Origins of Intraindividual Genetic Variation in Human Fetuses.
BACKGROUND
Intraindividual copy number variation (CNV) origin is largely unknown. They might be due to aging and/or common genome instability at the preimplantation stage while contribution of preimplantation in human intraindividual CNVs occurrence is unknown. To address this question, we investigated mosaicism and its origin in the fetuses of natural conception.


METHODS
We studied normal fetuses following therapeutic abortion due to maternal indications. We analyzed the genome of 22 tissues of each fetus by array comparative genomic hybridization for intraindividual CNVs. Each tissue was studied in 2 microarray experiments; the reciprocal aberrations larger than 40 Kb, identified by comparing tissues of each fetus, were subsequently validated using quantitative polymerase chain reaction.


RESULTS
Through intraindividual comparison, frequency of reciprocal events varied from 2 to 9. According to the distribution pattern of the frequent CNV in derivatives of different germ layers, we found that its origin is early development including preimplantation, whereas CNVs with low frequency have occurred in later stages. Shared CNVs in both fetuses were belonged to thymus and related to the functional role of genes located in these CNVs.


CONCLUSIONS
The origin of some of fetal CNVs is preimplantation stage. Each organ might inherit CNVs with an unpredictable pattern due to the extensive cell mixing/migration in embryonic development.
['Bazrgar|Masood|M|0000-0002-5453-9576', 'Gourabi|Hamid|H|', 'Karimpour-Fard|Anis|A|', 'Boroujeni|Parnaz Borjian|PB|', 'Anisi|Khadije|K|', 'Movaghar|Bahar|B|', 'Valojerdi|Mojtaba Rezazadeh|MR|']
D055028:Comparative Genomic Hybridization D056915:DNA Copy Number Variations D004252:DNA Mutational Analysis D005260:Female D005333:Fetus D014644:Genetic Variation D006801:Humans D008297:Male D009030:Mosaicism D011247:Pregnancy
copy number variation preimplantation mosaicism fetus