Broken chromosomes are highly unstable and are subject to chromosome fusion or loss. As an exception, healing of human chromosomes occurs which can lead to constitutional or acquired terminal chromosome deletion disorders. Both de novo telomere addition at the breakpoint and telomere capture have been implicated as healing mechanisms. We investigated the origin of the novel ends of chromosomes 4p and 5p in a patient with the Wolf-Hirschhorn syndrome and in 4 patients with the Cri-du-Chat syndrome by chromosome microdissection. Our results suggest that de novo telomere synthesis by telomerase is the main mechanism of chromosome healing in constitutional chromosome deletions.

1.
Anonymous: A complete set of human telomeric probes and their clinical application. National Institutes of Health and Institute of Molecular Medicine collaboration. Nature Genet 14:86–89 (1996).
2.
Blackburn E, Greider CW: Telomeres. Cold Spring Harbor Monograph Series, no 29. (Cold Spring Harbor Press, Cold Spring Harbor 1995).
3.
Church DM, Bengtsson U, Nielsen KV, Wasmuth JJ, Niebuhr E: Molecular definition of deletions of different segments of distal 5p that result in distinct phenotypic features. Am J hum Genet 56:1162–1172 (1995).
4.
Biessmann H, Mason JM: Genetics and molecular biology of telomeres. Adv Genet 30:185–249 (1992).
5.
Flint J, Craddock CF, Villegas A, Bentley DP, Williams HJ, Galanello R, Cao A, Wood WG, Ayyub H, Higgs DR: Healing of broken human chromosomes by the addition of telomeric repeats. Am J hum Genet 55:505–512 (1994).
6.
Greider CW: Telomere length regulation. A Rev Biochem 65:337–365 (1996).
7.
Lamb J, Harris PC, Wilkie AO, Wood WG, Dauwerse JG, Higgs DR: De novo truncation of chromosome 16p and healing with (TTAGGG)n in the alpha-thalassemia/mental retardation syndrome (ATR-16). Am J hum Genet 52:668–676 (1993).
8.
Lansdorp PM, Verwoerd NP, van de Rijke FM, Dragowska V, Little M-T, Dirks RW, Raap AK, Tanke HJ: Heterogeneity in telomere length of human chromosomes. Hum molec Genet 5:685–691 (1996).
9.
Maraschio P, Tupler R, Barbierato L, Dainotti E, Larizza D, Bernardi F, Hoeller H, Garau A, Tiepolo L: An analysis of Xq deletions. Hum Genet 97:375–381 (1996).
10.
Melek M, Shippen DE: Chromosome healing: spontaneous and programmed de novo telomere formation by telomerase. Bioessays 18:301 (1996).
11.
Meltzer PS, Guan XY, Trent JM: Telomere capture stabilizes chromosome breakage. Nature Genet 4:252–255 (1993).
12.
Rubtsov N, Senger G, Kuzcera H, Neumann A, Kelbova C, Junker K, Beensen V, Claussen U: Interstitial deletion of chromosome 6q: precise definition of the breakpoints by microdissection, DNA amplification, and reverse painting. Hum Genet 97:705–709 (1996).
13.
Schröck E, Du Manoir S, Veldman T, Schoell B, Wienberg J, Ferguson-Smith MA, Ning Y, Ledbetter DH, Bar-Am I, Soenksen D, Garini Y, Ried T: Multicolor spectral karyotyping of human chromosomes. Science 273:494–497 (1996).
14.
Silverman GA, Schneider SS, Massa HF, Flint A, Lalande M, Leonard JC, Overhauser J, van den Engh G, Trask BJ: The 18q– syndrome: analysis of chromosomes by bivariate flow karyotyping and the PCR reveals a successive set of deletion breakpoints within 18q21.2→q22.2. Am J hum Genet 56:926–937 (1995).
15.
Simmons AD, Goodart SA, Gallardo TD, Overhauser J, Lovett M: Five novel genes from the Cri-du-chat critical region isolated by direct selection. Hum Mol Genet 4:295–302 (1995).
16.
Speicher MR, Gwyn Ballard S, Ward DC: Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nature Genet 12:368–375 (1996).
17.
Telenius H, Carter NP, Bebb CE, Nordenskjold M, Ponder BAJ, Tunnacliffe A: Degenerate oligonucleotide-primed PCR: general amplification of target DNA by a single degenerate primer. Genomics 13:718–725 (1992).
18.
Wilkie AO, Lamb J, Harris PC, Finney RD, Higgs DR: A truncated human chromosome 16 associated with alpha-thalassaemia is stabilized by addition of telomeric repeat (TTAGGG)n. Nature 346:868–871 (1990).
19.
Wintle RF, Costa T, Haslam RH, Teshima IE, Cox DW: Molecular analysis redefines three human chromosome 14 deletions. Hum Genet 95:495–500 (1995).
20.
Yu GL, Blackburn EH: Developmentally programmed healing of chromosomes by telomerase in Tetrahymena. Cell 67:823–832 (1991).
21.
Zhang J, Meltzer P, Jenkins R, Guan XY, Trent J: Application of chromosome microdissection probes for elucidation of BCR-ABL fusion and variant Philadelphia chromosome translocations in chronic myelogenous leukemia. Blood 81:3365–3371 (1993a).
22.
Zhang J, Trent JM, Meltzer PS: Rapid isolation and characterization of amplified DNA by chromosome microdissection: identification of IGF1R amplification in malignant melanoma. Oncogene 8:2827–2831 (1993b).
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