1994 Fiscal Year Final Research Report Summary
Analysis of molecular abnormalities in DiGeorge syndrome
| Project/Area Number |
05670673
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | Osaka University |
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Principal Investigator |
KURAHASHI Hiroki Osaka University, Medical School, Assistant Professor, 医学部, 助手 (30243215)
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| Co-Investigator(Kenkyū-buntansha) |
NISHISYO Isamu Osaka University, Medical School, Associate Professor, 医学部, 助教授 (10228182)
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| Project Period (FY) |
1993 – 1994
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| Keywords | DiGeorge syndrome(DGS) / conotruncal anomaly face / chromosome 22 / microdeletion / cDNA / leucine zipper / transcriptional factor |
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| Research Abstract |
The microdeletion in DiGeorge syndrome(DGS) and conotruncal anomaly face syndrome has been localized at 22q11. In order to iosolate responsible gene for these syndromes, cosmid library was constructed from the somatic cell hybrid containing human intact chromosome 22 as its only human component. Another somatic cell hybrids carrying a different human chromosome translocation allowed us to assign some of these cosmids to 22q11, and then the cosmids which are located in the microdeletion were selected by dosage analysis. Further to isolate deleted clones, microclone library was constructed with the aid of microdissection of 22q11, and the deleted clones were also selected by dosage analysis. Screening of cosmid library and subsequent cosmid walking allowed us to obtain two cosmid contigs, whose order was identified by fluorescence in situ hybridization. By direct selection strategy, a 4.3kb cDNA was obtained from fetal brain cDNA library. Sequence analysis of the cDNA revealed an open reading frame encoding 552 amino acids which had several characteristics of DNA-binding proteins, such as basic-leucine-zipper domain. The gene, designated LZTR-1, which was transcribed in several essential fetal organs, proved to be hemizygously deleted in most patients, but not in GM00980, which has a deletion that demarcates the shortest region of overlap. However, several of its structural characteristics identifying it as transcriptional factor suggest that it plays a crucial role in embryogenesis and that haploinsufficiency of this gene may be partly related to development of DGS.
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