Y chromosome microdeletion
Encyclopedia
Y chromosome microdeletion (YCM) is a family of genetic disorder
s caused by missing gene(s) in the Y chromosome
. Many men with YCM exhibit no symptoms and lead normal lives. However, YCM is also known to be present in a significant number of men with reduced fertility
. Men with reduced sperm production (in up to 20% of men with reduced sperm count, some form of YCM has been detected) varies from oligozoospermia, significant lack of sperm, or azoospermia
, complete lack of sperm.
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.
s for sequence-tagged site
s (STS) on the Y chromosome, and then using polymerase chain reaction
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 gold standard test for genetic mutation, namely complete DNA sequencing
of a patient's Y chromosome, is still far too expensive for use in epidemiologic research or even clinical diagnostics.
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.
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
s caused by missing gene(s) in the Y chromosome
Y chromosome
The Y chromosome is one of the two sex-determining chromosomes in most mammals, including humans. In mammals, it contains the gene SRY, which triggers testis development if present. The human Y chromosome is composed of about 60 million base pairs...
. Many men with YCM exhibit no symptoms and lead normal lives. However, YCM is also known to be present in a significant number of men with reduced fertility
Fertility
Fertility is the natural capability of producing offsprings. As a measure, "fertility rate" is the number of children born per couple, person or population. Fertility differs from fecundity, which is defined as the potential for reproduction...
. Men with reduced sperm production (in up to 20% of men with reduced sperm count, some form of YCM has been detected) varies from oligozoospermia, significant lack of sperm, or azoospermia
Azoospermia
Azoospermia is the medical condition of a male not having any measurable level of sperm in his semen. It is associated with very low levels of fertility or even sterility, but many forms are amenable to medical treatment...
, complete lack of sperm.
Cause
The mechanism of mutationMutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
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
Natural selection is the nonrandom process by which biologic traits become either more or less common in a population as a function of differential reproduction of their bearers. It is a key mechanism of evolution....
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 markerGenetic marker
A genetic marker is a gene or DNA sequence with a known location on a chromosome that can be used to identify cells, individuals or species. It can be described as a variation that can be observed...
s for sequence-tagged site
Sequence-tagged site
A sequence-tagged site is a short DNA sequence that has a single occurrence in the genome and whose location and base sequence are known....
s (STS) on the Y chromosome, and then using polymerase chain reaction
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....
amplification and gel electrophoresis
Gel electrophoresis
Gel electrophoresis is a method used in clinical chemistry to separate proteins by charge and or size and in biochemistry and molecular biology to separate a mixed population of DNA and RNA fragments by length, to estimate the size of DNA and RNA fragments or to separate proteins by charge...
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
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a 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 gold standard test for genetic mutation, namely complete DNA sequencing
DNA sequencing
DNA sequencing includes several methods and technologies that are used for determining the order of the nucleotide bases—adenine, guanine, cytosine, and thymine—in a molecule of DNA....
of a patient's Y chromosome, is still far too expensive for use in epidemiologic research or even clinical diagnostics.
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
Male infertility
Male infertility refers to the inability of a male to achieve a pregnancy in a fertile female. In humans it accounts for 40-50% of infertility. Male infertility is commonly due to deficiencies in the semen, and semen quality is used as a surrogate measure of male fecundity.-Pre-testicular...
among Caucasians in Europe and the Western Pacific region.
Additional genes associated with spermatogenesis
Spermatogenesis
Spermatogenesis is the process by which male primary germ cells undergo division, and produce a number of cells termed spermatogonia, from which the primary spermatocytes are derived. Each primary spermatocyte divides into two secondary spermatocytes, and each secondary spermatocyte into two...
in men and reduced fertility upon Y chromosome deletions include RBM, DAZ, SPGY, and TSPY.