Mutational landscape of the human Y chromosome-linked genes and loci in patients with hypogonadism

Journal of genetics

Sandeep Kumar Yadav¹  Deepali Pathak¹  Leena Rawal¹  Sher Ali1¹ 

[1] Molecular Genetics Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India$$

关键词: genome instability;    male infertility;    Y chromosome;    hypogonadism;    sex chromosome-related anomalies.;   

DOI  :  

学科分类：生物科学（综合）

来源: Indian Academy of Sciences

【 摘 要 】

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 (495–6201copies) 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.

【 授权许可】

Unknown