title: Somatic mosaicism for chromosome X and Y aneuploidies in monozygotic twins heterozygous for sickle cell disease mutation.
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.
authors: Rudbeck Laboratory, Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors: Hamid Reza
authors: HR
authors: Razzaghian
authors: Mehdi Hayat
authors: MH
authors: Shahi
authors: Lars A
authors: LA
authors: Forsberg
authors: Teresita Diaz
authors: TD
authors: de Ståhl
authors: Devin
authors: D
authors: Absher
authors: Niklas
authors: N
authors: Dahl
authors: Maxwell P
authors: MP
authors: Westerman
authors: Jan P
authors: JP
authors: Dumanski
mesh_terms: D000755:Anemia, Sickle Cell / Q000235:genetics*; D000782:Aneuploidy; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics*; D041322:Chromosomes, Human, Y / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D014424:Turner Syndrome / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics*