TY - JOUR
T1 - Content and performance of the MiniMUGA genotyping array
T2 - A new tool to improve rigor and reproducibility in mouse research
AU - Sigmon, John Sebastian
AU - Blanchard, Matthew W.
AU - Baric, Ralph S.
AU - Bell, Timothy A.
AU - Brennan, Jennifer
AU - Brockmann, Gudrun A.
AU - Wesley Burks, A.
AU - Mauro Calabrese, J.
AU - Caron, Kathleen M.
AU - Cheney, Richard E.
AU - Ciavatta, Dominic
AU - Conlon, Frank
AU - Darr, David B.
AU - Faber, James
AU - Franklin, Craig
AU - Gershon, Timothy R.
AU - Gralinski, Lisa
AU - Gu, Bin
AU - Gaines, Christiann H.
AU - Hagan, Robert S.
AU - Heimsath, Ernest G.
AU - Heise, Mark T.
AU - Hock, Pablo
AU - Ideraabdullah, Folami
AU - Charles Jennette, J.
AU - Kafri, Tal
AU - Kashfeen, Anwica
AU - Kulis, Mike
AU - Kumar, Vivek
AU - Linnertz, Colton
AU - Livraghi-Butrico, Alessandra
AU - Kent Lloyd, K. C.
AU - Lutz, Cathleen
AU - Lynch, Rachel M.
AU - Magnuson, Terry
AU - Matsushima, Glenn K.
AU - McMullan, Rachel
AU - Miller, Darla R.
AU - Mohlke, Karen L.
AU - Moy, Sheryl S.
AU - Murphy, Caroline E.Y.
AU - Najarian, Maya
AU - O’Brien, Lori
AU - Palmer, Abraham A.
AU - Philpot, Benjamin D.
AU - Randell, Scott H.
AU - Reinholdt, Laura
AU - Ren, Yuyu
AU - Rockwood, Steve
AU - Rogala, Allison R.
AU - Saraswatula, Avani
AU - Sassetti, Christopher M.
AU - Schisler, Jonathan C.
AU - Schoenrock, Sarah A.
AU - Shaw, Ginger D.
AU - Shorter, John R.
AU - Smith, Clare M.
AU - St. Pierre, Celine L.
AU - Tarantino, Lisa M.
AU - Threadgill, David W.
AU - Valdar, William
AU - Vilen, Barbara J.
AU - Wardwell, Keegan
AU - Whitmire, Jason K.
AU - Williams, Lucy
AU - Zylka, Mark J.
AU - Ferris, Martin T.
AU - McMillan, Leonard
AU - Manuel de Villena, Fernando Pardo
N1 - Publisher Copyright:
Copyright © 2020 by the Genetics Society of America
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - Chromosomal sex
KW - Diagnostic SNPs
KW - Genetic background
KW - Genetic constructs
KW - Genetic QC
KW - Substrains
UR - http://www.scopus.com/inward/record.url?scp=85096707589&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85096707589&partnerID=8YFLogxK
U2 - 10.1534/genetics.120.303596
DO - 10.1534/genetics.120.303596
M3 - Article
C2 - 33067325
AN - SCOPUS:85096707589
VL - 216
SP - 905
EP - 930
JO - Genetics
JF - Genetics
SN - 0016-6731
IS - 4
ER -