Y chromosome microdeletion ''(YCM)'' is a family of

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

s caused by missing genes in the

Y chromosome The Y chromosome is one of two sex chromosomes (allosomes) in therian mammals, including humans, and many other animals. The other is the X chromosome. Y is normally the sex-determining chromosome in many species, since it is the presence or abse ...

. Many men with YCM exhibit no symptoms and lead normal lives. It is present in a significant number of men with reduced

fertility Fertility is the capability to produce offspring through reproduction following the onset of sexual maturity. The fertility rate is the average number of children born by a female during her lifetime and is quantified demographically. Fertili ...

. Reduced sperm production varies from

oligozoospermia Terms oligospermia, oligozoospermia, and low sperm count refer to semen with a low concentration of sperm and is a common finding in male infertility. Often semen with a decreased sperm concentration may also show significant abnormalities in sperm ...

, significant lack of sperm, or azoospermia, complete lack of sperm.

Cause

The mechanism of

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA replication, DNA or viral repl ...

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 Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the heritable traits characteristic of a population over generations. Cha ...

as the primary repair mechanism for the Y chromosome.

Diagnosis

Y chromosome microdeletion is currently diagnosed by extracting DNA from

leukocytes White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...

in a man's blood sample, mixing it with some of the about 300 known

genetic marker A genetic marker is a gene or DNA sequence with a known location on a chromosome that can be used to identify individuals or species. It can be described as a variation (which may arise due to mutation or alteration in the genomic loci) that can be ...

s for

sequence-tagged site A sequence-tagged site (or STS) is a short (200 to 500 base pair) DNA sequence that has a single occurrence in the genome and whose location and base sequence are known. Usage STSs can be easily detected by the polymerase chain reaction (PCR) usin ...

s (STS) on the Y chromosome, and then using

polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) ...

amplification and gel electrophoresis 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 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 of a patient's Y chromosome, is too expensive for use in

epidemiological research Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants of health and disease conditions in a defined population. It is a cornerstone of public health, and shapes policy decisions and evidenc ...

or clinical diagnostics. In up to 20% of men with reduced

sperm count A semen analysis (plural: semen analyses), also called seminogram or spermiogram, evaluates certain characteristics of a male's semen and the sperm contained therein. It is done to help evaluate male fertility, whether for those seeking pregna ...

, some form of YCM has been detected.

Infertility

Microdeletions in the Y chromosome have been found at a much higher rate in infertile 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" (AZF), at Yq11. A specific partial deletion of AZFc called ''gr/gr deletion'' is significantly associated with male infertility among Caucasians in Europe and the Western Pacific region. Additional genes associated with spermatogenesis in men and reduced fertility upon Y chromosome deletions include RBM, DAZ, SPGY, and TSPY.

Cause

Diagnosis

Infertility

See also

References

Further reading