title: HSFY genes and the P4 palindrome in the AZFb interval of the human Y chromosome are not required for spermatocyte maturation.
abstract: BACKGROUND
  Recurrent AZFb deletions on the human Y chromosome are associated with an absence of ejaculated spermatozoa consequent to a meiotic maturation arrest that prevents the progression of germ cells to haploid stages. The extreme rarity of partial deletions has hampered the identification of the AZFb genes required for normal meiotic stages. The critical interval, refined by two overlapping deletions associated with full spermatogenesis (AZFc and b1/b3), measures over 4 Mb and contains 13 coding genes: CDY2, XKRY, HSFY1, HSFY2, CYORF15A, CYORF15B, KDM5D, EIF1AY, RPS4Y2 and four copies of RBMY.
  
  
  RESULTS
  We screened 1186 men from infertile couples for Y chromosome deletions, and identified three unrelated oligozoospermic men and one azoospermic man who carry an identical 768 kb deletion resulting in loss of the entire P4 palindrome, including both HSFY genes, the only coding genes within the deletion interval. This 768 kb deletion was not found in 1179 control men. The deletion breakpoints share only 4 bp of nucleotide identity, revealing that the deletions are not recurrent, but are descendants of a founding deletion. Confirming this, we find that all four men carry a Y chromosome of the same highly defined haplogroup (R1b1b1a1b) (incidence 30% in Southern France), although further haplotype analyses showed that they were not closely related.
  
  
  CONCLUSIONS
  Although the HSFY deletion is restricted to our infertile group, it has been transmitted naturally over many generations, indicating that HSFY genes make only a slight contribution to male fertility. Importantly, our study formally excludes HSFY genes as the AZFb factor required for progression through meiosis.
authors.affiliation: Inserm UMR_S 910, Faculté de Médecine de Marseille, Université de la Méditerranée, Marseille 13385, France.
authors.forename: Elsa
authors.initials: E
authors.lastname: Kichine
authors.forename: Virginie
authors.initials: V
authors.lastname: Rozé
authors.forename: Julie
authors.initials: J
authors.lastname: Di Cristofaro
authors.forename: Daniel
authors.initials: D
authors.lastname: Taulier
authors.forename: André
authors.initials: A
authors.lastname: Navarro
authors.forename: Eric
authors.initials: E
authors.lastname: Streichemberger
authors.forename: Fanny
authors.initials: F
authors.lastname: Decarpentrie
authors.forename: Catherine
authors.initials: C
authors.lastname: Metzler-Guillemain
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lévy
authors.forename: Jacques
authors.initials: J
authors.lastname: Chiaroni
authors.forename: Veronique
authors.initials: V
authors.lastname: Paquis-Flucklinger
authors.forename: Florence
authors.initials: F
authors.lastname: Fellmann
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mitchell
mesh_terms: D000328:Adult; D053713:Azoospermia / Q000235:genetics / Q000503:physiopathology; D056905:Chromosome Breakpoints; D002872:Chromosome Deletion; D041322:Chromosomes, Human, Y / Q000235:genetics*; D018703:Founder Effect; D005602:France; D056726:Genetic Association Studies; D000076249:Heat Shock Transcription Factors; D006801:Humans; D055029:Inverted Repeat Sequences; D008297:Male; D016324:Sequence Tagged Sites; D012720:Severity of Illness Index; D013076:Sperm Count; D013090:Spermatocytes / Q000166:cytology*; D013091:Spermatogenesis; D014157:Transcription Factors / Q000737:chemistry / Q000172:deficiency / Q000235:genetics*
chemical_list: C572209:HSFY1 protein, human; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors