Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0020438 (
hypercalciuria
)
2,502
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Background:
Neuromusculoskeletal anomalies generally in combination with severe clinical symptoms, comprise a heterogeneous group of fairly common and mostly fatal disorders in man and animals. Osteogenesis imperfecta (OI), also known as brittle bone disease, causes bone fragility and deformity. Prominent extra-skeletal accessory manifestations of OI comprise blue/gray sclerae, hearing impairment, lung abnormalities and
hypercalciuria
. Cases of OI in cattle have been reported. However, no causative mutations have been identified in cattle so far.
Aim:
To report a possible oligogenic origin identified in a calf from clinically healthy parents suffering from OI.
Materials and Methods:
A neonatal embryo transfer male Holstein calf developing multiple fractures with bone tissue showing marked osteopenia was used for whole genome re-sequencing as well as its parents. In addition, 2,612 randomly chosen healthy Holstein cattle were genotyped as well as controls.
Results:
Sixteen candidate genes with potential protein-altering variants were selected revealing non-synonymous variants only within
IFITM5
and
CRTAP
genes. However, in-depth gene analysis did not result in the identification of a single causative mutation in the OI calf.
Conclusion:
The analysis of the OI case revealed a possible oligogenic origin of the disease attributable to additive effects of three candidate genes, i.e.,
ABCA13
,
QRFPR
, and
IFTIM5
.
Clinical relevance:
Most OI cases in humans and domestic animals reported so far are caused by distinct dominant or recessive monogenic mutations, therefore a potential oligogenic additive genetic effect is a novel finding. Furthermore, the case presented here demonstrates that cross-species genetic analyses might not always be straightforward.
...
PMID:Osteogenesis imperfecta in a male holstein calf associated with a possible oligogenic origin. 3198 12
