Hydrops associated with chondrodysplasia of the fetus in a miniature Scottish Highland cow

Cabrera, Lissette; McNabb, Bret R.; Woods, S E; Cartoceti, Andrew N.; R, Busch

doi:10.2460/javma.248.5.552

Cited by 6 publications

(7 citation statements)

References 11 publications

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“…Heterozygous dominant mutations of COL2A1 associated with bulldog calves have been identified in progeny of a French [ 7 ] and a Danish Holstein bull [ 6 ]. The gross, microscopic and CT findings were highly similar with these previous cases in Holsteins [ 3 , 6 , 7 ] as well as in Dexter [ 1 ] and miniature Highland cattle [ 2 ]. The lesions found in bulldog calves are consistent with the signs of a generalized chondrodysplasia [ 1 – 7 ].…”

Section: Discussionsupporting

confidence: 83%

“…In Dexter cattle the disease is associated with two mutations (BD-1 and BD-2) in the aggrecan gene (OMIA 001271–9913, dwarfism, aggrecan type in Bos taurus (cattle), gene: ACAN, http://omia.angis.org.au /) [ 1 ]. In miniature Highland cattle, a case of chondrodystrophic dwarfism with hydrocephalus due to the BD-1 mutation in ACAN was demonstrated [ 2 ]. In several cattle breeds from Europe and USA, “bulldog calf” phenotypes have been reported [ 2 – 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…In miniature Highland cattle, a case of chondrodystrophic dwarfism with hydrocephalus due to the BD-1 mutation in ACAN was demonstrated [ 2 ]. In several cattle breeds from Europe and USA, “bulldog calf” phenotypes have been reported [ 2 – 6 ]. These cases are characterized by a disproportionate dwarfism showing severely shortened limbs, a short and compressed body, facial dysplasia and additional malformations (OMIA 001926–9913 achondrogenesis, type II in Bos taurus (cattle), gene: COL2A1 , http://omia.angis.org.au /).…”

Section: Introductionmentioning

confidence: 99%

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Germline mutation within COL2A1 associated with lethal chondrodysplasia in a polled Holstein family

Reinartz

Mohwinkel²,

Sürie³

et al. 2017

BMC Genomics

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BackgroundThe bulldog calf syndrome is a lethal form of the inherited congenital chondrodysplasias. Among the progeny of the polled Holstein bull Energy P cases of lethal chondrodysplasia were observed. Pedigrees of the cases and the frequency of 3/8 cases among the offspring of Energy P at our teaching and experimental farm Ruthe (LuFG Ruthe) supported the assumption of a germline mutation with a mosaic of normal and defective sperm.ResultsAll three malformed calves were examined using necropsy, histopathology and computed tomography scanning. The phenotypic appearance of the affected calves was highly similar; they presented with severe disproportionate dwarfism and reduced body weight. The syndrome was characterized by brachygnathia superior, bilateral palatoschisis, shortening and compression of the body due to malformed vertebrae, in their size reduced and malformed ribs and reduced length of the long bones of the limbs. The bones had small irregular diaphyses and enlarged epiphyses. Whole genome sequencing of one bulldog calf, sperm of its sire Energy P and a normal progeny of Energy P identified a deleterious missense mutation (g.32476082G > A, c.2986G > A, ss2019324576) within COL2A1 on bovine chromosome (BTA) 5. Sanger sequencing confirmed the ss2019324576 variant in the affected calves and sperm of Energy P. This mutation is located within the collagen triple helix repeat and causes an exchange of glycine to serine (p.996G > S) in COL2A1. This private single nucleotide variant (SNV) was present as a gonadal mosaic in sperm of the bull. All affected calves were in a heterozygous state whereas normal half-siblings and all dams of the progeny from Energy P were missing this SNV. Validation in polled Holstein bulls and normal Holstein calves randomly sampled from several herds and from the LuFG Ruthe confirmed this SNV as private.ConclusionsThe identified spontaneous missense mutation within COL2A1 is most likely the cause of lethal chondrodysplasia in the progeny of Energy P through a dominant negative effect. This example suggests that it would be beneficial to conduct whole genome sequencing of sperm from bulls widely used in artificial insemination in order to detect germline mosaicism.Electronic supplementary materialThe online version of this article (10.1186/s12864-017-4153-0) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Germline mutation within COL2A1 associated with lethal chondrodysplasia in a polled Holstein family

Reinartz

Mohwinkel²,

Sürie³

et al. 2017

BMC Genomics

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“…The head shows a shortened nose, cleft palate and a protruding tongue [ 7 , 8 ]. This anomaly has been observed in several cattle breeds including Dexter [ 1 , 3 ], Holstein Friesian [ 9 – 12 ], Miniature Scottish Highland [ 8 , 13 , 14 ], Miniature Belted Galloway [ 8 ], Nellore [ 15 ], Charolais x Salers crosses [ 10 ] and in Nganda cattle, a small Zebu crossbred [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

“…An insertion in exon 11 (BD1) and a second variant in exon 1 (BD2) were identified in bulldog affected Dexter calves [ 17 ]. The BD1 mutation was also found in bulldog phenotypes of Miniature Scottish Highland and Miniature Belted Galloway [ 8 , 13 ]. In these breeds potentially derived from intermixes with Dexter cattle, the mode of inheritance was also suggested to be incomplete dominant [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

A recessive lethal chondrodysplasia in a miniature zebu family results from an insertion affecting the chondroitin sulfat domain of aggrecan

et al. 2018

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BackgroundCongenital skeletal malformations represent a heterogeneous group of disorders affecting bone and cartilage development. In cattle, particular chondrodysplastic forms have been identified in several miniature breeds. In this study, a phenotypic characterization was performed of an affected Miniature Zebu calf using computed tomography, necropsy and histopathological examinations, whole genome sequencing of the case and its parents on an Illumina NextSeq 500 in 2 × 150 bp paired-end mode and validation using Sanger sequencing and a Kompetitive Allele Specific PCR assay. Samples from the family of an affected Miniature Zebu with bulldog syndrome including parents and siblings, 42 healthy Miniature Zebu not related with members of the herd and 88 individuals from eight different taurine cattle breeds were available for validation.ResultsA bulldog-like Miniature Zebu calf showing a large bulging head, a short and compressed body and extremely short and stocky limbs was delivered after a fetotomy. Computed tomography and necropsy revealed severe craniofacial abnormalities including a shortening of the ventral nasal conchae, a cleft hard palate, rotated limbs as well as malformed and fused vertebrae and ribs. Histopathologic examination showed a disorganization of the physeal cartilage with disorderly arranged chondrocytes in columns and a multifocal closed epiphyseal plate. Whole-genome sequencing of this malformed Miniature Zebu calf, its dam and sire and subsequent comparative sequence analysis revealed a one base pair insertion (ACAN:c.5686insC) located within the cartilage development gene aggrecan (ACAN) exclusively homozygous in the affected calf and heterozygous in its parents. This variant was predicted to cause a frameshift (p.Val1898fsTer9) and thus a truncation of the chondroitin sulfate domain as well as a loss of the C-terminal globular domain of ACAN. It perfectly co-segregated with the lethal bulldog syndrome in Miniature Zebus.ConclusionsWe found a novel mutation in ACAN causing a recessive lethal chondrodysplasia in Miniature Zebu cattle. A diagnostic test for this mutation is now available for Miniature Zebu breeders preventing further cases of bulldog syndrome by targeted matings. To the authors’ best knowledge, this is the first case of a Miniature Zebu associated with an ACAN mutation.Electronic supplementary materialThe online version of this article (10.1186/s12863-018-0678-8) contains supplementary material, which is available to authorized users.

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dwarfism, chondrodystrophy, in cattle

2020

CABI Compendium

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Hydrops associated with chondrodysplasia of the fetus in a miniature Scottish Highland cow

Cited by 6 publications

References 11 publications

Germline mutation within COL2A1 associated with lethal chondrodysplasia in a polled Holstein family

Germline mutation within COL2A1 associated with lethal chondrodysplasia in a polled Holstein family

A recessive lethal chondrodysplasia in a miniature zebu family results from an insertion affecting the chondroitin sulfat domain of aggrecan

dwarfism, chondrodystrophy, in cattle

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