title: Mutational landscape of the human Y chromosome-linked genes and loci in patients with hypogonadism.
abstract: Sex chromosome-related anomalies engender plethora of conditions leading to male infertility. Hypogonadotropic hypogonadism (HH) is a rare but well-known cause of male infertility. Present study was conducted to ascertain possible consensus on the alterations of the Y-linked genes and loci in males representing hypogonadism (H), which in turn culminate in reproductive dysfunction. A total of nineteen 46, XY males, clinically diagnosed with H (11 representative HH adults and eight prepubertal boys suspected of having HH) were included in the study. Sequence-tagged site screening,SRY gene sequencing,fluorescence in situ hybridization mapping (FISH), copy number and relative expression studies by real-time PCR were conducted to uncover the altered status of the Y chromosome in the patients. The result showed random microdeletions within the AZFa (73%)/b (78%) and c(26%) regions. Sequencing of the SRY gene showed nucleotide variations within and outside of the HMG box in four males (21%). FISH uncovered mosaicism for SRY, AMELY,DAZ genes and DYZ1 arrays, structural rearrangement for AMELY (31%) and duplication of DAZ (57%) genes. Copy number variation for seven Y-linked genes (2-8 rounds of duplication), DYZ1 arrays (495-6201 copies) and differential expression of SRY,UTY and VCY in the patients' blood were observed. Present work demonstrates the organizational vulnerability of several Y-linked genes in H males. These results are envisaged to be useful during routine diagnosis of H patients.
authors.affiliation: Molecular Genetics Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067,India. alisher@nii.ac.in.
authors.forename: Deepali
authors.initials: D
authors.lastname: Pathak
authors.forename: Sandeep Kumar
authors.initials: SK
authors.lastname: Yadav
authors.forename: Leena
authors.initials: L
authors.lastname: Rawal
authors.forename: Sher
authors.initials: S
authors.lastname: Ali
mesh_terms: D000293:Adolescent; D041322:Chromosomes, Human, Y / Q000235:genetics*; D056426:Genetic Loci / Q000235:genetics*; D006801:Humans; D007006:Hypogonadism / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*