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

• Published in: Mammalian genome 2011-12, Vol.22 (11-12), p.685-691
• Main Authors: Reinholdt, Laura G, Ding, Yueming, Gilbert, Griffith T, Czechanski, Anne, Solzak, Jeffrey P, Roper, Randall J, Johnson, Mark T, Donahue, Leah Rae, Lutz, Cathleen, Davisson, Muriel T
• Format: Article
• Language: English
• Subjects: Alzheimer disease; Alzheimer's disease; Animal Genetics and Genomics; Animal models; Animals; Base Sequence; Biomedical and Life Sciences; Breakpoints; Cell Biology; chromosome translocation; Chromosome translocations; chromosomes; Cognitive ability; congenital abnormalities; Congenital defects; Data processing; Disease Models, Animal; Down syndrome; Down Syndrome - genetics; Down Syndrome - pathology; Down's syndrome; Evolutionary conservation; Female; Gene Dosage; Genotype; Genotyping; High-Throughput Nucleotide Sequencing; Human Genetics; humans; Life Sciences; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Molecular modelling; Neurodegenerative diseases; Polymorphism, Single Nucleotide; Sequence Alignment; Sequence Analysis, DNA; Synteny; Translocation, Genetic; trisomics; Trisomy
• ISSN: 0938-8990; 1432-1777
• DOI: 10.1007/s00335-011-9357-z

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.