4.1.1 Eukaryotic Chromosomes
4.1.2 Definitions
4.1.3 Gene mutation.
4.1.4 Sickle cell anaemia
The chromosome is composed of two main molecules.
a) DNA
b) Proteins called histones.
This image was taken shortly after DNA a replication but before the prophase. It is composed of two daughter chromatids joined at the centromere.
The chromosome is super coiled by a factor around x16,000. The DNA molecule is about 1.8m long but is located in the nucleus which is only 10um in diameter!
Gene:a heritable factor that controls a specific characteristic.
Allele: one specific form of a gene, differing form other alleles by one or a few bases only and occupying the same gene locus as other alleles of that gene.
Genome: the whole genetic information of the organism.
Gene mutation is a change in the base sequence of an allele.
The changed base sequence may produce a different amino acid sequence in the protein translated.
The changed base sequence may not change the protein because of the degenerate nature of the genetic code.
The expression of the mutated gene may or may not be beneficial to the organism.
Substances that cause mutation are called mutagens and include chemicals and radiation.
Sickle cell anaemia is a genetic disease.
Frequency ia about 1 in 655 African Americans
The disease is inherited not contracted by infectious routes.
Sickle cell anaemia at the tissue level:
(a) Normal haemoglobin has two of four proteins changed in the mutation.
(b) The normal biconcave disc shape of the red blood cell is changed to a 'sickle' shape.
(c) In addition to not carrying oxygen correctly (anaemia) the cells also causes local clots (infarctions) such as is shown in the kidney tubules. This leads to necrosis (death) of the tubules, kidney damage, kidney failure and possible to death.
Genetic of Sickle Cell.
The gene loci for the normal beta chain of haemoglobin is on chromosome 11.
The normal allele carried the triplet GAG at the sixth amino acid position for the beta chain (146 amino acids).
This transcribed and translates into the negatively charged Glutamic acid.
The mutation changes a single base ( T replaces A) and this transcribes and translates into the amino acid Valine.
Valine has a neutral charge and the result is a change in the shape of the beta chain with long needle like structures forming.
This gene is noted for many mutations and it is estimated that some 5% of humans carry one or other variants.
TOKBIT
Global distribution of sickle cell:
This is a map of the distribution of endemic falciparum malaria.
The major areas are the Mediterranean, tropical Africa, middle east and Asia.
The regions of the World are well known as the endemic malaria regions of the world with the associated debilitation and deaths in the local populations.
This map show the distribution of the sickle cell allele Hbs
The regions noted as having high frequency of Hbs are the same as the regions above noted for malaria.
There appears to be a correlations between the distribution of malaria and the frequency of sickle cell allele.
The questions therefore: 'Is this just correlation or is there a causation' for the coincidence of malaria and sickle distribution?'
There are many instances when correlation and causation are just a coincidence and there is no causation or mechanism that likes the two variables.
Distribution of malaria and sickle cell:
There is however a well established causation between the sickle cell allele and the distribution of malaria.
In these regions sickle cell trait ( HbAHbs ) are resistant to the malaria parasite. This is because the Hbs allele makes it difficult for the parasite to live inside the red cells. Sickle cell trait (carriers) therefore survive malaria infection.
HbAHbA normal haemoglobin people are susceptible to malaria infection and do not survive well.
HbsHbs have sickle disease and do not survive well.
The sickle allele survives well in malaria regions accounting for its high frequency in these regions.
The CDC have an excellent reference site giving further information on sickle cell anaemia.
Sickle cell links: