Heterogeneity in telomere length of human chromosomes.

Vertebrate chromosomes terminate in variable numbers of T2AG3 nucleotide repeats. In order to study telomere repeats at individual chromosomes, we developed novel, quantitative fluorescence in situ hybridization procedures using labeled (C3TA2)3 peptide nucleic acid and digital imaging microscopy. Telomere fluorescence intensity values from metaphase chromosomes of cultured human hematopoietic cells decreased with the replication history of the cells, varied up to six-fold within a metaphase, and were similar between sister chromatid telomeres. Surprisingly, telomere fluorescence intensity values within normal adult bone marrow metaphases did not show a normal distribution, suggesting that a minimum number of repeats at each telomere is required and/or maintained during normal hematopoiesis.

[1]  C. Harley,et al.  Differential Expression of Telomerase Activity in Hematopoietic Progenitors from Adult Human Bone Marrow , 1996, Stem cells.

[2]  J. Shay,et al.  Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. , 1995, Journal of immunology.

[3]  D. Broccoli,et al.  Telomerase activity in normal and malignant hematopoietic cells. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[4]  E. Blackburn,et al.  Runaway telomere elongation caused by telomerase RNA gene mutations , 1995, Nature.

[5]  J. Shay,et al.  Time, telomeres and tumours: is cellular senescence more than an anticancer mechanism? , 1995, Trends in cell biology.

[6]  K. Oshimi,et al.  Telomeric DNA in normal and leukemic blood cells. , 1995, The Journal of clinical investigation.

[7]  S. Kolvraa,et al.  Staining of human telomeres with primed in situ labeling (PRINS). , 1995, Cytogenetics and cell genetics.

[8]  C B Harley,et al.  Specific association of human telomerase activity with immortal cells and cancer. , 1994, Science.

[9]  C B Harley,et al.  Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[10]  C. Cremer,et al.  Rapid fluorescence in situ hybridization with repetitive DNA probes: quantification by digital image analysis. , 1994, Cytometry.

[11]  E. Blackburn.  Telomeres: No end in sight , 1994, Cell.

[12]  R. Moyzis,et al.  In situ hybridization using synthetic oligomers as probes for centromere and telomere repeats. , 1994, Methods in molecular biology.

[13]  Virginia A. Zakian,et al.  Loss of a yeast telomere: Arrest, recovery, and chromosome loss , 1993, Cell.

[14]  Peter E. Nielsen,et al.  PNA hybridizes to complementary oligonucleotides obeying the Watson–Crick hydrogen-bonding rules , 1993, Nature.

[15]  C B Harley,et al.  Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. , 1993, American journal of human genetics.

[16]  C B Harley,et al.  Telomere length predicts replicative capacity of human fibroblasts. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[17]  C. Harley,et al.  The telomere hypothesis of cellular aging , 1992, Experimental Gerontology.

[18]  C B Harley,et al.  Telomere end-replication problem and cell aging. , 1992, Journal of molecular biology.

[19]  P. Nederlof,et al.  Quantification of inter- and intra-nuclear variation of fluorescence in situ hybridization signals. , 1992, Cytometry.

[20]  P. Nederlof,et al.  Quantification of fluorescence in situ hybridization signals by image cytometry. , 1992, Cytometry.

[21]  M. Egholm,et al.  Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. , 1991, Science.

[22]  Robin C. Allshire,et al.  Telomere reduction in human colorectal carcinoma and with ageing , 1990, Nature.

[23]  C. Harley,et al.  Telomeres shorten during ageing of human fibroblasts , 1990, Nature.

[24]  R. Myers,et al.  Structure and variability of human chromosome ends , 1990, Molecular and cellular biology.

[25]  L. S. Cram,et al.  A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[26]  S. Cross,et al.  Telomeric repeat from T. thermophila cross hybridizes with human telomeres , 1988, Nature.