Increased instability of human CTG repeat tracts on yeast artificial chromosomes during gametogenesis

Haim Cohen, Dorothy D. Sears, Drora Zenvirth, Philip Hieter, Giora Simchen

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Expansion of trinucleotide repeat tracts has been shown to be associated with numerous human diseases. The mechanism and timing of the expansion events are poorly understood, however, we show that CTG repeats, associated with the human DMPK gene and implanted in two homologous yeast artificial chromosomes (YACs), are very unstable. The instability is 6 to 10 times more pronounced in meiosis than during mitotic division. The influence of meiosis on instability is 4.4 times greater when the second YAC with a repeat tract is not present. Most of the changes we observed in trinucleotide repeat tracts are large contractions of 21 to 50 repeats. The orientation of the insert with the repeats has no effect on the frequency and distribution of the contractions. In our experiments, expansions were found almost exclusively during gametogenesis. Genetic analysis of segregating markers among meiotic progeny excluded unequal crossover as the mechanism for instability. These unique patterns have novel implications for possible mechanisms of repeat instability.

Original languageEnglish (US)
Pages (from-to)4153-4158
Number of pages6
JournalMolecular and cellular biology
Volume19
Issue number6
DOIs
StatePublished - Jun 1999
Externally publishedYes

Fingerprint

Yeast Artificial Chromosomes
Gametogenesis
Meiosis
Trinucleotide Repeat Expansion
Trinucleotide Repeats
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Increased instability of human CTG repeat tracts on yeast artificial chromosomes during gametogenesis. / Cohen, Haim; Sears, Dorothy D.; Zenvirth, Drora; Hieter, Philip; Simchen, Giora.

In: Molecular and cellular biology, Vol. 19, No. 6, 06.1999, p. 4153-4158.

Research output: Contribution to journalArticle

Cohen, Haim ; Sears, Dorothy D. ; Zenvirth, Drora ; Hieter, Philip ; Simchen, Giora. / Increased instability of human CTG repeat tracts on yeast artificial chromosomes during gametogenesis. In: Molecular and cellular biology. 1999 ; Vol. 19, No. 6. pp. 4153-4158.
@article{e975f2343c164392863b95ec72b46fa7,
title = "Increased instability of human CTG repeat tracts on yeast artificial chromosomes during gametogenesis",
abstract = "Expansion of trinucleotide repeat tracts has been shown to be associated with numerous human diseases. The mechanism and timing of the expansion events are poorly understood, however, we show that CTG repeats, associated with the human DMPK gene and implanted in two homologous yeast artificial chromosomes (YACs), are very unstable. The instability is 6 to 10 times more pronounced in meiosis than during mitotic division. The influence of meiosis on instability is 4.4 times greater when the second YAC with a repeat tract is not present. Most of the changes we observed in trinucleotide repeat tracts are large contractions of 21 to 50 repeats. The orientation of the insert with the repeats has no effect on the frequency and distribution of the contractions. In our experiments, expansions were found almost exclusively during gametogenesis. Genetic analysis of segregating markers among meiotic progeny excluded unequal crossover as the mechanism for instability. These unique patterns have novel implications for possible mechanisms of repeat instability.",
author = "Haim Cohen and Sears, {Dorothy D.} and Drora Zenvirth and Philip Hieter and Giora Simchen",
year = "1999",
month = "6",
doi = "10.1128/MCB.19.6.4153",
language = "English (US)",
volume = "19",
pages = "4153--4158",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "6",

}

TY - JOUR

T1 - Increased instability of human CTG repeat tracts on yeast artificial chromosomes during gametogenesis

AU - Cohen, Haim

AU - Sears, Dorothy D.

AU - Zenvirth, Drora

AU - Hieter, Philip

AU - Simchen, Giora

PY - 1999/6

Y1 - 1999/6

N2 - Expansion of trinucleotide repeat tracts has been shown to be associated with numerous human diseases. The mechanism and timing of the expansion events are poorly understood, however, we show that CTG repeats, associated with the human DMPK gene and implanted in two homologous yeast artificial chromosomes (YACs), are very unstable. The instability is 6 to 10 times more pronounced in meiosis than during mitotic division. The influence of meiosis on instability is 4.4 times greater when the second YAC with a repeat tract is not present. Most of the changes we observed in trinucleotide repeat tracts are large contractions of 21 to 50 repeats. The orientation of the insert with the repeats has no effect on the frequency and distribution of the contractions. In our experiments, expansions were found almost exclusively during gametogenesis. Genetic analysis of segregating markers among meiotic progeny excluded unequal crossover as the mechanism for instability. These unique patterns have novel implications for possible mechanisms of repeat instability.

AB - Expansion of trinucleotide repeat tracts has been shown to be associated with numerous human diseases. The mechanism and timing of the expansion events are poorly understood, however, we show that CTG repeats, associated with the human DMPK gene and implanted in two homologous yeast artificial chromosomes (YACs), are very unstable. The instability is 6 to 10 times more pronounced in meiosis than during mitotic division. The influence of meiosis on instability is 4.4 times greater when the second YAC with a repeat tract is not present. Most of the changes we observed in trinucleotide repeat tracts are large contractions of 21 to 50 repeats. The orientation of the insert with the repeats has no effect on the frequency and distribution of the contractions. In our experiments, expansions were found almost exclusively during gametogenesis. Genetic analysis of segregating markers among meiotic progeny excluded unequal crossover as the mechanism for instability. These unique patterns have novel implications for possible mechanisms of repeat instability.

UR - http://www.scopus.com/inward/record.url?scp=0032973426&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032973426&partnerID=8YFLogxK

U2 - 10.1128/MCB.19.6.4153

DO - 10.1128/MCB.19.6.4153

M3 - Article

C2 - 10330155

AN - SCOPUS:0032973426

VL - 19

SP - 4153

EP - 4158

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 6

ER -