Editing Protein biosynthesis (section)

===Sickle cell disease===
[[File:Sickle Cell Anaemia red blood cells in blood vessels.png|450px|thumb|alt=two blood curved vessels are shown, on the left one blood vessel contain normal red blood cells throughout the vessel. On the right, the red blood cells have a dish shape due to being sickled, a blockage composed of these distorted red blood cells is present at the curve in the blood vessel.| A comparison between an unaffected individual and an individual with sickle cell anaemia illustrating the different red blood cell shapes and differing blood flow within blood vessels.]]

Sickle cell disease is a group of diseases caused by a mutation in a subunit of hemoglobin, a protein found in red blood cells responsible for transporting oxygen. The most dangerous of the sickle cell diseases is known as sickle cell anemia. Sickle cell anemia is the most common [[genetic disorder|homozygous recessive single gene disorder]], meaning the affected individual must carry a mutation in both copies of the affected gene (one inherited from each parent) to experience the disease. Hemoglobin has a complex quaternary structure and is composed of four polypeptide subunits{{Snd}}two A subunits and two B subunits.<ref name="Steinberg 2016">{{Cite journal |vauthors=Habara A, Steinberg MH |date=April 2016 |title=Minireview: Genetic basis of heterogeneity and severity in sickle cell disease |journal=Experimental Biology and Medicine |volume=241 |issue=7 |pages=689–696 |doi=10.1177/1535370216636726 |pmc=4950383 |pmid=26936084}}</ref> Patients with sickle cell anemia have a missense or substitution mutation in the gene encoding the hemoglobin B subunit polypeptide chain. A missense mutation means the nucleotide mutation alters the overall codon triplet such that a different amino acid is paired with the new codon. In the case of sickle cell anemia, the most common missense mutation is a single nucleotide mutation from thymine to adenine in the hemoglobin B subunit gene.<ref name="StatPearls 2020">{{Cite journal |last=Mangla |first=A. |last2=Ehsan |first2=M. |last3=Agarwal |first3=N. |last4=Maruvada |first4=S. |year=2020 |title=Sickle Cell Anemia |url=https://www.ncbi.nlm.nih.gov/books/NBK482164/ |publisher=StatPearls Publishing |pmid=29489205 |access-date=12 March 2020 |website=StatPearls}}</ref> This changes codon 6 from encoding the amino acid glutamic acid to encoding valine.<ref name="Steinberg 2016" />

This change in the primary structure of the hemoglobin B subunit polypeptide chain alters the functionality of the hemoglobin multi-subunit complex in low oxygen conditions. When red blood cells unload oxygen into the tissues of the body, the mutated haemoglobin protein starts to stick together to form a semi-solid structure within the red blood cell. This distorts the shape of the red blood cell, resulting in the characteristic "sickle" shape, and reduces cell flexibility. This rigid, distorted red blood cell can accumulate in blood vessels creating a blockage. The blockage prevents blood flow to tissues and can lead to [[necrosis|tissue death]] which causes great pain to the individual.<ref name="Ilesanmi 2010">{{Cite journal |vauthors=Ilesanmi OO |date=January 2010 |title=Pathological basis of symptoms and crises in sickle cell disorder: implications for counseling and psychotherapy |journal=Hematology Reports |volume=2 |issue=1 |pages=e2 |doi=10.4081/hr.2010.e2 |pmc=3222266 |pmid=22184515 |doi-access=free}}</ref>