Data from: A missense mutation in AGTPBP1 was identified in sheep with a lower motor neuron disease

A type of lower motor neuron (LMN) disease inherited as autosomal
recessive in Romney sheep was characterized with normal appearance at
birth, but with progressive weakness and tetraparesis after the first week
of life. Here, we carried out genome-wide homozygosity mapping using
Illumina Ovine SNP50 BeadChips on lambs descended from one carrier ram,
including 19 sheep diagnosed as affected and 11 of their parents that were
therefore known carriers. A homozygous region of 136 consecutive
single-nucleotide polymorphism (SNP) loci on chromosome 2 was common to
all affected sheep and it was the basis for searching for the positional
candidate genes. Other homozygous regions shared by all affected sheep
spanned eight or fewer SNP loci. The 136-SNP region contained the sheep
ATP/GTP-binding protein 1 (AGTPBP1) gene. Mutations in this gene have been
shown to be related to Purkinje cell degeneration (pcd) phenotypes
including ataxia in mice. One missense mutation c.2909G>C on exon
21 of AGTPBP1 was discovered, which induces an Arg to Pro substitution
(p.Arg970Pro) at amino-acid 970, a conserved residue for the catalytic
activity of AGTPBP1. Genotyping of this mutation showed 100% concordant
rate with the recessive pattern of inheritance in affected, carrier,
phenotypically normal and unrelated normal individuals. This is the first
report showing a mutant AGTPBP1 is associated with a LMN disease in a
large mammal animal model. Our finding raises the possibility of human
patients with the same etiology caused by this gene or other genes in the
same pathway of neuronal development.