Physical and Comparative Mapping of Distal Mouse Chromosome 16

Abstract

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 fromCbr1 to Ets2; distal to Ets2, the human map is expanded.[The sequence data described in this paper have been submitted to GenBank. See Tables 1 and 2 for accession nos.]

Sequence-ready physical map of the mouse Chromosome 16 region with conserved synteny to the human Velocardiofacial syndrome region on 22q11.2

“…However, the genomic segment from D16h22s1738e to Hira spans 620 kb in the mouse and 820 kb in humans. Similar compression of mouse physical maps in regions of perfectly conserved linkage with human has been observed between mouse Chr 16 and Chr 10 and corresponding regions of human Chr 21 (Cabin et al 1998;Cole et al 1999). It is not clear whether this phenomenon is general.…”

Chromosome Evolution: The Junction of Mammalian Chromosomes in the Formation of Mouse Chromosome 10

“…In contrast, the interstitial position on MMU 10 of a segment corresponding to the distal end of HSA 21 and the junction of this information with material from HSA 22 has been seen only in the rodent lineage, suggesting a relatively more recent reorganization in mice. Despite these rearrangements, gene content and order on HSA 21 are highly conserved with MMU 10 (Cole et al 1998;Wiltshire et al 1999) and with MMU 16 (Cabin et al 1998).…”

Perfect Conserved Linkage Across the Entire Mouse Chromosome 10 Region Homologous to Human Chromosome 21

“…Others have shown a high degree of conservation for 2 Mb segments of HSA1/MMU3 (Kingsmore et al 1989), and for human and mouse X chromosomes (Cooper et al 1993). A high-resolution YAC-based fragmentation map of distal MMU16 shows perfect conservation of gene order across 4.5 Mb of conserved linkage with HSA21, with conserved gene spacing for about two thirds of this length (Cabin et al 1998). This MMU10 contig also shows perfect conservation of gene content and order when compared to the orthologous region of HSA21, with average conserved marker spacing of 90 kb.…”