Content and Performance of the MiniMUGA Genotyping Array: A New Tool To Improve Rigor and Reproducibility in Mouse Research.
Content and Performance of the MiniMUGA Genotyping Array: A New Tool To Improve Rigor and Reproducibility in Mouse Research.
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DOI：
10.1534/genetics.120.303596
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发表时间：
2020-12
期刊：
影响因子：
3.3
通讯作者：
Manuel de Villena FP
中科院分区：
文献类型：
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作者：
Sigmon JS;Blanchard MW;Baric RS;Bell TA;Brennan J;Brockmann GA;Burks AW;Calabrese JM;Caron KM;Cheney RE;Ciavatta D;Conlon F;Darr DB;Faber J;Franklin C;Gershon TR;Gralinski L;Gu B;Gaines CH;Hagan RS;Heimsath EG;Heise MT;Hock P;Ideraabdullah F;Jennette JC;Kafri T;Kashfeen A;Kulis M;Kumar V;Linnertz C;Livraghi-Butrico A;Lloyd KCK;Lutz C;Lynch RM;Magnuson T;Matsushima GK;McMullan R;Miller DR;Mohlke KL;Moy SS;Murphy CEY;Najarian M;O'Brien L;Palmer AA;Philpot BD;Randell SH;Reinholdt L;Ren Y;Rockwood S;Rogala AR;Saraswatula A;Sassetti CM;Schisler JC;Schoenrock SA;Shaw GD;Shorter JR;Smith CM;St Pierre CL;Tarantino LM;Threadgill DW;Valdar W;Vilen BJ;Wardwell K;Whitmire JK;Williams L;Zylka MJ;Ferris MT;McMillan L;Manuel de Villena FP
实验室小鼠是生物医学研究中使用最广泛的动物模型，部分原因在于其基因组注释良好、丰富的遗传资源以及精确操纵其基因组的能力。尽管遗传学对于小鼠研究很重要，但遗传质量控制 (QC) 尚未标准化，部分原因是缺乏经济高效、信息丰富且强大的平台。基因分型芯片是小鼠研究的标准工具，即使在高通量全基因组测序时代，它仍然是一个有吸引力的替代方案。在这里，我们描述了新一代小鼠通用基因分型阵列 (MUGA) MiniMUGA 的内容和性能，MiniMUGA 是一个基于阵列的遗传 QC 平台，拥有超过 11,000 个探针。除了对大多数经典和野生来源的实验室菌株进行强有力的区分之外，MiniMUGA 还被设计为包含其他平台中不具备的功能：(1) 染色体性别测定，(2) 区分来自多个商业供应商的亚菌株，(3) 流行实验室菌株的诊断 SNP，(4) 检测基因工程小鼠中使用的构建体，以及 (5) 总结这些结果的易于解释的报告。所有探针的深入注释应有助于个别研究人员进行定制分析。为了确定 MiniMUGA 的性能，我们对来自各种遗传背景的 6899 个样本进行了基因分型。无论是在辨别能力还是鲁棒性方面，MiniMUGA 的性能均优于 MUGA 系列阵列的前三代产品。我们已经为 241 个近交系生成了公开的共有基因型，包括经典、野生和重组自交系。在这里，我们还报告了在各种样本类型中检测到大量 XO 和 XXY 个体、将降低复杂性杂交的效用扩展到 C57BL/6 以外的遗传背景的新标记，以及对 17 种遗传构建体的稳健检测。我们提供的初步证据表明，该阵列可用于识别部分性染色体重复和嵌合现象，并且诊断性 SNP 可用于确定近交小鼠与相关主要种群独立繁殖的时间。我们得出的结论是，MiniMUGA 是遗传质量控制的一个有价值的平台，也是提高小鼠研究的严谨性和可重复性的重要新工具。
The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well-annotated genome, wealth of genetic resources, and the ability to precisely manipulate its genome. Despite the importance of genetics for mouse research, genetic quality control (QC) is not standardized, in part due to the lack of cost-effective, informative, and robust platforms. Genotyping arrays are standard tools for mouse research and remain an attractive alternative even in the era of high-throughput whole-genome sequencing. Here, we describe the content and performance of a new iteration of the Mouse Universal Genotyping Array (MUGA), MiniMUGA, an array-based genetic QC platform with over 11,000 probes. In addition to robust discrimination between most classical and wild-derived laboratory strains, MiniMUGA was designed to contain features not available in other platforms: (1) chromosomal sex determination, (2) discrimination between substrains from multiple commercial vendors, (3) diagnostic SNPs for popular laboratory strains, (4) detection of constructs used in genetically engineered mice, and (5) an easy-to-interpret report summarizing these results. In-depth annotation of all probes should facilitate custom analyses by individual researchers. To determine the performance of MiniMUGA, we genotyped 6899 samples from a wide variety of genetic backgrounds. The performance of MiniMUGA compares favorably with three previous iterations of the MUGA family of arrays, both in discrimination capabilities and robustness. We have generated publicly available consensus genotypes for 241 inbred strains including classical, wild-derived, and recombinant inbred lines. Here, we also report the detection of a substantial number of XO and XXY individuals across a variety of sample types, new markers that expand the utility of reduced complexity crosses to genetic backgrounds other than C57BL/6, and the robust detection of 17 genetic constructs. We provide preliminary evidence that the array can be used to identify both partial sex chromosome duplication and mosaicism, and that diagnostic SNPs can be used to determine how long inbred mice have been bred independently from the relevant main stock. We conclude that MiniMUGA is a valuable platform for genetic QC, and an important new tool to increase the rigor and reproducibility of mouse research.