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.

HLA-G allele and haplotype frequencies in a healthy population of Iran.

The human leukocyte antigen (HLA)-G molecule is expressed in cytotrophoblast cells, adult thymic epithelial cells, erythroblasts, pancreatic islets and mesenchymal stem cells. Although, HLA-G expression in allotransplanted patients is correlated with a better allograft acceptance, it is associated with an advanced grade of the tumor in cancer. In addition to the role on the immune system, HLA-G is also involved in successful pregnancy through the embryo implantation, fetal survival and the initial steps of hematopoiesis and angiogenesis. The aim of this study was determination of HLA-G allele frequencies in a healthy population of Iran. In this research, we selected 100 samples from healthy Iranian individuals and henceforth, we used polymerase chain reaction (PCR) followed by sequencing technique for exon 2, 3, 4 and intron 2 of the gene for evaluating the HLA-G alleles frequencies. Investigation of intronic (intron 2) variation is the novelty of our study. The obtained results indicated thirteen alleles of HLA-G in Iranian individuals including G*01:01:01:01, G*01:06, G*01:01:01:06, G*01:01:02, G*01:01:03, G*01:01:05, G*01:01:06, G*01:01:07, G*01:01:08, G*01:03, G*01:04:01, G*01:04:03, and G*01:04:04. According to this study, the most prevalent alleles in the Iranian population were G*01:01:01:01 (52.5%), G*01:01:02 (16%) and G*01:04:03 (14.5%) and also the lowest alleles regarding the frequency were G*01:01:01:06 (0.5%) and G*01:03 (0.5%). The results of G*01:01:01:01 and G*01:04:01 frequencies showed some similarities with the polish population. Our results were similar to the north Indian population for the frequencies of G*01:06 and G*01:01:02.