Studies are also in progress to develop a dense gene-based interspecific backcross linkage map of the mouse genome. Such studies have many important applications for mouse genome research, including 1) providing insights into mammalian genome evolution through comparative mapping, 2) facilitating the candidate positional cloning of mouse mutations, 3) helping to develop new mouse models of human disease, and 4) identifying new human disease genes through comparative mapping. Large-scale DNA sequencing and homologous recombination in yeast and bacteria are also being used to expedite the generation of targeting vectors for embryonic stem cell knockouts and for modifying bacterial artificial chromosomes for transgenesis. We are also attempting to develop an efficient Cre/loxP-mediated mitotic recombination system for mouse genome research. In Drosophila, mitotic recombination has been a powerful tool for addressing biological questions such as the developmental potential of cell clones, the autonomy of gene action, cell fact restriction, and patterns of cell division. An efficient mitotic recombination system also has enormous potential for mouse genetics. For example, it could greatly simplify ethylnitrosourea mutagenesis screens that are designed to uncover new recessive mutations as well as facilitate studies of genomic imprinting.
| Dave, Utpal P; Jenkins, Nancy A; Copeland, Neal G (2004) Gene therapy insertional mutagenesis insights. Science 303:333 |
