Molecular definition of breakpoints associated with human Xq isochromosomes: Implications for mechanisms of formation

Daynna J. Wolff, Andrew P. Miller, Daniel L. Van Dyke, Stuart Schwartz, Huntington F. Willard

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

To test the centromere misdivision model of isochromosome formation, we have defined the breakpoints of cytogenetically monocentric and dicentric Xq isochromosomes (i(Xq)) from Turner syndrome probands, using FISH with cosmids and YACs derived from a contig spanning proximal Xp. Seven different pericentromeric breakpoints were identified, with 10 of 11 of the i(Xq)s containing varying amounts of material from Xp. Only one of the eight cytogenetically monocentric i(Xq)s demonstrated a single alpha-satellite (DXZ1) signal, consistent with classical models involving centromere misdivision. The remaining seven were inconsistent with such a model and had breakpoints that spanned proximal Xp11.21: one was between DXZ1 and the most proximal marker, ZXDA; one occurred between the duplicated genes, ZXDA and ZXDB; two were ~2 Mb from DXZ1; two were adjacent to ALAS2 located 3.5 Mb from DXZ1; and the largest had a breakpoint just distal to DXS1013E, indicating the inclusion of 8 Mb of Xp DNA between centromeres. The three cytologically dicentric i(Xq)s had breakpoints distal to DXS423E in Xp11.22 and therefore contained ≥12 Mb of DNA between centromeres. These data demonstrate that the majority of breakpoints resulting in i(Xq) formation are in band Xp11.2 and not in the centromere itself. Therefore, we hypothesize that the predominant mechanism of i(Xq) formation involves sequences in the proximal short arm that are prone to breakage and reunion events between sister chromatids or homologous X chromosomes.

Original languageEnglish (US)
Pages (from-to)154-160
Number of pages7
JournalAmerican Journal of Human Genetics
Volume58
Issue number1
StatePublished - 1996
Externally publishedYes

Fingerprint

Isochromosomes
Centromere
Reunion
Cosmids
Turner Syndrome
Chromatids
DNA
X Chromosome
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Wolff, D. J., Miller, A. P., Van Dyke, D. L., Schwartz, S., & Willard, H. F. (1996). Molecular definition of breakpoints associated with human Xq isochromosomes: Implications for mechanisms of formation. American Journal of Human Genetics, 58(1), 154-160.

Molecular definition of breakpoints associated with human Xq isochromosomes : Implications for mechanisms of formation. / Wolff, Daynna J.; Miller, Andrew P.; Van Dyke, Daniel L.; Schwartz, Stuart; Willard, Huntington F.

In: American Journal of Human Genetics, Vol. 58, No. 1, 1996, p. 154-160.

Research output: Contribution to journalArticle

Wolff, DJ, Miller, AP, Van Dyke, DL, Schwartz, S & Willard, HF 1996, 'Molecular definition of breakpoints associated with human Xq isochromosomes: Implications for mechanisms of formation', American Journal of Human Genetics, vol. 58, no. 1, pp. 154-160.
Wolff, Daynna J. ; Miller, Andrew P. ; Van Dyke, Daniel L. ; Schwartz, Stuart ; Willard, Huntington F. / Molecular definition of breakpoints associated with human Xq isochromosomes : Implications for mechanisms of formation. In: American Journal of Human Genetics. 1996 ; Vol. 58, No. 1. pp. 154-160.
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