Comparative mapping, which compares the location of homologous genes in different species, is a powerful tool for studying genome evolution. Comparative maps suggest that rates of chromosomal change in mammals can vary from one to ten rearrangements per million years. On the basis of these rates we would expect 84 to 600 conserved segments in a chicken comparison with human or mouse. Here we build comparative maps between these species and estimate that numbers of conserved segments are in the lower part of this range. We conclude that the organization of the human genome is closer to that of the chicken than the mouse and by adding comparative mapping results from a range of vertebrates, we identify three possible phases of chromosome evolution. The relative stability of genomes such as those of the chicken and human will enable the reconstruction of maps of ancestral vertebrates.
The chicken karyotype comprises six pairs of large macrochromosomes and 33 pairs of smaller microchromosomes. Cytogenetic evidence suggests that microchromosomes may be more gene-dense than macrochromosomes. In this paper, we compare the gene densities on macrochromosomes and microchromosomes based on sequence sampling of cloned genomic DNA, and from the distribution of genes mapped by genetic linkage and physical mapping. From these different approaches we estimate that microchromosomes are twice as gene-dense as macrochromosomes and show that sequence sampling is an effective means of gene discovery in the chicken. Using this method we have also detected a conserved linkage between the genes for serotonin 1D receptor (HTR1D) and the platelet-activating factor receptor protein gene (PTAFR) on chicken chromosome 5 and human chromosome 1p34.3. Taken together with its advantages as an experimental animal, and public access to genetic and physical mapping resources, the chicken is a useful model genome for studies on the structure, function and evolution of the vertebrate genome.
The ability to carry out high-resolution genetic mapping at high throughput in the mouse is a critical rate-limiting step in the generation of genetically anchored contigs in physical mapping projects and the mapping of genetic loci for complex traits. To address this need, we have developed an efficient, high-resolution, large-scale genome mapping system. This system is based on the identification of polymorphic DNA sites between mouse strains by using interspersed repetitive sequence (IRS) PCR. Individual cloned IRS PCR products are hybridized to a DNA array of IRS PCR products derived from the DNA of individual mice segregating DNA sequences from the two parent strains. Since gel electrophoresis is not required, large numbers of samples can be genotyped in parallel. By using this approach, we have mapped >450 polymorphic probes with filters containing the DNA of up to 517 backcross mice, potentially allowing resolution of 0.14 centimorgan. This approach also carries the potential for a high degree of efficiency in the integration of physical and genetic maps, since pooled DNAs representing libraries of yeast artificial chromosomes or other physical representations of the mouse genome can be addressed by hybridization of filter representations of the IRS PCR products of such libraries.Mouse genetics is one of the most powerful tools for the analysis of almost all aspects of vertebrate biology including development, physiology, and pathobiology. Mouse models have already been developed for many human diseases (1-6).
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