Aneuploidy is a genetic disorder in which an abnormal amount of chromosomes is contained in an organism cell. To learn more about how aneuploidy manifests itself and what are its causes, we briefly analyze the structure of a living cell, cell nucleus, and chromosomes themselves.
Bit of theory
As you know, in every somatic cell of the human body 46 chromosomes are normal, 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 DNA helix. DNA, in turn, consists of monomers - polypeptides. A specific sequence of polypeptides defines a gene, a structural unit of heredity. DNA contains the entire genetic development program 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 sites. This phenomenon is called crossing over. The long and short shoulders are distinguished in the chromosome.
Chromosome set
The totality of the body's chromosomes is called a karyotype. Normally, in a person, as already mentioned, the karyotype is represented by 46 chromosomes, 23 from each parent, but there is an anomaly in which the karyotype is presented differently. This disorder is called aneuploidy.
Aneuploidy is a type 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 appear in the karyotype, then this is trisomy. Any change in the number of chromosomes causes serious developmental disorders. Some of them can be fatal.
Non-sex chromosome aneuploidy (autosomes)
There are many genetic diseases that aneuploidy causes. Examples of such diseases are Down Syndrome, Patau Syndrome, Edwards Syndrome. All these diseases are caused by the presence of an additional chromosome in different homologous pairs. Down syndrome is the most common of these diseases. It manifests itself as mental retardation, impaired communication, learning difficulties.
However, trisomy on the 21st chromosome, which causes the disease, does not affect life expectancy. Classes using certain methods can help patients achieve certain successes in learning and socialization.
Another disease, Patau syndrome, also causes aneuploidy. This most serious violation is the result of trisomy on the 13th chromosome. Patients rarely live to 10 years, more than 80% die in the first year of life, the rest suffer from severe oligophrenia. In children with Patau's syndrome, microcephaly is expressed, heart problems are often observed, clouding of the cornea, cleft palate, auricles are slightly 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 oligophrenia and are practically uneducable.
Trisomy on the 16th chromosome is more common than any other aneuploidy. This genetic disorder is fatal; the fetus dies in the womb during the first three months of pregnancy.
Aneuploidy in humans can manifest itself as a rare genetic disease - Warkani syndrome, trisomy on the 8th chromosome. The main symptoms are mental retardation, heart defects, skeletal abnormalities.
Sex chromosome aneuploidy
A kind of aneuploidy, which does not always lead to serious consequences, is trisomy on the X chromosome. Such a violation 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 following symptoms are characteristic of the remaining 70%: dyslexia, agraphia, speech and motor impairment. The symptomatic treatment used in such cases is very effective and helps to completely or partially eliminate these symptoms.
Other abnormalities associated with 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, low growth, impaired development of the genitals, a mild form of mental retardation is possible.
There is another serious illness caused by aneuploidy. This is Klinefelter syndrome - the presence of one or more additional X- or Y-chromosomes in men. Symptoms do not appear until 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 entered the gamete or not a single one. If in one gamete the number of chromosomes is normal, and in the other it is abnormal, then the zygote karyotype 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 that of healthy parents.
Frequency
We can say that the basic risk of chromosomal aneuploidy diseases is on average small, since all genetic diseases are rare. The overall probability of having a baby with a karyotype anomaly leaves 5% if both parents are healthy. 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 karyotype pathology is Klinefelter syndrome, sex chromosome aneuploidy, frequency 1 per 500 newborn boys, the most rare - Warkany syndrome, chromosome 8th aneuploidy, frequency 1:50 000.
Treatment
Treatment of aneuploidy is always symptomatic. With Shereshevsky-Turner syndrome, there is a low growth and a lack of female sex hormones, therefore anabolic steroids are used for treatment.
With Down syndrome, treatment is reduced to classes with the patient according to special programs aimed at developing cognitive abilities.
Patients with Warkani syndrome rarely live up to 20 years. Over time, new anatomical changes appear, mental retardation progresses. If necessary, they resort to surgery to correct the condition of the spine and treat contractures.
If girls with trisomy on the X chromosome have a delay in speech development, a speech therapist may need to be consulted. In case of problems with writing and reading, you should contact a dyslexia specialist.
Klinefelter's syndrome does not always affect the quality of life of patients. In rare cases, mental retardation is noted. Depending on its degree (light, medium, heavy), an individual training program is developed. If gynecomastia is manifested, decreased sexual function, infertility, then resort to hormone therapy.
Diagnostics
It is possible to identify genetic diseases of the fetus using a number of methods (ultrasound examination, the method of biochemical markers).
With the help of ultrasound, the fetus can have Down syndrome at an early stage of development.
Non-invasive prenatal diagnosis of aneuploidy is a safe and accurate method for determining possible karyotype abnormalities. The essence of the method is simple - a specialist examines fragments of a child’s DNA located in the mother’s blood. Invasive diagnosis of aneuploidy is a more accurate method, but since it carries the risk of spontaneous abortion, they resort to it only in extreme cases.
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 probability of having a baby with Down Syndrome, Patau Syndrome or Edwards Syndrome. The older the woman, the higher the likelihood of having a child with an abnormal karyotype.
What factors play a decisive role in the development of sex chromosome aneuploidy is unknown. It is assumed that a key role in such cases belongs to heredity.