Guevar Julien, Olby Natasha J, Meurs Kathryn M, Yost Oriana, Friedenberg Steven G
School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin.
College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina.
J Vet Intern Med. 2018 Mar;32(2):665-669. doi: 10.1111/jvim.15060. Epub 2018 Feb 20.
A congenital syndrome of hearing loss and vestibular dysfunction affects Doberman Pinschers. Its inheritance pattern is suspected to be autosomal recessive and it potentially represents a spontaneous animal model of an autosomal recessive syndromic hearing loss.
HYPOTHESIS/OBJECTIVES: The objectives of this study were to use whole genome sequencing (WGS) to identify deleterious genetic variants in candidate genes associated with the syndrome and to study the prevalence of candidate variants among a population of unaffected Doberman Pinschers.
One affected Doberman Pinscher and 202 unaffected Doberman Pinschers.
WGS of the affected dog with filtering of variants against a database of 154 unaffected dogs of diverse breeds was performed. Confirmation of candidate variants was achieved by Sanger sequencing followed by genotyping of the control population of unaffected Doberman Pinschers.
WGS and variant filtering identified an alteration in a gene associated with both deafness and vestibular disease in humans: protein tyrosine phosphatase, receptor type Q (PTPRQ). There was a homozygous A insertion at CFA15: 22 989 894, causing a frameshift mutation in exon 39 of the gene. This insertion is predicted to cause a protein truncation with a premature stop codon occurring after position 2054 of the protein sequence that causes 279 C-terminal amino acids to be eliminated. Prevalence of the variant was 1.5% in a cohort of 202 unaffected Doberman Pinschers; all unaffected Doberman Pinschers were heterozygous or heterozygous for the reference allele.
We report the identification of a genetic alteration on the PTPRQ gene that is associated with congenital hearing and vestibular disorder in a young Doberman Pinscher dog.
一种先天性听力丧失和前庭功能障碍综合征影响杜宾犬。其遗传模式被怀疑为常染色体隐性遗传，它可能代表了一种常染色体隐性综合征性听力丧失的自发动物模型。
假设/目的：本研究的目的是使用全基因组测序（WGS）来鉴定与该综合征相关的候选基因中的有害遗传变异，并研究候选变异在未受影响的杜宾犬群体中的患病率。
一只受影响的杜宾犬和202只未受影响的杜宾犬。
对受影响的犬进行全基因组测序，并根据154只不同品种未受影响犬的数据库对变异进行筛选。通过桑格测序确认候选变异，随后对未受影响的杜宾犬对照群体进行基因分型。
全基因组测序和变异筛选确定了一个与人类耳聋和前庭疾病相关的基因发生改变：蛋白酪氨酸磷酸酶，受体型Q（PTPRQ）。在CFA15: 22 989 894处有一个纯合的A插入，导致该基因第39外显子发生移码突变。该插入预计会导致蛋白质截短，在蛋白质序列的第2054位之后出现提前终止密码子，导致279个C端氨基酸被消除。在202只未受影响的杜宾犬队列中，该变异的患病率为1.5%；所有未受影响的杜宾犬均为该变异的杂合子或参考等位基因的杂合子。
我们报告在一只年轻的杜宾犬中鉴定出与先天性听力和前庭障碍相关的PTPRQ基因的遗传改变。
