Categories: Immune system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 602450 (trait) , 605988 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: 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 (Pig) (VBO_0001212).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: