High-resolution comparative physical mapping of mouse chromosome 10 in the region of homology with human chromosome 21.

Comparative mapping of human and mouse chromosomes can be used to predict locations of homologous loci between the species, provides the substrate to examine the process of chromosomal evolution, and facilitates the continuing development of mouse genetic models for human disorders. A YAC contig of the region of mouse Chromosome (Chr) 10 (MMU10) that demonstrates conserved linkage with the distal portion of human Chr 21 (HSA21) has been constructed. The contig contains all known genes mapped in both species, defines the proximal region of homology between MMU10 and HSA22, and contains the evolutionary junction between HSA21 and HSA22 on MMU10. It consists of 23 YACs and 2 PACs, and covers 3.2 Mb of MMU10. The average marker density for this region is 1 marker/69 kb. Nine of 22 expressed sequences are mapped here for the first time in mouse, and two are newly characterized expressed sequences. The contig also contains 12 simple sequence repeats (SSRs) and 16 YAC and PAC endclone markers. YAC fragmentation analysis was used to create a physical map for the proximal 2.2 Mb of the contig. Cloning of the corresponding region of HSA21 has proven difficult, and the mouse contig includes segments absent from previously described sequence ready maps of HSA21.

Physical and comparative mapping of distal mouse chromosome 16. 5 p5.

Distal mouse Chromosome 16 (Chr. 16) includes a region of conserved linkage with human Chromosome 21 (Chr. 21). Mouse models of Down syndrome based on trisomy of distal Chr. 16 have several phenotypes similar to those seen in human patients and have proven useful for correlating dosage imbalance of specific genes with specific developmental anomalies. The degree to which such findings can be related to Down syndrome depends on how well the conserved synteny is maintained. Twenty-four genes have been mapped in both species and there are no discordancies, but the region could carry hundreds of genes. Comparative sequence represents the ultimate comparative map and will aid in identification of genes and their regulatory sequences. A physical map of the distal 4.5 Mb of Chr. 16 has been assembled as an essential step toward a map of sequence-ready templates. The map consists of 51 YACs and 15 BACs and includes 18 transcripts, 9 of which are mapped for the first time in mouse, and 3 of which are, for the first time, described in either species. YAC fragmentation was used to precisely localize the 49 markers on the map. Comparison of this physical map with that of the corresponding region on Chr. 21 shows conservation not only of gene order but of size in the 3 Mb from Cbr1 to Ets2; distal to Ets2, the human map is expanded.

High-resolution recombinational map of mouse chromosome 16.

Five intersubspecific backcrosses and an intercross were used to establish a sex-averaged recombinational map spanning 56 cM across most of mouse Chromosome 16 (Chr 16). A total of 123 markers were ordered using an interval mapping approach to identify 425 recombination sites in a collection of 1154 meioses from 1155 progeny generated in the six crosses. The markers include the 10 "classic" Chr 16 reference markers, 26 additional genes or transcripts including two phenotypic markers (Pit1dw and Kcnj6wv), and 87 simple sequence length polymorphisms (SSLPs). One set of monozygotic twins was detected among the 304 meioses mapped to highest resolution. The reference markers and SSLPs allow the map to be well integrated with existing maps of Chr 16. The average distance between crossover sites is less than 500 kb for most chromosomes, making this collection of recombinant chromosomes useful as a binning and ordering resource for YAC-based physical map assembly on Chr 16.