Chromosomal imbalance in pigs showing a syndromic form of cleft palate

Alexander Grahofer,Irene Monika Häfliger,Vidhya Jagannathan,Olivia Richard,Heiko Nathues,Anna Letko,Alain Ducos,Cord Drögemüller,Vanessa Peter

doi:10.1186/s12864-019-5711-4

Abstract

BackgroundPalatoschisis or cleft palate is a known anomaly in pigs resulting in their death. However, little is known about its aetiology. A detailed description of the phenotype was derived from necropsy and by computed tomography revealing that all 20 cases also exhibited hypodontia and renal cysts. Furthermore, a genetic origin was assumed due to dominant inheritance as all 20 recorded cases were confirmed offspring of a single boar.ResultsSingle nucleotide variant (SNV) genotyping data were used to map the defect in the porcine genome and led to the detection of a chromosomal imbalance in the affected offspring. Whole genome sequencing of an affected piglet and a normal full sib was used to identify a chromosomal translocation and to fine map the breakpoints in the genome. Finally, we proved that the boar, which sired the malformed piglets, carried a balanced translocation. The detected translocation of Mb-sized segments of chromosome 8 and 14 had not been previously observed during karyotyping. All affected offspring were shown to be carriers of a partial trisomy of chromosome 14 including the FGFR2 gene, which is associated with various dominant inherited craniofacial dysostosis syndromes in man, and partial monosomy of chromosome 8 containing MSX1 known to be associated with tooth agenesis and orofacial clefts in other species.ConclusionsThis study illustrates the usefulness of recently established genomic resources in pigs. In this study, the application of genome-wide genotyping and sequencing methods allowed the identification of the responsible boar and the genetic cause of the observed defect. By implementing systematic surveillance, it is possible to identify genetic defects at an early stage and avoid further distribution of congenital disorders.

Highlights

Palatoschisis or cleft palate is a known anomaly in pigs resulting in their death
This study reports detailed phenotypic and molecular investigations, which were performed in order to identify a reciprocal translocation in the sire as the most likely genetic cause for the observed malformations noticed in some of the offspring
According to good ethical and welfare standards, all 12 affected piglets were euthanized by intravenous injection of an overdose of sodium pentobarbital once blood samples had been obtained for further genetic investigations

Summary

Introduction

Palatoschisis or cleft palate is a known anomaly in pigs resulting in their death. Unilateral and bilateral palatoschisis or cleft palate is a well-known congenital anomaly of craniofacial development in several animal species including pigs (OMIA 000197–9823) due to a failure of fusion of the maxillary and medial nasal prominences or between the palatal processes [1,2,3,4]. Little is known about its aetiology, environmental and genetic factors have been considered [1, 8,9,10]. A known environmental factor, which could induce palatoschisis in piglets, is feeding the sow Conium maculatum seed or plant from gestation day 30 to 45 [11]. Palatoschisis in a piglet was reported after infecting a sow with Classical Swine Fever Virus during gestation [10]

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