Estimation of Genetic Parameters for Chronic Progressive Lymphedema

The Estimation of Genetic Parameters for Chronic Progressive Lymphedema and Body Traits in the Rhenish German Draught Horse

Animals (Basel). 2024 Apr 18;14(8):1214. doi: 10.3390/ani14081214.
Authors
Johanna Sievers 1 , Ottmar Distl 1
Affiliation

1 Institute of Animal Breeding and Genetics, University of Veterinary Medicine Hannover (Foundation), 30559 Hannover, Germany.

PMID: 38672362
DOI: 10.3390/ani14081214

Abstract

Chronic progressive lymphedema (CPL) is a prevalent and progressive disease in Rhenish German draught horses. The objective of our follow-up study was to evaluate the heritability of this disease in Rhenish German draught horses using pedigree-based and genomic relationship matrices. We employed linear and threshold animal models. Models included the random animal effect and effects of breeding association, coat colour, sex, and age within sex, and farm-related factors, on CPL scores. In addition, we estimated heritabilities in models assuming censoring for data when horses were below an age of 1-15 years. The heritabilities of CPL scores across all ages were 0.595 ± 0.131 and 0.482 ± 0.105 in the threshold and linear animal model with pedigree-based relationship matrices, respectively. The restriction of data to horses with a minimum age at examination or accounting for censored data in younger animals showed an increase in heritabilities of CPL scores up to 0.788 ± 0.168 (threshold model) and 0.752 ± 0.153 (linear model) at an age of 7-8 years. Analyses including genomic relationship matrices yielded very similar estimates, but with smaller standard errors than pedigree-based analyses. Heritabilities in threshold models for CPL prevalence (CPL-bin-score) and the number of affected limbs (CPL-bin-sum) were 0.176-0.189 ± 0.061-0.064 and 0.375-0.433 ± 0.164-0.170, respectively. We were able to show moderately to highly positive genetic correlations between the CPL score and cannon bone circumference (0.529-0.825), height at withers (0.338-0.555), and skinfold thickness (0.241-0.517). Using the dichotomous trait for the CPL score and the genomic relationship matrix resulted in corresponding estimates of 0.868, 0.793, and 0.784, respectively. This study showed the great importance of additive genetic variation influencing the expression of chronic progressive lymphedema in Rhenish German draught horses. Therefore, further research is warranted to implement breeding programmes in a small breeding population that exploit the potential of additive genetic differences among animals for reducing the prevalence and severity of lesions of this incurable disease.

Keywords: animal model; censoring; genetic correlation; genomic relationship matrix; heritability; threshold model.

Simple Summary
Chronic progressive lymphedema is an incurable disease in draught horse breeds, particularly prevalent in breeds with genealogical relationships with Belgian draught horses. In this follow-up study, we analysed the heritabilities of this condition in Rhenish German draught horses and in addition, evaluated the genetic and phenotypic correlations with body size, skinfold thickness, and hoof characteristics. Furthermore, we studied heritabilities of chronic progressive lymphedema with models assuming censored data due to the progressive course of the disease. We found high heritabilities of chronic progressive lymphedema in the Rhenish German draught horses, even when we regarded all horses of any age. Over all age groups, the heritability of the score for chronic progressive lymphedema across all four limbs was 0.595 ± 0.131 in the threshold animal model based on pedigree data. Using a genomic relationship matrix yielded very similar estimates, but with slightly smaller standard errors. When assuming censored data for horses with an age below 7 and 8 years, heritabilities reached values of 0.774 ± 0.157 and 0.788 ± 0.168, respectively. Particularly, horses with higher cannon bone circumference, larger frames, and higher skinfold thickness appeared to be disposed to chronic progressive lymphedema. Horses with softer hoof horns seemed to be more susceptible to chronic progressive lymphedema than horses with harder hoof horns. This study showed that genetic disposition to chronic progressive lymphedema is the most important issue and therefore, breeding measures should be initiated to reduce the prevalence of severe cases of this incurable disease in Rhenish German draught horses.

Conclusions
The results of this study demonstrate high heritabilities with reasonable small standard errors for CPL scores using pedigree-based and genomic relationship matrices. Differentiation only between unaffected and affected horses revealed moderate heritabilities, suggesting that heritabilities increase with increasing severity of CPL lesions. The lower heritability for CPL prevalence may suggest that the genetic disposition for CPL is widespread in the Rhenish German population studied here and that the additive genetic differences between horse families are not as great as the differences in the severity of CPL lesions. We propose that breeding for lower CPL scores can exploit larger additive genetic differences among breeding animals. We recommend as a first step that a breeding programme should achieve a lower rate of CPL progression and thus contribute to less harmful lesions, particularly in older animals. A breeding programme aiming to reduce the prevalence in the shortest possible time may not be feasible due to the small population size and a very limited number of stallions being unaffected until more than 10 years of age. Further studies seem necessary for implementing an effective genomic breeding programme based on single-step BLUP approaches against CPL without negative effects on the genetic diversity in the Rhenish German population.