Phenotypic Variation Within European Carriers of the Y-chromosomal Gr/gr Deletion is Independent of Y-chromosomal Background

Overview

Journal J Med Genet

Specialty Genetics

Date 2008 Sep 11

PMID 18782837

Citations 32

Authors

C Krausz

C Giachini

Y Xue

M K OBryan

J Gromoll

E Rajpert-De Meyts

R Oliva

I Aknin-Seifer

E Erdei

N Jorgensen

M Simoni

J L Ballesca

R Levy

G Balercia

P Piomboni

E Nieschlag

G Forti

R McLachlan

C Tyler-Smith

Affiliations

Soon will be listed here.

Abstract

Background: Previous studies have compared sperm phenotypes between men with partial deletions within the AZFc region of the Y chromosome and non-carriers, with variable results. In this study, a separate question was investigated, the basis of the variation in sperm phenotype within gr/gr deletion carriers, which ranges from normozoospermia to azoospermia. Differences in the genes removed by independent gr/gr deletions, the occurrence of subsequent duplications or the presence of linked modifying variants elsewhere on the chromosome have been suggested as possible causal factors. This study set out to test these possibilities in a large sample of gr/gr deletion carriers with known phenotypes spanning the complete range.

Results: In total, 169 men diagnosed with gr/gr deletions from six centres in Europe and one in Australia were studied. The DAZ and CDY1 copies retained, the presence or absence of duplications and the Y-chromosomal haplogroup were characterised. Although the study had good power to detect factors that accounted for >or=5.5% of the variation in sperm concentration, no such factor was found. A negative effect of gr/gr deletions followed by b2/b4 duplication was found within the normospermic group, which remains to be further explored in a larger study population. Finally, significant geographical differences in the frequency of different subtypes of gr/gr deletions were found, which may have relevance for the interpretation of case control studies dealing with admixed populations.

Conclusions: The phenotypic variation of gr/gr carriers in men of European origin is largely independent of the Y-chromosomal background.

Citing Articles

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A common 1.6 mb Y-chromosomal inversion predisposes to subsequent deletions and severe spermatogenic failure in humans.

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References

Semino O, Passarino G, Oefner P, Lin A, Arbuzova S, Beckman L . The genetic legacy of Paleolithic Homo sapiens sapiens in extant Europeans: a Y chromosome perspective. Science. 2000; 290(5494):1155-9. DOI: 10.1126/science.290.5494.1155. View

Choe J, Kim J, Lee J, Seo J . Routine screening for classical azoospermia factor deletions of the Y chromosome in azoospermic patients with Klinefelter syndrome. Asian J Androl. 2007; 9(6):815-20. DOI: 10.1111/j.1745-7262.2007.00315.x. View

Ravel C, Chantot-Bastaraud S, El Houate B, Mandelbaum J, Siffroi J, McElreavey K . GR/GR deletions within the azoospermia factor c region on the Y chromosome might not be associated with spermatogenic failure. Fertil Steril. 2006; 85(1):229-31. DOI: 10.1016/j.fertnstert.2005.07.1278. View

Rosser Z, Zerjal T, Hurles M, Adojaan M, Alavantic D, Amorim A . Y-chromosomal diversity in Europe is clinal and influenced primarily by geography, rather than by language. Am J Hum Genet. 2000; 67(6):1526-43. PMC: 1287948. DOI: 10.1086/316890. View

Giachini C, Nuti F, Marinari E, Forti G, Krausz C . Partial AZFc deletions in infertile men with cryptorchidism. Hum Reprod. 2007; 22(9):2398-403. DOI: 10.1093/humrep/dem186. View

Repping S, Skaletsky H, Brown L, van Daalen S, Korver C, Pyntikova T . 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(3):247-51. DOI: 10.1038/ng1250. View

Krausz C, Giachini C . Genetic risk factors in male infertility. Arch Androl. 2007; 53(3):125-33. DOI: 10.1080/01485010701271786. View

Becherini L, Guarducci E, DeglInnocenti S, Rotondi M, Forti G, Krausz C . DAZL polymorphisms and susceptibility to spermatogenic failure: an example of remarkable ethnic differences. Int J Androl. 2004; 27(6):375-81. DOI: 10.1111/j.1365-2605.2004.00520.x. View

Vogt P . AZF deletions and Y chromosomal haplogroups: history and update based on sequence. Hum Reprod Update. 2005; 11(4):319-36. DOI: 10.1093/humupd/dmi017. View

10.

Ferlin A, Tessari A, Ganz F, Marchina E, Barlati S, Garolla A . Association of partial AZFc region deletions with spermatogenic impairment and male infertility. J Med Genet. 2005; 42(3):209-13. PMC: 1736009. DOI: 10.1136/jmg.2004.025833. View

11.

Fernandes S, Huellen K, Goncalves J, Dukal H, Zeisler J, Rajpert De Meyts E . High frequency of DAZ1/DAZ2 gene deletions in patients with severe oligozoospermia. Mol Hum Reprod. 2002; 8(3):286-98. DOI: 10.1093/molehr/8.3.286. View

12.

Repping S, van Daalen S, Brown L, Korver C, Lange J, Marszalek J . High mutation rates have driven extensive structural polymorphism among human Y chromosomes. Nat Genet. 2006; 38(4):463-7. DOI: 10.1038/ng1754. View

13.

Giachini C, Guarducci E, Longepied G, DeglInnocenti S, Becherini L, Forti G . The gr/gr deletion(s): a new genetic test in male infertility?. J Med Genet. 2005; 42(6):497-502. PMC: 1736069. DOI: 10.1136/jmg.2004.028191. View

14.

Karafet T, Mendez F, Meilerman M, Underhill P, Zegura S, Hammer M . New binary polymorphisms reshape and increase resolution of the human Y chromosomal haplogroup tree. Genome Res. 2008; 18(5):830-8. PMC: 2336805. DOI: 10.1101/gr.7172008. View

15.

Krausz C, DeglInnocenti S . Y chromosome and male infertility: update, 2006. Front Biosci. 2006; 11:3049-61. DOI: 10.2741/2032. View

16.

Paracchini S, Arredi B, Chalk R, Tyler-Smith C . Hierarchical high-throughput SNP genotyping of the human Y chromosome using MALDI-TOF mass spectrometry. Nucleic Acids Res. 2002; 30(6):e27. PMC: 101371. DOI: 10.1093/nar/30.6.e27. View

17.

Skaletsky H, Kuroda-Kawaguchi T, Minx P, Cordum H, Hillier L, Brown L . The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature. 2003; 423(6942):825-37. DOI: 10.1038/nature01722. View

18.

Noordam M, Repping S . The human Y chromosome: a masculine chromosome. Curr Opin Genet Dev. 2006; 16(3):225-32. DOI: 10.1016/j.gde.2006.04.018. View

19.

Lynch M, Cram D, Reilly A, OBryan M, Baker H, de Kretser D . The Y chromosome gr/gr subdeletion is associated with male infertility. Mol Hum Reprod. 2005; 11(7):507-12. DOI: 10.1093/molehr/gah191. View

20.

de Llanos M, Ballesca J, Gazquez C, Margarit E, Oliva R . High frequency of gr/gr chromosome Y deletions in consecutive oligospermic ICSI candidates. Hum Reprod. 2004; 20(1):216-20. DOI: 10.1093/humrep/deh582. View