Open Journal of Genetics, 2013, 3, 27-32 OJGen
http://dx.doi.org/10.4236/ojgen.2013.32A3004 Published Online August 2013 (http://www.scirp.org/journal/ojgen/)
SRY in an XX male does not influence random
chromosome X inactivation: Cytogenetic evidence.
Definition of the boundaries of the translocated Y
segment through FISH and PCR-RT in a case
report and review of the literature
Mariano Stabile1*, Vincenzo Altieri2, Rosa Salzillo1, Panfilo Marrollo1, Guglielmo Stabile3,
Tina Iuorio1, Bianca Moscato1
1“Zigote” Genetic and Prenatal Diagnosis Centre, Salerno, Italy
2Genetic Department, Hosp. “Elena d’Aosta”, Naples, Italy
3Department of Obstetrics and Gynecology, IRCCS Burlo Garofalo, University of Trieste, Trieste, Italy
Received 29 May 2013; revised 13 June 2013; accepted 21 June 2013
Copyright © 2013 Mariano Stabile et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
We report a case of an SRY positive XX male. The
phenotype was completely masculinised except for the
reduced facial hair; testes were small, and azoosper-
mia was present. The patient’s metaphases, coloured
with acridine-orange to reveal the late replicating X
chromosome, were sequentially hybridised with SRY
and X centromeric probes: a random X chromosome
inactivation pattern (XCIP) was present, with SRY
present about half the time on both the active X and
the inactive X. The most likely hypothesis is that the
translocated SRY gene escaped inactivation as part of
the entire X Pseudo Autosomal telomeric Region 1
(PAR 1). This hypothesis can explain the masculine
phenotype, which would be incompatible with a
halved expression of SRY. Review of the literature
about the association of 46, XX males with a specific
XCI pattern is made. The analysis of region AZF and
QF-PCR for Y polymorphic loci allowed us to define
the boundaries of the translocated Y segment as re-
stricted to the region around the SRY locus. Chro-
mosomal fragility analysis, using SCE (Sister Chro-
matid Exchanges), ruled out chromosomal fragility as
a predisposing factor in the proband’s father; in ad-
dition, no chromosome Y polymorphic variant (in-
version, Y qh +/−), was present in the proband’s fa-
ther. However, like the AZF region c microdeletions
and PRKX/PRKY translocation XX males, a par-
ticular Y haplotype could be also in this case a pre-
disposing factor.
Keywords: XX Male; SRY; Translocation X-Y;
X Chromosome Inactivatio n; Y Chromosome
1. INTRODUCTION
Two types of XX male are distinguishable from the pa-
thogenetic point of view: XX males with SRY and XX
males without SRY. The frequency in the population of
Sex Reversal Syndrome (the diagnostic definition of which
includes three conditions: hermaph roditism and XX SRY
positive and negativ e males) is 1 :20,000 [1]. In XX ma l e s
without SRY, a mutation occurs in the SOX gene cascade
that can cause a gain of function. Instead, in males with
SRY, the cause is a translocation between the X chromo-
some and the Y chromosome that transfers the SRY gene
onto the X chromosome [2,3]. Normally, the Y chromo-
some is not able to undergo crossover with the homolo-
gous X chromosome, except for small parts of the Pseu-
doAutosomal telomeric Regions (PAR1 and PAR2) (Yp-
ter ed Yqter) representing about 5% of the chromosome
length [4]. Approximately half of Y genetic loci, which
have homologous genes on the X chromosome, are in
PAR regions. The translocation takes place during pater-
nal meiosis. The gene SRY maps to Yp11.31, which is
immediately contiguous to the PAR region in pter: the
spatial proximity can account for its occasional involve-
ment in a meiotic crossover with a resulting transfer onto
*Corresponding a uthor.

M. Stabile et al. / Open Journal of Genetics 3 (2013) 27-32 28
X. In a few cases of XX males, SRY is not transferred
onto X but onto an autosome: onto chromosome 3 in the
case of Chien [5] and onto chromosome 1 in the case of
Queralt [6]. The first case is interesting because it im-
plies two subsequent events: a first event that involved
translocation from Yp to Xpter, and a second event that
involved tran slocation from Xpter to 3 pter. The bound a-
ries of the translocated region can be established by ana-
lysing the various genetic markers on Yp and Yq. In the-
ory, an SRY gene translocated onto X could be involved in
X inactivation, even though the telomeric X pter is pre-
served from the process. Bouayed Abdelmo ula N et al. [7]
have hypothesised that the complete masculinised phe-
notype in an XX male was related to a preferential inac-
tivation of the X chromosome that was not rearranged,
on the basis of highly skewed X-chromosome inactiva-
tion patterns (XCIP) determined by analysis of the me-
thylation status of the androgen receptor gene. Measur-
ing XCI pattern using the methylation assay at the an-
drogen receptor locus in two patients 46, XX, Minor et al.
found a random patter n in one p atient and non-rando m in
the other [8]. Using the same method, Gunes et al. [9]
found a random pattern of XCI in two male patients 46,
XX. No random pattern was found instead by Vorona et
al. [10] in a XX male. Sharp et al. [11] studied causes of
incomplete masculinisation in 15 individuals with seg-
ments of Yp traslocated onto distal Xp; expression stud-
ies of translocated Y genes by allele specific RT-PCR
found very littl e eviden ce for sp reading of X inactivatio n
into Yp chromatin. Instead, the above mentioned authors
found that translocation carriers with an intersex phenol-
type showed either translocation breakpoints very close
to SRY, or disrupted expression of genes near SRY in a
manner unrelated to X inactivation. Using the cytoge-
netic method, here we provide direct cytogenetic evi-
dence that XCIP maintains its random pattern in an XX
SRY male, using sequential banding on the same meta-
phase (orange-acridine b anding, which stains th e inactive
X chromosome) and subsequent hybridisation with pr ob es
for the X centromere and SRY.
The second aim of our report is the definition of the
boundaries of the translocated Y region. FISH confirmed
the translocation of SRY onto chromosome X; in addi-
tion, the study of DYS393-AMGY markers for the Yp
arm and the AZF gene for the Yq arm allowed us to de-
fine the limits of the translocated region at a definite
level of about 7 Mb, which encompasses PAR1 and SRY.
Only a few cases in the literature have an exact definitio n
of the translocated region [11,12]. The third contribution
of this paper is the investigation into chromosomal fra-
gility as predisposing factor for X/Y translocation. Con-
sidering the infrequency of SRY positive XX males com-
pared to the hypothetical possibility of an abnormal re-
combination in the process of X/Y crossover which oc-
curs during each male meiosis, we have investigated the
possible presence of predisposing factors (Y inversion,
chromosomal fragility) in the father of our proband.
2. CASE REPORT
A 35-year-old married man was referred to our centre
with a 5 year history of male factor infertility. The pro-
band was the third son of healthy, non-consanguineous
couple; his two brothers were fertile with normal chil-
dren. His height was 173 cm, and his arm span was equal
to his height. Apparent masculinisation was complete, ex-
cept for the reduced facial hair; testes were small (<10
ml). Azoospermia was present at semen analysis. Hor-
monal studies revealed hypergonadotropic hypogonad-
ism (LH 35 ml.U./ml, FSH 80 ml.U./ml). He refused a
testicular biopsy. Cytogenetic investigation of blood lym-
phocytes revealed a 46 , XX chromosomal constitution in
100 metaphases.
3. MATERIALS AND METHODS
3.1. SRY FISH
FISH analysis on proband metaphases was performed
using SRY and X centromeric probes (Vysis SRY Probe
LSI SRY Spectrum Orange/CEP X Spectrum Green
ABBOTT MOLECULAR).
3.2. X-Chromosome Inactivation Patterns
(XCIP) Analysis
We studied “late replicating” X chromosomes on the pro-
band’s lymphocyte culture using the BrdU method, which
involves the add itio n of BrdU (0 .5 mg/ml) 7 hours before
stopping the reaction with colchicine; subsequently slides
were pre-treated with 33,258 Hoescht colorant (5 mg/100
ml) for 20 min ute s and th en we re ex posed to an Ultr aphi l
sunlamp MLU 300 W for 20 minutes and coloured with
Acridine-Oran ge (5 m g/100 ml).
3.3. Chromosomal Fragility Analysis
To determine the presence of chromosomal fragility, we
used the SCE (Sister Chromatid Exchanges) method for
lymphocyte cultures of the proband and his father. We
performed SCE by adding 0.1 ml BrdU solution (0.5
mg/ml) in 10 ml medium at the beginning of the culture.
The slides were treated in the same way as for the ex-
amination of late replicating X chromosomes. Using this
method, the tintorial painting of the sister chromatides is
different (one pale and the other black), providing evi-
dence of crossovers.
3.4. Microdeletion Chromosome Y Analysis
The genomic DNA of the proband was extracted from
blood lymphocytes using a commercial kit (“High Pure

M. Stabile et al. / Open Journal of Genetics 3 (2013) 27-32 29
PCR Template Preparation Kit”-Roche-). Amplification
was performed through a PCR multiplex reaction; spe-
cifically, the following Y-STSs regions were amplified:
sY84, sY86 (on re gion AZFa); sY127, sY134 (on region
AZFb); sY254, sY255 (on region AZFc). Amplification
products were subsequently revealed through reverse dot
blot, (KIT “RhyMA TEST IVF AZF” EUROCLONE).
In addition to the AZFa, AZFb, AZFc regions, the pro-
cedure involves the amplification and revelation of two
additional genes: ZFX/ ZFY and SRY (see the Y chro-
mos ome map).
3.5. Quantitative Fluorescent-Polymerase
Chain Reaction (QF-PCR)
Molecular analysis was performed on DNA extracted
from the proband’s peripherical blood through 4 reac-
tions for the polymorphism analysis (STR) of the Y chro-
mosome (Gen-Probe Elucigene QST*Rplusv2 cat. AN0-
PLB2). Quantitative fluorescence PCR (QF-PCR) is a
Multiplex PCR with fluorescent primers followed by ca-
pillary electrophoresis using Beckman CEQ800 Genetic
Analysis System. The kit is made by the following mar-
kers:
Cr. X : DXS6803, DXS8377, DXS6807, XHPRT;
Common X/Y markers: Amelogenin, X2 2 , X Y 218;
Cr. Y: SRY, DYS393, DYS392, DYS288, DYS19,
DYS390, DYS389 I-II, DYS385, DYS388, DYS437,
DYS438, DYS439
4. RESULTS
The FISH analysis of 50 metaphases showed an X chro-
mosome containing the SRY gene (Sex determining Re-
gion of the Y chromosome) at the terminal short arm.
This cytogenetic eviden ce confirms the translocation of a
small Y segment, including the SRY gene, on one X
chromosome (Figure 1). XCIP analysis revealed a pale,
inactive X chromosome in all metaphases. The hybridi-
sation with SRY and X centromeric probes on 50 meta-
phases, already treated for the evidence of late replicat-
ing X chromosomes, allowed us to establish that the X
translocated chromosome remained active 27/50 and in-
active 23/50 (Figure 2), demonstrating that the XCIP
random pattern was substantially preserved. Chromoso-
mal fragility analysis using SCE numbers found an av-
erage of 6 - 7 SCE for each methaphase, which is not
greater than the value found in a population of normal
subjects that were not exposed to clastogenic substances
[13]. With respect to the Y microdeletion, the deletions
mapped to the male specific region on Y chromosome
(MSY), which is localised on Yq and is subdivided into
three zones: AZFa, AZFb and AZFc. The AZFc region is
the most frequently involved in microdeletions (ap-
proximately 80%), compared to AZFb (about 9%) and
AZFa (3%). The proband’s strip is shown in Figure 3. It
can be seen all the STS markers are absent, and instead,
the ZFX and SRY genes are present. This procedure is
not able to distinguish the slight nucleotide difference
between the homologous ZFX (Xp22.2 position map)
and ZFY (Yp11.3 position map). The human ZFX and
ZFY loci have CpG islands near their 5’ ends. These is-
lands are typical in that they span approximately 1.5 kb,
Figure 1. FISH analysis using SRY and X centromeric
probes: the double SRY signal on the two chromatides of one
X chromosome.

M. Stabile et al. / Open Journal of Genetics 3 (2013) 27-32 30
(a) (a1)
(b) (b1)
Figure 2. (a) Metaphase coloured with acridine-orange; the
inactive X (Xi) is pale compared to the active X (Xa); (b) The
same metaphase after hybridization with SRY and X centro-
meric probes. The X with SRY is inactive in the metaphase on
the left (a), (b), and it is active in the metaphase on the right.
Figure 3. The proband’s strip for Y microdeletion: all the STS
markers are absent, and instead, the ZFX and SRY genes are
present.
contain transcription initiation sites, and encompass
some 5’ untranslated exons and introns. In one stretch
of 165 nucleotides containing 19 CpGs, human ZFX dif-
fers from human ZFY at only 9 positions. Schneider-
Gadicke [14] also showed that ZFX escapes X inactiva-
tion in humans. The QF-PCR (Table 1) revealed that
only DYS393 and SRY are present in the Y DNA of the
patient. DYS393 maps to just at the boundary between
PAR1 and SRY [15].
5. DISCUSSION
The Y chromosome can be involved in translocations
with all the autosomes; the Y; 15 translocation has been
Table 1. QF-PCR of the proband’s Y DNA polymorphic loci:
only SRY and DYS393 are present.
Chromosome Locus Results
DYS393 Present
SRY Present
DYS392 Absent
DYS288 Absent
DYS19 Absent
DYS390 Absent
DYS389 I-II Absent
DYS385 Absent
DYS388 Absent
DYS437 Absent
DYS438 Absent
Y
DYS439 Absent
found to have an incidence of 5% in an Ethiopian Com-
munity of Ebraic origin [16]. Translocations between
chromosomes X and Y are less frequent and generally
involve Xq [17]. The first meiotic division in males on
testicular biopsies appears as a prophase plate with biva-
lents (paired homologous chromosomes) with crossing-
over between homologous chromatids; in this phase,
chromosomes X and Y are located distant from each
other or have only one point of connection, at the extre-
mity. X-Y crossing over occurs between the two homo-
logous PAR regions [4]. The male recombination activ ity
in PAR1 is much higher than in the autosomes [18].
Burgoyne [19] proposed that analogous to the autosomes
a mechanism exists that ensures at least one chiasma per
bivalent in PAR1, and the small size of PAR1 should
prevent the formation of more than one chiasma: “Theory
of the single obligatory crossover in PAR1”. Because
double recombinants have been observed—although very
few—in different independent studies, the term “single
obligatory” is no longer appropriate. While Y PAR 1
crossover is obligatory, the Y PAR 2 crossover is op-
tional. Using one polymorphic marker in PAR2 and male
sex, it has been shown that crossover events in PAR2 are
possible and occur in approximately 2% of male meioses.
No recombinants have been observed for PAR2 in
women. In PAR2, the male recombination rate is higher
than the autosomal average but lower th an in PAR1 [20].
The SRY locus maps immediately outside the region
PAR1: a crossover with a breakpoint that is a little be-
yond the boundary of PAR1 has as a consequence the
translocation of SRY onto the X chromosome. The pre-
cise delimitation of a translocated Y segment has been
performed in this study (Figure 4), and it further con-
firms that the complete masculinisation of our patient de-

M. Stabile et al. / Open Journal of Genetics 3 (2013) 27-32 31
Figure 4. Map of Y with STRs markers, locus SRY and AZF a
b c: the translocated region is delimited in the red box.
pended exclusively on the presence of an active SRY
locus in an individual’s genome. XCIP analysis revealed
random inactivation, likely because the translocation is
in the PAR region, which normally escapes inactivation.
However, spermatogenesis requires the AZF locus and
other loci on Yq, and therefore it is defective in XX SRY
positive males.
Studies on the hypothesis of chromosomal fragility or
Y chromosomal structural variants as predisposing fac-
tors for SRY translocation in the proband’s father are
lacking in the scientific literature. Structural abnormali-
ties include various types of translocations, inversions,
deletions, duplications and isochromosomes. Structural
abnormalities of the Y chromosome are estimated to af-
fect less than 1% of the newborn male population and are
particularly hazardous for male reproductive function . In
the review of Kim JW [21] in 26 men with Y structural
variants who consulted a genetic clinic for various rea-
sons, 11 patients had an isodicentric Y chromosome, 7
had an inversion, 3 had a translocation, 2 had a deriva-
tive, 2 had a Yqs and 1 had a deletion. Sixteen were di-
agnosed with azoospermia, 8 were normally fertile and 1
was a man who was unable to donate semen due to men-
tal retardation.
Despite the fact that a large part of the Y chromosome
is spared from genetic recombination deriving from
crossovers, some loci, in particular the AZF region, are
genetically dynamic regions in the human genome [22-
24]. In a study of susceptibility to azoospermia factor c
microdeletions in a northern Italian population, Arredi et
al. [25] found that Y-chromosome haplogroups affect the
occurrence of AZFc b2/b4 deletions. Rosser et al. [26]
found gene conversion (nonreciprocal transfer of sequence
without crossover), frequent among sequences on the male-
specific region of the Y chromo so me ( MSY ) and tha t the
rate of X to Y conversion is fo ur to five order s of magni-
tude more rapid than the rate of Y-chromosomal base-
substitution mutatio n. Jobling et al. [27] showed that one
class of infertile males, PRKX/PRKY translocation XX
males, arises predominantly on a particular Y haplotypic
background. In our patient’s father, no structural anom-
aly of the Y chromosome was present, and chromosomal
fragility analysis did not provide evidence of spontane-
ous fragility or an increase in SCE. However we cannot
rule out that a particular Y haplotype could be also in this
case a predisposing factor.
REFERENCES
[1] Wang, T., Liu, J.H., Yang, J., Chen, J. and Ye, Z.Q.
(2009) XX male sex reversal syndrome: A case report
and review of the genetic basis. Andrologia, 41, 59-62.
doi:10.1111/j.1439-0272.2008.00889.x
[2] Heather, P. and Michael, W. (1996) Sox genes: Archi-
tects of development. Molecular Medicine, 2, 405-412.
[3] Harley, V.R., Clarkson, M.J. and Argentaro, A. (2003)
The molecular action and regulation of the testis-deter-
mining factors, SRY (sex-determining region on the Y
chromosome) and SOX9 [SRY-related high-mobility group
(HMG) box 9]. Endocrine Reviews, 24, 466-487.
doi:10.1210/er.2002-0025
[4] Flaquer, A., Rappold, G.A., Wienker, T.F. and Fischer, C.
(2008) The human pseudoautosomal regions: A review
for genetic epidemiologists. European Journal of Human
Genetics, 16, 771-779. doi:10.1038/ejhg.2008.63
[5] Chien, S.C., Li, Y.C., Ho, M., Hsu, P.C., Teng, R.H., Lin,
W.D., Tsai, F.J. and Lin, C.C. (2009) Rare rearrange-
ments: A “jumping satellite” in one family and autosomal
location of the SRY gene in an XX male. American
Journal of Medical Genetics Part A, 149A, 2775-2781.
doi:10.1002/ajmg.a.32958
[6] Queralt, R., Madrigal, I., Vallecillos, M.A., Morales, C.,
Ballescá, J.L., Oliva, R., Soler, A., Sánchez, A. and Mar-
garit, E. (2008) Atypical XX male with the SRY gene lo-
cated at the long arm of chromosome 1 and a 1qter mi-
crodeletion. American Journal of Medical Genetics Part
A, 146A, 1335-1340. doi:10.1002/ajmg.a.32284
[7] Bouayed Abdelmoula, N., Portnoi, M.F., Keskes, L., Re-
can, D., Bahloul, A., Boudawara, T., Saad, A. and Rebai,
T. (2003) Skewed X-chromosome inactivation pattern in
SRY positive XX maleness: A case report and review of
literature. Annales de Genetique, 46, 11-18.
doi:10.1016/S0003-3995(03)00011-X
[8] Minor, A., Mohammed, F., Farouk, A., Hatakeyama, C.,
Johnson, K., Chow, V. and Ma, S. (2008) Genetic char-
acterization of two 46,XX males without gonadal ambi-
guities. Journal of Assisted Reproduction and Genetics,
25, 547-552. doi:10.1007/s10815-008-9265-7
[9] Gunes, S., Asci, R., Okten, G., Atac, F., Onat, O.E., Ogur,
G., Aydin, O., Ozcelik, T. and Bagci, H. (2013) Two
males with SRY-positive 46,XX testicular disorder of sex
development. Systems Biology in Reproductive Medicine,
59, 42-47. doi:10.3109/19396368.2012.731624
[10] Vorona, E., Zitzmann, M., Gromoll, J., Schüring, A.N.
and Nieschlag, E. (2007) Clinical, endocrinological, and
epigenetic features of the 46,XX male syndrome, com-
pared with 47,XXY Klinefelter patients. Journal of Cli-
nical Endocrinology & Metabolism, 92, 3458-3465.
doi:10.1210/jc.2007-0447

M. Stabile et al. / Open Journal of Genetics 3 (2013) 27-32 32
[11] Sharp, A., Kusz, K., Jaruzelska, J., Tapper, W., Szarras-
Czapnik, M., Wolski, J. and Jacobs, P. (2005) Variability
of sexual phenotype in 46,XX(SRY+) patients: The in-
fluence of spreading X inactivation versus position ef-
fects. Journal of Medical Genetics, 42, 420-427.
doi:10.1136/jmg.2004.022053
[12] Xia, X.Y., Cui, Y.X., Lu, H.Y., Yang, B., Wang, G.H.,
Pan, L.J., Hou, B.S., Ge, Y.F., Shao, Y., Yao, B. and
Huang, Y.F. (2012) Clinical, molecular and cytogenetic
studies on 4 patients with 46, XX (SRY positive) male
syndrome. Cytogenetic and Genome Research, 136, 270-
277.
[13] Ben Salah, G., Kamoun, H., Rebai, A., Ben Youssef, A.,
Ayadi, H., Belghith-Mahfoudh, N., Fourati, A., Ayadi, H.
and Fakhfakh, F. (2010) Sister chromatid exchange (SCE)
and high-frequency cells (HFC) in peripheral blood lym-
phocytes of healthy Tunisian smokers. Mutation Re sea rc h,
719, 1-6. doi:10.1016/j.mrgentox.2010.09.003
[14] Schneider-Gädicke, A., Beer-Romero, P., Brown, L.G.,
Nussbaum, R. and Page, D.C. (1989) ZFX has a gene
structure similar to ZFY, the putative human sex deter-
minant, and escapes X inactivati on. Cell, 57, 1247-1258.
doi:10.1016/0092-8674(89)90061-5
[15] Hammer, M.F., Chamberlain, V., Kearney, V.F., Stover,
D., Zhang, G., Karafet, T., Walsh, B. and Redd, A.J.
(2005) Population structure of Y chromosome SNP hap-
logroups in the United States and forensic implications
for constructing Y chromosome STR databases. Forensic
Science International.
[16] Chen-Shtoyerman, R., Josefsberg Ben-Yehoshua, S., Nis-
sani, R., Rosensaft, J. and Appelman, Z. (2012) A preva-
lent Y;15 translocation in the Ethiopian Beta Israel com-
munity in Israel. Cytogenetic and Genome Research, 136,
171-174. doi:10.1159/000336201
[17] Palka-Bayard-de-Volo, C., De Marco, S., Chiavaroli, V.,
Alfonsi, M., Calabrese, G., Chiarelli, F. and Mohn, A.
(2012) Array-CGH characterization of a de novo t(X;Y)
(p22;q11) in a female with short stature and mental re-
tardation. Gene, 504, 107-110.
doi:10.1016/j.gene.2012.05.009
[18] Kong, X., Murphy, K., Raj, T., He, C., White, P.S. and
Matise, T.C. (2004) A combined linkage—Physical map
of the human genome. American Journal of Human Ge-
netics, 75, 1143-1148. doi:10.1086/426405
[19] Burgoyne, P.S. (1982) Genetic homology and crossing
over in the X and Y chromosomes of Mammals. Human
Genetics, 61, 85-90. doi:10.1007/BF00274192
[20] Freije, D., Helms, C., Watson, M.S. and Donis-Keller, H.
(1992) Identification of a second pseudoautosomal region
near the Xq and Yq telomeres. Science, 258, 1784-1787.
doi:10.1126/science.1465614
[21] Kim, J.W., Park, S.Y., Ryu, H.M., Lee, D.E., Lee, B.Y.,
Kim, S.Y., Park, Y.S., Lee, H.S. and Seo, J.T. (2010)
Molecular and clinical characteristics of 26 cases with
structural y chromosome aberrations. Mutation Research,
719, 1-6. doi:10.1016/j.mrgentox.2010.09.003
[22] Navarro-Costa, P., Plancha Carlos, E. and Gonçalves J.
(2010) Genetic dissection of the AZF regions of the hu-
man Y chromosome: Thriller or filler for male (in)fertil-
ity? Journal of Biomedicine and Biotechnology, 2010,
936569. doi:10.1155/2010/936569
[23] Navarro-Costa, P., Gonçalves, J. and Plancha Carlos, E.
(2010) The AZFc region of the Y chromosome: At the
cross-roads between genetic diversity and male infertil-
ity. Human Reproduction Update, 16, 525-542.
doi:10.1093/humupd/dmq005
[24] Navarro-Costa, P., Pereira, L., Alves, C., Gusmão, L.,
Proença, C., Marques-Vidal, P., Rocha, T., Correia, S.,
Sónia, C.J., Neves, A., Soares Ana, P., Nunes, J., Calhaz-
Jorge, Carlos., Amorim, A., Plancha Carlos, E. and Gon-
çalves, J. (2007) Characterizing partial AZFc deletions of
the Y chromosome with amplicon-specific sequence mar-
kers. BMC Genomics, 8, 342.
doi:10.1186/1471-2164-8-342
[25] Arredi, B., Ferlin, A., Speltra, E., Bedin, C., Zuccarello,
D., Ganz, F., Marchina, E., Stuppia, L., Krausz, C. and
Foresta, C. (2007) Y-chromosome haplogroups and sus-
ceptibility to azoospermia factor c microdeletion in an
Italian population. Journal of Medical Genetics, 44, 205-
208. doi:10.1136/jmg.2006.046433
[26] Rosser, Z.H., Balaresque, P. and Jobling, M.A. (2009)
Gene conversion between the X chromosome and the
male-specific region of the Y chromosome at a transloca-
tion hotspot. American Journal of Human Genetics, 85,
130-134. doi:10.1016/j.ajhg.2009.06.009
[27] Jobling, M.A., Williams, G.A., Schiebel, G.A., Pandya,
G.A., McElreavey, G.A., Salas, G.A., Rappold, G.A.,
Affara, N.A. and Tyler-Smith, C. (1998) A selective dif-
ference between human Y-chromosomal DNA haplo-
types. Current Biology, 8, 1391-1394.
doi:10.1016/S0960-9822(98)00020-7