OMIA 002238-9913 : Ichthyosis, ABCA12-related in Bos taurus

In other species: pig

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 601277 , 242500

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2008

Mapping: In a pioneering use of tens of thousands of SNP markers ("using either the 25K Affymetrix SNP panel or a custom-made 60K Illumina panel"), Charlier et al. (2008) identified a single 11.78 Mb region on BTA2 in which 3 affected calves were significantly more homozygous for the same allele at each of many SNPs, when compared with 9 normal controls. An investigation of comparative candidate genes in this region identified the ABCA12 gene as a likely culprit. This gene encodes the 12th member of the A subfamily of ATP-binding cassette transporters. Some sequencing of this gene quickly identified the molecular lesion.

Molecular basis: In the words of Charlier et al. (2008): "a missense mutation in exon 39 (A5804G) resulting in an H1935R substitution in the fourth extracellular loop". The His (normal) form of the peptide is conserved in all vertebrates sequenced to date. (FN 080330)

Whole-genome sequencing of the affected Shorthorn calf described by O'Rourke et al. (2017), and subsequent checking for deleterious variants in functional candidate genes, enabled Woolley et al. (2019) to identify "a likely causal missense variant on chromosome 2 in the ABCA12 gene (NM_001191294.2:c.6776T>C)". The authors also reported that "Sanger sequencing of the affected calf and the dam confirmed the variant was homozygous in the affected calf and heterozygous in the dam."

Clinical features: In the words of Charlier et al. (2008), "Affected calves show cutaneous lesions, with deep fissures separating hyperkeratotic skin plaques and eversion of mucocutaneous junctions (ectropion and eclabium), reminiscent of harlequin ichthyosis in humans".

Prevalence: O'Rourke et al. (2017) reported that "The known mutation (H1935R) in gene ABCA12, responsible for ichthyosis fetalis in Chianina cattle, was shown to be absent in . . . [one Polled Hereford and one Shorthorn affected calf] and their obligate heterozygous parents."

Woolley et al. (2019) reported that "genotyping of 130 Shorthorn animals from the same property [as the affected calf described by O'Rourke et al. (2017)] revealed an estimated [c.6776T>C] allele frequency of 3.8%."

Breeds: Chianina, Shorthorn.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ABCA12 ATP binding cassette subfamily A member 12 Bos taurus 2 NC_037329.1 (103202095..103002532) ABCA12 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Shorthorn Ichthyosis, ABCA12-related ABCA12 missense ARS‐UCD1.2 2 g.103,016,791T>C c.6776T>C p.(Leu2259Pro) NM_001191294.2:c.6776T>C; NP_001178223.2:p.(Leu2259Pro) 2019 31568573
Chianina Ichthyosis, ABCA12-related ABCA12 missense UMD3.1 2 g.103,543,077A>G c.5,804A>G p.H1,935R 2008 18344998 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2019 Woolley, S.A., Eager, K.L.M., Häfliger, I.M., Bauer, A., Drögemüller, C., Leeb, T., O'Rourke, B.A., Tammen, I. :
An ABCA12 missense variant in a Shorthorn calf with ichthyosis fetalis. Anim Genet :, 2019. Pubmed reference: 31568573. DOI: 10.1111/age.12856.
2017 O'Rourke, B.A., Kelly, J., Spiers, Z.B., Shearer, P.L., Porter, N.S., Parma, P., Longeri, M. :
Ichthyosis fetalis in Polled Hereford and Shorthorn calves. J Vet Diagn Invest :, 2017. Pubmed reference: 28782451. DOI: 10.1177/1040638717724186.
2008 Charlier, C., Coppieters, W., Rollin, F., Desmecht, D., Agerholm, JS., Cambisano, N., Carta, E., Dardano, S., Dive, M., Fasquelle, C., Frennet, JC., Hanset, R., Hubin, X., Jorgensen, C., Karim, L., Kent, M., Harvey, K., Pearce, BR., Simon, P., Tama, N., Nie, H., Vandeputte, S., Lien, S., Longeri, M., Fredholm, M., Harvey, RJ., Georges, M. :
Highly effective SNP-based association mapping and management of recessive defects in livestock. Nat Genet 40:449-54, 2008. Pubmed reference: 18344998. DOI: 10.1038/ng.96.
Dardano, S., Gandolfi, B., Parma, P., Polli, M., Bighignoli, B., Strillacci, MG., Cozzi, MC., Molteni, L., Longeri, M. :
Characterization of Bovine TGM1 and Exclusion as Candidate Gene for Ichthyosis in Chianina. J Hered 99:81-83, 2008. Pubmed reference: 18165261. DOI: 10.1093/jhered/esm101.
2006 Molteni, L., Dardano, S., Parma, P., Polli, M., De Giovanni, AM., Sironi, G., Longeri, M. :
Ichthyosis in Chianina cattle. Vet Rec 158:412-4, 2006. Pubmed reference: 16565341.
Testoni, S., Zappulli, V., Gentile, A. :
Ichthyosis in two Chianina calves. Dtsch Tierarztl Wochenschr 113:351-4, 2006. Pubmed reference: 17009813.

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  • Created by Frank Nicholas on 31 Jan 2020