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

• Published in: American journal of medical genetics. Part A Vol. 152A; no. 10; pp. 2595 - 2598
• Main Authors: Razzaghian, Hamid Reza, Shahi, Mehdi Hayat, Forsberg, Lars A., de Ståhl, Teresita Diaz, Absher, Devin, Dahl, Niklas, Westerman, Maxwell P., Dumanski, Jan P.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.10.2010; Wiley-Liss
• Subjects: Anemia, Sickle Cell - genetics; Anemias. Hemoglobinopathies; Aneuploidy; Biological and medical sciences; Chromosome aberrations; chromosome X; chromosome Y; Chromosomes, Human, Pair 18 - genetics; Chromosomes, Human, X - genetics; Chromosomes, Human, Y - genetics; Clinical genetics; copy number variation; Dermatologi och venerologi, klinisk genetik, invärtesmedicin; Dermatology and venerology,clinical genetics, internal medicine; Diseases of red blood cells; Female; Genetic Variation; Genotype; Gynecology. Andrology. Obstetrics; Hematologic and hematopoietic diseases; Heterozygote; Humans; Klinisk genetik; Male; Male and female genital diseases. Gonadal dysgenesis. Hermaphroditism. Sex hormones resistance; Medical genetics; Medical sciences; MEDICIN; MEDICINE; Medicinsk genetik; Middle Aged; monozygotic twins; sickle cell trait; somatic mosaicism; Turner Syndrome - genetics; Twins, Monozygotic - genetics; Ullrich-Turner syndrome; Chromosomal aberration; Dysgenesia; Sickle cell anemia; Genetic variability; Copy number; sickle cell trait; Variations; Aneuploidy; Somatic cell; Hemopathy; monozygotic twins; chromosome X; chromosome Y; Hemolytic anemia; copy number variation; Gonad; Monozygotic twin; Hemoglobinopathy; Genetic variant; Chromosome; genetic variation; Sexual differentiation disorder; Turner syndrome; Female genital diseases; Genetic disease; Ullrich—Turner syndrome; Malformation; Mosaicism; somatic mosaicism; Mutation
• ISSN: 1552-4825; 1552-4833; 1552-4833
• DOI: 10.1002/ajmg.a.33604

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. © 2010 Wiley‐Liss, Inc.