Human Biology- Sickle-cell Anaemia

what is sickle-cell anaemia?

Sickle-cell is a hereditary blood condition that impacts the oxygen-transporting molecule in red blood cells (haemoglobin).

how is sickle-cell anaemia caused?

Homozygous for a certain recessive allele causes sickle-cell disease. This allele is due to a point mutation in the DNA sequence of the HBB gene. This gene codes for one of the beta-globulin proteins that make up haemoglobin in the red blood cells. Due to the altered base sequence, valine is inserted in place of glutamic acid as an amino acid. As a result, the protein takes on a new structure, changing the amount of haemoglobin generated and changing the red blood cell's shape.

effects of sickle-cell anaemia on the body?

Sickle-cell anaemia causes the body to produce haemoglobin S, an abnormal form of the molecule that distorts the shape of red blood cells (resembling a sickle), disrupting their function.

What is the function of haemoglobin?

The complex protein known as haemoglobin is present in red blood cells that carry an iron molecule. It is composed of four interconnected protein chains: two alpha globin chains and two beta globin chains. The primary role of haemoglobin is to transport oxygen from the lungs to the body's tissues, where it is exchanged for carbon dioxide, and then return the carbon dioxide to the lungs for retransmission.

What is thalassemia?

Thalassaemia is a hereditary blood illness that damages the red blood cells and results in permanent anaemia.

What are the effects of Thalassemia on the body?

People with thalassaemia do not produce enough healthy haemoglobin, which makes their blood cells small and pale. Red blood cells contain a protein called haemoglobin, which transports oxygen from the bloodstream to the body's tissues. Thalassemia trait, aka thalassemia minor, usually doesn’t cause health issues. However, the impacted gene can still be inherited by future generations.

What are the forms of thalassemia?

1. Alpha thalassemia is due to a mutation in the HBA gene on chromosome 16. As a result, there is less alpha globin in the haemoglobin.

2.       Beta thalassemia is due to a mutation in the HBB gene on chromosome 11. As a result, haemoglobin’s beta globin content decreases. 

Similarities between the two forms

Both disorders have an autosomal recessive inheritance pattern. Individuals suffering with thalassemia are unable to carry as much oxygen in their blood due to a decrease in haemoglobin in their red blood cells. 

Differences between the two forms

The severity of this disorder varies, depending on the number of affected genes, ranging from mild anaemia and fatigue to an enlarged liver and heart.

The allele frequency may also be influenced by other variables. These consist of the founder effect, genetic drift, and migration.

Treatment of thalassemia

Treatment is based on the severity of thalassemia and includes blood transfusion, bone marrow transplant, medications, and surgery.

what happens to the allele frequency when the body is exposed to thalassemia?

1.    Selection Pressure: There may be a selection pressure on the population due to thalassemia. Individuals with thalassemia major (severe form) often experience decreased fitness due to serious medical issues associated with the disorder. Over time, this may cause the population's frequency of thalassemia-related alleles to decline.

what happens to the allele frequency when the body is exposed to thalassemia?

2.    Heterozygote Advantage: A thalassemia-related phenomena known as heterozygote advantage, often referred to as balancing selection, is observed in regions where malaria is endemic. Heterozygous carriers of thalassemia (thalassemia trait) are more resistant to malaria. This can lead to an increase in the frequency of thalassemia alleles in populations where malaria is prevalent, as carriers have a higher chance of survival and reproduction compared to non-carriers.

what happens to the allele frequency when the body is exposed to thalassemia?

3.    Genetic Drift: Genetic drift can affect allele frequencies in smaller populations or remote communities. Over generations, random occurrences may result in variations in the frequency of thalassemia alleles.

what happens to the allele frequency when the body is exposed to thalassemia?

4.    Migration and Gene Flow: Depending on the relative frequencies in the source populations, gene flow can change allele frequencies in either direction if individuals from populations with different thalassemia allele frequencies migrate and intermix.

CTX001 Therapy

Clustered regularly interspaced short palindromic repeats (CRISPR) is a new-found rapid and easily programmed genome editing tool that holds potential use to cure genetic diseases.

CRISPR-associated (Cas) proteins, such as Cas9, form complexes with programmable guide RNA (gRNA) to bind DNA.

Progressive direct target base pairing through sequence complementarity leads to conformational change to activate Cas9 and induce a particular DNA double-strand break.

Natural pathways for DNA repair, primarily non-homologous end joining and homology-directed repair, subsequently facilitate genome editing.

Speciation

1.    Variation: Individuals within a species differ from one another.

2.    Isolation: populations of the same species are isolated lacking gene flow.

3.    Selection: Different selective agents are applied to each population.

4.    Speciation: the allele frequency varies until the two groups are unable to reproduce together due to their extreme differences.

Genetic mutations

A genetic mutation is an alteration to an organism's DNA sequence.

How are mutations formed?

The building components of DNA, known as nucleotides, have four distinct basses. Viral infection, exposure to mutagens, and mistakes in DNA replication can all lead to mutations.

Mutations can affect the framework and function of cells, and may cause diseases, such as cancer, or aid humans adapt to their environment over time- This is known as evolution.

What are the two types of mutations?

1. Gene mutations: alterations to a single gene that result in the modification or eradication of the characteristics that the gene typically produces.

2. Chromosome mutations: a chromosome may be impacted entirely or partially.

Sickle-cell as a mechanism of resistance against malaria

The distorted shape of sickled red blood cells makes it difficult for the malaria parasite to complete its life cycle. Infected red blood cells tend to be cleared from the bloodstream faster than normal due to their altered shape and reduced lifespan.