A truncated human chromosome 16 associated with α thalassaemia is stabilized by addition of telomeric repeat (TTAGGG)n

Andrew O M Wilkie, Janette Lamb, Peter C Harris, Roger D. Finney, Douglas R. Higgs

Research output: Contribution to journalArticle

215 Citations (Scopus)

Abstract

THE instability of chromosomes with breaks induced by X-irradiation led to the proposal that the natural ends of chromosomes are capped by a specialized structure, the telomere1. Telomeres prevent end-to-end fusions and exonucleolytic degradation, enable the end of the linear DNA molecule to replicate, and function in cell division (reviewed in ref. 2). Human telomeric DNA comprises ∼ 2-20 kilobases (kb) of the tandemly repeated sequence (TTAGGG)n oriented 5′ → 3′ towards the end of the chromosome3,4, interspersed with variant repeats in the proximal region5. Immediately subtelomeric lie families of unrelated repeat motifs (telomere-associated sequences) whose function, if any, is unknown6,7. In lower eukaryotes the formation and maintenance of telomeres may be mediated enzymatically (by telomerase)8 or by recombination9; in man the mechanisms are poorly understood, although telomerase has been identified in HeLa cells4. Here we describe an α thalassaemia10 mutation associated with terminal truncation of the short arm of chromosome 16 (within band 16p13.3) to a site 50 kb distal to the α globin genes, and show that (TTAGGG)n has been added directly to the site of the break. The mutation is stably inherited, proving that telomeric DNA alone is sufficient to stabilize the broken chromosome end. This mechanism may occur in any genetic disease associated with chromosome truncation.

Original languageEnglish (US)
Pages (from-to)868-871
Number of pages4
JournalNature
Volume346
Issue number6287
StatePublished - Aug 30 1990
Externally publishedYes

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Chromosomes, Human, Pair 16
Thalassemia
Telomere
Human Chromosomes
Chromosomes
Telomerase
DNA
Chromosome Breakage
Mutation
Inborn Genetic Diseases
Globins
Eukaryota
Cell Division
Maintenance
Genes

ASJC Scopus subject areas

  • General

Cite this

A truncated human chromosome 16 associated with α thalassaemia is stabilized by addition of telomeric repeat (TTAGGG)n . / Wilkie, Andrew O M; Lamb, Janette; Harris, Peter C; Finney, Roger D.; Higgs, Douglas R.

In: Nature, Vol. 346, No. 6287, 30.08.1990, p. 868-871.

Research output: Contribution to journalArticle

Wilkie, Andrew O M ; Lamb, Janette ; Harris, Peter C ; Finney, Roger D. ; Higgs, Douglas R. / A truncated human chromosome 16 associated with α thalassaemia is stabilized by addition of telomeric repeat (TTAGGG)n In: Nature. 1990 ; Vol. 346, No. 6287. pp. 868-871.
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abstract = "THE instability of chromosomes with breaks induced by X-irradiation led to the proposal that the natural ends of chromosomes are capped by a specialized structure, the telomere1. Telomeres prevent end-to-end fusions and exonucleolytic degradation, enable the end of the linear DNA molecule to replicate, and function in cell division (reviewed in ref. 2). Human telomeric DNA comprises ∼ 2-20 kilobases (kb) of the tandemly repeated sequence (TTAGGG)n oriented 5′ → 3′ towards the end of the chromosome3,4, interspersed with variant repeats in the proximal region5. Immediately subtelomeric lie families of unrelated repeat motifs (telomere-associated sequences) whose function, if any, is unknown6,7. In lower eukaryotes the formation and maintenance of telomeres may be mediated enzymatically (by telomerase)8 or by recombination9; in man the mechanisms are poorly understood, although telomerase has been identified in HeLa cells4. Here we describe an α thalassaemia10 mutation associated with terminal truncation of the short arm of chromosome 16 (within band 16p13.3) to a site 50 kb distal to the α globin genes, and show that (TTAGGG)n has been added directly to the site of the break. The mutation is stably inherited, proving that telomeric DNA alone is sufficient to stabilize the broken chromosome end. This mechanism may occur in any genetic disease associated with chromosome truncation.",
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