Document Detail

Increased rate of spontaneous mitotic recombination in T lymphocytes from a Bloom's syndrome patient using a flow-cytometric assay at HLA-A locus.
MedLine Citation:
PMID:  8063614     Owner:  NLM     Status:  MEDLINE    
Bloom's syndrome (BS) is an autosomal recessive disorder conferring high propensity for cancer and displaying a high degree of genetic instability; the frequency of sister chromatid exchange is characteristically 10 times above background. The symmetrical four-armed chromatid interchanges are much more readily detected in peripheral blood lymphocytes of BS patients, suggesting that the frequency of somatic recombination is also increased. In the present study, the rate of spontaneous loss of HLA-A allele expression was estimated following fluctuation analysis in cultured T lymphocytes using a flow-cytometric assay. It was found to be 10 times or more higher than normal in lymphocytes from a BS patient. Molecular and chromosome analyses showed that all 13 independent variants from the patient were most likely derived from somatic recombinations. Further tests for loss of heterozygosity at a closely linked proximal locus, HLA-DQA1, showed that as many as half of the recombinants retained heterozygosity irrespective of the donor. The results suggest that the HLA region is hyperrecombinogenic in somatic cells and that the elevated recombination rate in BS cells results from the general increase at ordinary sites and not from random creation of unusual sites for recombination.
Y Kusunoki; T Hayashi; Y Hirai; J Kushiro; K Tatsumi; T Kurihara; M Zghal; M R Kamoun; H Takebe; A Jeffreys
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Japanese journal of cancer research : Gann     Volume:  85     ISSN:  0910-5050     ISO Abbreviation:  Jpn. J. Cancer Res.     Publication Date:  1994 Jun 
Date Detail:
Created Date:  1994-09-21     Completed Date:  1994-09-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8509412     Medline TA:  Jpn J Cancer Res     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  610-8     Citation Subset:  IM    
Department of Radiobiology, Radiation Effects Research Foundation, Hiroshima.
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MeSH Terms
Bloom Syndrome / blood*,  genetics*
Cell Cycle / physiology
Cells, Cultured
Chromosomes, Human
Flow Cytometry
HLA-A Antigens / genetics*
HLA-DQ Antigens / genetics
Middle Aged
Mitosis / physiology*
Polymerase Chain Reaction
Recombination, Genetic*
Sister Chromatid Exchange
T-Lymphocytes / cytology*,  physiology*
Reg. No./Substance:
0/HLA-A Antigens; 0/HLA-DQ Antigens; 0/HLA-DQA1

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