer Niederlaufhund, that segregate both of these retrogenes. Using individual measurements of height at the shoulder, back length, head width, thorax depth and width, and thoracic limb measurements, we evaluated the combined effects of FGF4 retrogenes within these breeds. We applied multivariable linear regression analysis to determine the effects of retrogene copy numbers on the measurements. Copy numbers of both retrogenes had significant effects reducing height at the shoulders and antebrachial length, with FGF4L1 having a much greater effect than FGF4L2. FGF4L1 alone influenced the degree of carpal valgus and FGF4L2 alone increased head width. Neither retrogene had an effect on thorax width or depth. Selectively breeding dogs with FGF4L1 and without FGF4L2 would likely lead to a reduction in the FGF4L2-related risk of intervertebral disc herniation while maintaining the reduction in leg length resulting from FGF4L1.

Highlights

  • Introduction published maps and institutional affilDog breeds come in a wide variety of shapes and sizes

  • Two breeds of dogs which segregated different copy numbers of FGF4 retrogenes were chosen to study the effects of the retrogenes on morphology

  • Based on comparing the mean height of each genotype class, there was an additive effect of copy number for each retrogene and between FGF4L1 and FGF4 retrogene is located on chromosome 12 (FGF4L2) on reducing height at the shoulder

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Summary

Introduction

Dog breeds come in a wide variety of shapes and sizes. Dwarfism or skeletal dysplasia characterizes many dog breeds and was selected to slow the speed of hunting dogs, allow entry into small burrows to pursue game and to reduce overall size for companion dogs (www.fci.be and www.akc.org (accessed on 25 January 2021)). Two different FGF4 retrogenes have been associated with dwarfism across dog breeds [1,2]. The most common form of human dwarfism is caused by reoccurring activating mutations in the FGFR3 gene, which is one of the receptors for FGF4 [3]. Retrogenes are functional, active intronless copies of the parent gene that integrate into chromosomal DNA through the action of endogenous LINE 1 retrotransposons [4]. The exact mechanism linking FGF4 retrogene expression and skeletal dysplasia is not defined; limited data are available relating to temporal and spatial expression of FGF4 retrogenes and FGF4 protein overexpression acting through FGFR3 is an intriguing comparative model, FGF ligands are iations

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