Molecular cell biology and genetic disorders

Published on 05/05/2015 by admin

Filed under Internal Medicine

Last modified 22/04/2025

Print this page

This article have been viewed 1043 times

2 Molecular cell biology and genetic disorders

Questions

As cells grow and regenerate, what mechanism does the body use to get rid of the continuously dying cells? And what kind of cells can’t be replaced once dead?

I cannot find out why some of the autosomal dominant diseases have a male or female preponderance, e.g. I have never seen a female Marfans. I was attributing it to imprinting but on reading about imprinting in detail it cannot be the case.

We have been told that some tumours in the colon are associated with microsatellite instability. What does this mean?

I understand that microarrays are being used to define the molecular abnormality and the prognosis in some patients with leukaemia. What are microarrays?

Why do mitochondrial diseases cause a myopathy?

Why do successive generations of patients with some genetic disorders present earlier and with progressively worse symptoms.

Does a normal serum uric acid level exclude the diagnosis of Lesch-Nyhan syndrome?

How is retinoblastoma an autosomal dominant disease if the mutation of both RB genes is required to express the disease?

Cells are continually dying by a process of apoptosis (programmed cell death). These cells (or their fragments) are phagocytosed by macrophages or neutrophils where they undergo autolysis within these phagosomes. Brain cells cannot be replaced when dead, although recent evidence challenges this view.

Further reading

Voss H. V. et al (2006) Journal of Clinical Investigation116: 2005-2011.

By definition, the genes responsible for autosomal dominant diseases must be located on the 22 autosomes; thus both males and females are affected. Males and females are affected in equal proportions except in sex-limited disorders, e.g. ovarian cancer with BRCA1 locus.

Microsatellites are short sequences of randomly repeated segments of DNA, two to five nucleotides in length. These regions are inherently unstable and susceptible to mutations. They have been found in tumours, notably colonic, particularly in individuals with hereditary non-polyposis colorectal cancer (HNPCC).

Microarrays are, as you say, used to analyse gene expression. The technique is a significant advance because thousands of genes can be screened at any one time. The assays work by using a fluorescently tagged known mRNA, binding to the specific DNA template from which it originated. The amount of bound mRNA can be measured accurately.

Muscles derive energy via oxidative phosphorylation. Mutations in mitochrondrial DNA impair oxidative phosphorylation.

This process is called ‘genetic anticipation’ and is due to expansion of the trinucleotide repeat within the disease gene with each generation. It has been shown in, for example, Huntington’s disease (CAG) and dystrophia myotonica (CTG).

A raised serum uric acid level is usually, but not always, present. The urate to creatinine concentration ratio in urine is elevated. The diagnosis is confirmed by measuring hypoxanthine-guanine-phosphoribosyl transferase (HGPRT) enzyme in cultured cells.

Retinoblastoma (RB) is due to a mutational inactivation of both alleles of the RB gene. A ‘two-hit’ model has been proposed involving a second somatic mutation later in development.

Related

1000 Questions and Answers from Kumar _ Clarks Clinical Medicine