Screening ADAMTS10 in Dog Populations Supports Gly661Arg as the Glaucoma-Causing Variant in Beagles
Screening ADAMTS10 in Dog Populations Supports Gly661Arg as the Glaucoma-Causing Variant in Beagles
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DOI：
10.1167/iovs.12-10796
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发表时间：
2013-03-01
影响因子：
4.4
通讯作者：
Kuchtey, Rachel W.
中科院分区：
文献类型：
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作者：
Kuchtey, John;Kunkel, Jessica;Kuchtey, Rachel W.
目的。此前，我们将常染色体隐性遗传原发性开角型青光眼 (POAG) 的 Beagle 模型中的疾病位点定位到 20 号染色体上的 4 Mb 区间，并确定 ADAMTS10 中的 Gly661Arg 变异为候选致病变异。本研究的目的是通过对受原发性青光眼影响和未受原发性青光眼影响的各种品种的狗进行基因分型，检验 ADAMTS10 的 Gly661Arg 变体导致青光眼的假设。对患有或未患有原发性青光眼的各种品种的狗进行了 ADAMTS10 的 Gly661Arg 变体的基因分型，以及比格犬 POAG 基因座中与疾病分离的其他基因中的 7 个其他非同义单核苷酸多态性 (SNP)。使用 95% 置信区间计算替代等位基因频率，并与相对于疾病患病率或病例与对照之间的预期等位基因频率进行比较。 结果。对于除 ADAMTS10 变体之外的非同义 SNP，对照狗被鉴定为替代等位基因纯合的，从而排除了这些变体的致病因素。在美国可卡犬中，没有发现与原发性青光眼相关的非同义 SNP。 ADAMTS10 的 Gly661Arg 变体是唯一具有较小等位基因频率的变体，其与一般比格犬群体中原发性青光眼的患病率一致。唯一发现 ADAMTS10 的 Gly661Arg 变体纯合的狗是一只受影响的比格犬，与 POAG 群体无关。结论。这些发现支持 ADAMTS10 的 Gly661Arg 突变是比格犬 POAG 的可能原因。 （投资眼科可见科学。2013 年；54：1881-1886）DOI：10.1167/iovs.12-10796
PURPOSE. Previously, we mapped the disease locus in the beagle model of autosomal recessive primary open angle glaucoma (POAG) to a 4-Mb interval on chromosome 20, and identified a Gly661Arg variant in ADAMTS10 as the candidate disease-causing variant. The purpose of this study was to test the hypothesis that the Gly661Arg variant of ADAMTS10 causes glaucoma by genotyping dogs of various breeds affected and unaffected by primary glaucoma.METHODS. Dogs of various breeds, affected or unaffected with primary glaucoma, were genotyped for the Gly661Arg variant of ADAMTS10, as well as 7 other nonsynonymous single nucleotide polymorphisms (SNPs) in other genes in the beagle POAG locus that segregate with disease. Alternate allele frequencies were calculated with 95% confidence intervals and comparisons made to expected allele frequency relative to disease prevalence or between cases and controls.RESULTS. For the nonsynonymous SNPs other than the ADAMTS10 variant, control dogs were identified that were homozygous for the alternative alleles, ruling out those variants as causative. None of the nonsynonymous SNPs were found associated with primary glaucoma in American cocker spaniels. The Gly661Arg variant of ADAMTS10 was the only variant with minor allele frequency consistent with the prevalence of primary glaucoma in the general beagle population. The only dog found homozygous for the Gly661Arg variant of ADAMTS10 was an affected beagle, unrelated to the POAG colony.CONCLUSIONS. These findings support the Gly661Arg mutation of ADAMTS10 as the likely cause of POAG in beagles. (Invest Ophthalmol Vis Sci. 2013;54:1881-1886) DOI:10.1167/iovs.12-10796