Content and performance of the MiniMUGA genotyping array, a new tool to improve rigor and reproducibility in mouse research

Abstract

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 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 6,899 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, the extension of the utility of reduced complexity crosses to genetic backgrounds other than C57BL/6, and the robust detection of 17 genetic constructs. There is preliminary but striking 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 main stock for a significant action of the genotyped inbred samples. We conclude that MiniMUGA is a valuable platform for genetic QC and important new tool to the increase rigor and reproducibility of mouse research.

Collaborative Cross mice reveal extreme epilepsy phenotypes and genetic loci for seizure susceptibility

“…The Mini Mouse Universal Genotyping Array (MiniMUGA) by GeenSeek (Neogen Genomics, Lincoln, NE) was used for genotyping. 18 Informative markers were selected by taking markers that discriminated between B6J and CC027. Next, we identified the frequency of these markers in the F2 population and tested for expected Mendelian ratios.…”

Polymorphic SNPs, short tandem repeats and structural variants are responsible for differential gene expression across C57BL/6 and C57BL/10 substrains

“…Because crosses among closely related substrains segregate fewer variants than crosses of more divergent strains, identification of causal alleles is greatly simplified 21 . Such crosses have been referred to as a reduced complexity cross (RCC) 24 and have been further simplified by the recent development of an inexpensive microarray explicitly designed for mapping studies that use RCCs 25 .…”

QTL-mapping in the obese Berlin Fat Mouse identifies additional candidate genes for obesity and fatty liver disease

“…Genotypes of all 123 mice were generated by Neogen GeneSeek (Lincoln, NE, USA) using the Mini Mouse Universal Genotyping Array (MiniMUGA; Illumina, San Diego, CA, USA). The MiniMUGA array contains probes targeting 10,171 known SNPs (markers) (19). Markers were removed when all genotypes were missing or when the marker was not segregating.…”