Usingmousegeneticstounderstandhumandisease.pptVIP

Using mouse genetics to understand human disease What we do Genetics: the study of the inheritance of biological phenotype Mendel recognized discrete units of inheritance Theories rediscovered and disputed ca. 1900 Experiments on mouse coat color proved Mendel correct and generalizable to mammals We now recognize this inheritance as being carried by variation in DNA Why mice? Mammals, much better biological model Easy to breed, feed, and house Can acclimatize to human touch Most important: we can experiment in many ways not possible in humans Mice are close to humans Mouse sequence reveals great similarity with the human genome Genomes are rearranged copiesof each other Mouse sequence reveals great similarity with the human genome What we can do Directed matings Inbred lines and crosses Knockouts Transgenics Mutagenesis Nuclear transfer Control exposure to pathogens, drugs, diet, etc. Example: diabetes related miceavailable from The Jackson Labs Type I diabetes (3) Type II diabetes (3) Hyperglycemic (27) Hyperinsulinemic (25) Hypoglycemic (1) Hypoinsulinemic (5) Insulin resistant (30) Impaired insulin processing (7) Impaired wound healing (13) Inbreeding Repeated brother-sister mating leads to completely homozygous genome – no variation! Experimental Crosses Breed two distinct inbred lines Offspring (F1) are all genetically identical – they each have one copy of each chromosome from each parent Further crosses involving F1 lead to mice with unique combinations of the two original strains Experimental Cross Experimental Cross: backcross F1 bred back to one of the parents Backcross (F1 x RED) offspring: 50% red-red 50% red-blue Experimental Cross: F2 intercross One F1 bred to another F1 F2 intercross (F1xF1) offspring: 25% red-red 50% red-blue 25% blue-blue Trait mapping Trait mapping How do we distinguish chromosomes from different strains? Polymorphic DNA markers such as Single Nucleotide Polymorphisms (SNPs) can be used to distinguish the pa