Chromosomal mosaicism in cleavage-stage human embryos and the accuracy of single-cell genetic analysis.
OBJECTIVE
Our purpose was to assess the effect of chromosomal mosaicism in cleavage-stage human embryos on the accuracy of single-cell analysis for preimplantation genetic diagnosis.


METHODS
Multicolor fluorescence in situ hybridization with X, Y, and 7 or X, Y, 7, and 18 chromosome-specific probes was used to detect aneuploidy in cleavage-stage human embryos.


RESULTS
Most nuclei were diploid for the chromosomes tested but there was extensive mosaicism including monosomic, double-monosomic, nullisomic, chaotic, and haploid nuclei.


CONCLUSIONS
Identification of sex by analysis of a single cleavage-stage nucleus is accurate but 7% of females are not identified. One or both parental chromosomes 7 were absent in at least 6.5% of the nuclei. With autosomal recessive conditions such as cystic fibrosis, carriers would be misdiagnosed as normal or affected. With autosomal dominant conditions, failure to analyze the affected parents allele (1.6-2.5%) would cause a serious misdiagnosis and analysis of at least two nuclei is necessary to reduce errors.
Kuo
H C
HC
Department of Obstetrics and Gynaecology, St. Thomas' Hospital, London, UK.
Ogilvie
C M
CM
Handyside
A H
AH
D002869:Chromosome Aberrations / Q000175:diagnosis / Q000235:genetics; D025063:Chromosome Disorders; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D002970:Cleavage Stage, Ovum / Q000166:cytology*; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D009030:Mosaicism / Q000175:diagnosis* / Q000235:genetics*; D011247:Pregnancy; D019836:Preimplantation Diagnosis; D014960:X Chromosome / Q000235:genetics; D014998:Y Chromosome / Q000235:genetics