Primary azoospermia factor C duplication associated with spermatogenic impariment: a case-control study based on Y-chromosome haplogrouping in a Han Chinese population.
Y-chromosome haplogroup
copy number variant
male infertility
primary AZFc duplication
spermatogenic impairment
Journal
Andrology
ISSN: 2047-2927
Titre abrégé: Andrology
Pays: England
ID NLM: 101585129
Informations de publication
Date de publication:
18 Aug 2023
18 Aug 2023
Historique:
revised:
22
06
2023
received:
24
03
2023
accepted:
06
08
2023
medline:
18
8
2023
pubmed:
18
8
2023
entrez:
18
8
2023
Statut:
aheadofprint
Résumé
Azoospermia factor C (AZFc) in the male-specific region of Y-chromosome (MSY) presents wide structure variation mainly due to frequent non-allele homologous recombination, leading to significant copy number variation of the AZFc-linked coding sequences involving in spermatogenesis. A large number of studies had been conducted to investigate the association between AZFc deletions and male infertility in certain Y chromosome genetic backgrounds, however, the influence of primary AZFc duplication on spermatogenesis remained controversial and the cause of the discrepant outcomes is unknown. In the present study, a total of 1,102 unrelated Han Chinese males without any detectable AZF deletions were recruited from 2014 to 2019, including 411 controls with normozoospermia and 691 patients with idiopathic spermatogenic failure. Using multiple paralog ratio tests (PRTs), the structure duplications were classified by the copy number of the AZFc-linked amplicons and genes. The Y-chromosome haplogroup (Y-hg) was categorized by genetyping of MSY-linked polymorphism loci. The association of primary AZFc duplication with spermatogenic phenotype was investigated in males with the same Y-hg. Within Y-hg O3 The results suggest that, in the Han Chinese population, the gr/gr duplication is a predisposing genetic factor for spermatogenic impairment in males harboring Y-hg O3
Sections du résumé
BACKGROUND
BACKGROUND
Azoospermia factor C (AZFc) in the male-specific region of Y-chromosome (MSY) presents wide structure variation mainly due to frequent non-allele homologous recombination, leading to significant copy number variation of the AZFc-linked coding sequences involving in spermatogenesis. A large number of studies had been conducted to investigate the association between AZFc deletions and male infertility in certain Y chromosome genetic backgrounds, however, the influence of primary AZFc duplication on spermatogenesis remained controversial and the cause of the discrepant outcomes is unknown.
METHODS
METHODS
In the present study, a total of 1,102 unrelated Han Chinese males without any detectable AZF deletions were recruited from 2014 to 2019, including 411 controls with normozoospermia and 691 patients with idiopathic spermatogenic failure. Using multiple paralog ratio tests (PRTs), the structure duplications were classified by the copy number of the AZFc-linked amplicons and genes. The Y-chromosome haplogroup (Y-hg) was categorized by genetyping of MSY-linked polymorphism loci. The association of primary AZFc duplication with spermatogenic phenotype was investigated in males with the same Y-hg.
RESULTS
RESULTS
Within Y-hg O3
CONCLUSION
CONCLUSIONS
The results suggest that, in the Han Chinese population, the gr/gr duplication is a predisposing genetic factor for spermatogenic impairment in males harboring Y-hg O3
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Natural Science Foundation of China
ID : 81871203
Informations de copyright
© 2023 American Society of Andrology and European Academy of Andrology.
Références
Repping S, van Daalen SKM, Brown LG, et al. High mutation rates have driven extensive structural polymorphism among human Y chromosomes. Nat Genet. 2006;38:463-467. doi:10.1038/ng1754
Punab M, Poolamets O, Paju P, et al. Causes of male infertility: a 9-year prospective monocentre study on 1737 patients with reduced total sperm counts. Hum Reprod. 2017;32:18-31. doi:10.1093/humrep/dew284
Kohn TP, Kohn JR, Owen RC, Coward RM. The prevalence of Y-chromosome microdeletions in oligozoospermic men: a systematic review and meta-analysis of European and North American studies. Eur Urol. 2019;76:626-636. doi:10.1016/j.eururo.2019.07.033
Navarro-Costa P, Goncalves J, Plancha CE. The AZFc region of the Y chromosome: at the crossroads between genetic diversity and male infertility. Hum Reprod Update. 2010;16:525-542. doi:10.1093/humupd/dmq005
Colaco S, Modi D. Genetics of the human Y chromosome and its association with male infertility. Reprod Biol Endocrinol. 2018;16:14. doi:10.1186/s12958-018-0330-5
Bansal SK, Gupta G, Rajender S. Y chromosome b2/b3 deletions and male infertility: a comprehensive meta-analysis, trial sequential analysis and systematic review. Mutat Res Rev Mutat Res. 2016;768:78-90. doi:10.1016/j.mrrev.2016.04.007
Hallast P, Kibena L, Punab M, et al. A common 1.6 mb Y-chromosomal inversion predisposes to subsequent deletions and severe spermatogenic failure in humans. Elife. 2021;10: e65420. doi:10.7554/eLife.65420
Lahoz Alonso R, Sienes Bailo P, César Márquez MÁ, et al. AZF gene microdeletions in azoospermic-oligozoospermic males. Med Clin (Barc). 2023;160:151-155. doi:10.1016/j.medcli.2022.06.016
Xie S, Zhang Y, Yang Y. Is the primary AZFc duplication a potential risk for male infertility?: a systematic review and meta-analysis. Andrology. 2020;8:996-1004. doi:10.1111/andr.12800
Lin YW, Chia-Ling Hsu L, Kuo P-L, et al. Partial duplication at AZFc on the Y chromosome is a risk factor for impaired spermatogenesis in Han Chinese in Taiwan. Hum Mutat. 2007;28:486-494. doi:10.1002/humu.20473
Lu C, Zhang F, Yang H, et al. Additional genomic duplications in AZFc underlie the b2/b3 deletion-associated risk of spermatogenic impairment in Han Chinese population. Hum Mol Genet. 2011;20:4411-4421. doi:10.1093/hmg/ddr369
Saito K, Miyado M, Kobori Y, et al. Copy-number variations in Y-chromosomal azoospermia factor regions identified by multiplex ligation-dependent probe amplification. J Hum Genet. 2015;60:127-131. doi:10.1038/jhg.2014.115
Machev N. Sequence family variant loss from the AZFc interval of the human Y chromosome, but not gene copy loss, is strongly associated with male infertility. J Med Genet. 2004;41:814-825. doi:10.1136/jmg.2004.022111
Anderson EC, Garza JC. The power of single-nucleotide polymorphisms for large-scale parentage inference. Genetics. 2006;172:2567-2582. doi:10.1534/genetics.105.048074
Qu W, Shen Z, Zhao D, Yang Y, Zhang C. MFEprimer: multiple factor evaluation of the specificity of PCR primers. Bioinformatics. 2009;25:276-278. doi:10.1093/bioinformatics/btn614
Karafet TM, Mendez FL, Meilerman MB, Underhill PA, Zegura SL, Hammer MF. New binary polymorphisms reshape and increase resolution of the human Y chromosomal haplogroup tree. Genome Res. 2008;18:830-838. doi:10.1101/gr.7172008
Repping S, Skaletsky H, Brown L, et al. Polymorphism for a 1.6-Mb deletion of the human Y chromosome persists through balance between recurrent mutation and haploid selection. Nat Genet. 2003;35:247-251. doi:10.1038/ng1250
Jobling MA, Tyler-Smith C. The human Y chromosome: an evolutionary marker comes of age. Nat Rev Genet. 2003;4:598-612. doi:10.1038/nrg1124
Krausz C, Hoefsloot L, Simoni M, Tüttelmann F. EAA/EMQN best practice guidelines for molecular diagnosis of Y-chromosomal microdeletions: state-of-the-art 2013. Andrology. 2014;2:5-19. doi:10.1111/j.2047-2927.2013.00173.x
Bansal SK, Jaiswal D, Gupta N, et al. Gr/gr deletions on Y-chromosome correlate with male infertility: an original study, meta-analyses, and trial sequential analyses. Sci Rep. 2016;6:19798. doi:10.1038/srep19798
Rozen SG, Marszalek JD, Irenze K, et al. AZFc deletions and spermatogenic failure: a population-based survey of 20,000 Y chromosomes. Am J Hum Genet. 2012;91:890-896. doi:10.1016/j.ajhg.2012.09.003
de Carvalho CMB, Zuccherato LW, Fujisawa M, et al. Study of AZFc partial deletion gr/gr in fertile and infertile Japanese males. J Hum Genet. 2006;51:794-799. doi:10.1007/s10038-006-0024-2
Teitz LS, Pyntikova T, Skaletsky H, Page DC. Selection has countered high mutability to preserve the ancestral copy number of Y chromosome amplicons in diverse human lineages. Am J Hum Genet. 2018;103:261-275. doi:10.1016/j.ajhg.2018.07.007
Ye JJ, Ma L, Yang L, et al. Partial AZFc duplications not deletions are associated with male infertility in the Yi population of Yunnan Province, China. J Zhejiang Univ Sci B. 2013;14:807-815. doi:10.1631/jzus.B1200301
Giachini C, Laface I, Guarducci E, Balercia G, Forti G, Krausz C. Partial AZFc deletions and duplications: clinical correlates in the Italian population. Hum Genet. 2008;124:399-410. doi:10.1007/s00439-008-0561-1
Writzl K, Zorn B, Peterlin B. Copy number of DAZ genes in infertile men. Fertil Steril. 2005;84:1522-1525. doi:10.1016/j.fertnstert.2005.06.021
Yang Y, Ma M, Li L, et al. Evidence for the association of Y-chromosome haplogroups with susceptibility to spermatogenic failure in a Chinese Han population. J Med Genet. 2008;45:210-215. doi:10.1136/jmg.2007.054478
Su B, Xiao J, Underhill P, et al. Y-Chromosome evidence for a northward migration of modern humans into Eastern Asia during the last Ice Age. Am J Hum Genet. 1999;65:1718-1724. doi:10.1086/302680
Jin L, Su B. Natives or immigrants: modern human origin in east Asia. Nat Rev Genet. 2000;1:126-133. doi:10.1038/35038565
Fernandes S, Paracchini S, Meyer LH, Floridia G, Tyler-Smith C, Vogt PH. A large AZFc deletion removes DAZ3/DAZ4 and nearby genes from men in Y haplogroup N. Am J Hum Genet. 2004;74:180-187. doi:10.1086/381132
Repping S, van Daalen SKM, Korver CM, et al. A family of human Y chromosomes has dispersed throughout northern Eurasia despite a 1.8-Mb deletion in the azoospermia factor c region. Genomics. 2004;83:1046-1052. doi:10.1016/j.ygeno.2003.12.018
Hsu HK, Su MT, Chen M, Yen P, Kuo PL. Two Y chromosomes with duplication of the distal long arm including the entire AZFc region. Gene. 2014;536:444-448. doi:10.1016/j.gene.2013.11.061