Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA.
VCA Veterinary Specialty & Emergency Center of Kalamazoo, Kalamazoo, MI 49001, USA.
Genes (Basel). 2024 Jan 31;15(2):193. doi: 10.3390/genes15020193.
Miniature Schnauzers are predisposed to primary hypertriglyceridemia (HTG). In this study, we performed whole genome sequencing (WGS) of eight Miniature Schnauzers with primary HTG and screened for risk variants in six HTG candidate genes: , , , , , and . Variants were filtered to identify those present in ≥2 Miniature Schnauzers with primary HTG and uncommon (<10% allele frequency) in a WGS variant database including 613 dogs from 61 other breeds. Three variants passed filtering: an TATA box deletion, an intronic SNP, and a missense variant. The and variants were genotyped in a cohort of 108 Miniature Schnauzers, including 68 with primary HTG and 40 controls. A multivariable regression model, including age and sex, did not identify an effect of (estimate = 0.18, std. error = 0.14; = 0.20) or genotypes (estimate = -0.26, std. error = 0.42; = 0.54) on triglyceride concentration. In conclusion, we did not identify a monogenic cause for primary HTG in Miniature Schnauzers in the six genes evaluated. However, if HTG in Miniature Schnauzers is a complex disease resulting from the cumulative effects of multiple variants and environment, the identified variants cannot be ruled out as contributing factors.
迷你雪纳瑞易患原发性高甘油三酯血症（HTG）。在本研究中，我们对 8 只原发性 HTG 迷你雪纳瑞进行了全基因组测序（WGS），并在 6 个 HTG 候选基因中筛选了风险变异： 、 、 、 、和 。对变异进行过滤，以鉴定在≥2 只原发性 HTG 迷你雪纳瑞中存在且在包括 61 个其他品种的 613 只狗的 WGS 变异数据库中罕见（<10%等位基因频率）的变异。三种变异通过过滤：TATA 框缺失、内含子 SNP 和 错义变异。在 108 只迷你雪纳瑞的队列中对 和 变异进行了基因分型，包括 68 只原发性 HTG 和 40 只对照。多变量回归模型包括年龄和性别，但未鉴定出 （估计值=0.18，标准误差=0.14； = 0.20）或 基因型（估计值=-0.26，标准误差=0.42； = 0.54）对甘油三酯浓度有影响。总之，我们未在评估的六个基因中发现原发性 HTG 与迷你雪纳瑞的单基因病因。然而，如果迷你雪纳瑞的 HTG 是由多个变异和环境的累积效应导致的复杂疾病，那么不能排除已鉴定的变异是致病因素。
