Cytogenetics and Cancer Research

Prader-Willi syndrome or PWS syndrome is thought to be one of the most common genetic disorders. Prader-Willi syndrome and Angelman syndrome were the first examples in humans of genomic imprinting in Cytogenetics. Angelman syndrome has an entirely different clinical condition with PWS syndrome. I will explain about the Angelman syndrome in my future post.
 
What is genomic imprinting? Imprinting is a type of marking process that has a memory. Genomic imprinting is where a segment of DNA is marked or imprinted during gametogenesis. This mark will be retained and recognized throughout the life of the individual. Maternal and paternal inherited alleles will be marked differently and are expressed differently in the offsprings. Therefore, the offspring with the same genetic material will have different appearances. The individual with Prader-Willi syndrome is because the loss of paternally inherited region 15q11 – q13 of chromosome 15. Simple to say, the PWS individual does not inherit the region 15q11 – q13 of chromosome 15 from his/her father but only from mother.

Prader-Willi syndrome is the most common genetic cause of marked obesity in humans according to Cytogenetics. It is a complex disorder with cardinal features of
 
i)    Infantile hypotonia (low muscle tone)
 
ii)   Mild growth retardation
 
iii)  Frequent occurrence of breech presentation (baby enters the birth canal with the buttocks or feet first)
 
iv)  Small hands and feet with gracile and tapering fingers
 
v)   Microcephaly (smaller head)
 
vi)  Almond-shaped eyes
 
vii) Mental deficiency (average IQ of 65)
 
viii) Short stature and so on.
 
From the age of about one and half years onward, hyperphagia becomes a serious problem, leading to gross obesity. Due to hyperphagia and gross obesity, diabetes often sets in during adolescence or later. Epilepsy is found in a minority of cases. Mental development is characterised by moderate to severe retardation with tendency to behaviour disorders, especially reactive to food deprivation. Patients with this syndrome may need specialists for assessment and treatment of their behavioural and learning problems, at the beginning of childhood. Prader-Willi syndrome is present in all races and ethnic groups and most cases are sporadic.
 
In conclusion, Prader-willi syndrome is a genetic disorder that needs treatment and assessment to overcome the learning problem and obesity problem of the patients. I will write a series of Prader-Willi syndrome in this Cytogenetics and Cancer Research blog in order to give people a clear mind about this syndrome. Stay tuned!

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!