Department of Biology, College of Saint Benedict & Saint John's University, Collegeville, Minnesota, United States of America.
Department of Molecular Physiology and Biophysics, The University of Iowa, Iowa City, Iowa, United States of America.
PLoS One. 2023 Aug 25;18(8):e0286897. doi: 10.1371/journal.pone.0286897. eCollection 2023.
Anterior chamber depth (ACD) is a quantitative trait associated with primary angle closure glaucoma (PACG). Although ACD is highly heritable, known genetic variations explain a small fraction of the phenotypic variability. The purpose of this study was to identify additional ACD-influencing loci using strains of mice. Cohorts of 86 N2 and 111 F2 mice were generated from crosses between recombinant inbred BXD24/TyJ and wild-derived CAST/EiJ mice. Using anterior chamber optical coherence tomography, mice were phenotyped at 10-12 weeks of age, genotyped based on 93 genome-wide SNPs, and subjected to quantitative trait locus (QTL) analysis. In an analysis of ACD among all mice, six loci passed the significance threshold of p = 0.05 and persisted after multiple regression analysis. These were on chromosomes 6, 7, 11, 12, 15 and 17 (named Acdq6, Acdq7, Acdq11, Acdq12, Acdq15, and Acdq17, respectively). Our findings demonstrate a quantitative multi-genic pattern of ACD inheritance in mice and identify six previously unrecognized ACD-influencing loci. We have taken a unique approach to studying the anterior chamber depth phenotype by using mice as genetic tool to examine this continuously distributed trait.
前房深度 (ACD) 是与原发性闭角型青光眼 (PACG) 相关的定量特征。尽管 ACD 具有高度遗传性，但已知的遗传变异仅能解释表型变异性的一小部分。本研究的目的是使用小鼠品系来鉴定其他影响 ACD 的基因座。从重组近交系 BXD24/TyJ 和野生型 CAST/EiJ 小鼠的杂交后代中生成了 86 只 N2 和 111 只 F2 小鼠。使用前房光学相干断层扫描，在 10-12 周龄时对小鼠进行表型分析，基于 93 个全基因组 SNP 进行基因分型，并进行数量性状基因座 (QTL) 分析。在对所有小鼠的 ACD 分析中，有六个基因座通过了 p = 0.05 的显著性阈值，并在多重回归分析后仍然存在。这些基因座位于 6、7、11、12、15 和 17 号染色体上（分别命名为 Acdq6、Acdq7、Acdq11、Acdq12、Acdq15 和 Acdq17）。我们的研究结果表明，在小鼠中，ACD 的遗传是一种多基因的定量模式，并鉴定了六个以前未被识别的影响 ACD 的基因座。我们采用了一种独特的方法来研究前房深度表型，利用小鼠作为遗传工具来研究这种连续分布的特征。
