And yet, the very nature of the exalted genetic company kept by the zebrafish makes comparisons inevitable and serves to reveal its lack of molecular sophistication. In brief, cloning of the mutations can be hard. The majority of mutations generated to date are single-base-pair changes generated by exposure to the chemical ethylnitrosourea. Mutation cloning requires assignment of chromosomal position to the mutant locus, a process that begins with meiotic mapping, and may then require laborious “walks” along genomic DNA. Dense genetic and physical maps, accompanied by the placement of many known genes along both, are now under construction to facilitate the cloning process. Gene mapping is key to abbreviating mutation cloning time, because such mapping provides candidate genes for the mutations. A combination of genetic and physical maps has been the hallmark of success of the Human Genome Project, facilitating cloning of genes in the other model organisms, including human, and forming the underpinning for the most powerful tool, sequencing of the entire genome. Radiation hybrid (RH) maps, reported by Hukriede et al. (1) in a recent issue of the Proceedings and by Geisler et al. (2), add an important buttress to the cloning infrastructure.
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Mark C. Fishman (1999) studied this question.
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