An excess of chromosome 1 breakpoints in male infertility.
In a search for potential infertility loci, which might be revealed by clustering of chromosomal breakpoints, we compiled 464 infertile males with a balanced rearrangement from Mendelian Cytogenetics Network database (MCNdb) and compared their karyotypes with those of a Danish nation-wide cohort. We excluded Robertsonian translocations, rearrangements involving sex chromosomes and common variants. We identified 10 autosomal bands, five of which were on chromosome 1, with a large excess of breakpoints in the infertility group. Some of these could potentially harbour a male-specific infertility locus. However, a general excess of breakpoints almost everywhere on chromosome 1 was observed among the infertile males: 26.5 versus 14.5% in the cohort. This excess was observed both for translocation and inversion carriers, especially pericentric inversions, both for published and unpublished cases, and was significantly associated with azoospermia. The largest number of breakpoints was reported in 1q21; FISH mapping of four of these breakpoints revealed that they did not involve the same region at the molecular level. We suggest that chromosome 1 harbours a critical domain whose integrity is essential for male fertility.
Bache
Iben
I
Wilhelm Johannsen Centre for Functional Genome Research, Department of Medical Biochemistry and Genetics, The Panum Institute, University of Copenhagen, Denmark. iben@medgen.ku.dk
Assche
Elvire Van
EV
Cingoz
Sultan
S
Bugge
Merete
M
Tümer
Zeynep
Z
Hjorth
Mads
M
Lundsteen
Claes
C
Lespinasse
James
J
Winther
Kirsten
K
Niebuhr
Anita
A
Kalscheuer
Vera
V
Liebaers
Inge
I
Bonduelle
Maryse
M
Tournaye
Herman
H
Ayuso
Carmen
C
Barbi
Gotthold
G
Blennow
Elisabeth
E
Bourrouillou
Georges
G
Brondum-Nielsen
Karen
K
Bruun-Petersen
Gert
G
Croquette
Marie-Francoise
MF
Dahoun
Sophie
S
Dallapiccola
Bruno
B
Davison
Val
V
Delobel
Bruno
B
Duba
Hans-Christoph
HC
Duprez
Laurence
L
Ferguson-Smith
Malcolm
M
Fitzpatrick
David R
DR
Grace
Elizabeth
E
Hansmann
Ingo
I
Hultén
Maj
M
Jensen
Peter Ka
PK
Jonveaux
Philippe
P
Kristoffersson
Ulf
U
Lopez-Pajares
Isidora
I
McGowan-Jordan
Jean
J
Murken
Jan
J
Orera
Maria
M
Parkin
Tony
T
Passarge
Eberhard
E
Ramos
Carmen
C
Rasmussen
Kirsten
K
Schempp
Werner
W
Schubert
Regine
R
Schwinger
Eberhard
E
Shabtai
Fiorella
F
Smith
Kim
K
Stallings
Raymond
R
Stefanova
Margarita
M
Tranebjerg
Lisbeth
L
Turleau
Catherine
C
van der Hagen
Carl Birger
CB
Vekemans
Michel
M
Vokac
Nadja Kokalj
NK
Wagner
Klaus
K
Wahlstroem
Jan
J
Zelante
Leopoldo
L
Tommerup
Niels
N
D002869:Chromosome Aberrations; D007446:Chromosome Inversion; D002878:Chromosomes, Human, Pair 1; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D009845:Oligospermia / Q000235:genetics; D014178:Translocation, Genetic