Y chromosome microdeletion ''(YCM)'' is a family of genetic disorders caused by missing genes in the Y chromosome. Many men with YCM exhibit no symptoms and lead normal lives. It is present in a significant number of men with reduced fertility. Reduced sperm production varies from oligozoospermia, significant lack of sperm, or

azoospermia Azoospermia is the medical condition of a man whose semen contains no sperm. It is associated with male infertility, but many forms are amenable to medical treatment. In humans, azoospermia affects about 1% of the male population and may be seen ...

, complete lack of sperm.

Cause

The mechanism of mutation is not different for Y-chromosome microdeletion. However, the ability to repair it differs from other chromosomes. The human Y chromosome is passed directly from father to son, and is not protected against accumulating copying errors, whereas other chromosomes are error corrected by recombining genetic information from mother and father. This may leave natural selection as the primary repair mechanism for the Y chromosome.

Diagnosis

Y chromosome microdeletion is currently diagnosed by extracting DNA from leukocytes in a man's blood sample, mixing it with some of the about 300 known genetic markers for sequence-tagged sites (STS) on the Y chromosome, and then using polymerase chain reaction amplification and

gel electrophoresis Gel electrophoresis is a method for separation and analysis of biomacromolecules ( DNA, RNA, proteins, etc.) and their fragments, based on their size and charge. It is used in clinical chemistry to separate proteins by charge or size (IEF ...

in order to test whether the DNA sequence corresponding to the selected markers is present in the DNA. Such procedures can test only the integrity of a tiny part of the overall 23 million

base pair A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...

long Y chromosome. Therefore, the sensitivity of such tests depends on the choice and number of markers used. Present diagnostic techniques can only discover certain types of deletions and mutations on a chromosome and give therefore no complete picture of genetic causes of infertility. They can only demonstrate the presence of some defects, but not the absence of any possible genetic defect on the chromosome. The preferred test for genetic mutation, namely complete

DNA sequencing DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, guanine, cytosine, and thymine. Th ...

of a patient's Y chromosome, is too expensive for use in epidemiological research or clinical diagnostics. In up to 20% of men with reduced sperm count, some form of YCM has been detected.

Infertility

Microdeletions in the Y chromosome have been found at a much higher rate in

infertile Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species (mostly haplodiploid insects). It is the normal state ...

men than in fertile controls and the correlation found may still go up as improved genetic testing techniques for the Y chromosome are developed. Much study has been focused upon the "

azoospermia factor locus Azoospermia factor (AZF) is one of several proteins or their genes, which are coded from the AZF region on the human male Y chromosome. Deletions in this region are associated with inability to produce sperm. Subregions within the AZF region are ...

" (AZF), at Yq11. A specific partial deletion of AZFc called ''gr/gr deletion'' is significantly associated with

male infertility Male infertility refers to a sexually mature male's inability to impregnate a fertile female. In humans it accounts for 40–50% of infertility. It affects approximately 7% of all men. Male infertility is commonly due to deficiencies in the semen, ...

among Caucasians in Europe and the Western Pacific region. Additional genes associated with

spermatogenesis Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testis. This process starts with the mitotic division of the stem cells located close to the basement membrane of the tubule ...

in men and reduced fertility upon Y chromosome deletions include

RBM RBM is a three-letter acronym. It refers to: *89.1 Radio Blue Mountains, Radio station in Katoomba, New South Wales *The Roll Back Malaria (RBM) Partnership, the global framework to implement coordinated action against malaria. *Restricted Boltzmann ...

, DAZ,

SPGY Deleted in azoospermia 1, also known as DAZ1, is a protein which in humans is encoded by the ''DAZ1'' gene. Function This gene is a member of the DAZ gene family and is a candidate for the human Y-chromosomal azoospermia factor (AZF). Its ex ...

, and

TSPY Testis-specific Y-encoded protein 1 is a protein that in humans is encoded by the ''TSPY1'' gene. The protein encoded by this gene is found only in testicular tissue and may be involved in spermatogenesis. Approximately 35 copies of this gene are ...

Cause

Diagnosis

Infertility

See also

References

Further reading