GEPHE SUMMARY
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Gephebase Gene
Entry Status
Published
GepheID
GP00002140
Main curator
Martin
PHENOTYPIC CHANGE
Trait Category
Trait
Trait State in Taxon A
European cattle breeds with normal size
Trait State in Taxon B
Dexter cattle (dwarf = dominant trait ; recessive lethal)
Ancestral State
Taxon A
Taxonomic Status
Taxon A
Latin Name
Common Name
cattle
Synonyms
Bos bovis; Bos primigenius taurus; cattle; bovine; cow; dairy cow; domestic cattle; domestic cow; Bos taurus Linnaeus, 1758; Bos Tauurus
Rank
species
Lineage
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a; Teleostomi; Euteleostomi; Sarcopterygii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Mammalia; Theria; Eutheria; Boreoeutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; Bovinae; Bos
NCBI Taxonomy ID
is Taxon A an Infraspecies?
No
Taxon B
Latin Name
Common Name
cattle
Synonyms
Bos bovis; Bos primigenius taurus; cattle; bovine; cow; dairy cow; domestic cattle; domestic cow; Bos taurus Linnaeus, 1758; Bos Tauurus
Rank
species
Lineage
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a; Teleostomi; Euteleostomi; Sarcopterygii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Mammalia; Theria; Eutheria; Boreoeutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; Bovinae; Bos
NCBI Taxonomy ID
is Taxon B an Infraspecies?
No
GENOTYPIC CHANGE
Generic Gene Name
ACAN
Synonyms
AGC1; SEDK; AGCAN; CSPG1; MSK16; CSPGCP; SSOAOD
String
Sequence Similarities
Belongs to the aggrecan/versican proteoglycan family.
GO - Molecular Function
GO:0046872 : metal ion binding
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GO - Biological Process
GO:0007155 : cell adhesion
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GO - Cellular Component
GO:0005576 : extracellular region
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UniProtKB
Homo sapiens
Homo sapiens
Presumptive Null
Molecular Type
Aberration Type
Insertion Size
1-9 bp
Molecular Details of the Mutation
2266_2267insGGCA mutation introduces a frameshift and a premature termination codon into exon 11; the frameshift occurs at amino acid position 756 ; the termination codon occurs at position 914 compared to the normal aggrecan product of 2327 amino acids
Experimental Evidence
Authors
Cavanagh JA; Tammen I; Windsor PA; Bateman JF; Savarirayan R; Nicholas FW; Raadsma HW
Abstract
Bulldog dwarfism in Dexter cattle is one of the earliest single-locus disorders described in animals. Affected fetuses display extreme disproportionate dwarfism, reflecting abnormal cartilage development (chondrodysplasia). Typically, they die around the seventh month of gestation, precipitating a natural abortion. Heterozygotes show a milder form of dwarfism, most noticeably having shorter legs. Homozygosity mapping in candidate regions in a small Dexter pedigree suggested aggrecan (ACAN) as the most likely candidate gene. Mutation screening revealed a 4-bp insertion in exon 11 (2266_2267insGGCA) (called BD1 for diagnostic testing) and a second, rarer transition in exon 1 (-198C>T) (called BD2) that cosegregate with the disorder. In chondrocytes from cattle heterozygous for the insertion, mutant mRNA is subject to nonsense-mediated decay, showing only 8% of normal expression. Genotyping in Dexter families throughout the world shows a one-to-one correspondence between genotype and phenotype at this locus. The heterozygous and homozygous-affected Dexter cattle could prove invaluable as a model for human disorders caused by mutations in ACAN.
Additional References
RELATED GEPHE
Related Genes
Related Haplotypes
EXTERNAL LINKS
COMMENTS
https://omia.org/OMIA001271/9913/
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