CHP2 Molecular cell biology and genetic disorders
1. 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?
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. It is important to noted that brain cells cannot be replaced once dead.
2. Why some of the autosomal dominant diseases have a male or female preponderance?
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.
Characteristics of X-linked dominant disorders includes
no male-to-male transmission, no skipped generations, females are affected twice as often as males. Affected females transmit the disease to 50% of their daughters and 50% of their sons. Affected males transmit the disease to all of their daughters and none of their sons.
Characteristics of X-linked recessive disorders include:
an affected male does not transmit the disease to his sons, but all daughters are carriers, sons of carrier females have a one in two chance of the disorder, but all daughters are asymptomatic, and the trait occurs in maternal uncles and in male cousins descended from the mother’s sisters (oblique transmission). Affected females are rare and may be homozygous for the disease or may have an unfavorable lyonization.
3. We have been told that some tumours in the colon are associated with microsatellite instability. What does this mean?
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 nonpolyposis colorectal cancer (HNPCC).
4. What are microarrays?
Microarrays are 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.
5. Why do mitochondrial diseases cause a myopathy?
Muscles derive energy via oxidative phosphorylation. Mutations in mitochrondrial DNA impair oxidative phosphorylation.
6. Why do successive generations of patients with some genetic disorders present earlier and with progressively worse symptoms?
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).
7. Does a normal serum uric acid level exclude the diagnosis of Lesch–Nyhan syndrome?
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.
8. How is retinoblastoma an autosomal dominant disease if the mutation of both RB genes is required to express the disease?
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.
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