Sickle cell anaemia - Revision history

150088574 at 20:04, 3 December 2015

2015-12-03T20:04:22Z

← Older revision		Revision as of 20:04, 3 December 2015
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	=== Inheritance    ===		=== Inheritance    ===

	Sickle cell is a [[Recessive autosomal disorder\|recessive autosomal disorder]], therefore two defected [[Gene\|genes]] are needed (SS) for sickle cell anaemia. If one ~~parents were~~ to be a carrier of the [[Gene\|gene]], (SA), each child would have a 25% chance of inheriting two sickle cell [[Gene\|genes]], 25% chance of inheriting two normal [[Gene\|genes]], and 50% chance of becoming a carrier like the parents.<br>		Sickle cell is a [[Recessive autosomal disorder\|recessive autosomal disorder]], therefore two defected [[Gene\|genes]] are needed (SS) for sickle cell anaemia. If one parent was to be a carrier of the [[Gene\|gene]], (SA), each child would have a 25% chance of inheriting two sickle cell [[Gene\|genes]], 25% chance of inheriting two normal [[Gene\|genes]], and 50% chance of becoming a carrier like the parents.<br>

	=== Sickle-Cell Trait ===		=== Sickle-Cell Trait ===

150015259 at 01:28, 22 October 2015

2015-10-22T01:28:50Z

← Older revision		Revision as of 01:28, 22 October 2015
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	=== Effects of the HbS Mutation ===		=== Effects of the HbS Mutation ===

	When red blood cells with the [[Wild - type\|wildtype]] form of the gene (HbA) are subjected to low oxygen concentration the [[~~Javascript:void(0);/1322703978627/~~\|haemoglobin]] in the cell remains fully functional. However, in cells with the HbS mutation the haemoglobin polymerizes in environments where oxygen concentration is low. The [[Haemoglobin\|haemoglobin]] polymers are responsible for the change in red blood cell shape; the cells become long, sickle shaped and fragile. The sickle cells do not deliver oxygen to tissues with the same efficiency as normal blood cells, and they often get caught in small blood vessels leading to blockages. This causes extreme pain and leads to damage of major organs such as the [[Brain\|brain]], heart, [[Kidney\|kidneys]] and [[Muscle\|muscles]] <ref>Essentials of Genetics 6th Edition. William S. Klug, Michael R. Cummings, Charlotte A. Spencer. Peterson International Edition, pg 7</ref>. Due to the stress placed on the heart to move the sickled cells around the body, it is often seen that people with sickle cell disease have issues with [[Hypertension\|hypertension]]. It can result in death and is present in one third of adults with sickle cell disease. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>As a result of the rapid breakdown of red blood cells, a jaundice like yellowing of the eyes and skin can occur. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>The solubility of deoxyhaemoglobin also decreases. <ref>Berg,M.J., Tymoczko, J.L. and Stryer L. (2012) Biochemistry. 7th ed. p.216.</ref>		When red blood cells with the [[Wild - type\|wildtype]] form of the gene (HbA) are subjected to low oxygen concentration the [[Heamoglobin\|haemoglobin]] in the cell remains fully functional. However, in cells with the HbS mutation the haemoglobin polymerizes in environments where oxygen concentration is low. The [[Haemoglobin\|haemoglobin]] polymers are responsible for the change in red blood cell shape; the cells become long, sickle shaped and fragile. The sickle cells do not deliver oxygen to tissues with the same efficiency as normal blood cells, and they often get caught in small blood vessels leading to blockages. This causes extreme pain and leads to damage of major organs such as the [[Brain\|brain]], heart, [[Kidney\|kidneys]] and [[Muscle\|muscles]] <ref>Essentials of Genetics 6th Edition. William S. Klug, Michael R. Cummings, Charlotte A. Spencer. Peterson International Edition, pg 7</ref>. Due to the stress placed on the heart to move the sickled cells around the body, it is often seen that people with sickle cell disease have issues with [[Hypertension\|hypertension]]. It can result in death and is present in one third of adults with sickle cell disease. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>As a result of the rapid breakdown of red blood cells, a jaundice like yellowing of the eyes and skin can occur. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>The solubility of deoxyhaemoglobin also decreases. <ref>Berg,M.J., Tymoczko, J.L. and Stryer L. (2012) Biochemistry. 7th ed. p.216.</ref>

	=== Inheritance    ===		=== Inheritance    ===

Nnjm2 at 22:59, 26 November 2014

2014-11-26T22:59:02Z

← Older revision		Revision as of 22:59, 26 November 2014
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	=== Genetics   ===		=== Genetics   ===

	Sickle cell is a genetic disorder caused by a [[Missense mutation\|missense mutation]] in the [[Amino acids\|amino acid]] sequence coding for the [[Haemoglobin gene\|haemoglobin gene]] in [[Red blood cells\|red blood cells]] <ref>Biochemistry 6th edition Jeremy M. Berg, John L Tymoczko, Lubert Stryer pg 195</ref>. The haemoglobin molecule is a tetramer with two alpha subunits and two beta subunits. The mutation occurs in the beta subunit when a [[Valine\|valine]](V) replaces [[Glutamate\|glutamate]](E) in position 6 of the beta subunit, the replacement is referred to as Glu6Val <ref>• Page 524, Hartl, D. L. ~~&amp;amp;amp;amp;amp;amp;~~ Ruvolo, M., 2012, Genetics: Analysis Of Genes And Genomes, Eighth Edition, Burlington: Jones ~~&amp;amp;amp;amp;amp;amp~~; Bartlett Learning</ref>.In those who show symptonms of sickle cell anaemia, on the beta globin chain in the sixth amino acid position the base A, which is the second [[Codon\|codon]] for the amino acid, is swapped with a T during transcription of the DNA duplex, causing an A-T —> T -A transgression. This causes a change in the amino acid coded for and hence known as a glu6val or E6V mutation. <ref>Ruvolo, D.H. and M., 2011. Genetics 8E: Analysis of Genes and Genomes Intl Version, Jones ~~&amp;amp;amp;amp;amp;~~ Bartlett Learning, LLC. page 520-525</ref> The mutation occurs on the p arm of chromosome 11 which is an autosome and as mentioned effects the beta subunit.<ref>U.S National Library of medicine, 2009</ref> [[Phenylalanine\|phenylalanine]] 85 and [[Leucine\|leucine]] 88 - which are both non-polar hydrophobic amino acids on the gene - form a socket in which the valine side chain can fuse. This is possible because valine is also [[Hydrophobic\|hydrophobic]] unlike glutamate and so form sticky ends with the hydrophobic leucine and phenylalanine, thus resulting in a polymerisation of the molecule which alters the tetramer structure of haemoglobin. The mutation is known as HbS, the normal [[Haemoglobin\|haemoglobin]] is referred to as HbA.<br>		Sickle cell is a genetic disorder caused by a [[Missense mutation\|missense mutation]] in the [[Amino acids\|amino acid]] sequence coding for the [[Haemoglobin gene\|haemoglobin gene]] in [[Red blood cells\|red blood cells]] <ref>Biochemistry 6th edition Jeremy M. Berg, John L Tymoczko, Lubert Stryer pg 195</ref>. The haemoglobin molecule is a tetramer with two alpha subunits and two beta subunits. The mutation occurs in the beta subunit when a [[Valine\|valine]](V) replaces [[Glutamate\|glutamate]](E) in position 6 of the beta subunit, the replacement is referred to as Glu6Val <ref>• Page 524, Hartl, D. L. and Ruvolo, M., 2012, Genetics: Analysis Of Genes And Genomes, Eighth Edition, Burlington: Jones and ; Bartlett Learning</ref>.In those who show symptonms of sickle cell anaemia, on the beta globin chain in the sixth amino acid position the base A, which is the second [[Codon\|codon]] for the amino acid, is swapped with a T during transcription of the DNA duplex, causing an A-T —> T -A transgression. This causes a change in the amino acid coded for and hence known as a glu6val or E6V mutation. <ref>Ruvolo, D.H. and M., 2011. Genetics 8E: Analysis of Genes and Genomes Intl Version, Jones and Bartlett Learning, LLC. page 520-525</ref> The mutation occurs on the p arm of chromosome 11 which is an autosome and as mentioned effects the beta subunit.<ref>U.S National Library of medicine, 2009</ref> [[Phenylalanine\|phenylalanine]] 85 and [[Leucine\|leucine]] 88 - which are both non-polar hydrophobic amino acids on the gene - form a socket in which the valine side chain can fuse. This is possible because valine is also [[Hydrophobic\|hydrophobic]] unlike glutamate and so form sticky ends with the hydrophobic leucine and phenylalanine, thus resulting in a polymerisation of the molecule which alters the tetramer structure of haemoglobin. The mutation is known as HbS, the normal [[Haemoglobin\|haemoglobin]] is referred to as HbA.<br>

	=== Effects of the HbS Mutation ===		=== Effects of the HbS Mutation ===

Nnjm2: Previous editor managed to completely break the page. Reformatted it.

2014-11-26T22:58:24Z

Previous editor managed to completely break the page. Reformatted it.

← Older revision		Revision as of 22:58, 26 November 2014
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	Sickle cell anaemia is an autosomal [[Recessive disorder\|recessive disorder]], which causes deformation to the shape of the [[Red blood cells\|red blood cells]], preventing the [[Cell\|cells]] from being able to travel through small[[Blood vessels\|blood vessels]]. This deprives organs and tissues of [[Oxygen\|oxygen]]. Sufferers experience severe pain, referred to as a crisis and the condition can lead to other serious medical problems. === Genetics   === Sickle cell is a genetic disorder caused by a [[Missense mutation\|missense mutation]] in the [[Amino acids\|amino acid]] sequence coding for the [[Haemoglobin gene\|haemoglobin gene]] in [[Red blood cells\|red blood cells]] <ref>Biochemistry 6th edition Jeremy M. Berg, John L Tymoczko, Lubert Stryer pg 195</ref>. The haemoglobin molecule is a tetramer with two alpha subunits and two beta subunits. The mutation occurs in the beta subunit when a [[Valine\|valine]](V) replaces [[Glutamate\|glutamate]](E) in position 6 of the beta subunit, the replacement is referred to as Glu6Val <ref>• Page 524, Hartl, D. L. &amp;amp;amp;amp; Ruvolo, M., 2012, Genetics: Analysis Of Genes And Genomes, Eighth Edition, Burlington: Jones &amp;amp;amp;amp; Bartlett Learning</ref>.In those who show symptonms of sickle cell anaemia, on the beta globin chain in the sixth amino acid position the base A, which is the second [[Codon\|codon]] for the amino acid, is swapped with a T during transcription of the DNA duplex, causing an A-T —> T -A transgression. This causes a change in the amino acid coded for and hence known as a glu6val or E6V mutation. <ref>Ruvolo, D.H. and M., 2011. Genetics 8E: Analysis of Genes and Genomes Intl Version, Jones &amp;amp;amp; Bartlett Learning, LLC. page 520-525</ref> The mutation occurs on the p arm of chromosome 11 which is an autosome and as mentioned effects the beta subunit.<ref>U.S National Library of medicine, 2009</ref> [[Phenylalanine\|phenylalanine]] 85 and [[Leucine\|leucine]] 88 - which are both non-polar hydrophobic amino acids on the gene - form a socket in which the valine side chain can fuse. This is possible because valine is also [[Hydrophobic\|hydrophobic]] unlike glutamate and so form sticky ends with the hydrophobic leucine and phenylalanine, thus resulting in a polymerisation of the molecule which alters the tetramer structure of haemoglobin. The mutation is known as HbS, the normal [[Haemoglobin\|haemoglobin]] is referred to as HbA.<br> === Effects of the HbS Mutation === When red blood cells with the [[Wild - type\|wildtype]] form of the gene (HbA) are subjected to low oxygen concentration the [[Javascript:void(0);/1322703978627/\|haemoglobin]] in the cell remains fully functional. However, in cells with the HbS mutation the haemoglobin polymerizes in environments where oxygen concentration is low. The [[Haemoglobin\|haemoglobin]] polymers are responsible for the change in red blood cell shape; the cells become long, sickle shaped and fragile. The sickle cells do not deliver oxygen to tissues with the same efficiency as normal blood cells, and they often get caught in small blood vessels leading to blockages. This causes extreme pain and leads to damage of major organs such as the [[Brain\|brain]], heart, [[Kidney\|kidneys]] and [[Muscle\|muscles]] <ref>Essentials of Genetics 6th Edition. William S. Klug, Michael R. Cummings, Charlotte A. Spencer. Peterson International Edition, pg 7</ref>. Due to the stress placed on the heart to move the sickled cells around the body, it is often seen that people with sickle cell disease have issues with [[Hypertension\|hypertension]]. It can result in death and is present in one third of adults with sickle cell disease. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>As a result of the rapid breakdown of red blood cells, a jaundice like yellowing of the eyes and skin can occur. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>The solubility of deoxyhaemoglobin also decreases. <ref>Berg,M.J., Tymoczko, J.L. and Stryer L. (2012) Biochemistry. 7th ed. p.216.</ref>  === Inheritance    === Sickle cell is a [[Recessive autosomal disorder\|recessive autosomal disorder]], therefore two defected [[Gene\|genes]] are needed (SS) for sickle cell anaemia. If one parents were to be a carrier of the [[Gene\|gene]], (SA), each child would have a 25% chance of inheriting two sickle cell [[Gene\|genes]], 25% chance of inheriting two normal [[Gene\|genes]], and 50% chance of becoming a carrier like the parents.<br> === ~~'''~~Sickle-Cell Trait~~'''~~ === When people carry both the [[Haemoglobin\|Hb]]B [[Gene\|gene]] and the mutated [[Haemoglobin\|Hb]]S [[Gene\|gene]] they are said to have sickle-cell trait, a form of [[Heterozygous advantage\|heterozygous advantage]]. They are relatively unaffected by the symptoms associated with sickle cell anaemia, however they can pass the HbS [[Mutation\|mutation]] onto their offspring. The interesting point here is that people with sickle-cell trait are resisitant to malaria. The reason for this higher resistance is because the plasmodium falciparum parasite that is responsible for malaria grows poorly in sickled cells.<ref>Bruce Alberts et al.,(2009) Essential Cell Biology, 3rd edition, Newyork:Garlands Science</ref> This means that in a carrier a proportion of the parasite will affect the sickled cells, rather than the normal red blood cells. A high proportion of the parasite attempting to grow in Sickled cells will not survive, so there will be a lower concentration of P.falciparum to affect the normal cells and this gives the [[Carrier\|carrier]] a higher probability of surviving the attack. It has been predicted that those who have sickle-cell trait may have a 20% increase in fitness over those in the population without sickle-cell trait in areas where malaria is common<ref>Gelehrter, T. D., Collins, F. S. and Ginsburg, D., 1998. Principles of Medical Genetics. p.51</ref>. HbS is hence thought to be reccessive for SCD, but dominant for Malaria resistance <ref>Daniel L.Hartl and Elizabeht W.Jones (2009) Genetics: Analysis of Genes and Genomes,p.513-515</ref>. The lethal nature of malaria and its prevalance in West Africa goes towards explaining the prevalance of the [[Haemoglobin\|Hb]]S [[Alleles\|allele]] in West African populations (1 in 100 West Africans being Sickle Cell Anaemia sufferers), due to  the presence of the [[Haemoglobin\|Hb]]S [[Alleles\|allele]] favouring the survival of its carriers <ref>Biochemistry 6th edition Jeremy M. Berg, John L Tymoczko, Lubert Stryer pg 195-196</ref>. === References~~ <br>~~ === <references />		Sickle cell anaemia is an autosomal [[Recessive disorder\|recessive disorder]], which causes deformation to the shape of the [[Red blood cells\|red blood cells]], preventing the [[Cell\|cells]] from being able to travel through small[[Blood vessels\|blood vessels]]. This deprives organs and tissues of [[Oxygen\|oxygen]]. Sufferers experience severe pain, referred to as a crisis and the condition can lead to other serious medical problems.

			=== Genetics   ===

			Sickle cell is a genetic disorder caused by a [[Missense mutation\|missense mutation]] in the [[Amino acids\|amino acid]] sequence coding for the [[Haemoglobin gene\|haemoglobin gene]] in [[Red blood cells\|red blood cells]] <ref>Biochemistry 6th edition Jeremy M. Berg, John L Tymoczko, Lubert Stryer pg 195</ref>. The haemoglobin molecule is a tetramer with two alpha subunits and two beta subunits. The mutation occurs in the beta subunit when a [[Valine\|valine]](V) replaces [[Glutamate\|glutamate]](E) in position 6 of the beta subunit, the replacement is referred to as Glu6Val <ref>• Page 524, Hartl, D. L. &amp;amp;amp;amp;amp;amp; Ruvolo, M., 2012, Genetics: Analysis Of Genes And Genomes, Eighth Edition, Burlington: Jones &amp;amp;amp;amp;amp;amp; Bartlett Learning</ref>.In those who show symptonms of sickle cell anaemia, on the beta globin chain in the sixth amino acid position the base A, which is the second [[Codon\|codon]] for the amino acid, is swapped with a T during transcription of the DNA duplex, causing an A-T —> T -A transgression. This causes a change in the amino acid coded for and hence known as a glu6val or E6V mutation. <ref>Ruvolo, D.H. and M., 2011. Genetics 8E: Analysis of Genes and Genomes Intl Version, Jones &amp;amp;amp;amp;amp; Bartlett Learning, LLC. page 520-525</ref> The mutation occurs on the p arm of chromosome 11 which is an autosome and as mentioned effects the beta subunit.<ref>U.S National Library of medicine, 2009</ref> [[Phenylalanine\|phenylalanine]] 85 and [[Leucine\|leucine]] 88 - which are both non-polar hydrophobic amino acids on the gene - form a socket in which the valine side chain can fuse. This is possible because valine is also [[Hydrophobic\|hydrophobic]] unlike glutamate and so form sticky ends with the hydrophobic leucine and phenylalanine, thus resulting in a polymerisation of the molecule which alters the tetramer structure of haemoglobin. The mutation is known as HbS, the normal [[Haemoglobin\|haemoglobin]] is referred to as HbA.<br>

			=== Effects of the HbS Mutation ===

			When red blood cells with the [[Wild - type\|wildtype]] form of the gene (HbA) are subjected to low oxygen concentration the [[Javascript:void(0);/1322703978627/\|haemoglobin]] in the cell remains fully functional. However, in cells with the HbS mutation the haemoglobin polymerizes in environments where oxygen concentration is low. The [[Haemoglobin\|haemoglobin]] polymers are responsible for the change in red blood cell shape; the cells become long, sickle shaped and fragile. The sickle cells do not deliver oxygen to tissues with the same efficiency as normal blood cells, and they often get caught in small blood vessels leading to blockages. This causes extreme pain and leads to damage of major organs such as the [[Brain\|brain]], heart, [[Kidney\|kidneys]] and [[Muscle\|muscles]] <ref>Essentials of Genetics 6th Edition. William S. Klug, Michael R. Cummings, Charlotte A. Spencer. Peterson International Edition, pg 7</ref>. Due to the stress placed on the heart to move the sickled cells around the body, it is often seen that people with sickle cell disease have issues with [[Hypertension\|hypertension]]. It can result in death and is present in one third of adults with sickle cell disease. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>As a result of the rapid breakdown of red blood cells, a jaundice like yellowing of the eyes and skin can occur. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>The solubility of deoxyhaemoglobin also decreases. <ref>Berg,M.J., Tymoczko, J.L. and Stryer L. (2012) Biochemistry. 7th ed. p.216.</ref>

			=== Inheritance    ===

			Sickle cell is a [[Recessive autosomal disorder\|recessive autosomal disorder]], therefore two defected [[Gene\|genes]] are needed (SS) for sickle cell anaemia. If one parents were to be a carrier of the [[Gene\|gene]], (SA), each child would have a 25% chance of inheriting two sickle cell [[Gene\|genes]], 25% chance of inheriting two normal [[Gene\|genes]], and 50% chance of becoming a carrier like the parents.<br>

			=== Sickle-Cell Trait ===

			When people carry both the [[Haemoglobin\|Hb]]B [[Gene\|gene]] and the mutated [[Haemoglobin\|Hb]]S [[Gene\|gene]] they are said to have sickle-cell trait, a form of [[Heterozygous advantage\|heterozygous advantage]]. They are relatively unaffected by the symptoms associated with sickle cell anaemia, however they can pass the HbS [[Mutation\|mutation]] onto their offspring. The interesting point here is that people with sickle-cell trait are resisitant to malaria. The reason for this higher resistance is because the plasmodium falciparum parasite that is responsible for malaria grows poorly in sickled cells.<ref>Bruce Alberts et al.,(2009) Essential Cell Biology, 3rd edition, Newyork:Garlands Science</ref> This means that in a carrier a proportion of the parasite will affect the sickled cells, rather than the normal red blood cells. A high proportion of the parasite attempting to grow in Sickled cells will not survive, so there will be a lower concentration of P.falciparum to affect the normal cells and this gives the [[Carrier\|carrier]] a higher probability of surviving the attack. It has been predicted that those who have sickle-cell trait may have a 20% increase in fitness over those in the population without sickle-cell trait in areas where malaria is common<ref>Gelehrter, T. D., Collins, F. S. and Ginsburg, D., 1998. Principles of Medical Genetics. p.51</ref>. HbS is hence thought to be reccessive for SCD, but dominant for Malaria resistance <ref>Daniel L.Hartl and Elizabeht W.Jones (2009) Genetics: Analysis of Genes and Genomes,p.513-515</ref>. The lethal nature of malaria and its prevalance in West Africa goes towards explaining the prevalance of the [[Haemoglobin\|Hb]]S [[Alleles\|allele]] in West African populations (1 in 100 West Africans being Sickle Cell Anaemia sufferers), due to  the presence of the [[Haemoglobin\|Hb]]S [[Alleles\|allele]] favouring the survival of its carriers <ref>Biochemistry 6th edition Jeremy M. Berg, John L Tymoczko, Lubert Stryer pg 195-196</ref>.

			=== References ===

			<references />

150015112 at 13:18, 26 November 2014

2014-11-26T13:18:52Z

← Older revision		Revision as of 13:18, 26 November 2014
Line 1:		Line 1:
	Sickle cell anaemia is an autosomal [[Recessive disorder\|recessive disorder]], which causes deformation to the shape of the [[Red blood cells\|red blood cells]], preventing the [[Cell\|cells]] from being able to travel through small blood vessels. This deprives organs and tissues of [[Oxygen\|oxygen]]. Sufferers experience severe pain, referred to as a crisis and the condition can lead to other serious medical problems.		Sickle cell anaemia is an autosomal [[Recessive disorder\|recessive disorder]], which causes deformation to the shape of the [[Red blood cells\|red blood cells]], preventing the [[Cell\|cells]] from being able to travel through small[[Blood vessels\|blood vessels]]. This deprives organs and tissues of [[Oxygen\|oxygen]]. Sufferers experience severe pain, referred to as a crisis and the condition can lead to other serious medical problems. === Genetics   === Sickle cell is a genetic disorder caused by a [[Missense mutation\|missense mutation]] in the [[Amino acids\|amino acid]] sequence coding for the [[Haemoglobin gene\|haemoglobin gene]] in [[Red blood cells\|red blood cells]] <ref>Biochemistry 6th edition Jeremy M. Berg, John L Tymoczko, Lubert Stryer pg 195</ref>. The haemoglobin molecule is a tetramer with two alpha subunits and two beta subunits. The mutation occurs in the beta subunit when a [[Valine\|valine]](V) replaces [[Glutamate\|glutamate]](E) in position 6 of the beta subunit, the replacement is referred to as Glu6Val <ref>• Page 524, Hartl, D. L. &amp;amp;amp;amp; Ruvolo, M., 2012, Genetics: Analysis Of Genes And Genomes, Eighth Edition, Burlington: Jones &amp;amp;amp;amp; Bartlett Learning</ref>.In those who show symptonms of sickle cell anaemia, on the beta globin chain in the sixth amino acid position the base A, which is the second [[Codon\|codon]] for the amino acid, is swapped with a T during transcription of the DNA duplex, causing an A-T —> T -A transgression. This causes a change in the amino acid coded for and hence known as a glu6val or E6V mutation. <ref>Ruvolo, D.H. and M., 2011. Genetics 8E: Analysis of Genes and Genomes Intl Version, Jones &amp;amp;amp; Bartlett Learning, LLC. page 520-525</ref> The mutation occurs on the p arm of chromosome 11 which is an autosome and as mentioned effects the beta subunit.<ref>U.S National Library of medicine, 2009</ref> [[Phenylalanine\|phenylalanine]] 85 and [[Leucine\|leucine]] 88 - which are both non-polar hydrophobic amino acids on the gene - form a socket in which the valine side chain can fuse. This is possible because valine is also [[Hydrophobic\|hydrophobic]] unlike glutamate and so form sticky ends with the hydrophobic leucine and phenylalanine, thus resulting in a polymerisation of the molecule which alters the tetramer structure of haemoglobin. The mutation is known as HbS, the normal [[Haemoglobin\|haemoglobin]] is referred to as HbA.<br> === Effects of the HbS Mutation === When red blood cells with the [[Wild - type\|wildtype]] form of the gene (HbA) are subjected to low oxygen concentration the [[Javascript:void(0);/1322703978627/\|haemoglobin]] in the cell remains fully functional. However, in cells with the HbS mutation the haemoglobin polymerizes in environments where oxygen concentration is low. The [[Haemoglobin\|haemoglobin]] polymers are responsible for the change in red blood cell shape; the cells become long, sickle shaped and fragile. The sickle cells do not deliver oxygen to tissues with the same efficiency as normal blood cells, and they often get caught in small blood vessels leading to blockages. This causes extreme pain and leads to damage of major organs such as the [[Brain\|brain]], heart, [[Kidney\|kidneys]] and [[Muscle\|muscles]] <ref>Essentials of Genetics 6th Edition. William S. Klug, Michael R. Cummings, Charlotte A. Spencer. Peterson International Edition, pg 7</ref>. Due to the stress placed on the heart to move the sickled cells around the body, it is often seen that people with sickle cell disease have issues with [[Hypertension\|hypertension]]. It can result in death and is present in one third of adults with sickle cell disease. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>As a result of the rapid breakdown of red blood cells, a jaundice like yellowing of the eyes and skin can occur. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>The solubility of deoxyhaemoglobin also decreases. <ref>Berg,M.J., Tymoczko, J.L. and Stryer L. (2012) Biochemistry. 7th ed. p.216.</ref>  === Inheritance    === Sickle cell is a [[Recessive autosomal disorder\|recessive autosomal disorder]], therefore two defected [[Gene\|genes]] are needed (SS) for sickle cell anaemia. If one parents were to be a carrier of the [[Gene\|gene]], (SA), each child would have a 25% chance of inheriting two sickle cell [[Gene\|genes]], 25% chance of inheriting two normal [[Gene\|genes]], and 50% chance of becoming a carrier like the parents.<br> === '''Sickle-Cell Trait''' === When people carry both the [[Haemoglobin\|Hb]]B [[Gene\|gene]] and the mutated [[Haemoglobin\|Hb]]S [[Gene\|gene]] they are said to have sickle-cell trait, a form of [[Heterozygous advantage\|heterozygous advantage]]. They are relatively unaffected by the symptoms associated with sickle cell anaemia, however they can pass the HbS [[Mutation\|mutation]] onto their offspring. The interesting point here is that people with sickle-cell trait are resisitant to malaria. The reason for this higher resistance is because the plasmodium falciparum parasite that is responsible for malaria grows poorly in sickled cells.<ref>Bruce Alberts et al.,(2009) Essential Cell Biology, 3rd edition, Newyork:Garlands Science</ref> This means that in a carrier a proportion of the parasite will affect the sickled cells, rather than the normal red blood cells. A high proportion of the parasite attempting to grow in Sickled cells will not survive, so there will be a lower concentration of P.falciparum to affect the normal cells and this gives the [[Carrier\|carrier]] a higher probability of surviving the attack. It has been predicted that those who have sickle-cell trait may have a 20% increase in fitness over those in the population without sickle-cell trait in areas where malaria is common<ref>Gelehrter, T. D., Collins, F. S. and Ginsburg, D., 1998. Principles of Medical Genetics. p.51</ref>. HbS is hence thought to be reccessive for SCD, but dominant for Malaria resistance <ref>Daniel L.Hartl and Elizabeht W.Jones (2009) Genetics: Analysis of Genes and Genomes,p.513-515</ref>. The lethal nature of malaria and its prevalance in West Africa goes towards explaining the prevalance of the [[Haemoglobin\|Hb]]S [[Alleles\|allele]] in West African populations (1 in 100 West Africans being Sickle Cell Anaemia sufferers), due to  the presence of the [[Haemoglobin\|Hb]]S [[Alleles\|allele]] favouring the survival of its carriers <ref>Biochemistry 6th edition Jeremy M. Berg, John L Tymoczko, Lubert Stryer pg 195-196</ref>. === References <br> === <references />

	=== Genetics   ===

	Sickle cell is a genetic disorder caused by a missense ~~[[Mutation\|~~mutation]] in the [[Amino acids\|amino acid]] sequence coding for the [[Haemoglobin gene\|haemoglobin gene]] in [[Red blood cells\|red blood cells]] <ref>Biochemistry 6th edition Jeremy M. Berg, John L Tymoczko, Lubert Stryer pg 195</ref>. The haemoglobin molecule is a tetramer with two alpha subunits and two beta subunits. The mutation occurs in the beta subunit when a [[Valine\|valine]](V) replaces [[Glutamate\|glutamate]](E) in position 6 of the beta subunit, the replacement is referred to as Glu6Val <ref>• Page 524, Hartl, D. L. &amp;amp; Ruvolo, M., 2012, Genetics: Analysis Of Genes And Genomes, Eighth Edition, Burlington: Jones &amp;amp; Bartlett Learning</ref>.In those who show symptonms of sickle cell anaemia, on the beta globin chain in the sixth amino acid position the base A, which is the second codon for the amino acid, is swapped with a T during transcription of the DNA duplex, causing an A-T —> T -A transgression. This causes a change in the amino acid coded for and hence known as a glu6val or E6V mutation. <ref>Ruvolo, D.H. and M., 2011. Genetics 8E: Analysis of Genes and Genomes Intl Version, Jones &amp; Bartlett Learning, LLC. page 520-525</ref> The mutation occurs on the p arm of chromosome 11 which is an autosome and as mentioned effects the beta subunit.<ref>U.S National Library of medicine, 2009</ref> [[Phenylalanine\|phenylalanine]] 85 and [[Leucine\|leucine]] 88 - which are both non-polar hydrophobic amino acids on the gene - form a socket in which the valine side chain can fuse. This is possible because valine is also hydrophobic unlike glutamate and so form sticky ends with the hydrophobic leucine and phenylalanine, thus resulting in a polymerisation of the molecule which alters the tetramer structure of haemoglobin. The mutation is known as HbS, the normal [[Haemoglobin\|haemoglobin]] is referred to as HbA.<br>

	=== Effects of the HbS Mutation ===

	When red blood cells with the [[Wild - type\|wildtype]] form of the gene (HbA) are subjected to low oxygen concentration the [[Javascript:void(0);/1322703978627/\|haemoglobin]] in the cell remains fully functional. However, in cells with the HbS mutation the haemoglobin polymerizes in environments where oxygen concentration is low. The [[Haemoglobin\|haemoglobin]] polymers are responsible for the change in red blood cell shape; the cells become long, sickle shaped and fragile. The sickle cells do not deliver oxygen to tissues with the same efficiency as normal blood cells, and they often get caught in small blood vessels leading to blockages. This causes extreme pain and leads to damage of major organs such as the [[Brain\|brain]], heart, [[Kidney\|kidneys]] and [[Muscle\|muscles]] <ref>Essentials of Genetics 6th Edition. William S. Klug, Michael R. Cummings, Charlotte A. Spencer. Peterson International Edition, pg 7</ref>. Due to the stress placed on the heart to move the sickled cells around the body, it is often seen that people with sickle cell disease have issues with hypertension. It can result in death and is present in one third of adults with sickle cell disease. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>As a result of the rapid breakdown of red blood cells, a jaundice like yellowing of the eyes and skin can occur. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>The solubility of deoxyhaemoglobin also decreases. <ref>Berg,M.J., Tymoczko, J.L. and Stryer L. (2012) Biochemistry. 7th ed. p.216.</ref>

	=== Inheritance    ===

	Sickle cell is a [[Recessive autosomal disorder\|recessive autosomal disorder]], therefore two defected [[Gene\|genes]] are needed (SS) for sickle cell anaemia. If one parents were to be a carrier of the [[Gene\|gene]], (SA), each child would have a 25% chance of inheriting two sickle cell [[Gene\|genes]], 25% chance of inheriting two normal [[Gene\|genes]], and 50% chance of becoming a carrier like the parents.<br>

	=== '''Sickle-Cell Trait''' ===

	When people carry both the [[Haemoglobin\|Hb]]B [[Gene\|gene]] and the mutated [[Haemoglobin\|Hb]]S [[Gene\|gene]] they are said to have sickle-cell trait, a form of [[Heterozygous advantage\|heterozygous advantage]]. They are relatively unaffected by the symptoms associated with sickle cell anaemia, however they can pass the HbS [[Mutation\|mutation]] onto their offspring. The interesting point here is that people with sickle-cell trait are resisitant to malaria. The reason for this higher resistance is because the plasmodium falciparum parasite that is responsible for malaria grows poorly in sickled cells.<ref>Bruce Alberts et al.,(2009) Essential Cell Biology, 3rd edition, Newyork:Garlands Science</ref> This means that in a carrier a proportion of the parasite will affect the sickled cells, rather than the normal red blood cells. A high proportion of the parasite attempting to grow in Sickled cells will not survive, so there will be a lower concentration of P.falciparum to affect the normal cells and this gives the carrier a higher probability of surviving the attack. It has been predicted that those who have sickle-cell trait may have a 20% increase in fitness over those in the population without sickle-cell trait in areas where malaria is common<ref>Gelehrter, T. D., Collins, F. S. and Ginsburg, D., 1998. Principles of Medical Genetics. p.51</ref>. HbS is hence thought to be reccessive for SCD, but dominant for Malaria resistance <ref>Daniel L.Hartl and Elizabeht W.Jones (2009) Genetics: Analysis of Genes and Genomes,p.513-515</ref>.

	The lethal nature of malaria and its prevalance in West Africa goes towards explaining the prevalance of the [[Haemoglobin\|Hb]]S [[Alleles\|allele]] in West African populations (1 in 100 West Africans being Sickle Cell Anaemia sufferers), due to  the presence of the [[Haemoglobin\|Hb]]S [[Alleles\|allele]] favouring the survival of its carriers <ref>Biochemistry 6th edition Jeremy M. Berg, John L Tymoczko, Lubert Stryer pg 195-196</ref>.

	=== References <br> ===

	<references />

140657812 at 20:45, 25 November 2014

2014-11-25T20:45:58Z

← Older revision		Revision as of 20:45, 25 November 2014
Line 7:		Line 7:
	=== Effects of the HbS Mutation ===		=== Effects of the HbS Mutation ===

	When red blood cells with the [[Wild - type\|wildtype]] form of the gene (HbA) are subjected to low oxygen concentration the [[Javascript:void(0);/1322703978627/\|haemoglobin]] in the cell remains fully functional. However, in cells with the HbS mutation the haemoglobin polymerizes in environments where oxygen concentration is low. The [[Haemoglobin\|haemoglobin]] polymers are responsible for the change in red blood cell shape; the cells become long, sickle shaped and fragile. The sickle cells do not deliver oxygen to tissues with the same efficiency as normal blood cells, and they often get caught in small blood vessels leading to blockages. This causes extreme pain and leads to damage of major organs such as the [[Brain\|brain]], heart, [[Kidney\|kidneys]] and [[Muscle\|muscles]] <ref>Essentials of Genetics 6th Edition. William S. Klug, Michael R. Cummings, Charlotte A. Spencer. Peterson International Edition, pg 7</ref>. Due to the ~~stres splaced~~ on the heart to move the ~~sickeld~~ cells around the body it is ~~oftne~~ seen that people with sickle cell disease have issues with hypertension. It can result in death and is present in one third of adults with sickle cell disease. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>As a result of the rapid breakdown of red blood cells a jaundice like yellowing of the eyes and skin can occur. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>The solubility of deoxyhaemoglobin also decreases. <ref>Berg,M.J., Tymoczko, J.L. and Stryer L. (2012) Biochemistry. 7th ed. p.216.</ref>		When red blood cells with the [[Wild - type\|wildtype]] form of the gene (HbA) are subjected to low oxygen concentration the [[Javascript:void(0);/1322703978627/\|haemoglobin]] in the cell remains fully functional. However, in cells with the HbS mutation the haemoglobin polymerizes in environments where oxygen concentration is low. The [[Haemoglobin\|haemoglobin]] polymers are responsible for the change in red blood cell shape; the cells become long, sickle shaped and fragile. The sickle cells do not deliver oxygen to tissues with the same efficiency as normal blood cells, and they often get caught in small blood vessels leading to blockages. This causes extreme pain and leads to damage of major organs such as the [[Brain\|brain]], heart, [[Kidney\|kidneys]] and [[Muscle\|muscles]] <ref>Essentials of Genetics 6th Edition. William S. Klug, Michael R. Cummings, Charlotte A. Spencer. Peterson International Edition, pg 7</ref>. Due to the stress placed on the heart to move the sickled cells around the body, it is often seen that people with sickle cell disease have issues with hypertension. It can result in death and is present in one third of adults with sickle cell disease. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>As a result of the rapid breakdown of red blood cells, a jaundice like yellowing of the eyes and skin can occur. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>The solubility of deoxyhaemoglobin also decreases. <ref>Berg,M.J., Tymoczko, J.L. and Stryer L. (2012) Biochemistry. 7th ed. p.216.</ref>

	=== Inheritance    ===		=== Inheritance    ===

Nnjm2 at 13:03, 24 November 2014

2014-11-24T13:03:40Z

← Older revision		Revision as of 13:03, 24 November 2014
Line 3:		Line 3:
	=== Genetics   ===		=== Genetics   ===

	Sickle cell is a genetic disorder caused by a missense [[Mutation\|mutation]] in the [[Amino acids\|amino acid]] sequence coding for the [[Haemoglobin gene\|haemoglobin gene]] in [[Red blood cells\|red blood cells]] <ref>Biochemistry 6th edition Jeremy M. Berg, John L Tymoczko, Lubert Stryer pg 195</ref>. The haemoglobin molecule is a tetramer with two alpha subunits and two beta subunits. The mutation occurs in the beta subunit when a [[Valine\|valine]](V) replaces [[Glutamate\|glutamate]](E) in position 6 of the beta subunit, the replacement is referred to as Glu6Val <ref>• Page 524, Hartl, D. L. &amp; Ruvolo, M., 2012, Genetics: Analysis Of Genes And Genomes, Eighth Edition, Burlington: Jones &amp; Bartlett Learning</ref>.In those who show symptonms of sickle cell anaemia, on the beta globin chain in the sixth amino acid position the base A, which is the second codon for the amino acid, is swapped with a T during transcription of the DNA duplex, causing an A-T —> T -A transgression. This causes a change in the amino acid coded for and hence known as a glu6val or E6V mutation. <ref>Ruvolo, D.H. and M., 2011. Genetics 8E: Analysis of Genes and Genomes Intl Version, Jones & Bartlett Learning, LLC. page 520-525</ref> The mutation occurs on the p arm of chromosome 11 which is an autosome and as mentioned effects the beta subunit.<ref>U.S National Library of medicine, 2009</ref> [[Phenylalanine\|phenylalanine]] 85 and [[Leucine\|leucine]] 88 - which are both non-polar hydrophobic amino acids on the gene - form a socket in which the valine side chain can fuse. This is possible because valine is also hydrophobic unlike glutamate and so form sticky ends with the hydrophobic leucine and phenylalanine, thus resulting in a polymerisation of the molecule which alters the tetramer structure of haemoglobin. The mutation is known as HbS, the normal [[Haemoglobin\|haemoglobin]] is referred to as HbA.<br>		Sickle cell is a genetic disorder caused by a missense [[Mutation\|mutation]] in the [[Amino acids\|amino acid]] sequence coding for the [[Haemoglobin gene\|haemoglobin gene]] in [[Red blood cells\|red blood cells]] <ref>Biochemistry 6th edition Jeremy M. Berg, John L Tymoczko, Lubert Stryer pg 195</ref>. The haemoglobin molecule is a tetramer with two alpha subunits and two beta subunits. The mutation occurs in the beta subunit when a [[Valine\|valine]](V) replaces [[Glutamate\|glutamate]](E) in position 6 of the beta subunit, the replacement is referred to as Glu6Val <ref>• Page 524, Hartl, D. L. &amp;amp; Ruvolo, M., 2012, Genetics: Analysis Of Genes And Genomes, Eighth Edition, Burlington: Jones &amp;amp; Bartlett Learning</ref>.In those who show symptonms of sickle cell anaemia, on the beta globin chain in the sixth amino acid position the base A, which is the second codon for the amino acid, is swapped with a T during transcription of the DNA duplex, causing an A-T —> T -A transgression. This causes a change in the amino acid coded for and hence known as a glu6val or E6V mutation. <ref>Ruvolo, D.H. and M., 2011. Genetics 8E: Analysis of Genes and Genomes Intl Version, Jones &amp; Bartlett Learning, LLC. page 520-525</ref> The mutation occurs on the p arm of chromosome 11 which is an autosome and as mentioned effects the beta subunit.<ref>U.S National Library of medicine, 2009</ref> [[Phenylalanine\|phenylalanine]] 85 and [[Leucine\|leucine]] 88 - which are both non-polar hydrophobic amino acids on the gene - form a socket in which the valine side chain can fuse. This is possible because valine is also hydrophobic unlike glutamate and so form sticky ends with the hydrophobic leucine and phenylalanine, thus resulting in a polymerisation of the molecule which alters the tetramer structure of haemoglobin. The mutation is known as HbS, the normal [[Haemoglobin\|haemoglobin]] is referred to as HbA.<br>

	=== Effects of the HbS Mutation ===		=== Effects of the HbS Mutation ===

	When red blood cells with the [[Wild - type\|wildtype]] form of the gene (HbA) are subjected to low oxygen concentration the [[Javascript:void(0);/1322703978627/\|haemoglobin]] in the cell remains fully functional. However, in cells with the HbS mutation the haemoglobin polymerizes in environments where oxygen concentration is low. The [[Haemoglobin\|haemoglobin]] polymers are responsible for the change in red blood cell shape; the cells become long, sickle shaped and fragile. The sickle cells do not deliver oxygen to tissues with the same efficiency as normal blood cells, and they often get caught in small blood vessels leading to blockages. This causes extreme pain and leads to damage of major organs such as the [[Brain\|brain]], heart, [[Kidney\|kidneys]] and [[Muscle\|muscles]] <ref>Essentials of Genetics 6th Edition. William S. Klug, Michael R. Cummings, Charlotte A. Spencer. Peterson International Edition, pg 7</ref>. Due to the stres splaced on the heart to move the sickeld cells around the body it is oftne seen that people with sickle cell disease have issues with hypertension. It can result in death and is present in one third of adults with sickle cell disease. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>As a result of the rapid breakdown of red blood cells a jaundice like yellowing of the eyes and skin can occur. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>The solubility of deoxyhaemoglobin also decreases. <ref>Berg,M.J., Tymoczko, J.L. and Stryer L. (2012) Biochemistry. 7th ed. p.216.</ref>		When red blood cells with the [[Wild - type\|wildtype]] form of the gene (HbA) are subjected to low oxygen concentration the [[Javascript:void(0);/1322703978627/\|haemoglobin]] in the cell remains fully functional. However, in cells with the HbS mutation the haemoglobin polymerizes in environments where oxygen concentration is low. The [[Haemoglobin\|haemoglobin]] polymers are responsible for the change in red blood cell shape; the cells become long, sickle shaped and fragile. The sickle cells do not deliver oxygen to tissues with the same efficiency as normal blood cells, and they often get caught in small blood vessels leading to blockages. This causes extreme pain and leads to damage of major organs such as the [[Brain\|brain]], heart, [[Kidney\|kidneys]] and [[Muscle\|muscles]] <ref>Essentials of Genetics 6th Edition. William S. Klug, Michael R. Cummings, Charlotte A. Spencer. Peterson International Edition, pg 7</ref>. Due to the stres splaced on the heart to move the sickeld cells around the body it is oftne seen that people with sickle cell disease have issues with hypertension. It can result in death and is present in one third of adults with sickle cell disease. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>As a result of the rapid breakdown of red blood cells a jaundice like yellowing of the eyes and skin can occur. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>The solubility of deoxyhaemoglobin also decreases. <ref>Berg,M.J., Tymoczko, J.L. and Stryer L. (2012) Biochemistry. 7th ed. p.216.</ref>

	=== Inheritance    ===		=== Inheritance    ===
Line 17:		Line 17:
	When people carry both the [[Haemoglobin\|Hb]]B [[Gene\|gene]] and the mutated [[Haemoglobin\|Hb]]S [[Gene\|gene]] they are said to have sickle-cell trait, a form of [[Heterozygous advantage\|heterozygous advantage]]. They are relatively unaffected by the symptoms associated with sickle cell anaemia, however they can pass the HbS [[Mutation\|mutation]] onto their offspring. The interesting point here is that people with sickle-cell trait are resisitant to malaria. The reason for this higher resistance is because the plasmodium falciparum parasite that is responsible for malaria grows poorly in sickled cells.<ref>Bruce Alberts et al.,(2009) Essential Cell Biology, 3rd edition, Newyork:Garlands Science</ref> This means that in a carrier a proportion of the parasite will affect the sickled cells, rather than the normal red blood cells. A high proportion of the parasite attempting to grow in Sickled cells will not survive, so there will be a lower concentration of P.falciparum to affect the normal cells and this gives the carrier a higher probability of surviving the attack. It has been predicted that those who have sickle-cell trait may have a 20% increase in fitness over those in the population without sickle-cell trait in areas where malaria is common<ref>Gelehrter, T. D., Collins, F. S. and Ginsburg, D., 1998. Principles of Medical Genetics. p.51</ref>. HbS is hence thought to be reccessive for SCD, but dominant for Malaria resistance <ref>Daniel L.Hartl and Elizabeht W.Jones (2009) Genetics: Analysis of Genes and Genomes,p.513-515</ref>.		When people carry both the [[Haemoglobin\|Hb]]B [[Gene\|gene]] and the mutated [[Haemoglobin\|Hb]]S [[Gene\|gene]] they are said to have sickle-cell trait, a form of [[Heterozygous advantage\|heterozygous advantage]]. They are relatively unaffected by the symptoms associated with sickle cell anaemia, however they can pass the HbS [[Mutation\|mutation]] onto their offspring. The interesting point here is that people with sickle-cell trait are resisitant to malaria. The reason for this higher resistance is because the plasmodium falciparum parasite that is responsible for malaria grows poorly in sickled cells.<ref>Bruce Alberts et al.,(2009) Essential Cell Biology, 3rd edition, Newyork:Garlands Science</ref> This means that in a carrier a proportion of the parasite will affect the sickled cells, rather than the normal red blood cells. A high proportion of the parasite attempting to grow in Sickled cells will not survive, so there will be a lower concentration of P.falciparum to affect the normal cells and this gives the carrier a higher probability of surviving the attack. It has been predicted that those who have sickle-cell trait may have a 20% increase in fitness over those in the population without sickle-cell trait in areas where malaria is common<ref>Gelehrter, T. D., Collins, F. S. and Ginsburg, D., 1998. Principles of Medical Genetics. p.51</ref>. HbS is hence thought to be reccessive for SCD, but dominant for Malaria resistance <ref>Daniel L.Hartl and Elizabeht W.Jones (2009) Genetics: Analysis of Genes and Genomes,p.513-515</ref>.

	The lethal nature of malaria and its prevalance in West Africa goes towards explaining the prevalance of the [[Haemoglobin\|Hb]]S [[Alleles\|allele]] in West African populations (1 in 100 West Africans being Sickle Cell Anaemia sufferers), due to  the presence of the [[Haemoglobin\|Hb]]S [[Alleles\|allele]] favouring the survival of its carriers <ref>Biochemistry 6th edition Jeremy M. Berg, John L Tymoczko, Lubert Stryer pg 195-196</ref>.		The lethal nature of malaria and its prevalance in West Africa goes towards explaining the prevalance of the [[Haemoglobin\|Hb]]S [[Alleles\|allele]] in West African populations (1 in 100 West Africans being Sickle Cell Anaemia sufferers), due to  the presence of the [[Haemoglobin\|Hb]]S [[Alleles\|allele]] favouring the survival of its carriers <ref>Biochemistry 6th edition Jeremy M. Berg, John L Tymoczko, Lubert Stryer pg 195-196</ref>.

	=== References <br> ===		=== References <br> ===

	<references />		<references />

130051910 at 10:36, 24 November 2014

2014-11-24T10:36:30Z

← Older revision		Revision as of 10:36, 24 November 2014
Line 3:		Line 3:
	=== Genetics   ===		=== Genetics   ===

	Sickle cell is a genetic disorder caused by a missense [[Mutation\|mutation]] in the [[Amino acids\|amino acid]] sequence coding for the [[Haemoglobin gene\|haemoglobin gene]] in [[Red blood cells\|red blood cells]] <ref>Biochemistry 6th edition Jeremy M. Berg, John L Tymoczko, Lubert Stryer pg 195</ref>. The haemoglobin molecule is a tetramer with two alpha subunits and two beta subunits. The mutation occurs in the beta subunit when a [[Valine\|valine]](V) replaces [[Glutamate\|glutamate]](E) in position 6 of the beta subunit, the replacement is referred to as Glu6Val <ref>• Page 524, Hartl, D. L. & Ruvolo, M., 2012, Genetics: Analysis Of Genes And Genomes, Eighth Edition, Burlington: Jones & Bartlett Learning</ref>. [[Phenylalanine\|phenylalanine]] 85 and [[Leucine\|leucine]] 88 - which are both non-polar hydrophobic amino acids on the gene - form a socket in which the valine side chain can fuse. This is possible because valine is also hydrophobic unlike glutamate and so form sticky ends with the hydrophobic leucine and phenylalanine, thus resulting in a polymerisation of the molecule which alters the tetramer structure of haemoglobin. The mutation is known as HbS, the normal [[Haemoglobin\|haemoglobin]] is referred to as HbA.<br>		Sickle cell is a genetic disorder caused by a missense [[Mutation\|mutation]] in the [[Amino acids\|amino acid]] sequence coding for the [[Haemoglobin gene\|haemoglobin gene]] in [[Red blood cells\|red blood cells]] <ref>Biochemistry 6th edition Jeremy M. Berg, John L Tymoczko, Lubert Stryer pg 195</ref>. The haemoglobin molecule is a tetramer with two alpha subunits and two beta subunits. The mutation occurs in the beta subunit when a [[Valine\|valine]](V) replaces [[Glutamate\|glutamate]](E) in position 6 of the beta subunit, the replacement is referred to as Glu6Val <ref>• Page 524, Hartl, D. L. &amp; Ruvolo, M., 2012, Genetics: Analysis Of Genes And Genomes, Eighth Edition, Burlington: Jones &amp; Bartlett Learning</ref>.In those who show symptonms of sickle cell anaemia, on the beta globin chain in the sixth amino acid position the base A, which is the second codon for the amino acid, is swapped with a T during transcription of the DNA duplex, causing an A-T —> T -A transgression. This causes a change in the amino acid coded for and hence known as a glu6val or E6V mutation. <ref>Ruvolo, D.H. and M., 2011. Genetics 8E: Analysis of Genes and Genomes Intl Version, Jones & Bartlett Learning, LLC. page 520-525</ref> The mutation occurs on the p arm of chromosome 11 which is an autosome and as mentioned effects the beta subunit.<ref>U.S National Library of medicine, 2009</ref> [[Phenylalanine\|phenylalanine]] 85 and [[Leucine\|leucine]] 88 - which are both non-polar hydrophobic amino acids on the gene - form a socket in which the valine side chain can fuse. This is possible because valine is also hydrophobic unlike glutamate and so form sticky ends with the hydrophobic leucine and phenylalanine, thus resulting in a polymerisation of the molecule which alters the tetramer structure of haemoglobin. The mutation is known as HbS, the normal [[Haemoglobin\|haemoglobin]] is referred to as HbA.<br>

	=== Effects of the HbS Mutation ===		=== Effects of the HbS Mutation ===

130051910 at 10:30, 24 November 2014

2014-11-24T10:30:05Z

← Older revision		Revision as of 10:30, 24 November 2014
Line 7:		Line 7:
	=== Effects of the HbS Mutation ===		=== Effects of the HbS Mutation ===

	When red blood cells with the [[Wild - type\|wildtype]] form of the gene (HbA) are subjected to low oxygen concentration the [[Javascript:void(0);/1322703978627/\|haemoglobin]] in the cell remains fully functional. However, in cells with the HbS mutation the haemoglobin polymerizes in environments where oxygen concentration is low. The [[Haemoglobin\|haemoglobin]] polymers are responsible for the change in red blood cell shape; the cells become long, sickle shaped and fragile. The sickle cells do not deliver oxygen to tissues with the same efficiency as normal blood cells, and they often get caught in small blood vessels leading to blockages. This causes extreme pain and leads to damage of major organs such as the [[Brain\|brain]], heart, [[Kidney\|kidneys]] and [[Muscle\|muscles]] <ref>Essentials of Genetics 6th Edition. William S. Klug, Michael R. Cummings, Charlotte A. Spencer. Peterson International Edition, pg 7</ref>. The solubility of deoxyhaemoglobin also decreases. <ref>Berg,M.J., Tymoczko, J.L. and Stryer L. (2012) Biochemistry. 7th ed. p.216.</ref>		When red blood cells with the [[Wild - type\|wildtype]] form of the gene (HbA) are subjected to low oxygen concentration the [[Javascript:void(0);/1322703978627/\|haemoglobin]] in the cell remains fully functional. However, in cells with the HbS mutation the haemoglobin polymerizes in environments where oxygen concentration is low. The [[Haemoglobin\|haemoglobin]] polymers are responsible for the change in red blood cell shape; the cells become long, sickle shaped and fragile. The sickle cells do not deliver oxygen to tissues with the same efficiency as normal blood cells, and they often get caught in small blood vessels leading to blockages. This causes extreme pain and leads to damage of major organs such as the [[Brain\|brain]], heart, [[Kidney\|kidneys]] and [[Muscle\|muscles]] <ref>Essentials of Genetics 6th Edition. William S. Klug, Michael R. Cummings, Charlotte A. Spencer. Peterson International Edition, pg 7</ref>. Due to the stres splaced on the heart to move the sickeld cells around the body it is oftne seen that people with sickle cell disease have issues with hypertension. It can result in death and is present in one third of adults with sickle cell disease. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>As a result of the rapid breakdown of red blood cells a jaundice like yellowing of the eyes and skin can occur. <ref>http://ghr.nlm.nih.gov/condition/sickle-cell-disease</ref>The solubility of deoxyhaemoglobin also decreases. <ref>Berg,M.J., Tymoczko, J.L. and Stryer L. (2012) Biochemistry. 7th ed. p.216.</ref>

	=== Inheritance    ===		=== Inheritance    ===

140092541 at 17:03, 23 November 2014

2014-11-23T17:03:52Z

← Older revision		Revision as of 17:03, 23 November 2014
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	=== '''Sickle-Cell Trait''' ===		=== '''Sickle-Cell Trait''' ===

	When people carry both the [[Haemoglobin\|Hb]]B [[Gene\|gene]] and the mutated [[Haemoglobin\|Hb]]S [[Gene\|gene]] they are said to have sickle-cell trait, a form of [[Heterozygous advantage\|heterozygous advantage]]. They are relatively unaffected by the symptoms associated with sickle cell anaemia, however they can pass the HbS [[Mutation\|mutation]] onto their offspring. The interesting point here is that people with sickle-cell trait are resisitant to malaria. The reason for this higher resistance is because the plasmodium falciparum parasite that is responsible for malaria grows poorly in sickled cells.<ref>Bruce Alberts et al.,(2009) Essential Cell Biology, 3rd edition, Newyork:Garlands Science</ref> This means that in a carrier a proportion of the parasite will affect the sickled cells, rather than the normal red blood cells. A high proportion of the parasite attempting to grow in Sickled cells will not survive, so there will be a lower concentration of P.falciparum to affect the normal cells and this gives the carrier a higher probability of surviving the attack. It has been predicted that those who have sickle-cell trait may have a 20% increase in fitness over those in the population without sickle-cell trait in areas where malaria is common<ref>Gelehrter, T. D., Collins, F. S. ~~&amp;amp;~~ Ginsburg, D., 1998. Principles of Medical Genetics.p.51</ref>. HbS is hence thought to be reccessive for SCD, but dominant for Malaria resistance <ref>Daniel L.Hartl and Elizabeht W.Jones (2009) Genetics: Analysis of Genes and Genomes,p.513-515</ref>.		When people carry both the [[Haemoglobin\|Hb]]B [[Gene\|gene]] and the mutated [[Haemoglobin\|Hb]]S [[Gene\|gene]] they are said to have sickle-cell trait, a form of [[Heterozygous advantage\|heterozygous advantage]]. They are relatively unaffected by the symptoms associated with sickle cell anaemia, however they can pass the HbS [[Mutation\|mutation]] onto their offspring. The interesting point here is that people with sickle-cell trait are resisitant to malaria. The reason for this higher resistance is because the plasmodium falciparum parasite that is responsible for malaria grows poorly in sickled cells.<ref>Bruce Alberts et al.,(2009) Essential Cell Biology, 3rd edition, Newyork:Garlands Science</ref> This means that in a carrier a proportion of the parasite will affect the sickled cells, rather than the normal red blood cells. A high proportion of the parasite attempting to grow in Sickled cells will not survive, so there will be a lower concentration of P.falciparum to affect the normal cells and this gives the carrier a higher probability of surviving the attack. It has been predicted that those who have sickle-cell trait may have a 20% increase in fitness over those in the population without sickle-cell trait in areas where malaria is common<ref>Gelehrter, T. D., Collins, F. S. and Ginsburg, D., 1998. Principles of Medical Genetics. p.51</ref>. HbS is hence thought to be reccessive for SCD, but dominant for Malaria resistance <ref>Daniel L.Hartl and Elizabeht W.Jones (2009) Genetics: Analysis of Genes and Genomes,p.513-515</ref>.

	The lethal nature of malaria and its prevalance in West Africa goes towards explaining the prevalance of the [[Haemoglobin\|Hb]]S [[Alleles\|allele]] in West African populations (1 in 100 West Africans being Sickle Cell Anaemia sufferers), due to  the presence of the [[Haemoglobin\|Hb]]S [[Alleles\|allele]] favouring the survival of its carriers <ref>Biochemistry 6th edition Jeremy M. Berg, John L Tymoczko, Lubert Stryer pg 195-196</ref>.		The lethal nature of malaria and its prevalance in West Africa goes towards explaining the prevalance of the [[Haemoglobin\|Hb]]S [[Alleles\|allele]] in West African populations (1 in 100 West Africans being Sickle Cell Anaemia sufferers), due to  the presence of the [[Haemoglobin\|Hb]]S [[Alleles\|allele]] favouring the survival of its carriers <ref>Biochemistry 6th edition Jeremy M. Berg, John L Tymoczko, Lubert Stryer pg 195-196</ref>.