Etiology of the most common constitutional translocation in human, t(11;22)

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Constitutional t(11;22) is the only known recurrent non-Robertsonian translocation in human. In my previous study, I demonstrated that the breakpoints of t(11;22) were located within palindromic AT-rich repeats. (PATRR). I proposed that the PATRR forms cruciform structure as a mechanism for the translocation. Using translocation-specific PCR, I also identified de novo t(11;22) at high frequency in sperm samples obtained from healthy individuals. In the study of these two years, I have examined the breakpoints of two neurofibromatosis-type 1 (NF1) cases with t(17;22). The breakpoints on chromosome 22 were located within the PATRR where those of t(11;22) resided. The translocations disrupted NF1 gene on chromosome 17. I have localized the breakpoints within a novel PATRR at intron 31 of the gene (Am J Hum Genet, 2003). This added support to my hypothesis for mechanism of palindrome-mediated translocation. Next, 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. I am currently creating model-system of the PATRR-mediated chromosomal translocationusing E. coli or yeast as hosts.