| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2005: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2004: ¥7,700,000 (Direct Cost: ¥7,700,000)
|
|---|
| Research Abstract |
Constitutional t(11;22) is the only known recurrent non-Robertsonian translocation in humans. The breakpoints of t(11;22) are located within palindromic AT-rich repeats (PATRRs) on 11q23 and 22q11. I proposed that the PATRR forms cruciform structure that induces genomic instability leading to the translocation. In this study, I analyzed the tertiary structure of the cloned PATRR of chromosome 11. I demonstrated that the PATRR formed cruciform structure in vitro using 2-dimensional agarose gel electrophoresis, nuclease sensitivity assay, electrophoresis mobility shift assay, and atomic force microscopy (J Biol Chem, 2004). The sequence analysis of the PATRR is difficult because of its potential secondary structure. I optimized the PCR, sequencing, and cloning condition to overcome the difficulty and analyzed polymorphism of the PATRR successfully (Hum Mutat, 2005). Using translocation-specific PCR, I detected de novo t(11;22) at high frequency in sperm samples obtained from normal healthy individuals. I also demonstrated that the polymorphism of the PATRR affects the frequency of de novo translocation (Science, 2006). These observations added support to my hypothesis for mechanism of palindrome-mediated translocation.
|
