Mouse Telocentric Sequences Reveal a High Rate of Homogenization and Possible Role in Robertsonian Translocation

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 23; pp. 8786 - 8791
• Main Authors: Kalitsis, Paul, Griffiths, Belinda, Choo, K. H. Andy
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 06-06-2006; National Acad Sciences
• Subjects: Animals; Artificial satellites; Base Sequence; Biological Sciences; Centromere - genetics; Centromeres; Chromosomes; Chromosomes, Mammalian - genetics; Clone Cells; Conserved Sequence - genetics; DNA; DNA Methylation; DNA, Satellite - genetics; Eukaryotes; Evolution; Female; Genome - genetics; Genomes; Genomics; Homogenization; Long Interspersed Nucleotide Elements - genetics; Male; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Monomers; Regional identity; Rodents; Satellite DNA; Telomere - genetics; Telomeres; Translocation, Genetic - genetics
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0600250103

The telomere and centromere are two specialized structures of eukaryotic chromosomes that are essential for chromosome stability and segregation. These structures are usually characterized by large tracts of tandemly repeated DNA. In mouse, the two structures are often located in close proximity to form telocentric chromosomes. To date, no detailed sequence information is available across the mouse telocentric regions. The antagonistic mechanisms for the stable maintenance of the mouse telocentric karyotype and the occurrence of whole-arm Robertsonian translocations remain enigmatic. We have identified large-insert fosmid clones that span the telomere and centromere of several mouse chromosome ends. Sequence analysis shows that the distance between the telomeric T₂AG₃ and centromeric minor satellite repeats range from 1.8 to 11 kb. The telocentric regions of different mouse chromosomes comprise a contiguous linear order of T₂AG₃ repeats, a highly conserved truncated long interspersed nucleotide element 1 repeat, and varying amounts of a recently discovered telocentric tandem repeat that shares considerable identity with, and is inverted relative to, the centromeric minor satellite DNA. The telocentric domain as a whole exhibits the same polarity and a high sequence identity of >99% between nonhomologous chromosomes. This organization reflects a mechanism of frequent recombinational exchange between nonhomologous chromosomes that should promote the stable evolutionary maintenance of a telocentric karyotype. It also provides a possible mechanism for occasional inverted mispairing and recombination between the oppositely oriented TLC and minor satellite repeats to result in Robertsonian translocations.