Dataset Information

Interdigital Hyperplasia in Holstein Cattle Is Associated With a Missense Mutation in the Signal Peptide Region of the Tyrosine-Protein Kinase Transmembrane Receptor Gene.

ABSTRACT: Bovine interdigital hyperplasia (IH) is a typical disease of the foot with varying prevalence depending on age, breed, and environmental factors resulting in different degrees of lameness. In studies based on assessments of claw health status at time of hoof trimming and applying genetic-statistical models to analyze this data, IH consistently exhibits high estimates of heritability in the range of 0.30-0.40. Although some studies have identified chromosomal regions that could possibly harbor causative genes, a clear identification of molecular causes for IH is lacking. While analyzing the large database of claw health status as documented at time of hoof trimming, we identified one herd with extreme prevalence of IH of > 50% of affected Holstein dairy cows. This herd subsequently was chosen as the object of a detailed study. A total of n = 91 cows was assessed and revealed a prevalence of 59.3% and 38.5% for IH cases, documented as "one-sided" or "two-sided", respectively. Cows were genotyped using the BovineSNP50 BeadChip. A genome wide association study revealed two significantly associated chromosomal positions (-log10P = 5.57) on bovine chromosome 8 (BTA8) located in intron 5 and downstream of the receptor tyrosine kinase-like orphan receptor 2 (ROR2) gene. As ROR2 plays a key role in ossification of the distal limbs and is associated with brachydactylies in humans, it was a reasonable candidate for IH. A comparative sequencing of the ROR2 gene between cases and controls revealed two missense variants in exon 1 (NC_037335.1:g.85,905,534T > A, ARS-UCD1.2) and exon 9 (NC_037335.1:g.86,140,379A > G, ARS-UCD1.2), respectively. Genotyping of both variants in the cohort of 91 cattle showed that the exon 1 variant (rs377953295) remained significantly associated with IH (p < 0.0001) as a risk factor of the disease. This variant resulted in an amino acid exchange (ENSBTAP00000053765.2:p.Trp9Arg) in the N-terminal region of the ROR2 signal peptide which is necessary for proper topology of the polypeptide during translocation. Quantification of ROR2 mRNA and ROR2 protein showed that the variant resulted in a significant suppression of ROR2 expression in homozygous affected compared to wild type and carrier cows.

SUBMITTER: Zhang X

PROVIDER: S-EPMC6863962 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Interdigital Hyperplasia in Holstein Cattle Is Associated With a Missense Mutation in the Signal Peptide Region of the Tyrosine-Protein Kinase Transmembrane Receptor Gene.

Zhang Xuying X Swalve Hermann H HH Pijl René R Rosner Frank F Wensch-Dorendorf Monika M Brenig Bertram B

Frontiers in genetics 20191113

Bovine interdigital hyperplasia (IH) is a typical disease of the foot with varying prevalence depending on age, breed, and environmental factors resulting in different degrees of lameness. In studies based on assessments of claw health status at time of hoof trimming and applying genetic-statistical models to analyze this data, IH consistently exhibits high estimates of heritability in the range of 0.30-0.40. Although some studies have identified chromosomal regions that could possibly harbor ca ...[more]

PMID: 31798639

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Project description:BackgroundSurveillance for bovine genetic diseases in Denmark identified a hitherto unreported congenital syndrome occurring among progeny of a Holstein sire used for artificial breeding. A genetic aetiology due to a dominant inheritance with incomplete penetrance or a mosaic germline mutation was suspected as all recorded cases were progeny of the same sire. Detailed investigations were performed to characterize the syndrome and to reveal its cause.ResultsSeven malformed calves were submitted examination. All cases shared a common morphology with the most striking lesions being severe facial dysplasia and complete prolapse of the eyes. Consequently the syndrome was named facial dysplasia syndrome (FDS). Furthermore, extensive brain malformations, including microencephaly, hydrocephalus, lobation of the cerebral hemispheres and compression of the brain were present. Subsequent data analysis of progeny of the sire revealed that around 0.5% of his offspring suffered from FDS. High density single nucleotide polymorphism (SNP) genotyping data of the seven cases and their parents were used to map the defect in the bovine genome. Significant genetic linkage was obtained for three regions, including chromosome 26 where whole genome sequencing of a case-parent trio revealed two de novo variants perfectly associated with the disease: an intronic SNP in the DMBT1 gene and a single non-synonymous variant in the FGFR2 gene. This FGFR2 missense variant (c.927G>T) affects a gene encoding a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and across species. It is predicted to change an evolutionary conserved tryptophan into a cysteine residue (p.Trp309Cys). Both variant alleles were proven to result from de novo mutation events in the germline of the sire.ConclusionsFDS is a novel genetic disorder of Holstein cattle. Mutations in the human FGFR2 gene are associated with various dominant inherited craniofacial dysostosis syndromes. Given the phenotypic similarities in FDS affected calves, the genetic mapping and absence of further high impact variants in the critical genome regions, it is highly likely that the missense mutation in the FGFR2 gene caused the FDS phenotype in a dominant mode of inheritance.

Project description:Although transport and slaughter of cattle during the last 10% of the gestation period is prohibited in the European Union, such cattle are sometimes sent for slaughter. The late term pregnancy is usually not recognized by the authorities until the uterus is inspected after slaughter and a near term fetus is observed. Accurate post mortem determination of age of bovine fetuses is therefore of major importance as evidence for the subsequent prosecution of the owner. Fetometric measurements such as crown-rump length (CRL) have been used, but these existing estimators have often been established based on insufficiently described study populations or phenotypes that may have changed in the past decades. Morphological characteristics are also used, but few data are available on the correlation between fetal age and the development of these characteristics. The objectives of this study were to investigate the correlation between fetal age and morphological features of bovine Holstein fetuses and to evaluate the use of these features alone and in combination with fetometric measurements to predict fetal age. We collected fetuses from 274 pregnant Holstein cows with recorded insemination dates slaughtered at a Danish abattoir. Gender, teeth development, occurrence of pigmentation, coat, tactile hair and other morphological features were recorded along with CRL, head width, head length and body weight (BW). The gestational length was calculated based on recorded insemination and slaughter dates, and coefficients of variation (R2) were determined for all recorded variables. Notably, the highest R2 was recorded for head length (0.985) followed by CRL (0.979) and head width (0.974). The categorical (morphological) variables were less informative. When used in multivariable models, they did offer statistically significance, but for practical purposes, limited additional information. A multivariable model including the fetometric variables head length and width in combination with CRL resulted in R2 = 0.99 with predictions that were roughly within +/- 11-12 days in 95% of cases. We conclude that the model based on the fetometric variables only provided the most precise predictions, while combination with morphological features such as eruption of teeth, pigmentation and coat mostly increased the width of the prediction intervals.

Project description:Holstein cattle are well known for their high average milk yield but are more susceptible to disease and have lower fecundity than other breeds of cattle. The purpose of this study was to explore the relationship between ruminal metabolites and both milk performance and ruminal microbiota composition as a means of assessing the benefits of crossbreeding Montbéliarde and Holstein cattle. This experiment crossbred Holstein with Montbéliarde cattle, aimed to act as a reference for producing high-quality dairy products and improving the overall efficiency of dairy cattle breeding. Based on similar age, parity and lactation time, 46 cows were selected and divided into two groups (n = 23 per group) for comparison experiment and fed the same formula: Montbéliarde×Holstein (MH, DIM = 33.23 ± 5.61 d), Holstein (H, DIM = 29.27 ± 4.23 d). Dairy herd improvement (DHI) data is an important basis for evaluating the genetic quality of bulls, understanding the quality level of milk, and improving feeding management. We collected the DHI data of these cows in the early lactation, middle lactation and late lactation period of 10 months. The results showed that the average milk production and protein content in Montbéliarde×Holstein were 1.76 kg (34.41 kg to 32.65 kg, p > 0.05) and 0.1% (3.54 to 3.44%, p < 0.05) higher than in Holstein cattle. Moreover, milk from Montbéliarde×Holstein cattle had lesser somatic cell score (1.66 to 2.02) than Holstein cattle (p < 0.01). A total of 10 experimental cattle in early lactation were randomly selected in the two groups (Lactation time = 92.70 ± 6.81), and ruminal fluid were collected by oral gastric tube. Using 16S rRNA microbial sequencing, we compared the ruminal microbiota composition and found that Montbéliarde×Holstein cattle had a lower abundance of Alphaproteobacteria (p < 0.05) and higher abundance of Selenomonas than Holstein cattle (p < 0.05). These bacteria play roles in protein degradation, nitrogen fixation and lactic acid degradation. The abundance of Succiniclasticum was also greater in Montbéliarde×Holstein cattle (p = 0.053). Through ruminal metabolome analysis, we found that the levels of trans-ferulic acid, pyrrole-2-carboxylic acid, and quinaldic acid were significantly increased in Montbéliarde×Holstein cattle, while that of lathosterol was significantly decreased. The changes in the levels of these metabolites could confer improved antioxidant, anti-inflammatory, and antibacterial activities.

Dataset Information

Interdigital Hyperplasia in Holstein Cattle Is Associated With a Missense Mutation in the Signal Peptide Region of the Tyrosine-Protein Kinase Transmembrane Receptor Gene.

Publications

Interdigital Hyperplasia in Holstein Cattle Is Associated With a Missense Mutation in the Signal Peptide Region of the Tyrosine-Protein Kinase Transmembrane Receptor Gene.

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