• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jmedgeneJournal of Medical GeneticsVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
J Med Genet. Oct 2000; 37(10): 752–758.
PMCID: PMC1757162

Divergent outcomes of intrachromosomal recombination on the human Y chromosome: male infertility and recurrent polymorphism


The Y chromosome provides a unique opportunity to study mutational processes within the human genome, decoupled from the confounding effects of interchromosomal recombination. It has been suggested that the increased density of certain dispersed repeats on the Y could account for the high frequency of causative microdeletions relative to single nucleotide mutations in infertile males. Previously we localised breakpoints of an AZFa microdeletion close to two highly homologous complete human endogenous retroviral sequences (HERV), separated by 700 kb. Here we show, by sequencing across the breakpoint, that the microdeletion occurs in register within a highly homologous segment between the HERVs. Furthermore, we show that recurrent double crossovers have occurred between the HERVs, resulting in the loss of a 1.5 kb insertion from one HERV, an event underlying the first ever Y chromosomal polymorphism described, the 12f2 deletion. This event produces a substantially longer segment of absolute homology and as such may result in increased predisposition to further intrachromosomal recombination. Intrachromosomal crosstalk between these two HERV sequences can thus result in either homogenising sequence conversion or a microdeletion causing male infertility. This represents a major subclass of AZFa deletions.

Keywords: HERV; AZFa; infertility; Y chromosome

Full Text

The Full Text of this article is available as a PDF (230K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • López Correa C, Brems H, Lázaro C, Marynen P, Legius E. Unequal meiotic crossover: a frequent cause of NF1 microdeletions. Am J Hum Genet. 2000 Jun;66(6):1969–1974. [PMC free article] [PubMed]
  • Potocki L, Chen KS, Park SS, Osterholm DE, Withers MA, Kimonis V, Summers AM, Meschino WS, Anyane-Yeboa K, Kashork CD, et al. Molecular mechanism for duplication 17p11.2- the homologous recombination reciprocal of the Smith-Magenis microdeletion. Nat Genet. 2000 Jan;24(1):84–87. [PubMed]
  • Lupski JR. Genomic disorders: structural features of the genome can lead to DNA rearrangements and human disease traits. Trends Genet. 1998 Oct;14(10):417–422. [PubMed]
  • Lukacsovich T, Waldman AS. Suppression of intrachromosomal gene conversion in mammalian cells by small degrees of sequence divergence. Genetics. 1999 Apr;151(4):1559–1568. [PMC free article] [PubMed]
  • Löwer R, Löwer J, Kurth R. The viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5177–5184. [PMC free article] [PubMed]
  • Patience C, Wilkinson DA, Weiss RA. Our retroviral heritage. Trends Genet. 1997 Mar;13(3):116–120. [PubMed]
  • Sverdlov ED. Retroviruses and primate evolution. Bioessays. 2000 Feb;22(2):161–171. [PubMed]
  • Erlandsson R, Wilson JF, Päbo S. Sex chromosomal transposable element accumulation and male-driven substitutional evolution in humans. Mol Biol Evol. 2000 May;17(5):804–812. [PubMed]
  • McElreavey K, Krausz C. Sex Chromosome Genetics '99. Male infertility and the Y chromosome. Am J Hum Genet. 1999 Apr;64(4):928–933. [PMC free article] [PubMed]
  • Schwartz A, Chan DC, Brown LG, Alagappan R, Pettay D, Disteche C, McGillivray B, de la Chapelle A, Page DC. Reconstructing hominid Y evolution: X-homologous block, created by X-Y transposition, was disrupted by Yp inversion through LINE-LINE recombination. Hum Mol Genet. 1998 Jan;7(1):1–11. [PubMed]
  • Lahn BT, Page DC. Four evolutionary strata on the human X chromosome. Science. 1999 Oct 29;286(5441):964–967. [PubMed]
  • Vogt PH, Edelmann A, Kirsch S, Henegariu O, Hirschmann P, Kiesewetter F, Köhn FM, Schill WB, Farah S, Ramos C, et al. Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. Hum Mol Genet. 1996 Jul;5(7):933–943. [PubMed]
  • Sargent CA, Boucher CA, Kirsch S, Brown G, Weiss B, Trundley A, Burgoyne P, Saut N, Durand C, Levy N, et al. The critical region of overlap defining the AZFa male infertility interval of proximal Yq contains three transcribed sequences. J Med Genet. 1999 Sep;36(9):670–677. [PMC free article] [PubMed]
  • Sun C, Skaletsky H, Birren B, Devon K, Tang Z, Silber S, Oates R, Page DC. An azoospermic man with a de novo point mutation in the Y-chromosomal gene USP9Y. Nat Genet. 1999 Dec;23(4):429–432. [PubMed]
  • Jobling MA, Tyler-Smith C. Fathers and sons: the Y chromosome and human evolution. Trends Genet. 1995 Nov;11(11):449–456. [PubMed]
  • Hammer MF, Karafet T, Rasanayagam A, Wood ET, Altheide TK, Jenkins T, Griffiths RC, Templeton AR, Zegura SL. Out of Africa and back again: nested cladistic analysis of human Y chromosome variation. Mol Biol Evol. 1998 Apr;15(4):427–441. [PubMed]
  • Jobling MA, Samara V, Pandya A, Fretwell N, Bernasconi B, Mitchell RJ, Gerelsaikhan T, Dashnyam B, Sajantila A, Salo PJ, et al. Recurrent duplication and deletion polymorphisms on the long arm of the Y chromosome in normal males. Hum Mol Genet. 1996 Nov;5(11):1767–1775. [PubMed]
  • Hurles ME, Irven C, Nicholson J, Taylor PG, Santos FR, Loughlin J, Jobling MA, Sykes BC. European Y-chromosomal lineages in Polynesians: a contrast to the population structure revealed by mtDNA. Am J Hum Genet. 1998 Dec;63(6):1793–1806. [PMC free article] [PubMed]
  • Bouzekri N, Taylor PG, Hammer MF, Jobling MA. Novel mutation processes in the evolution of a haploid minisatellite, MSY1: array homogenization without homogenization. Hum Mol Genet. 1998 Apr;7(4):655–659. [PubMed]
  • Casanova M, Leroy P, Boucekkine C, Weissenbach J, Bishop C, Fellous M, Purrello M, Fiori G, Siniscalco M. A human Y-linked DNA polymorphism and its potential for estimating genetic and evolutionary distance. Science. 1985 Dec 20;230(4732):1403–1406. [PubMed]
  • Passarino G, Semino O, Quintana-Murci L, Excoffier L, Hammer M, Santachiara-Benerecetti AS. Different genetic components in the Ethiopian population, identified by mtDNA and Y-chromosome polymorphisms. Am J Hum Genet. 1998 Feb;62(2):420–434. [PMC free article] [PubMed]
  • Hammer MF. A recent insertion of an alu element on the Y chromosome is a useful marker for human population studies. Mol Biol Evol. 1994 Sep;11(5):749–761. [PubMed]
  • Whitfield LS, Sulston JE, Goodfellow PN. Sequence variation of the human Y chromosome. Nature. 1995 Nov 23;378(6555):379–380. [PubMed]
  • Foresta C, Ferlin A, Moro E. Deletion and expression analysis of AZFa genes on the human Y chromosome revealed a major role for DBY in male infertility. Hum Mol Genet. 2000 May 1;9(8):1161–1169. [PubMed]
  • Qureshi SJ, Ross AR, Ma K, Cooke HJ, Intyre MA, Chandley AC, Hargreave TB. Polymerase chain reaction screening for Y chromosome microdeletions: a first step towards the diagnosis of genetically-determined spermatogenic failure in men. Mol Hum Reprod. 1996 Oct;2(10):775–779. [PubMed]
  • Pryor JL, Kent-First M, Muallem A, Van Bergen AH, Nolten WE, Meisner L, Roberts KP. Microdeletions in the Y chromosome of infertile men. N Engl J Med. 1997 Feb 20;336(8):534–539. [PubMed]
  • Montermini L, Andermann E, Labuda M, Richter A, Pandolfo M, Cavalcanti F, Pianese L, Iodice L, Farina G, Monticelli A, et al. The Friedreich ataxia GAA triplet repeat: premutation and normal alleles. Hum Mol Genet. 1997 Aug;6(8):1261–1266. [PubMed]
  • Seielstad MT, Minch E, Cavalli-Sforza LL. Genetic evidence for a higher female migration rate in humans. Nat Genet. 1998 Nov;20(3):278–280. [PubMed]
  • Semino O, Passarino G, Brega A, Fellous M, Santachiara-Benerecetti AS. A view of the neolithic demic diffusion in Europe through two Y chromosome-specific markers. Am J Hum Genet. 1996 Oct;59(4):964–968. [PMC free article] [PubMed]
  • Jobling MA, Williams GA, Schiebel GA, Pandya GA, McElreavey GA, Salas GA, Rappold GA, Affara NA, Tyler-Smith C. A selective difference between human Y-chromosomal DNA haplotypes. Curr Biol. 1998 Dec 17;8(25):1391–1394. [PubMed]
  • Jobling MA, Tyler-Smith C. New uses for new haplotypes the human Y chromosome, disease and selection. Trends Genet. 2000 Aug;16(8):356–362. [PubMed]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Group


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • Nucleotide
    Published Nucleotide sequences
  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...