title: AZFc somatic microdeletions and copy number polymorphism of the DAZ genes in human males exposed to natural background radiation.
abstract: Ionizing radiations are known to induce tumors, chromosomal lesions and minisatellite length variations, yet no correlation has been demonstrated between radiation exposure and indels or copy number polymorphism (CNP) of the genes. We studied the impact of natural background radiation (NBR) on the human Y chromosome owing to its haploid status and clonal inheritance. We analyzed the AZFc region using the DNA from blood and semen of 100 males living near the coastal peninsula in Kerala (India), exposed to NBR along with other 50 normal fertile males. STS mapping of AZFc region showed random microdeletions without conclusive gr/gr or b1/b3 phenotypes. Using a highly specific novel Taqman assay based on sY587 sequence, we detected four copies of the DAZ genes in normal males and 4-16 in those exposed to NBR. Amongst NBR exposed males with multiples copies of the DAZ genes, 75% showed varying FISH signals for DAZ genes with cosmid 18E8 whereas 30% showed mosaicism in terms of presence/absence of the signals in 6-8% cells and unexpected number of signals in 9-12% interphase nuclei. Startlingly, all germline samples studied were found to be free from AZFc microdeletions and CNP of the DAZ genes. Since the DAZ genes are heavily implicated with the germ cell development, the cells with DAZ deletion/duplication are unlikely to survive. Alternatively, an innate mechanism may be operative to protect the germline from the effects of NBR.
authors.affiliation: Molecular Genetics Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110 067, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Premi
authors.forename: Jyoti
authors.initials: J
authors.lastname: Srivastava
authors.forename: Sebastian Padinjarel
authors.initials: SP
authors.lastname: Chandy
authors.forename: Sher
authors.initials: S
authors.lastname: Ali
mesh_terms: D000328:Adult; D001417:Background Radiation / Q000009:adverse effects*; D001483:Base Sequence; D041322:Chromosomes, Human, Y; D000075364:Deleted in Azoospermia 1 Protein; D017353:Gene Deletion; D018628:Gene Dosage; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009030:Mosaicism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D016601:RNA-Binding Proteins / Q000235:genetics*; D016324:Sequence Tagged Sites
chemical_list: C095668:DAZ1 protein, human; D000075364:Deleted in Azoospermia 1 Protein; D016601:RNA-Binding Proteins