title: The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men.
abstract: Deletions of the AZFc (azoospermia factor c) region of the Y chromosome are the most common known cause of spermatogenic failure. We determined the complete nucleotide sequence of AZFc by identifying and distinguishing between near-identical amplicons (massive repeat units) using an iterative mapping-sequencing process. A complex of three palindromes, the largest spanning 3 Mb with 99.97% identity between its arms, encompasses the AZFc region. The palindromes are constructed from six distinct families of amplicons, with unit lengths of 115-678 kb, and may have resulted from tandem duplication and inversion during primate evolution. The palindromic complex contains 11 families of transcription units, all expressed in testis. Deletions of AZFc that cause infertility are remarkably uniform, spanning a 3.5-Mb segment and bounded by 229-kb direct repeats that probably served as substrates for homologous recombination.
authors.affiliation: Howard Hughes Medical Institute, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kuroda-Kawaguchi
authors.forename: H
authors.initials: H
authors.lastname: Skaletsky
authors.forename: L G
authors.initials: LG
authors.lastname: Brown
authors.forename: P J
authors.initials: PJ
authors.lastname: Minx
authors.forename: H S
authors.initials: HS
authors.lastname: Cordum
authors.forename: R H
authors.initials: RH
authors.lastname: Waterston
authors.forename: R K
authors.initials: RK
authors.lastname: Wilson
authors.forename: S
authors.initials: S
authors.lastname: Silber
authors.forename: R
authors.initials: R
authors.lastname: Oates
authors.forename: S
authors.initials: S
authors.lastname: Rozen
authors.forename: D C
authors.initials: DC
authors.lastname: Page
mesh_terms: D001483:Base Sequence; D002872:Chromosome Deletion; D007446:Chromosome Inversion; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D000075364:Deleted in Azoospermia 1 Protein; D019143:Evolution, Molecular; D020440:Gene Duplication; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009845:Oligospermia / Q000235:genetics; D009928:Organ Specificity; D020161:Physical Chromosome Mapping; D016601:RNA-Binding Proteins / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D013094:Spermatozoa / Q000378:metabolism; D020080:Tandem Repeat Sequences / Q000235:genetics; D013737:Testis / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D014998:Y Chromosome / Q000235:genetics*
chemical_list: C095668:DAZ1 protein, human; D000075364:Deleted in Azoospermia 1 Protein; D016601:RNA-Binding Proteins