Chromosomal Abnormalities

Chromosomal abnormalities - sometimes also called cytogenetic disorders - are very common at all. Although we don´t see many affected people. How it is possible? The fetus with some chromosomal abnormality is usually not able to survive. About 50% of first-trimester abortions is connected with some cytogenetic mistake. The incidence of chromosomal abnormalities is approximately 1 from 200 of newborns. .

We recognize two types of chromosomal abnormalities:

1. numeric
2. structural

We are able to find the disorders due to karyotype testing. The cytogeneticists get the samples (blood, amnion fluid), then stained the chromosomes and put then in the right order by their length. Then we can see some changes in pattern (banding). The most typical method is Giemsa stain, so it is usually called "G banging". This is important for structural abnormalities. Numeral abnormalities we could find even easier.

Otherwise classification of chromosomal abnormalities depends on fact which type of chromosome is affected - autosomes (Down syndrome, DiGeorge syndrome) or sex chromosomes (Klinefelter syndrome, Turner syndrome).

Types of Structural Abnormalities

Translocation

Deletion

Ring chromosome

Isochomosomes

Inversion

Translocation

• During translocation some part of one chromosome is transfered to another one. It is very important if the translocation is balanced or unbalacted. Balanced means that two chromosomes just exchange their parts but the number of chromosomes stay the same (46 chromosomes). Fortunately - typical place of break is near to the centromere, we usually lost just a small parts of the acrocentric chromosomes. There are not so many important genes coded by these parts. So carrier can normally survive this cytogenetic change
• Unfortunately the problem occur during the fertilization. Carrier start to produce unbalanced gametes. It is very important because that leads to abnormalities in offsprings. Because they can receive changed chromosome from the carrier and miss some important genes.
• Types of translocation:

1. reciprocal - translocation between two chromosomes ("A segment" goes to "B chromosome" and "B segment" goes to "A chromosome")
2. robertsonian - translocation of two acrocentric chromosomes

Deletion

• Deletion is characterized by the lost of some part of chromosome. Two breaks have to occur for deletion of the interstitial segment. For deletion of terminal segment (telomere) one break is enough. Segments which were deleted from the chromosome are not able to "live" on their own. It is the reason why we lost genes which were coded by these part of chromosome.
• One special example of deletion exists. It is called "ring chromosome". It is a situation when chromosome lost both of its ends. The long and the small arms then connect together and chromosome became a ring shaped.

Isochromosomes

• Isochromosomes are created by the incorrect divides of centromere. Normally centromere divides vertically. In this case they divide horizontally.
• The result is usually the lost of one arm. It means that newly created chormosome has just two long arms or two short arms which are normally connected by centromere.
• We could find it on X chromosome very often.
• It is a huge problem during the fertilization. Because fetus then get a trisomy for one arm and a monosomy for the second arm.

Inversion

• For inversion are typical two breakages in the different part of the chromosome. The newly created segments then replace each other.
• Inversion was discovered in 1921.
• Although we still don´t know why inversion exists, we know that it is the most important mechanism of reorganizing of the genome.
• We recognize 2 types of inversion:

1. pericentric - causing deletions, insertions or abnormal centromeres
2. paracentric - more common type, it is less harmfull for its carrier

• Inversion suppress the recombination process.

How We Denote Parts of a Chromosome

Chromosomal marking

When we want to describe the location of some structural abnormality we used special marks. We have to count the regions always from the centromere - for both arms. Example: 1q13

• the first number is a number of chromosome - chromosome 1
• (p) and (q) are used for marking of arm - (p) for small arm and (q) for long arm - the long arm
• the third number is for the region of chromosome - region 1
• last number is for theband - band 3

So the change is located on the long arm of chromosome 1 (see Fig. Chromosomal marking).

Related articles

• Karyotype
• Disorders of the Autosomes
• Disorders of the Sex Chromosomes
• The Sex Chromosomes and Sex Determination

Sources

• KUMAR, ABBAS, FAUSTO, MITCHELL,, et al. Robbins Basic Pathology. 8th edition edition. 2007. ISBN 978-0-8089-2366-4.

References

• KUMAR, ABBAS, FAUSTO, MITCHELL,, et al. Robbins Basic Pathology. 8th edition edition. 2007. ISBN 978-0-8089-2366-4.