Mapping to Molecular Resolution in the T to H-2 Region of the Mouse Genome with a Nested Set of Meiotic Recombinants

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 86; no. 1; pp. 222 - 226
• Main Authors: King, Thomas R., Dove, William F., Herrmann, Bernhard, Moser, Amy R., Shedlovsky, Alexandra
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.01.1989; National Acad Sciences
• Subjects: Alleles; Animals; Antigens, Viral, Tumor - genetics; Biological and medical sciences; Chromosome Mapping; Chromosomes; Crossovers; DNA; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genes; Genes, Lethal; Genetic loci; Genetic mutation; Genetics of the immune response; Genotype; Genotypes; H-2 Antigens - genetics; Immunobiology; Medical genetics; Meiosis; Mice; Mice, Inbred Strains; Mice, Neurologic Mutants; Mutation; Phenotypes; Recombination, Genetic; Genetic mapping; Vertebrata; Mammalia; Investigation method; Mouse; Major histocompatibility system; Rodentia; Development; Meiosis; Mutation; Genome; H-2-System
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.1.222

We describe a meiotic fine-structure mapping strategy for achieving molecular access to developmental mutations in the mouse. The induction of lethal point mutations with the potent germ-line mutagen N-ethyl-N-nitrosourea has been reported. One lethal mutation of prime interest is an allele at the quaking locus on chromosome 17. To map this mutation, quakinglethal-1, we have intercrossed hybrid mice that carry distinct alleles at many classical and DNA marker loci on proximal chromosome 17. From this cross we have obtained 337 animals recombinant in the T to H-2 region. This number of crossovers provides a mapping resolution in the size range of single mammalian genes if recombinational hot spots are absent. DNA samples obtained from these recombinant animals can be used retrospectively to map any restriction fragment length polymorphism in the region. This set of DNA samples has been used to map the molecular marker D17RP17 just distal of quakinglethal-1. With the nested set of crossover DNA samples and appropriate cloning techniques, this tightly linked marker can be used to clone the quaking locus.