2004 Fiscal Year Final Research Report Summary
Study of Mutations in Boundary Regions of GC% Mosaic Domains On Human Genome Using Microarray-CGH technique
| Project/Area Number |
14580579
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
環境影響評価(含放射線生物学)
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| Research Institution | Radiation Effects Research Foundation |
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Principal Investigator |
KODAIRA Mieko , 財団法人・放射線影響研究所・遺伝学部, 副主任研究員 (60344412)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Norio , 財団法人・放射線影響研究所・遺伝学部, 副部長(研究員) (40333546)
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| Project Period (FY) |
2002 – 2004
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| Keywords | microarray-CGH technique / GC% transition regions in human genome / DNA-conformation / radiation / deletion mutation |
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| Research Abstract |
It is suggested that the sharp GC% transition regions between different components of megabase-level mosaic domains named isochors (hereinafter as referred to as "the boundary regions") construct special conformations and thus they are likely to have insertion-, deletion-, and rearrangement-type mutations. In this study, we elucidated the genetic instability and the radiation effects on these boundary regions in the somatic cells and germ cells.
1.We isolated 22 radiation-induced HPRT-deficients with large deletions and identified the range of deletions around the HPRT locus by PCR. The GC% distribution shows one possible "boundary region" around 4〜4.5 Mb from 5' of the HPRT, but most of deletion ends don't exist on this boundary. We also analyzed 7 clones for identifying the deletion and duplications by using the array-CGH method. The arrays for this analysis contain BAG clones distributed every 1.5 Mb on chromosome 5 to 22 and clones covering about 8 Mb of chromosome 11 containing two "boundary regions". We detected 5 large deletions (15 to>20 Mb) in 3 of 7 clones, but no deletion end was mapped on the boundary region identified on chromosome 11. We found 3 deletions extend from the "possible boundary region" suggested by the analysis of GC% distribution.
2.We also screened DNA from 80 children of A-bomb survivors by array-CGH analysis using the arrays containing 2300 BAG clones from chromosome 1 to 22 and 66 BAG clones covering two "boundary regions" on chromosome 11,but we didn't find any de novo mutations among them.
Although this result cannot show the evidence that radiation-induced deletions are mainly triggered by DNA damages on the boundary regions, it is still important to study the difference of mutation, spectrum between genome units having specific structures.
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Research Products
(31 results)
