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In a shake of a lamb's tail: using genomics to unravel a cause of chondrodysplasia in T exel sheep
Author(s) -
Zhao X.,
Onteru S. K.,
Piripi S.,
Thompson K. G.,
Blair H. T.,
Garrick D. J.,
Rothschild M. F.
Publication year - 2012
Publication title -
animal genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.756
H-Index - 81
eISSN - 1365-2052
pISSN - 0268-9146
DOI - 10.1111/j.1365-2052.2011.02304.x
Subject(s) - biology , genetics , candidate gene , locus (genetics) , single nucleotide polymorphism , gene , exon , disease gene identification , allele , genotype , microbiology and biotechnology , mutation , exome sequencing
Summary Chondrodysplasia in T exel sheep is a recessively inherited disorder characterized by dwarfism and angular deformities of the forelimbs. A genome‐wide association study using the I llumina O vine SNP 50 B ead C hip on 15 sheep diagnosed as affected and eight carriers descended from three affected rams was conducted to uncover the genetic cause. A homozygous region of 25 consecutive single nucleotide polymorphism ( SNP ) loci was identified in all affected sheep, covering a region of 1 M bp on ovine chromosome 4. Seven positional candidate genes – including the solute carrier family 13 (sodium / sulphate symporters), member 1 ( SLC13A1 ) – were identified and used to search for new SNP s for fine mapping of the causal locus. The SLC13A1 gene, encoding a sodium/sulphate transporter, was the primary candidate gene attributable to similar phenotypes observed in the Slc13a1 knockout mouse model. We discovered a 1‐bp deletion of T (g.25513del T ) at the 107 bp position of exon 3 in the SLC13A1 gene. Genotyping by direct sequencing and restriction fragment length polymorphism analysis for this mutation showed that all 15 affected sheep were g.25513del T /g.25513del T ; the eight carriers were g.25513del T / T and 54 normal controls were T / T . The mutation g.25513del T shifts the open reading frame of SLC13A1 to introduce a stop codon and truncate C ‐terminal amino acids. It was concluded that the g.25513del T mutation in the SLC13A1 gene was responsible for the chondrodysplasia seen in these T exel sheep. This knowledge can be used to identify carriers with the defective g.[25513del T ] allele to avoid at‐risk matings to improve animal welfare and decrease economic losses.