Aneuploidy is a genetic disorder in which an organism cell contains an abnormal number of chromosomes. To learn more about how aneuploidy manifests itself and what are its causes, let's briefly analyze the structure of a living cell, the cell nucleus and the chromosomes themselves.
A bit of theory
As you know, in each somatic cell of the human body there are normally 46 chromosomes, that is, a diploid set. Only in germ cells this set is single. Chromosomes are located in the cell nucleus and are a long, compacted helix of DNA. DNA, in turn, consists of monomers - polypeptides. A certain sequence of polypeptides determines the gene - the structural unit of heredity. DNA contains the entire genetic program for the development of a given organism.
In non-sex cells, each chromosome has a homologous sister chromosome very similar but not identical to the first. During meiosis, these chromosomes exchange regions. This phenomenon is called "crossover". ATthe chromosome is distinguished by long and short arms.
Chromosome set
The totality of an organism's chromosomes is called a karyotype. Normally, in humans, as already mentioned, the karyotype is represented by 46 chromosomes, 23 from each parent, but an anomaly occurs in which the karyotype is presented differently. This disorder is called "aneuploidy".
Aneuploidy is a kind of karyotype in which the number of chromosomes is not equal to normal. Aneuploidy of chromosomes, in which one chromosome is missing, is called monosomy. If there is no pair - nullisomy. If instead of a normal pair of homologous chromosomes, three homologous chromosomes appear in the karyotype, then this is a trisomy. Any change in the number of chromosomes causes serious developmental disorders. Some of them can be lethal.
Aneuploidy of non-sex chromosomes (autosomes)
There are many genetic diseases caused by aneuploidy. Examples of such diseases are Down syndrome, Patau syndrome, Edwards syndrome. All these diseases are caused by the presence of an extra chromosome in different homologous pairs. Down syndrome is the most common of these diseases. It is manifested by mental retardation, communication disorders, learning difficulties.
However, trisomy 21, which causes the disease, does not affect life expectancy. Classes in certain techniques can help patients achieve certain success in learning and socialization.
Another disease, Patau syndrome, also causesaneuploidy. This severe violation is the result of trisomy on the 13th chromosome. Patients rarely live up to 10 years, more than 80% die in the first year of life, the rest suffer from a severe form of mental retardation. Children with Patau syndrome have pronounced microcephaly, heart problems are often observed, corneal clouding, a cleft palate, and auricles are somewhat deformed.
The main cause of Edwards syndrome is also aneuploidy - trisomy on the 18th chromosome. More than 90% of children with this disease die from cardiac arrest in the first year of life, the rest suffer from severe mental retardation and are practically unteachable.
Trisomy 16 is more common than any other aneuploidy. This genetic disorder is lethal, the fetus dies in the womb during the first three months of pregnancy.
Aneuploidy in humans can be manifested by a rare genetic disease - Varkani's syndrome, trisomy on the 8th chromosome. The main symptoms are mental retardation, heart defects, skeletal anomalies.
Aneuploidy of sex chromosomes
A type of aneuploidy, which does not always lead to serious consequences, is trisomy on the X chromosome. This disorder occurs only in women. Trisomy on the X chromosome is relatively common - in 0.1% of women. The disease may not manifest itself throughout life, which happens in about 30% of cases. The remaining 70% are characterized by the following symptoms: dyslexia, agraphia, speech and movement disorders. The symptomatic treatment used in such cases is very effective andhelps to completely or partially eliminate these symptoms.
Other anomalies related to the number of sex chromosomes are much more serious. These include Shereshevskoro-Turner syndrome, a special case of aneuploidy in which a woman's karyotype has only one X chromosome instead of the normal two. Symptoms - mental retardation, short stature, impaired development of the genital organs, a mild form of mental retardation is possible.
There is another serious disease caused by aneuploidy. This is Klinefelter's syndrome - the presence of one or more extra X or Y chromosomes in men. Symptoms do not appear until the onset of puberty. Almost half of the patients have no symptoms throughout their lives, while others have gynecomastia, obesity, and infertility. In rare cases, oligophrenia is noted.
Causes of aneuploidy
Aneuploidy occurs due to the fact that during meiosis the homologous chromosomes did not separate and instead of one, a pair of chromosomes got into the gamete or none. If in one gamete the number of chromosomes is normal, and in the other - abnormal, then the karyotype of the zygote will be abnormal.
Non-separation of homologous chromosomes can occur due to adverse environmental conditions, exposure to toxins of various nature. But most often the reason is heredity: in families where there have already been cases of aneuploidy, the risk of having a child with an abnormal karyotype is higher than in he althy parents.
Frequency
It can be said that the underlying risk of chromosomalaneuploidy diseases is on average small, since all genetic diseases are classified as rare. The overall probability of having a child with a karyotype anomaly is 5% if both parents are he althy. If one of the parents has any pathology of the karyotype, the probability of having a sick child increases.
The frequency of aneuploidy depends on the chromosome. The most common pathology of the karyotype is Klinefelter's syndrome, aneuploidy of the sex chromosome, the frequency is 1 in 500 newborn boys, the rarest is Varkani's syndrome, the aneuploidy of the 8th chromosome, the frequency is 1:50,000.
Treatment
Treatment of aneuploidy is always symptomatic. With Shereshevsky-Turner syndrome, low growth and a lack of female sex hormones are noted, therefore anabolic steroids are used for treatment.
In Down's syndrome, treatment is reduced to classes with patients in special programs aimed at developing cognitive abilities.
Patients with Varkani syndrome rarely live past 20 years of age. Over time, new anatomical changes appear, mental retardation progresses. If necessary, they resort to surgical intervention to correct the condition of the spine and treat contractures.
If girls with trisomy X have delayed speech development, a speech pathologist may be needed. In case of problems with writing and reading, it is worth contacting a dyslexia specialist.
Klinefelter's syndrome does not always affect the quality of life of patients. In rare casesmarked mental retardation. Depending on its degree (light, medium, heavy), an individual training program is developed. If gynecomastia, decreased sexual function, infertility appear, then they resort to hormone therapy.
Diagnosis
Genetic diseases of the fetus can be detected using a number of methods (ultrasound examination, biochemical marker method).
Ultrasound can detect early fetal Down syndrome.
Non-invasive prenatal diagnosis of aneuploidy is a safe and accurate method for identifying possible karyotype abnormalities. The essence of the method is simple - a specialist examines fragments of the child's DNA that are in the mother's blood. Invasive aneuploidy diagnosis is more accurate, but because it carries the risk of miscarriage, it is used only as a last resort.
Factors that increase the likelihood of aneuploidy
Recent studies have shown that there is a definite correlation between the age of the mother and the likelihood of having a child with Down syndrome, Patau syndrome or Edwards syndrome. The older a woman is, the more likely she is to have a child with an abnormal karyotype.
What exactly factors play a decisive role in the development of sex chromosome aneuploidy is unknown. It is assumed that the keythe role in such cases belongs to heredity.
