What is a chromosome?

All human cells hold in their nucleus the genetic information in charge for the operation of the entire body. Such information is contained in the nuclear DNA; the DNA molecule in the nucleus is wrapped in microscopic structures called chromosomes. Chromosomes are not visible until the cells start dividing.During the cell division stage called metaphase, the chromosomes get more compact and can be seen using the optical microscope. Each chromosome has a constriction point called centromere, which provides the chromosome with a specific shape, by dividing it into two sections, or ends: a short end noted “p” and a long end noted as „q”.

Every individual has 46 chromosomes (23 pairs) in the nucleus of somatic cells. Each pair is constituted of a chromosome inherited from the father and one from the mother.

What is a chromosome abnormality?

Any change in the normal number or in the unique structure of chromosomes is considered an abnormality and may cause a genetic disorder.

Such changes can occur during the egg or the sperm cell formation, after the formation of the zygote (first cell of the embrio, after the egg and sperm cell fuse) or during an individual’s lifetime.

Inherited abnormalities come from a parent who may or may not have symptoms, and who produces genetically unstable gametes (sperms or eggs), which may cause a genetic condition if they are transmitted to the offspring. After the chromosomally abnormal gamete fuses with a normal one, a genetically abnormal zygote appears. The consequences are highly variable and can include failed fertilization, spontaneous abortion, perinatal death, congenital malformations, growth issues, intellectual disability,infertility.

Somatic abnormalities occur during an individual’s lifetime and can cause various types of cancers.

Chromosome abnormalities are divided into two groups: numerical and structural

1. Numerical abnormalities

Any change of the number of chromosomes is defined as a numerical abnormality (or aneuploidy) and it can either be inherited from a carrier parent, or occur “de novo” as a result of non-disjunction (lack of chromosome separation) which may occur during meiosis or mitosis.

Such abnormalities can be identified by genetic cytogenetic or molecular tests and, in most cases, they are non-viable.

The only viable aneuploidies are trisomies: 13 (Patau syndrome), 18 (Edwards syndrome), and 21 (Down syndrome) and sex chromosome aneuploidiessuch as Klinefelter syndrome (XXY), Turner syndrome (XO), trisomy X (XXX) and Jacob’s syndrome (XYY).

In certain cases, numeric abnormalities do not occur in all the cells. An individual may therefore have two or several cell lines with a different number of chromosomes. This phenomenon is called mosaicism.

1. Structural abnormalities

Structural abnormalities occur when one or several chromosomes have a change in their normal structure, that ca can be either inherited from one of the parents or”de novo”.

These abnormalities can also be transmitted to the individual’s children and cause disease.

The effects of structural abnormalities depend on their type, size and location.

Structural abnormalities can be identified through prenatal or postnatal cytogenetic testingand they can be:

• Deletions: chromosomes with missing genetic material
• Insertions: chromosomes with additional genetic material
• Translocations: the relocation of a chromosomal fragment from the original chromosome to another one
• Duplications: chromosomes with duplicated areas
• Inversions: chromosomes containing a fragment that has been detached, the two ends reversed and reattached
• Isochromosomes: chromosomes with 2 identical ends
• Dicentric chromosomes: chromosomes with 2 centromeres
• Ring chromosomes: chromosomes forming a circular structure

How can we study chromosome abnormalities?

Chromosome abnormalities can be identified using either the conventional karyotype (which can detect structural abnormalities and large deletions/duplications) or the molecular karyotype that can reveal very small deletions/duplications, invisible to the conventional karyotype but cannot reveal structural abnormalities).

The conventional karyotype implies arranging the chromosomes in homologous pairs depending on their size, shape, and banding.The chromosome pairs from 1 to 22 are called autosomes, while the 23^rd is the sex chromosome pair, called heterosomes/gonosomes. The two sex chromosomes are X and Y. Women have two X chromosomes (XX), whereas men have an X chromosome and a Y chromosome (XY).

The karyotype analysis can detect all numerical abnormalities and structural abnormalities larger than 5 Mb. Moreover, conventional karyotype is the only genetic diagnosis method able to detect balanced chromosomal changes such as translocations.