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Mammalian Genome

, Volume 22, Issue 11–12, pp 685–691 | Cite as

Molecular characterization of the translocation breakpoints in the Down syndrome mouse model Ts65Dn

  • Laura G. Reinholdt
  • Yueming Ding
  • Griffith T. Gilbert
  • Anne Czechanski
  • Jeffrey P. Solzak
  • Randall J. Roper
  • Mark T. Johnson
  • Leah Rae Donahue
  • Cathleen Lutz
  • Muriel T. Davisson
Article

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.

Keywords

Bacterial Artificial Chromosome Down Syndrome Translocation Chromosome Copy Number Gain Breakpoint Region 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

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).

Supplementary material

335_2011_9357_MOESM1_ESM.xlsx (93 kb)
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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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Laura G. Reinholdt
    • 1
  • Yueming Ding
    • 2
  • Griffith T. Gilbert
    • 1
  • Anne Czechanski
    • 1
  • Jeffrey P. Solzak
    • 3
  • Randall J. Roper
    • 3
  • Mark T. Johnson
    • 4
  • Leah Rae Donahue
    • 1
  • Cathleen Lutz
    • 1
  • Muriel T. Davisson
    • 1
  1. 1.The Jackson Laboratory, Genetic Resource ScienceBar HarborUSA
  2. 2.Regeneron Pharmaceuticals Inc.TarrytownUSA
  3. 3.Department of BiologyIndiana University-Purdue University IndianapolisIndianapolisUSA
  4. 4.Department of Obstetrics and GynecologyUniversity of Michigan Medical SchoolAnn ArborUSA

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