This essay got me 7 marks out of 8, and helped me get my scholarship X-P

QUESTION ONE(8 marks)
Sickle Cell Disease [SCD] is a human genetic disorder resulting from a mutant form of the Hb gene, which is located on chromosome 11. The Hb gene codes for the protein haemoglobin, which is found in red blood cells and transports oxygen. The mutant allele Hbs produces haemoglobin that differs in one amino acid from the normal haemoglobin. Red blood cells that contain the abnormal haemoglobin collapse into a jagged sickle shape in a low-oxygen environment. The Hbs allele produces pleiotropic effects in individuals who inherit it.
The sickled cells may clump and clog small blood vessels, often leading to other symptoms throughout the body. Individuals with sickle cell disease can suffer severe anaemia, pain, organ damage, and even paralysis. In Western countries, frequent blood transfusions can be used to treat individuals with SCD. This alleviates the symptoms and reduces the chances of organ damage.
Individuals can have the following genotypes / phenotypes:
HbHb have normal red blood cells•
HbHb• s have sickle cell trait with some of their red blood cells being sickled
Hb• sHbs have sickle cell disease [SCD] with all of their red blood cells being sickled. The severe physiological effects that result often cause death before the individual reaches reproductive age. SCD kills about 100 000 people annually throughout the world.
HbHb
All red blood cells are normal
HbsHb
Mixture of normal and sickle red blood cells
HbsHbs
All red blood cells are sickle-shaped

The frequency of the Hbs allele
The frequency of the Hbs allele varies between populations around the world, with the highest frequencies of up to 20% being found in Africa. In comparison, New Zealand has a very low frequency of less than 1%. In the USA the frequency is similar to New Zealand in the general population, but can approach 10% amongst black Americans.


Malaria is a major global disease with most cases seen in Asia, Africa, and countries bordering the Mediterranean [Fig 2]. About half a billion people annually contract the disease with about one million dying from it. Most of the fatalities are children under the age of five, most of whom live in Africa. Malaria is caused by Plasmodium, a unicellular parasite, which is transmitted from person to person by Anopheles mosquitoes. The plasmodia enter the red blood cells where they repeatedly reproduce to release large numbers of new parasites.
The mutant Hbs allele provides some protection against malaria because the parasites are unable to reproduce inside the sickled blood cells.

Discuss the genetics, inheritance and frequency of the Hbs allele and evaluate whether modern biotechnological applications could, in the future, provide a cure for sickle cell disease.
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MY ANSWER!!!
The mutant Hbs allele appeared in the gene pool through a random mutation, and passed down onto subsequent generations by inheritance. The Hbs allele shows codominance over the Hbs gene, therefore creating a combined phenotype: I.e. in the HbsHb heterozygous genotype, proteins that cause red blood cells to be sickle shaped and proteins that cause blood cells to be normal co-exist and form a combination of both normal and sickle blood cells in the body in equal volumes.
The mutation is located on chromosome 11 so is likely to have been an error made while replicating DNA in the formation of gametes; or caused by mutagens and carcinogens such as radiation, pollution and toxins in the gonads causing the gene to be spread down the lineage and passed onto subsequent generations.
The inheritance of the gene is most likely through the heterozygous individual who contains both the normal Hb allele and the Hbs sickle celled allele, as a carrier. The receissive allele and the dominant allele co-existing through co-dominance creates a lesser effect than homozygous recessive, by having both sickle celled and normal blood cells. The individual can then have enough normal blood cells to carry out general functions sufficiently and carry oxygen around the body as usual with less efficiency but the difference between the sickle cell trait and the sickle cell disease is that many affected by the homozygous recessive SCD die before reaching reproductive age. Through natural selection, this allele combination is selected against, and those alleles disappear from the population. However the alleles don't increase in frequency but remain in the population because those with sickle cell disease reach reproductive age and passes the recessive gene onto the carriers of the next generation.
In Western populations, where Malaria is not as common, the allele isnot so frequent, being less than 1% of the population in New Zealand and USA. This reflects the inheritance pattern described above, where HbsHbs is selected against but HbHbs is retained in the population as it is not significantly affecting the individual's health and they can reach reproductive age.
However in African countries, Malaria is more widespread, affecting half a billion people contracting it from Africa, Meditaranian and Asia combined.
In the areas where Malaria is caused by Plasmodium, there is a general geographic pattern that favours the presense of the sickle cell allele. E.g. Central Africa has the greatest concentration of the sickle cell allele, and is also an abudance of malaria in individuals. Having the sickle celled allele is beneficial to those in the malaria-stricken areas and therefore increase in frequency, being an added survival advantage. Most of the fatalities are children who live under the age of five in Africa, and coupled with the lack of access to healthcare resources for malaria, the sickle-cell allele is their best advantage for survival and is increased in frequency due to natural selection. The individuals with the genotype HbHb are likelier to die out due to the lack of protection against Malaria, and HbsHbs as they're incapable of carrying oxygen around the body as well as having no access to blood transfusions as Westerners do, will die from anaemia, organ damage and other illnesses caused by the loss of oxygen. The abundance of the genotype HbHbs will increase the frequency of the Hbs allele reflective of the 20% found in Africa.
The reason why sickle-cell allele is less prevalent in places like Asia or less coastal areas of the mediteranian or Egypt is to do with socioeconomic development rather than a biological one. Individuals there have greater access to Malaria cures and preventions and do not rely on the pleitropic effects of the sickle-cell allele as a survival agent.
That also explains why the poverty stricken West of North Africa has a higher frequency of the sickle-cell allele than the East, in Egypt, although Egypt has greater incidences of Malaria than the West. The frequency of the Hbs allele increases in the West because of lack of knowledge about the condition, and also gene flow from the surrounding Malaria stricken areas.
African Americans retain the gene from their roots, as immigrants to the country from Africa, however the frequency is levelling out, decreased to 10% after many generations since their arrival due to better access to healthcare, interracial marriages and an absense of Malaria.
The nature of sickle cell disease is that it is a genetic condition, not an infection or a cancer, therefore there cannot be a direct cure such as there is no direct cure for genetic illnesses such as cystic fibrosis. Currently blood transfusions are used as a treatment that alleviates the symptoms of the disease, but because a fault in a gene causes the wrong protein to be made, the resulting error in a process cannot be a reversed – the same genetic instructions are present in every bodily cell and therefore when replication of DNA happens, the wrong “message” is passed onto the new strand so all newly formed cells will contain the mutant gene, creating the difference in physiological structure.
But treatments such as the hormonal treatment for cystic fibrosis can help make living easier for the affected individual with SCD, by injecting a hormone that encourages the sickle-blood cell to carry oxygen and perform normal duties as a red blood cell however it is unknown whether this would be possible, as the sickle cell shape would prevent oxygen transport, therefore the hormone treatment wouldn't function.
The only other option for a genetic disease is not just to treat the individual, but the entire population, as the gene is spread to subsequent generations. Modern biotechnology have effective ways of genetic screening, through amniotic testing, a sample of amniotic fluid from the womb of a pregnant mother would give genetic information of whether the child has the gene or not, through gene mapping or karyotype and the position of the gene is identified and checked for its presense or absense. In the case that the sickle cell allele is found, the child can be aborted. While this method has moral implications in human society, it is an example of direct selection, a variance to natural selection that doesn't rely on mate selection to choose favourable genes; and ensures that the allele frequency will decrease, as well as the prevalence of sickle cell disease. If cure is not possible, then prevention should be implemented.


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