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 chromosome abnormality. Although polygenic disorders ...

s caused by missing genes in the

Y chromosome The Y chromosome is one of two sex chromosomes in therian mammals and other organisms. Along with the X chromosome, it is part of the XY sex-determination system, in which the Y is the sex-determining chromosome because the presence of the ...

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

fertility Fertility in colloquial terms refers the ability to have offspring. In demographic contexts, fertility refers to the actual production of offspring, rather than the physical capability to reproduce, which is termed fecundity. The fertility rate ...

. Reduced sperm production varies from oligozoospermia, 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 or viral replication, ...

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 Heredity, heritable traits characteristic of a population over generation ...

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 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 ...

s for sequence-tagged sites (STS) on the Y chromosome, and then using

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

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 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, thymine, cytosine, and guanine. The ...

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 men than in fertile controls and the correlation found may still go up as improved

genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

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 Male infertility refers to a sexually mature male's inability to impregnate a fertile female. Male infertility can wholly or partially account for 40% of infertility among couples who are trying to have children. "A problem with the male is the s ...

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