Evidence for a de novo, dominant germ-line mutation causative of osteogenesis imperfecta in two Red Angus calves

Mammalian Genome : Official Journal of the International Mammalian Genome Society
Jessica L PetersenDavid J Steffen

Abstract

A genetic disorder, osteogenesis imperfecta (OI) is broadly characterized by connective tissue abnormalities and bone fragility most commonly attributed to alterations in Type I collagen. Two Red Angus calves by the same sire presented with severe bone and dental fragility, blue sclera, and evidence of in utero fractures consistent with OI congenita. Comparative analyses with human cases suggested the OI in these calves most closely resembled that classified as OI Type II. Due to the phenotypic classification and shared paternity, a dominant, germ-line variant was hypothesized as causative although recessive genotypes were also considered due to a close relationship between the sire and dam of one calf. Whole-genome sequencing revealed the presence of a missense mutation in the alpha 1 chain of collagen Type I (COL1A1), for which both calves were heterozygous. The variant resulted in the substitution of a glycine residue with serine in the triple helical domain of the protein; in this region, glycine normally occupies every third position as is critical for correct formation of the Type I collagen molecule. Allele-specific amplification by droplet digital PCR further quantified the variant at a frequency of nearly 4.4% in the s...Continue Reading

References

Apr 1, 1979·Journal of Medical Genetics·D O SillenceD M Danks
Apr 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·J D TermineK G Thompson
Jan 1, 1995·Annual Review of Biochemistry·D J Prockop, K I Kivirikko
Mar 1, 1994·Zentralblatt für Veterinärmedizin. Reihe A·J S AgerholmJ Arnbjerg
Oct 1, 1961·Journal of Molecular Biology·A RICH, F H CRICK
Apr 28, 2004·Lancet·Frank Rauch, Francis H Glorieux
Dec 29, 2006·The New England Journal of Medicine·Aileen M BarnesJoan C Marini
Jun 21, 2008·Human Mutation·Dustin BaldridgeBrendan Lee
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Sep 29, 2009·American Journal of Human Genetics·Fleur S van DijkGerard Pals
Apr 7, 2010·American Journal of Human Genetics·Yasemin AlanayDeborah Krakow
Jan 12, 2011·Nature Biotechnology·James T RobinsonJill P Mesirov
Jun 15, 2011·Nature Reviews. Endocrinology·Antonella ForlinoJoan C Marini
Jan 28, 2012·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Wayne A CabralJoan C Marini
Apr 21, 2012·Briefings in Bioinformatics·Helga ThorvaldsdóttirJill P Mesirov
Jun 26, 2012·Nucleic Acids Research·Andreas UntergasserSteven G Rozen
Oct 12, 2012·PloS One·Yongwook ChoiAgnes P Chan
Jul 20, 2016·The Journal of Biological Chemistry·Sezin YigitBarbara Brodsky
May 15, 2018·Journal of Structural Biology·Yimin QiuBarbara Brodsky
Jul 25, 2018·Annals of Human Genetics·Mercedes Rodriguez CelinVirginia Fano

❮ Previous
Next ❯

Citations

Jan 26, 2020·The Veterinary Quarterly·Xuying ZhangBertram Brenig
Mar 7, 2021·Animals : an Open Access Journal From MDPI·Joana G P JacintoJørgen S Agerholm

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
genotyping

Software Mentioned

SAMtools
BWA
Cutadapt
PROVEAN
SeekSire
PolyPhen
Primer3
QuantaSoft
MEM
Integrative Genomics Viewer

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.