Cytogenetic abnormalities are what I have learnt during my internship in Hospital Kuala Lumpur. Today, I’m going to introduce Autosomal Aneuploidy in this Cytogenetics and Cancer Research blog.
 
In Cytogenetics, the term aneuploidy refers to cytogenetic abnormalities in which all or part of one or more chromosomes is added or deleted. Autosomal aneuploidy is the abnormality that does not involve the sex chromosomes. Sometimes, the abnormalities can be either numerical or structural. Normally we only have pair of chromosomes which are structurally similar. Other than that, it can be recognized as abnormal. Those cytogenetic abnormalities can be present only in some cells which we called mosaicism or in all cells.

Meiotic Nondisjunction Causes Autosomal Aneuploidy

The origin of autosomal aneuploidy is because of meiotic nondisjunction. The meiotic nondisjunction is random for all autosomes except for chromosome 21. Chromosome 21 has shown the highest frequency of autosomal aneuploidy.
 
According to cytogenetic studies, the incidence of autosomal aneuploidy in spontaneous abortuses (die before birth) is much higher than incidences in newborns. So, what is the case for aneuploidy actually observed in spontaneous abortuses or liveborns? All trisomies for all autosomes have been reported in spontaneous abortuses. The fetal only can survive if and only if the trisomies are in mosaic form. However, there are still many exceptions for the trisomies 13, 18 and 21. Some of the foetus still can survive even though the trisomies 13, 18 or 21 are in nonmosaic form.
 
Why the frequencies of trisomy for each chromosome might be similar at the time of conception but differ greatly among abortuses and liveborns especially for trisomy 21? It can be explained by the devastating effect of chromosomal imbalance. Most of the autosomal aneuploidies are very deleterious and lethal in the pre-embryonic stage. As a result, those abnormalities are unrecognized and, therefore, unstudied spontaneous abortions.
 
Furthermore, the lethality of a particular autosomal aneuploidy is related to the gene content of the particular chromosome. Aneuploidies for the gene rich chromosomes are less likely to survive. However, the less gene rich chromosomes like chromosome 13, 18 and 21 are more likely to survive to term.
 
Anyway, we will just focus on those observed in liveborns for the autosomal aneuploidy in Cytogenetics. I will talk more details about the monosomies and trisomies in my future post. Stay tuned!

MOSAICISM in Cytogenetics

Do you know human may consist more than one chromosomally distinct cell lines in Cytogenetics? Most of us believe that each person will just consist of one unique chromosome set (2n) which is the combination of our father’s sperm and our mother’s ovum. However, there is an abnormality that occurred when a person consists of more than one chromosome set in his body. We called this abnormality as Mosaicism in Cytogeetics.

It was the first ever time I heard about mosaicism last week. I was surprised to be informed that a patient has been diagnosed as normal in the first Cytogenetics test but abnormal in the second Cytogenetics test. After further investigation, the scientists found that the patient’s blood cell is normal but his bone marrow is abnormal. The scientists found out that the patient has two different chromosome cell lines in his body. It’s amazing!!

Since that, I just start to worry whether all part of my body is normal. There are several severity levels of mosaicism. Some low mosaicism even undetectable in Cytogenetics. Mosaicism arises after fertilization (occur when the sperm meets with the ovum) through inaccurate segregation of chromosomes at mitosis. The level of mosaicism depends on the stage of development of the organism when the error in division occurs. The level of abnormal effect could be dependent on the percentage and location of abnormal cells present in the body.

Figure 1: Level of Mosaicism

There are two mechanisms account for errors of segregation:

i.            Non-disjunction

-          The failure of the two chromatids to separate at the centromere at metaphase, causing both chromatids to go to the same daughter cell and leading to one hyperdiploid cell and one hypodiploid cell.

ii.            Anaphase lag

-          The loss of a chromatid at anaphase because it is not attached to the spindle and so does not get to the pole. This causes one hypodiploid cell, though the other daughter cell of the pair can be normal.

Figure 2: Segregation Errors At Mitosis

Mosaicism might cause minor abnormality or cause severe disorder. The scientists told me that sometimes the patient‘s parent will found it unacceptable to know that their son had been diagnosed as abnormal in the second test. They might claim that there was error occurred during the Cytogenetics test. The scientists sympathize to them but nothing can do except giving the condolence to them.

The chromosomal abnormalities are the things that we cannot deal with since we cannot change the chromosome inside our body. What we can do is to prevent it from occur. How to do that? Just look forward to my coming post in Cytogenetics and Cancer Research.