Y-chromosome microdeletions are common in
about 10-15% of men with azoospermia or severe oligospermia.
These microdeletions are too small to be detected by
karyotyping. They can be easily identified using polymerase
Most of the microdeletions that cause
azoospermia or oligospermia occur in the non-overlapping
regions of the long arm of the Y-chromsome. These regions,
also called azoospermia factor regions, are responsible for
spermatogenesis. The loci are termed AZFa, AZFb and AZFc
from proximal to distal Yq (Yq11.21-23 region). Several genes
located in AZF regions which are found to be associated with spermatogenesis
are viewed as “AZF
AZFa and candidate genes:
The size of the AZFa
region is estimated to be 1Mb. The frequency of deletions in AZFa
is lower than that of both AZFb
The important candidate genes include USP9Y (ubiquitin- specific protease 9, Y chromosome) and DBY
(dead box on the Y).
is a single copy gene that functions as a C-terminal ubiquitin
hydrolase. It is ubiquitously expressed in a wide variety of
is ubiquitously expressed in humans. In addition it exhibits
transcripts unique to the testis. The protein it encodes is an
RNA helicase. DBY is
more frequently deleted than USP9Y.
The other candidate genes include UTY (ubiquitous TPR motif on the Y) and TB4Y (thymosin B4-isoform).
AZFb and candidate genes:
locus spans about 1.5 Mb of the Y chromosome.
Two important candidate gene families
that have been mapped on the AZFb
locus are EIF1AY
(translation initiation factor 1 A, Y isoform) and RBMY
(RNA binding motif on Y).
encodes a ubiquitously expressed translation initiation
factor. However it also possesses abundant testis-specific
is a multicopy gene family thought to consist of 30-40
members, some of which are pseudogenes. Numerous RBMY
genes have been detected across both arms of the Y chromosome.
However, only genes within AZFb,
produce detectable levels of the protein. These proteins
contain an RNA- binding motif.
and candidate genes:
locus spans about 3Mb of the Y chromosome .Deletions of the AZFc
locus occur more frequently than AZFa
or AZFb locus.
(deleted in azoospermia) gene is an important candidate gene
located in AZFc.
This is the most frequently deleted gene in infertile men.
belongs to a multicopy gene family. Its autosomal copy is
found on short arm of chromosome 3 (DAZ- like). It has 16
exons. It is expressed exclusively in testicular tissue. The
protein has a regulatory role in RNA metabolism.
Other genes mapped to the AZFc region include CDY1
(chromodomain Y1) and BPY2
(basic protein Y2). Though the functions of these genes have
yet to be elucidated, they are found to be expressed uniquely
in the testis.