Affordable Access

deepdyve-link
Publisher Website

Somatic mosaicism for chromosome X and Y aneuploidies in monozygotic twins heterozygous for sickle cell disease mutation.

Authors
  • Razzaghian, Hamid Reza1
  • Shahi, Mehdi Hayat
  • Forsberg, Lars A
  • de Ståhl, Teresita Diaz
  • Absher, Devin
  • Dahl, Niklas
  • Westerman, Maxwell P
  • Dumanski, Jan P
  • 1 Rudbeck Laboratory, Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden. , (Sweden)
Type
Published Article
Journal
American Journal of Medical Genetics Part A
Publisher
Wiley (John Wiley & Sons)
Publication Date
Oct 01, 2010
Volume
152A
Issue
10
Pages
2595–2598
Identifiers
DOI: 10.1002/ajmg.a.33604
PMID: 20734341
Source
Medline
License
Unknown

Abstract

Somatic genetic variation in health and disease is poorly explored. Monozygotic (MZ) twins are a suitable model for studies of somatic mosaicism since genetic differences in twins derived from the same zygote represent an irrefutable example of somatic variation. We report the analysis of a pair of generally healthy female MZ twins, discordant for somatic mosaicism for aneuploidy of chromosomes X and Y. Both twins are heterozygous carriers of sickle cell disease mutation. Genotyping of blood DNA from both twins using Illumina Human 610 SNP array revealed a copy number imbalance for chromosome X in a proportion of cells in one twin. Fluorescent in situ hybridization (FISH) analysis confirmed monosomy X (45,X) in 7% of proband nucleated blood cells. Unexpectedly, FISH analysis of cells from the other twin revealed 45,X and 46,XY lineages, both present in 1% of cells. The mechanism behind formation of these aneuploidies suggests several aberrant chromosome segregation events in meiosis and mitoses following conception. Our report contributes to the delineation of the frequency of somatic structural genomic variation in normal MZ twins. These results also illustrate the plasticity of the human genome for tolerating large copy number changes in healthy subjects and show the sensitivity of the Illumina platform for detection of aberrations that are present in a minority of the studied cells.

Report this publication

Statistics

Seen <100 times