OMIA 001986-9823 : Severe combined immunodeficiency disease, autosomal, T cell-negative, B cell-negative, NK cell-positive, with sensitivity to ionizing radiation in Sus scrofa

Possibly relevant human trait(s) and/or gene(s) (MIM number): 602450

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2015

Cross-species summary: This form of T−B−NK+ SCID is known as Radiation-Sensitive-SCID or RS-SCID

History: This naturally occurring form of SCID was first reported by Basel et al. (2012) and Ozuna et al. (2013, having occurred in a selection line of Yorkshire pigs (Cai et al., 2008).

Inheritance: Waide et al. (2015) presented evidence indicative of autosomal recessive inheritance.

Mapping: By conducting a GWAS on "six carrier parents, 20 SCID affected piglets, 50 unaffected littermates of the SCID piglets, and 96 ancestors of these animals", each genotyped with more than 60,000 SNPs via the Illumina porcine SNP60 chip, Waide et al. (2015) mapped this disorder to a 5.6Mb region of chromosome SSC10.

Molecular basis: Noting that the candidate region on SSC10 includes the Artemis gene (DCLRE1C), which encodes a DNA repair enzyme, mutations in which cause the same disorder in humans and mice, Waide et al. (2015) sequenced the cDNA and some intronic regions of this positional candidate gene, revealing "a splice donor site mutation in intron 8 (g.51578763 G→A)" (which leads to the deletion of exon 8, and, consequently, "a protein missing 47 aa of the predicted full-length 712-aa Artemis protein"), and "a G→A nonsense point mutation at g.51584489 that changes the tryptophan amino acid codon at position 267 to a stop codon". Waide et al. (2015) provided strong evidence that homozygosity for either mutation or compound heterozygosity for both mutations causes this disorder.

Clinical features: As summarised by Waide et al. (2015), "Necropsy of four piglets that died abnormally early in a viral challenge study showed that they lacked functional adaptive immune systems [Ozuna et al., 2013]. In subsequent work, we [Basel et al., 2012] demonstrated that these immunodeficient pigs failed to reject human cancer cells, and Ewen et al. (2014) reported minimal circulating B and T cells but normal amounts of NK cells in a preliminary analysis of these SCID pigs."

Breed: Yorkshire.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
DCLRE1C DNA cross-link repair 1C Sus scrofa 10 NC_010452.4 (46820016..46863848) DCLRE1C 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
Severe combined immunodeficiency disease, autosomal, T cell-negative, B cell-negative, NK cell-positive, with sensitivity to ionizing radiation DCLRE1C splicing Sscrofa 10.2 10 g.51578763G>A 2015 26320255
Severe combined immunodeficiency disease, autosomal, T cell-negative, B cell-negative, NK cell-positive, with sensitivity to ionizing radiation DCLRE1C nonsense (stop-gain) Sscrofa 10.2 10 g.51584489G>A p.Trp267* 2015 26320255

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.
2015 Waide, E.H., Dekkers, J.C., Ross, J.W., Rowland, R.R., Wyatt, C.R., Ewen, C.L., Evans, A.B., Thekkoot, D.M., Boddicker, N.J., Serão, N.V., Ellinwood, N.M., Tuggle, C.K. :
Not All SCID Pigs Are Created Equally: Two Independent Mutations in the Artemis Gene Cause SCID in Pigs. J Immunol 195:3171-9, 2015. Pubmed reference: 26320255. DOI: 10.4049/jimmunol.1501132.
2014 Ewen, C.L., Cino-Ozuna, A.G., He, H., Kerrigan, M.A., Dekkers, J.C., Tuggle, C.K., Rowland, R.R., Wyatt, C.R. :
Analysis of blood leukocytes in a naturally occurring immunodeficiency of pigs shows the defect is localized to B and T cells. Vet Immunol Immunopathol 162:174-9, 2014. Pubmed reference: 25454085. DOI: 10.1016/j.vetimm.2014.10.003.
2013 Ozuna, A.G., Rowland, R.R., Nietfeld, J.C., Kerrigan, M.A., Dekkers, J.C., Wyatt, C.R. :
Preliminary findings of a previously unrecognized porcine primary immunodeficiency disorder. Vet Pathol 50:144-6, 2013. Pubmed reference: 22903400. DOI: 10.1177/0300985812457790.
2012 Basel, M.T., Balivada, S., Beck, A.P., Kerrigan, M.A., Pyle, M.M., Dekkers, J.C.M., Wyatt, C.R., Rowland, R.R.R., Anderson, D.E., Bossmann, S.H., Troyer, D.L. :
Human Xenografts Are Not Rejected in a Naturally Occurring Immunodeficient Porcine Line: A Human Tumor Model in Pigs. Biores Open Access 1:63-68, 2012. DOI: 10.1089/biores.2012.9902.
2008 Cai, W., Casey, D.S., Dekkers, J.C. :
Selection response and genetic parameters for residual feed intake in Yorkshire swine. J Anim Sci 86:287-98, 2008. Pubmed reference: 17998435. DOI: 10.2527/jas.2007-0396.

Edit History


  • Created by Frank Nicholas on 31 Mar 2016
  • Changed by Frank Nicholas on 31 Mar 2016
  • Changed by Frank Nicholas on 01 Apr 2016