2003 Fiscal Year Final Research Report Summary
Etiology of the most common constitutional translocation in human, t(11;22)
| Project/Area Number |
14370775
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human genetics
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| Research Institution | Fujita Health University (2003)
Osaka University (2002) |
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Principal Investigator |
KURAHASHI Hiroki Fujita Health University, Institute For Comprehensive Medical Science, Professor, 総合医科学研究所, 教授 (30243215)
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| Project Period (FY) |
2002 – 2003
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| Keywords | chromosome / translocation / breakpoint / palindrome / cruciform / chromosome 11 / chromosome 22 / t(11;22) |
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| Research Abstract |
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.
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Research Products
(10 results)
