Autosomal Chromosomal Alterations: What Are They?

Let’s find out why certain chromosomal changes occur and what diseases they cause.

Chromosomal changes are quite common and more serious than changes in a single gene because they involve the involvement of many genes. Each chromosome arm divides into 4 regions. Within each region, each band is listed in relation to the distance from the centromere.

The short arm is called “p” and the long arm “q”. For example, 1 q 23 indicates: chromosome 1, long arm, second region, third band. The characteristics common to this alteration are:

• Cognitive and intellectual retardation.
• Presence of dimorphic features and malformations.
• Growth delay.

Classification of chromosomal alterations

Among the chromosomal alterations are numerical aberrations and aberrations in the structure of chromosomes.

Numerical aberrations

Generally, the most frequent cause of numerical aberrations in chromosomes is disjunction. This consists of a failure in homologous chromosomes or chromatids during disjunction in the first meiotic division, in the second or during mitosis.

The consequences of this anomaly lie in the fact that the members of the chromosomal pair do not separate properly. Hence, in some gametes there may be too many chromosomes or even missing them.

When a gamete with an extra chromosome joins a normal gamete in fertilization, the resulting zygote will have three units of this particular chromosome. This phenomenon is known as trisomy.

When a gamete that lacks a particular chromosome joins a normal gamete, it will result in a monosomy. Nondisjunction can also occur during mitosis that occurs after the formation of the zygote.

If this happens at the beginning you will have trisomic cells, otherwise they will be monosomal. These patients are called mosaic. Nondisjunction almost always occurs with respect to the X chromosome (mosaics of other chromosomes are generally not viable).

Aberrations in the structure of chromosomes

The most frequent alterations in the structure of chromosomes are deletion, duplication, inversion and translocation.

• Deletion or insertion. Loss of a fragment of a chromosome: this means that in the affected chromosome all the genetic information stored in the lost fragment is missing.
• Duplication. Presence of an additional fragment of chromosome. Sometimes a deleted fragment of a chromosome can join the ends of the homologous chromosome. This alteration is much less harmful than the deletion.
• Inversion. It supposes the fragmentation of a chromosome by two breaks, followed by the adhesion to the same chromosome, but in the opposite way. In general, this change in the order of the genes does not result in an abnormal phenotype. But it can have consequences in the next generation, when the chromosome with the inversion joins a normal one.

• Translocation. Transfer from one chromosome to another non-homologous. Sometimes these translocations are reciprocal.

Structural aberrations generally occur during meiosis of one of the gametes (maternal or paternal).

Autosomal chromosomal alterations

Here, in summary, are the main autosomal chromosomal alterations:

Down syndrome

• It was first described by Langdon Down in 1866.
• Most known and frequent chromosomal anomaly (therefore it affects 1 in every 700 live births).
• People with Down syndrome have 47 chromosomes, with a trisomy on chromosome 21.
• It is usually identified at the time of birth or shortly after due to the presence of typical characteristics such as the following:
  -Hypotonia
  -Mental retardation
  -Brachycephaly (therefore excessive growth of the head due to the premature closure of the coronal suture).
  – Prominent tongue.
  -Small and wide hands.
  -Cardiac anomalies in 35% of cases.
  – Smaller size than normal.

• Although in 95% of cases Down syndrome is due to the trisomy of chromosome 21, about 4% has a translocation of the long arm of chromosome 21 (therefore to chromosome 13, 14, 15 and 22). These patients therefore have 46 chromosomes even if as a phenotype it is not different from trisomy 21.
• The average age of the mothers is 34 years.
• Male carriers are less likely than females to have children with this condition.

Trisomy 18 (Syndrome E)

• Syndrome associated with a trisomy of chromosome 18.
• It is related to multiple birth defects.
• It is much more severe than Down syndrome (so most patients die at 6 months).

• The most frequent symptoms include:
  – Mental retardation.
  Inability to grow.
  – Changes in the ears, hands and feet.

Trisomy 13 (Syndrome D)

• It is less frequent than the previous one and the alterations are much more severe (therefore patients do not survive beyond the first month of life).
• It includes defects in the nervous system, mental retardation, cleft lip, cleft palate, skin abnormalities, alteration in the heart, etc.

Cat cry syndrome or du cri du chat

• It is due to a partial monosomy of chromosome 5 (therefore the suppression of a fragment of the short arm).
• It causes several anomalies but the most characteristic is that of the baby ‘s cry which is similar to a cat’s meow. Other alterations are mental retardation and microcephaly.

Monosomy 4

• It occurs for the deletion of the short arm of chromosome 4.

• It is characterized by low weight at birth, lack of growth and an abnormal facial appearance.

Conclusions

To conclude, chromosomal alterations represent, nowadays, an important difficulty for the evolutionary development of the newborn. However, there are more and more ways to discover them in time. In addition, there are also increasingly advanced techniques for prevention and treatment.