Marker-assisted congenic screening (MACS): A database tool for the efficient production and characterization of congenic lines
Over the past decades, genetic studies in rodent models of human multifactorial disorders have led to the detection of numerous chromosomal regions associated with disease phenotypes. Owing to the complex control of these phenotypes and the size of the disease loci, identifying the underlying genes requires further analyses in new original models, including chromosome substitution (consomic) and congenic lines, derived to evaluate the phenotypic effects of disease susceptibility loci and fine-map the disease genes. We have developed a relational database (MACS) specifically designed for the genetic marker-assisted production of large series of rodent consomic and congenic lines (“speed congenics”), the organization of their genetic and phenotypic characterizations, and the acquisition and archiving of both genetic and phenotypic data. This database, originally optimized for the production of rat congenics, can also be applied to mouse mapping projects. MACS represents an essential system for significantly improving efficiency and accuracy in investigations of multiple consomic and congenic lines simultaneously derived for different disease loci, and ultimately cloning genes underlying complex phenotypes.
KeywordsQuantitative Trait Locus Radiation Hybrid Congenic Strain Experimental Cross Backcross Breeding
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This work is supported by the Wellcome Trust and grants from Diabetes UK (RD96/0001270) and the EC (“INFRAQTL”-QLRT-2000-00233). Dominique Gauguier holds a Wellcome Trust Senior Fellowship in basic biomedical science. Stephan C Collins is a recipient of a Wellcome Prize Studentship.
Bihoreau, MT, Sebag-Montefiore, L, Godfrey, RF, Wallis, RH, Brown, JH, et al. 2001A high resolution consensus linkage map of the rat integrating radiation hybrid and genetic maps.Genomics755769CrossRefPubMedGoogle Scholar
Collier, B, Danielsen, M 1994Grbase, a new gene regulation data base available by anonymous ftp.Nucleic Acids Res223625PubMedGoogle Scholar
Flint, J, Mott, R 2001Finding the molecular basis of quantitative traits: successes and pitfalls.Nat Rev Genet2437445CrossRefPubMedGoogle Scholar
Gottlieb, B, Beitel, LK, Lumbroso, R, Pinsky, L, Trifiro, M 1999Update of the androgen receptor gene mutations database.Hum Mutat14103114CrossRefPubMedGoogle Scholar
Hoeck, WG 1994Infotrac tfd: A microcomputer implementation of the transcription factor database tfd with a graphical user interface.Comput Appl Biosci10323327PubMedGoogle Scholar
Jacob, HJ, Kwitek, AE 2001Rat genetics: attaching physiology and pharmacology to the genome.Nat Rev Genet33342CrossRefGoogle Scholar
Jeffs, B, Negrin, CD, Graham, D, Clark, JS, Anderson, NH, et al. 2000Applicability of a “speed” congenic strategy to dissect blood pressure quantitative trait loci on rat chromosome 2.Hypertension35179187PubMedGoogle Scholar
Kierstead, TD, Pipas, JM 1996Database of mutations that alter the large tumor antigen in simian virus 40.Nucleic Acids Res24125126CrossRefPubMedGoogle Scholar
Markel, P, Shu, P, Ebeling, C, Carlson, GA, Nagle, DL, et al. 1997Theoretical and empirical issues for marker-assisted breeding of congenic mouse strains.Nat Genet17280284PubMedGoogle Scholar
Nadeau, JH, Singer, JB, Matin, A, Lander, ES 2000Analysing complex genetic traits with chromosome substitution strains.Nat Genet24221225CrossRefPubMedGoogle Scholar
Snell, GD 1948Methods for the study of histocompatability genes.J Genet4987108Google Scholar
Steen, RG, Kwitek Black, AE, Glenn, C, Gullings Handley, J, Van Etten, W, et al. 1999A high-density integrated genetic linkage and radiation hybrid map of the laboratory rat.Genome Res918PubMedGoogle Scholar
Stoll, M, Cowley Jr, AW, Tonellato, PJ, Greene, AS, Kaldunski, ML, et al. 2001A genomic-systems biology map for cardiovascular function.Science29417231726CrossRefPubMedGoogle Scholar
Watanabe, TK, Bihoreau, MT, McCarthy, LC, Kiguwa, SL, Hishigaki, H, et al. 1999A map of the rat genome containing 5,203 markers: 4,700 microsatellites and 605 genes in a rat, mouse and human comparative map.Nat Genet22736Google Scholar
© Springer-Verlag New York Inc. 2003