Abstract
Ts65Dn is a mouse model of Down syndrome: a syndrome that results from chromosome (Chr) 21 trisomy and is associated with congenital defects, cognitive impairment, and ultimately Alzheimer’s disease. Ts65Dn mice have segmental trisomy for distal mouse Chr 16, a region sharing conserved synteny with human Chr 21. As a result, this strain harbors three copies of over half of the human Chr 21 orthologs. The trisomic segment of Chr 16 is present as a translocation chromosome (Mmu1716), with breakpoints that have not been defined previously. To molecularly characterize the Chrs 16 and 17 breakpoints on the translocation chromosome in Ts65Dn mice, we used a selective enrichment and high-throughput paired-end sequencing approach. Analysis of paired-end reads flanking the Chr 16, Chr 17 junction on Mmu1716 and de novo assembly of the reads directly spanning the junction provided the precise locations of the Chrs 16 and 17 breakpoints at 84,351,351 and 9,426,822 bp, respectively. These data provide the basis for low-cost, highly efficient genotyping of Ts65Dn mice. More importantly, these data provide, for the first time, complete characterization of gene dosage in Ts65Dn mice.
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Acknowledgments
We are grateful to the High Throughput Sequencing and Genome Sciences cores at The Jackson Laboratory for their excellent services and advice. The Transgenic Genotyping core at The Jackson Laboratory provided DNA samples and genotyping data that were critical for validation. This work was supported by funding from NICHD CYTO-01, a Cancer Center Core Grant at The Jackson Laboratory (CA34196), and NIH DE021034 (RJR).
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An erratum to this article can be found at http://dx.doi.org/10.1007/s00335-011-9367-x
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335_2011_9357_MOESM1_ESM.xlsx
Supplementary Table 1 Ensembl and NCBI gene annotations and Ensembl-predicted human orthologs for Mmu17, from 0 to 9,426,822 bp. Ensembl prediction of orthology is based on maximum likelihood phylogenetic gene trees (Vilella et al. 2009). Orthology information is not available (N/A) from Ensembl for noncoding RNA genes and for genes that are predicted by NCBI (RefSeq) only. Supplementary material 1 (XLSX 92 kb)
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Reinholdt, L.G., Ding, Y., Gilbert, G.T. et al. Molecular characterization of the translocation breakpoints in the Down syndrome mouse model Ts65Dn. Mamm Genome 22, 685–691 (2011). https://doi.org/10.1007/s00335-011-9357-z
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DOI: https://doi.org/10.1007/s00335-011-9357-z