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Cystic fibrosis

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Cystic fibrosis (CF) also known as mucoviscidosis is an inherited disease characterized by an abnormality in the glands that produce sweat and [[Mucus|mucus]]. It is an autosomal recessive disorder which can be caused by various different mutations to the [[CFTR gene|CFTR gene]] which codes for the CFTR protein located in the epithelial cells. The CFTR [[Gene|gene]] is found on chromosome 7 and is 230kb in length with 27 coding exons within this<ref>Bean, lora J.H., Pratt, V.M. molecular Pathology in Clinical Practice. 2nd Edition. Switzerland: Springer International Publishing. 2016.</ref>., and there are multiple mutations that can lead to CFTR dysfunction and therefore Cystic Fibrosis<ref>Genetic Home Reference(2012) Cystic Fibrosis(online) Available from:http://ghr.nlm.nih.gov/condition/cystic-fibrosis</ref>. It is a chronic, progressive and usually fatal disease, however, the life expectancy of CF patients is increasing due to advances in medical sciences and treatment and the median predicted survival age is currently 41 years old<ref name="Cystic Fibrosis Trust FAQ's">http://www.cftrust.org.uk/aboutcf/faqs#life [Accessed on 25th October 2012]</ref>.

Cystic fibrosis affects various systems in children and young adults, including the following:

*[[Respiratory system|Respiratory system]]
*[[Digestive system|Digestive system]]
*[[Reproductive system|Reproductive system]]

There are approximately 30,000 people in the US who are affected by the disease, and about 1,000 babies are diagnosed with it each year. It occurs mainly in Caucasians, who have a northern European heredity, although it also occurs in African-Americans, Asian Americans, and Native Americans. Cystic Fibrosis is a disease which has been around since the middle ages.<ref>http://reliawire.com/who-discovered-cystic-fibrosis/</ref>.

Approximately one in 31 people in the US are carriers of the cystic fibrosis gene. These people are not affected by the disease and usually, do not know that they are carriers. The most common type of cystic fibrosis mutation, affecting 75% of patients, is the mutation phe508del, previously named deltaF508.

== How does CF affect the respiratory system? ==

The basis for the problem with CF lies in an abnormal [[Gene|gene]]. The result of this gene defect is an atypical electrolyte transport system within the cells of the body. The abnormal transport system causes the cells in the respiratory system, especially the [[Lungs|lungs]], to absorb too much [[Sodium|sodium]] and [[Water|water]]. This causes the normal, thin mucus secretions in our lungs to become very thick and hard to remove. These thick secretions put the child with CF at risk for constant infection.

The high risk of infection in the [[Respiratory system|respiratory system leads]] to damage in the lungs, leading to lungs that do not work properly, and eventually death of the cells in the lungs. The most common causes for infection in the lungs of the CF patient are the following bacteria:

*[[Staphylococcus aureus|''Staphylococcus aureus'']]
*[[Haemophilus influenzae|''Haemophilus influenzae'']]
*''[[Pseudomonas aeruginosa|Pseudomonas aeruginosa]]'' (PA)

Over a period of time, PA becomes the most common [[Bacteria|bacteria]] that causes infection and becomes difficult to fight. A large percentage of respiratory infections in the CF patient are due to PA.

As a result of the high rate of infection in the lower respiratory tract, people with CF may develop a chronic cough, blood in the sputum, and sometimes can even have a collapsed lung. The cough is usually worse in the morning or after activity.

People with CF also have involvement of the upper respiratory tract. Some patients have nasal polyps that need surgical removal. Nasal polyps are small protrusions of tissue from the lining of the nose that goes into the nasal cavity. Children also have a high rate of sinus infections.

Infections of the lungs due to increased bacteria can also lead to [[Respiratory failure|respiratory failure]] which is the main cause of mortality in cystic fibrosis individuals<ref>Vertex Pharmaceuticals Incorporated. A clinician's guide to CFTR. 2016. [Accessed 2ist November 2016}. Available from:http://www.cftrscience.com .</ref>.

== How does CF affect the gastrointestinal (GI) system? ==

The [[Organ|organ]] primarily affected is the pancreas, which secretes substances that aid digestion and help control blood-glucose levels.

As a result of the abnormal electrolyte transport system in the cells, the secretions from the pancreas become thick and lead to an obstruction of the ducts of the pancreas. This obstruction then causes a decrease in the secretion of[[Enzymes|enzymes]] from the pancreas that normally helps to digest food. A person with CF has difficulty absorbing proteins, fats, and vitamins [[Vitamin A|A]], [[Vitamin D|D]], [[Vitamin E|E]], and [[Vitamin K|K]].

The problems with the pancreas can become so severe that some of the cells, such as ß cells in the Islets of Langerhans, in the [[Pancreas|pancreas]] can become destroyed. This may lead to glucose intolerance and [[Cystic fibrosis-related diabetes|cystic fibrosis-related diabetes]]. The ß cells are therefore unable to produce insulin as efficiently so develop diabetes. About 35% of CF patients develop this type of diabetes in their 20s and 43% develop the disease after 30 years of age. This can present difficulties in CF patients who are advised to consume a diet very high in calories (including sugars and fats) to combat the weight lost through poor uptake of nutrients as a result of excess mucus lining the digestive system. The patient with CF coupled with cystic fibrosis-related diabetes would have to ensure a diet high in calories but also must maintain their blood sugar within normal range.

Another organ which may be affected by CF is the [[Small intestine|small intestine]]; its function is to digest and absorb the nutrients from the food.

In a person with CF the enzymes which help the digestion process become thick and sticky and therefore block these ducts between the pancreas and small intestine.

[[Meconium|Meconium]] (failure to pass faeces) is a condition that occurs in newborns with CF, where the intestines are completely blocked. This occurs in about 10% of newborns with the condition.

== The symptoms that may be present due to the involvement of the GI tract ==

*Bulky, greasy stools
*Rectal prolapse--a condition in which the end part of the bowels comes out of the anus.
*Delayed puberty
*Fat in the stools
*Stomach pain
*Bloody diarrhoea

The [[Liver|liver]] may also be affected. A small number of patients may actually develop liver disease. Symptoms of liver disease may include:

*Enlarged liver
*Swollen abdomen
*Yellow colour to the skin
*Vomiting of blood

== How does CF affect the reproductive system? ==

Most males with CF have obstruction of the sperm canal known as congenital bilateral absence of the vas deferens (CBAVD), in which the tubes that connect the testes to the penis are missing. This results from the abnormal electrolyte transport system in the cells (brought about by the absence of fine ducts), causing the secretions to become thick and lead to an obstruction and in male patients 95% become infertile. However, the sperm is not affected and can be used in IVF, if required. Women also have an increase in thick cervical mucus that may lead to a decrease in fertility, although many women with CF have children. This thick mucus acts as a plug, presenting a physical barrier to the [[Sperm cell|sperm cells]]' passage to the [[Uterus|uterus]].

== What are the symptoms of cystic fibrosis? ==

The following are the most common symptoms for cystic fibrosis. However, due to multiple mutations having the ability to cause disease, symptoms can vary amongst individuals and are, therefore, dependent upon the mutations the individual has inherited<ref>Cystic Fibrosis Trust. Cystic Fibrosis. 2016 [accessed 21st November 2016]. Available from:https://www.cysticfibrosis.org.uk/.</ref>. This is described as variable expressivity<ref>Hartl, D.L., Jones, E.W. Genetics: Analysis of genes and genomes. 7th Edition, Canada: Jones and Bartlett. 2009.</ref>.Symptoms may include:

*Abnormalities in the glands that produce sweat and mucus

This may cause a loss of salt. A loss of salt may cause an upset in the balance of minerals in the blood, abnormal heart rhythms, and, possibly, shock.

*Thick mucus that accumulates in the lungs and intestines as well as in the trachea. Figure below shows the difference.

[[Image:Cystic_fibrosis.png]]

This may cause malnutrition, poor growth, frequent respiratory infections, breathing difficulties, and/or lung disease.

Other medical problems, such as:

*Sinusitis
*Nasal polyps
*Clubbing of fingers and toes--a condition marked by the ends of the fingers and toes become enlarged; more prevalent in the fingers
*Pneumothorax--the presence of air or gas in the pleural cavity causing the lung to collapse
*Hemoptysis--coughing blood
*Cor pulmonale--enlargement of the right side of the heart
*Abdominal pain
*Gas in the intestines
*Rectal prolapse
*[[Liver|Liver]] disease
*[[Diabetes|Diabetes]]
*Pancreatitis
*Gallstones
*Congenital bilateral absence of the vas deferens (CBAVD) in males

As stated above, the symptoms of CF differ for each person. Infants born with CF usually show symptoms by age two. Some children, though, may not show symptoms until later in life. The following signs are suspicious of CF, and infants having these signs may be tested for CF:

*Diarrhea that does not go away
*Foul-smelling stools
*Greasy stools
*Frequent episodes of wheezing
*Frequent episodes of pneumonia or other lung infections
*Persistent cough
*Skin tastes like salt
*Poor growth despite a good appetite

The symptoms of cystic fibrosis may resemble other conditions or medical problems. Consult a physician for a diagnosis.

== How is cystic fibrosis diagnosed? ==

Most cases of cystic fibrosis are now identified with newborn screening. In addition to a complete medical history and physical examination, diagnostic procedures for cystic fibrosis include a sweat test to measure the amount of sodium chloride (salt) present. Higher than normal amounts of sodium and chloride suggest cystic fibrosis. A person with cystic fibrosis has about 5 times the normal salt concentration in their sweat. Other diagnostic procedures include:

*Chemical tests
*Chest X-rays
*Lung function tests
*Sputum cultures
*Stool evaluations

For babies, who do not produce enough sweat, blood tests may be used.

== Treatment for cystic fibrosis ==

Specific treatment for cystic fibrosis will be determined by your doctor based on:

*Your age, overall health, and medical history
*Extent of the disease
*Expectations for the course of the disease
*Your tolerance for specific medications, procedures, or therapies
*Your opinion or preference

Currently, there is no cure for CF. A cure would call for [[Gene therapy|gene therapy]] at an early age and this has not been developed yet, although research is being done in this direction. The gene that causes CF has been identified and there are hopes that this will lead to an increased understanding of the disease. Also being researched are different drug regimens to help stop CF. Goals of treatment are to ease the severity of symptoms and slow the progress of the disease. Treatment may include:

Management of problems that cause lung obstruction, which may involve:

*Physical therapy
*Exercise to loosen mucus, stimulate coughing, and improve overall physical condition
*Medications to reduce mucus and help breathing
*Antibiotics to treat infections
*Anti-inflammatories

Management of digestive problems, which may involve:

*Appropriate diet
*Pancreatic enzymes to aid digestion
*Vitamin supplements
*Treatments for intestinal obstructions
*Newer therapies include lung transplantation for patients with end-stage lung disease. The type of transplant done is usually a heart-lung transplant or a double lung transplant. Not everyone is a candidate for a lung transplant. Discuss this with your physician.

== The genetics of cystic fibrosis ==

Cystic fibrosis (CF) is a genetic disease. This means that CF is inherited. A person will be born with CF only if two CF genes are inherited - one from the mother and one from the father. A mutation in one of the copies of the cystic fibrosis gene has been shown to give protection against typhoid fever. However, this is not clearly understood. The cystic fibrosis gene is on the long q arm of autosomal chromosome 7 at position 31.2 A person who has only one CF gene is healthy and said to be a "carrier" of the disease. A carrier has an increased chance of having a child with CF. This type of inheritance is called "autosomal recessive." "Autosomal" means that the gene is on one of the first 22 pairs of chromosomes which do not determine gender so that the disease equally affects males and females. "Recessive" means that two copies of the gene, one inherited from each parent, are necessary to have the condition. Once parents have had a child with CF, there is a one in four, or 25% chance with each subsequent pregnancy, for another child to be born with CF. This means that there is a three out of four, or 75% chance, for another child to not have CF.

The birth of a child with CF is often a total surprise to a family since most of the time (in eight out of 10 families) there is no previous family history of CF. Many autosomal recessive conditions occur this way. Since both parents are healthy, they had no prior knowledge that they carried the gene, nor that they passed the gene to the pregnancy at the same time.

Genes are founds on structures in the cells of our body called chromosomes. There are normally 46 total or 23 pairs of chromosomes in each cell of our body. The seventh pair of chromosomes contains a gene called the [[CFTR|CFTR]] ([[Cystic fibrosis transmembrane regulator|cystic fibrosis transmembrane regulator]]) [[Gene|gene]]. It is a chloride [[Channel proteins|channel protein]] in the epithelial cell membrane<ref>Bourke, S.J., Respiratory Medicine, 7th Edition, 2007, Oxford: Blackwell Publishing Ltd</ref>. and contains 1,480 amino acids. It is a sub-member of the ABC family of transport proteins and as such, it has a motif in its amino acids sequence that is an ATP-binding cassette. It is thus phosphorylation regulated. It has a structure consisting of two nucleotide-binding sites and two domains made up of membrane that are separated by a cytoplasmic regulatory section (R) where phosphorylation sites are found. ATP controls the CFTR by protein phosphorylation and correlation with the nucleotide-binding sections The most common CF mutation is referred to as the delta F508 mutation and prevents the CFTR from reaching the membrane, it also affects the synthesis of the protein<ref>Bradley, J., and Johnson, D., and Pober, B., Medical Genetics, 3rd Edition, 2006, Oxford: Blackwell Publishing</ref>. Mutations or errors in this gene are what cause CF. This gene is quite large and complex. Over 1,000 different mutations in this gene have been found which cause CF.

The risk of having a mutation in the gene for CF depends on your ethnic background (for persons without a family history of CF):

=== Ethnic Background Risk of CF Mutation Risk of Child with CF ===

*Caucasian: 1 in 29 1 in 2,500-3,500
*Hispanic : 1 in 46 1 in 4,000-10,000
*African-American: 1 in 65 1 in 15,000-20,000
*Asian: 1 in 90 1 in 100,000

Testing for the CF gene can be done from a small blood sample or from a cheek swab, which is a brush rubbed against the inside of your cheek to obtain cells for testing. Laboratories generally test for the most common mutations.

There are many people with CF whose mutations have not been identified. In other words, all of the genetic errors that cause the disease have not been discovered. Because not all mutations are detectable, a person can still be a CF carrier even if no mutations were found by carrier testing.

Testing for the CF gene is recommended for anyone who has a family member with the disease, or whose partner is a known carrier of CF or affected with CF. The earlier screening is done, the earlier specific treatment can happen.

=== Heterozygous Advantage ===

There is a '''proposed''' Heterozygous Advantage for the [[Cystic Fibrosis|Cystic Fibrosis]] mutation which can be used to explain the prevalence of what could be considered a lethal [[Allele|allele]]. It has been proposed that being heterozygous for the mutation could provide a selective advantage against chloride secreting diarrhoeal diseases.

A study carried out by Garbriel ''et al.'' <ref name="Gabriel et al.">Gabriel, S., Brigman, K.,Koller, B., Boucher, R. and Stutts, M. (1994). Cystic fibrosis heterozygote resistance to cholera toxin in the cystic fibrosis mouse model. Science, 266(5182), pp.107-109</ref>. demonstrated this using a mouse [[Model organism|model organism]]. The CF mutation was introduced into the mice, some were homozygous and some were heterozygous. The mice were then injected with a dose [[Cholera toxin|Cholera Toxin]] and the [[Chloride|chloride]] secretion measured. Mice heterozygous for the CF mutation showed half the secretion of wild-type mice, suggesting that by reducing the amount of [[CFTR|CFTR in]] the [[Epithelium|epilthelium]] of the digestive tract, effects of cholera infection would be less severe.

== Cystic Fibrosis ==

[[Cyctic fibrosis|Cystic Fibrosis is]] an [[Autosomal recessive disease|autosomal recessive disease]] caused by a mutation on the long (q) arm of [[Chromosome|chromosome]] 7 on the q31-32 region<ref>Zieleneski, J., Rozmahel, R., Bozon, D., Kerem, B., Grzelzak, Z., Riordan J., Rommens, J. And Tsui, L. (1991) ‘Genomic DNA sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene’, Genomics, 10(1), pp. 214-228, Elsevier [online]. Available at: http://www.sciencedirect.com/science/article/pii/0888754391905037 (Accessed: 11 November 2014)</ref>. The mutation affects the [[CFTR|Cystic Fibrosis Transmembrane Conductance Regulator]] (CFTR) channel protein. The most common mutation is ΔF508, accounting for 70% of mutations in the [[Frequency of CFTR mutations by Ethnicity|Caucasian]] UK population, in which the [[Codon|triplet code]] ([[Codon|codon]]) for the [[Amino acid|amino acid]] [[Phenylalanine|phenylalanine]] is deleted, disrupting Cl- transport. This [[Mutation|mutation]] belongs to the Class II group of mutations causing Cystic Fibrosis.

[[CFTR|CFTR]] is composed of 3 types of domains. There are 12 [http://en.wikipedia.org/wiki/Transmembrane_protein Transmembrane] spanning domains, 2 Nucleotide Binding Domains (NBD’s - part of the ATP Binding Cassette domains) and an R domain (regulatory domain). The NBD’s are involved in the binding and hydrolysis of [[ATP|ATP]]. It is believed that the mutation that causes Cystic Fibrosis occurs on the Nucleotide Binding Domain 1.

CFTR is part of the [[ABC Superfamily|ABC ]](ATP Binding Cassette) superfamily of transporters.

== Cystic Fibrosis Classes ==

Class I: [[Premature Stop Codon|Premature Stop Codons]] (e.g. W1282X)

W1282X mutation can be found in approximately 7% of the European population. This mutation occurs by an insertion of an extra amino acid tryptophan at the position 1282 of the target chromosome (one letter code W, hence the name of the mutation). This results in the protein translation being prematurely stopped (shown in the name of the mutation as X) so that the protein is not produced at all. The absence of CFTR protein leads to the symptoms of CF.

Class II: [[Abnormal Processing|Abnormal Processing]] (e.g. ΔF508) This involves the deletion of the [[Amino acid|amino acid]], [[Phenylalanine|Phenylalanine]] at NBD1 (Nucleotide Binding Domain 1) of the [[CFTR|CFTR]] (Cystic Fibrosis transmembrane conductance receptor). This mutation takes effect on the processing of the [[Protein|protein]] after leaving the [[Endoplasmic Reticulum|Endoplasmic Reticulum]]. It adversely comprimises the trafficking/passage of the protein across the [[Cytosol|cytosol]] ultimately resulting in the the protein being degraded by the [[Proteasome|proteasome]]. This mutation is the most common mutation of the [[CFTR|CFTR]], causing >90% of [[Cystic_fibrosis|Cystic Fibrosis cases]]<ref>J Biol Chem. 2010 Nov 12;285(46):35825-35. Epub 2010 Jul 28.</ref>.

Deletion of phenylalanine causes the protein to be misfolded. It cannot adopt its tertiary structure and ends up in a wrong shape. There is an impact on CFTR not processing successfully to the apical plasma membrane. After the protein has folded, it is then degraded. This mutation causes common cystic fibrosis symptom “salty sweat”. In this occasion, due to the degraded CFTR protein in the duct cells of cuboidal epithelium Na+ and Cl- are not removed from the primary secretion of the sweat. So, it comes out to the surface of the skin very salty.

Class III: [[Altered Regulation|Altered Regulation]] (e.g. G551D)

At the position 551 of the target chromosome, an amino acid G (glycine) is replaced with aspartate (D).

Class IV: [[Conductance Defect|Conductance Defect]] (e.g. R117H)

Class V: [[Reduced Protein Synthesis|Reduced Protein Synthesis]] (e.g. A455E)<ref>David L. Rimoin, J. Michael Connor, Reed E. Pyeritz, Bruce R. Korf (2007). Emery and Rimoin's Principles and Practice of Medical Genetics edition. 5th ed. Amsterdam: Elsevier. p1354-1394.</ref>.

Class I,II and III mutations usually lead to a full loss of function. CFTR dysfunction can occur in the failure of 5 key mechanisms: defective protein processing, defective channel conduction, reduced protein stability, defective protein production and reduced protein synthesis.

== Approaches to Treatment ==

==== Lung Function ====

[[Physiotherapy and mucolytics|Physiotherapy and mucolytics]]

Oral and Inhaled [[Antibotics|Antibotics]]

[[Anti-Inflammatory|Anti-Inflammatory Drugs]]

[[Transplant|Lung Transplant]]

[[Gene therapy|Gene Therapy]]

[[Pharmacotherapy of Cystic Fibrosis|Pharmacotherapy]]

[[Alternative Channel Therapy|Alternative Channel Therapy]]

==== Pancreatic Function ====

[[Pancreatic Enzyme Replacement|Pancreatic Enzyme Replacement]]

Nutritional Regime

== How Does it affect everyday life? ==

[[Cystic Fibrosis|Cystic fibrosis]] affects everyone differently, common daily routines involve [[Physiotherapy|physiotherapy]] in order to lift the mucus off the chest, a range of [[Antibiotics|antibiotics]] which can be given orally, intravenously or through a nebuliser and [[Enzymes|enzymes]] which are given with food. Very ill patients find the most menial tasks difficult and can end up breathless and in some cases needing oxygen and wheelchairs<ref>http://cysticfibrosis.org.uk/about-cf/frequently-asked-questions#na (date accessed 19th October 2015)</ref><ref>http://reliawire.com/who-discovered-cystic-fibrosis/</ref>.

== References ==

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File:Cystic fibrosis.png

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Artery

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Arteries are the blood vessels in the [[The Cardiovascular System|Cardiovascular System]] which carry oxygenated [[Blood|blood]] from the [[Heart|heart]] to the rest of the body, with the exception of the Pulmonary Artery, which carries deoxygenated blood from the heart to the [[Lung|lungs]]. There is around 160 major arteries in the human body, and the largest artery is called the Aorta. Artieries branch into [[Arteriole|arterioles]].

Like all major blood vessels, arteries consist of a layer of [[Endothelial cells|endothelial cells]], a layer of [[Smooth muscle cells|smooth muscle cells]] and a layer of [[Collagen|collagen]]. However, arteries are distinguished from other blood vessels because their [[Smooth muscle|smooth muscle]] layer is comperatively thicker than in veins. This is so that the blood, which is pumped from the heart at higher pressure, won't loose the pressure as it reaches the capillaries and allowing for efficient material exchange in the tissues. The total wall thickness of artieries is around 1.0 mm and internal diameter of around 4.0 mm, with the exception of the Aorta, which has wall thickness of 2.0 mm and internal diameter of 25.0 mm <ref>McGrawHill LANGE "Cardiovascular Physiology" 7th Edition D. E. Mohrman, L. J. Heller chapter 1 "Overview of the cardiovascular system</ref>.[[Image:Artery_med.jpg|right|344x229px]] 

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Arteries

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An artery is a blood vessel which carries [[Blood|blood]] away from the [[Heart|heart]]. It is the largest of all types of blood vessel, with strong vascular walls, the strength of which is required to move blood to body tissues which require [[Oxygen|oxygen]].

[[Arterioles|Aterioles are]] small branches of arteries, and control the blood which is sent to [[Capillary|capillaries]]. These are an important part of the arterial system <ref>Guyton, A. and Hall, J. (2011) Textbook of Medical Physiology, 12th edition. Philadelphia: Saunders Elsevier</ref>.

=== Structure ===

The outer layer of an artery is called the tunica adventitia, which comes into contact with surrounding [[Organ|organs]] in order to protect the artery from wear. The inner layer is called a tunica intima has a smooth [[Epithelium|epithelium]] so that friction is reduced which is caused by blood flowing through the artery. The tunica media is the thickest layer and contains [[Smooth muscle|smooth muscle]] for [[Muscle contraction|contraction]], to allow blood to flow through the artery <ref>Rowland, M. (1992) Biology. Surrey: Thomas Nelson and Sons Ltd.</ref>.

In the heart, there are two main arteries; the pulmonary artery and the aorta. The pulmonary artery carries deoxygenated blood to the [[Lungs|lungs]] to become oxygenated (using [[Haemoglobin|haemoglobin]]) to bind [[Oxygen|oxygen]]. [[Image:Artery_med.jpg|right|380x219px]]

The aorta is the largest artery in the body and rises from the left ventricle of the [[Heart|heart]], carrying oxygenated [[Blood|blood]] which can then be used in [[Respiration|respiration]]. 

=== References ===

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File:Artery med.jpg

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170057943: Structure of the artery.

Structure of the artery.

Capillary

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The capillaries are the smallest [[Blood vessels|blood vessels]] in the body, they are one cell thick. These vessels are where the materials in the [[Blood stream|blood stream]] exchange with the [[Interstitial fluid|interstitial fluid]] <ref>Human Physiology, 5th edition, pg 469, Dee Unglaub et al.</ref>. Once the [[Oxygenated|oxygenated]] [[Blood|blood]] leaves the [[Heart|heart]] it is pumped down a series of increasingly smaller vessels until it reaches the capillery network. It is here where [[Oxygen|oxygen]] transfer takes place and also the exchange of other materials. The capillaries are mostly found at the surface of tissues, but are also responsible for the [[Oxygen|oxygen]] supply of [[Organs|organs]], and are therefore found in them. One example is the capillaries that run along the outside of the heart providing it with its oxygen supply. <ref>Human Physiology, 5th edition, pg 471</ref> 

As the capillaries are responsible for the exchange of [[Oxygen|oxygen]], [[Carbon dioxide|CO]][[Carbon dioxide|2]] and other materials the capillary walls must be very thin to provide a suitable exchange interface, it is therefore only made up of a single layer of [[Endothelium cells|endothelium cells]] and this allows easy exchange <ref>Human Physiology, 5th edition, pg 514, Dee Unglaub et al.</ref>.

 [[Image:Capillary_structure.jpg|365x279px]][[Image:Capillaries_network.jpg|382x251px]]

=== References ===

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File:Capillaries network.jpg

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170057943: Network of capillaries.

Network of capillaries.

File:Capillary structure.jpg

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170057943: Structure of the capillary.

Structure of the capillary.

Capillary

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The capillaries are the smallest [[Blood vessels|blood vessels]] in the body, they are one cell thick. These vessels are where the materials in the [[Blood stream|blood stream]] exchange with the [[Interstitial fluid|interstitial fluid]] <ref>Human Physiology, 5th edition, pg 469, Dee Unglaub et al.</ref>. Once the [[Oxygenated|oxygenated]] [[Blood|blood]] leaves the [[Heart|heart]] it is pumped down a series of increasingly smaller vessels until it reaches the capillery network. It is here where [[Oxygen|oxygen]] transfer takes place and also the exchange of other materials. The capillaries are mostly found at the surface of tissues, but are also responsible for the [[Oxygen|oxygen]] supply of [[Organs|organs]], and are therefore found in them. One example is the capillaries that run along the outside of the heart providing it with its oxygen supply. <ref>Human Physiology, 5th edition, pg 471</ref> 

As the capillaries are responsible for the exchange of [[Oxygen|oxygen]], [[Carbon dioxide|CO]][[Carbon dioxide|2]] and other materials the capillary walls must be very thin to provide a suitable exchange interface, it is therefore only made up of a single layer of [[Endothelium cells|endothelium cells]] and this allows easy exchange <ref>Human Physiology, 5th edition, pg 514, Dee Unglaub et al.</ref>.

[[Image:Capillary.gif|459x318px]]

=== References ===

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File:Capillary.gif

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Structure of the capillary

Capillary

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Vein

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Veins are one of the five different types of [[Blood vessels|blood vessels]] that make up the circulatory system. ([[Arteries|Arteries]], [[Arterioles|Arterioles]], [[Venules|Venules]] and [[Capillaries|Capillaries]] being the others)

The majority of veins carry [[Deoxygenated blood|deoxygenated blood]] to the [[Heart|heart]] apart from the [[Pulmonary vein|pulmonary vein]] that carries oxygenated blood to the [[Heart|heart]]. The walls of veins are made of three layers:

#The ''tunica intima ''consisting of a layer of flat [[Endothelial cells|endothelial cells]] overlaying a thin layer of connective tissue.
#The ''tunica media '' consisting of circular layer of [[Smooth muscle|smooth muscle]] containing [[Elastin|elastin]] and [[Collagen|collagen]]. This provides mechanical strength for the vein.
#The ''tunica adventitia ''consisting of a layer of elastic and collagenous fibres fixed along the length of the vessel.<strike></strike> <ref>Pocock G.,Richards C.(2006) Human Physiology: The Basis of Medicine, 3rd Edition, Oxford University Press. Chapter 15 - Pg 264</ref>

The blood pressure in veins in very low, compared to the blood pressure in arteries and therefore veins have valves which stop the backflow of blood. Skeletal muscles also help deoxygenated blood in the vein to get back into the heart by squeezing the vein when they contract. Finally, veins branch into venules which join the capillaries in the body. 

[[Image:Vein_med.jpg|411x254px]]

=== References: ===

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Veins

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Veins are blood vessels which carry [[deoxygenated blood|deoxygenated blood]] from body tissues back to the [[heart|heart]] and [[lungs|lungs]]. In the lungs, the deoxygenated blood is reoxygenated through [[Gaseous exchange|gaseous exchange]] in the [[Alveoli|alveoli]].

=== The structure of Veins ===

Veins are made of thin walls of [[Smooth muscle|smooth muscle]], and [[Endothelial tissue|endothelial tissue]]<ref>https://www.mananatomy.com/basic-anatomy/veins 28/10/2017</ref>. They also contain valves, which assist in moving blood at low pressure against the force of gravity back to the heart, in order to be recirculated through the lungs<ref>https://www.mananatomy.com/basic-anatomy/veins, 28/10/2017</ref>. [[Image:Vein_med.jpg|369x265px]]

=== References ===

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File:Vein med.jpg

2017-12-06T00:15:55Z

170057943: Structure of the vein.

Structure of the vein.

Heart

2017-12-06T00:06:07Z

170057943:

[[Image:Heart.jpg|frame|right|Heart.jpg]]

The heart is the driving force of the [[The Cardiovascular System|Cardiovascular System]] and is found in the human body in the left of the centre (between the [[Lungs|lungs]]). The heart is found between level T5-T9 which is a description of the location of the heart in relation to the levels of the vertebrae<ref>https://web.duke.edu/anatomy/Lab03/Lab4_preLab.html</ref>. The heart's function is to pump oxygenated [[Blood|blood]] around the body through [[Arteries|arteries]] and to accept deoxygenated [[Blood|blood]] through the veins. These two processes are separated into the heart's left and right-hand side respectively<ref>Parker S. (2007) The Human Body Book, 1st edition, London: Dorling Kindersley Limited.</ref> which are subdivided into four chambers<ref name="image">http://www.gknmhospital.org/ctvs/hevaldis.html</ref>. Temporal dispersion of recovery of excitability, measured as the range of local refractory period durations at numerous sites on the atrial and ventricular surfaces, was found to be a direct function of the basic cycle length except at very rapid driving frequencies<ref>Han et al. Temporal Dispersion Of Recovery Of Excitability In Atrium And Ventricle As A Function Of Heart Rate'. American Heart Journal 71.4 (1966): 481-487</ref>.The Upper chambers are known as the [[Atria|Atria]], and the lower chambers are called [[Ventricles|ventricles]]<ref>http://inspirations786.wordpress.com/2011/11/15/four-chambers-of-heart-islamic-polygamy-of-up-to-four-wives-and-miracle-of-allah/</ref>. The wall separating the [[Ventricles|ventricles]] is known as the [[Ventricular septum|ventricular septum]]<ref>http://www.gknmhospital.org/ctvs/hevaldis.html</ref>. The heart is essentially a muscle, known as the cardiac muscle. The ventricles have a thick muscular wall in comparison the atria. However, the left side is thicker than the right side because the left ventricle is required to send the blood all around the body rather than just to the lungs which is what the right ventricle does. The left ventricle requires a greater force, so hence more muscle is required to provide this<ref>http://www.nhlbi.nih.gov/health/health-topics/topics/hhw/anatomy</ref>.

The ventricles are the bottom 2 chambers of the heart with the [[Atria|atria]] being the top two chambers of the heart. The left atrium is located on the left posterior side<ref>http://www.healthline.com/human-body-maps/left-atrium</ref>. Its main roles are to act as a holding chamber for blood returning from the lungs as well as to act as a pump to transport blood to other areas of the heart. The right atrium is located on the top right-hand side next to the superior vena cava. Its primary function is to allow deoxygenated blood to enter vie the inferior and superior vena cava. The right side of the heart then pumps this deoxygenated blood from the heart to the lungs via the pulmonary artery where it then circulates back to the heart by the pulmonary veins, carrying oxygenated blood. Deoxygenated blood enters the right atrium through the inferior and superior vena cava<ref>http://www.healthline.com/human-body-maps/right-atrium</ref>.

The heartbeat is initiated by a bundle of nerves called the SA node, this is located in the right atrium of the heart. The SA node sends out electrical impulses which travel the walls of the atria, causing it to contract, pushing the atrioventricular valves open with the pressure of blood, and allowing blood to travel into the ventricles<ref>Rakesh K.p (2014).Electrical System of the Heart.[http://www.webmd.com/heart/tc/electrical-system-of-the-heart-topic-overview#1]</ref>. As the arteries contract, electrical impulses from the SA node continue to travel to the atrioventricular node (AV node), which is another relay point<ref>Reece, J. B., Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V. and Jackson, R. B.. Campbell Biology. 10th Edition, Boston: Pearson. 2014</ref>. The AV node is located in the wall between the left and right atria, and here, there is a 0.1 second delay before the electrical impulse travels further to the apex of the heart<ref>Reece, J. B., Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V. and Jackson, R. B.. Campbell Biology. 10th Edition, Boston: Pearson. 2014</ref>. This delay ensures that all the blood is emptied out of the atria and into the ventricles for effective ventricular contraction to be carried out<ref>Reece, J. B., Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V. and Jackson, R. B.. Campbell Biology. 10th Edition, Boston: Pearson. 2014</ref>. The electrical impulses travel from the AV node to the atrioventricular bundle, which splits into two branches called bundle branches<ref>Reece, J. B., Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V. and Jackson, R. B.. Campbell Biology. 10th Edition, Boston: Pearson. 2014</ref>. From here, the electrical impulses move down the apex through bundle branches and up the ventricular walls through Purkinje fibres<ref>Reece, J. B., Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V. and Jackson, R. B.. Campbell Biology. 10th Edition, Boston: Pearson. 2014</ref>. These impulses cause the ventricles to contract, pushing blood out from the ventricles, through the pulmonary valves and into the aorta, before bringing it to the rest of the body<ref>Reece, J. B., Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V. and Jackson, R. B.. Campbell Biology. 10th Edition, Boston: Pearson. 2014</ref>.

For the heart to function properly it should be healthy. A healthy heart will circulate blood throughout the body at the right pace providing sufficiently to all parts of the body. This vital organ is unable to perform this necessary function if weakened by disease or injury<ref>http://www.nhlbi.nih.gov/health/health-topics/topics/hhw</ref>.

=== References ===

<references />

Heart

2017-12-05T23:45:34Z

170057943:

[[Image:Heart.jpg|frame|right]]

The heart is the driving force of the [[The Cardiovascular System|Cardiovascular System]] and is found in the human body in the left of the centre (between the [[Lungs|lungs]]). The heart is found between level T5-T9 which is a description of the location of the heart in relation to the levels of the vertebrae<ref>https://web.duke.edu/anatomy/Lab03/Lab4_preLab.html</ref>. The heart's function is to pump oxygenated [[Blood|blood]] around the body through [[Arteries|arteries]] and to accept deoxygenated [[Blood|blood]] through the veins. These two processes are separated into the heart's left and right-hand side respectively<ref>Parker S. (2007) The Human Body Book, 1st edition, London: Dorling Kindersley Limited.</ref> which are subdivided into four chambers<ref name="image">http://www.gknmhospital.org/ctvs/hevaldis.html</ref>. Temporal dispersion of recovery of excitability, measured as the range of local refractory period durations at numerous sites on the atrial and ventricular surfaces, was found to be a direct function of the basic cycle length except at very rapid driving frequencies<ref>Han et al. Temporal Dispersion Of Recovery Of Excitability In Atrium And Ventricle As A Function Of Heart Rate'. American Heart Journal 71.4 (1966): 481-487</ref>.The Upper chambers are known as the [[Atria|Atria]], and the lower chambers are called [[Ventricles|ventricles]]<ref>http://inspirations786.wordpress.com/2011/11/15/four-chambers-of-heart-islamic-polygamy-of-up-to-four-wives-and-miracle-of-allah/</ref>. The wall separating the [[Ventricles|ventricles]] is known as the [[Ventricular septum|ventricular septum]]<ref>http://www.gknmhospital.org/ctvs/hevaldis.html</ref>. The heart is essentially a muscle, known as the cardiac muscle. The ventricles have a thick muscular wall in comparison the atria. However, the left side is thicker than the right side because the left ventricle is required to send the blood all around the body rather than just to the lungs which is what the right ventricle does. The left ventricle requires a greater force, so hence more muscle is required to provide this<ref>http://www.nhlbi.nih.gov/health/health-topics/topics/hhw/anatomy</ref>.

The ventricles are the bottom 2 chambers of the heart with the [[Atria|atria]] being the top two chambers of the heart. The left atrium is located on the left posterior side<ref>http://www.healthline.com/human-body-maps/left-atrium</ref>. Its main roles are to act as a holding chamber for blood returning from the lungs as well as to act as a pump to transport blood to other areas of the heart. The right atrium is located on the top right-hand side next to the superior vena cava. Its primary function if for allowing deoxygenated blood to enter through the inferior and superior vena cava. The right side of the heart then pumps this deoxygenated blood from the heart to the lungs where it then travels to the pulmonary veins around the lungs. Deoxygenated blood enters the right atrium through the inferior and superior vena cava<ref>http://www.healthline.com/human-body-maps/right-atrium</ref>.

The heartbeat is initiated by a bundle of nerves called the SA node, this is in the right atrium of the heart. The SA node sends out electrical impulses which travel the walls of the atria, causing it to contract, pushing the atrioventricular valves open with the pressure of blood, and allowing blood to travel into the ventricles<ref>Rakesh K.p (2014).Electrical System of the Heart.[http://www.webmd.com/heart/tc/electrical-system-of-the-heart-topic-overview#1]</ref>. As the arteries contract, electrical impulses from the SA node continue to travel to the atrioventricular node (AV node), which is another relay point<ref>Reece, J. B., Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V. and Jackson, R. B.. Campbell Biology. 10th Edition, Boston: Pearson. 2014</ref>. The AV node is located in the wall between the left and right atria, and here, there is a 0.1 second delay before the electrical impulse travels further to the apex of the heart<ref>Reece, J. B., Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V. and Jackson, R. B.. Campbell Biology. 10th Edition, Boston: Pearson. 2014</ref>. This delay ensures that all the blood is emptied out of the atria and into the ventricles for effective ventricular contraction to be carried out<ref>Reece, J. B., Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V. and Jackson, R. B.. Campbell Biology. 10th Edition, Boston: Pearson. 2014</ref>. The electrical impulses travel from the AV node to the atrioventricular bundle, which splits into two branches called bundle branches<ref>Reece, J. B., Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V. and Jackson, R. B.. Campbell Biology. 10th Edition, Boston: Pearson. 2014</ref>. From here, the electrical impulses move down the apex through bundle branches and up the ventricular walls through Purkinje fibres<ref>Reece, J. B., Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V. and Jackson, R. B.. Campbell Biology. 10th Edition, Boston: Pearson. 2014</ref>. These impulses cause the ventricles to contract, pushing blood out from the ventricles, through the pulmonary valves and into the aorta, before bringing it to the rest of the body<ref>Reece, J. B., Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V. and Jackson, R. B.. Campbell Biology. 10th Edition, Boston: Pearson. 2014</ref>.

For the heart to function properly it should be healthy. A healthy heart will circulate blood throughout the body at the right pace providing sufficiently to all parts of the body. This vital organ is unable to perform this necessary function if weakened by disease or injury<ref>http://www.nhlbi.nih.gov/health/health-topics/topics/hhw</ref>.

=== References ===

<references />

DNA

2017-12-05T22:24:05Z

170057943:

[[Image:BASE PAIRINGS.png|left|DNA Helix]]

DNA (deoxyribonucleic acid) is the genetic information found in the [[Nucleus|nuclei]] of most [[Organism|organisms]]. It is arranged into structures called [[Chromosome|chromosomes]]. The structure of DNA was first identified as having a [[Double helix|'double-helix' structure]] by [[Watson|Watson]] and [[Crick|Crick]] in 1953. DNA is composed of 4 [[Base|bases]]: the [[Purine|purines]], [[Adenine|adenine]] (A) and [[Guanine|guanine]] (G) and [[Pyrimidine|pyrimidines]] ,[[Thymine|thymine]] (T) and [[Cytosine|cytosine]] (C)<ref>HARTL AND JONES,2009:41, GENETICS : ANALYSIS OF GENES AND GENOMES SEVENTH EDITION.</ref>. These form complementary base pairs of A-T and G-C. DNA also contains a [[Phosphate|phosphate]] group connected to a [[Deoxyribose sugar|deoxyribose sugar]]. The phosphate group is attached to the sugar through a [[Phosphodiester bond|phosphodiester bond]]. Humans have 99.5% similarities with other humans in their DNA.

=== Structure of DNA ===

DNA ([[Deoxyribonucleic acid|deoxyribonucleic acid]]) is a chain of [[Monomers|monomers]] (repeating units) called "[[Nucleotides|nucleotides]]". A [[Nucleotide|nucleotide]] consists of: a [[Deoxyribose|2` deoxyribose sugar]] (A five-carbon [[Pentose sugar|pentose similar]] to that of [[Ribose|ribose]] [[Sugar|sugar found]] in [[RNA|RNA]]. Its chemical formula is C5H10O4), a [[Phosphate group|phosphate group]] (which forms a [[Phosphodiester bond|phosphodiester bond]]: connecting 2 [[Deoxyribose|deoxyribose sugars]] together) and a [[Nitrogenous base|nitrogenous base]] (one from [[Adenine|A]], [[Cytosine|C]], [[Guanine|G or]] [[Thymine|T]], which forms a side chain branching from the 1' carbon of the 2` [[Deoxyribose sugar|deoxyribose sugar]]).

The [[Deoxyribose sugar|deoxyribose sugar]]/[[Phosphate group|phosphate group]] region is regarded as the [[Sugar-phosphate backbone|'backbone']] of DNA strands due to its structural purpose and the sequence of [[DNA bases|bases carries]] the [[Genetics|gentic information]]. In order to produce a double-stranded DNA structure, interactions occur between [[Complementary base pairs|complementary bases.]] The [[Complementary base pairs|complementary base pairs]] in DNA interact with one another via [[Hydrogen bonds|hydrogen bonds]]: A-T interactions consist of 2 intermolecular [[Hydrogen bonds|hydrogen bonds]], whereas G-C interactions consist of 3 intermolecular [[Hydrogen bonds|hydrogen bonds]]. In between these bases are hydrophobic interactions known as van der Waal forces<ref>Lawrie Ryan and Roger Norris, Cambridge International AS and A Level, Second Edition, Cambridge United Kingdom, Latimer Trend 2014</ref>. These interactions form bridges between two DNA chains, thus creating a double-stranded 'ladder' shaped structure. Each strand acts as a template for the other one in DNA replication. DNA is copied into [[MRNA|mRNA]] (messenger RNA) which carries the information from the original DNA template strand to be involved in [[Protein synthesis|protein synthesis]]. The process of DNA being copied into mRNA is termed [[Transcription|transcription]]. The transcribed mRNA is then translated to a [[Polypeptide|polypeptide in]] a process called [[Translation|translation]] by [[TRNA|tRNA]].

In the DNA [[Double helix|double helix]] the strands of the [[Sugar phosphate backbone|backbone]] are closer together on one side of the [[Helix|helix]] than they are on the other. This leads to the formation of major and minor grooves<ref name="null">Boston University (N.d.) 'Major and Minor Grooves', Available at: https://tandem.bu.edu/knex/knex.pdf</ref>. The [[Major groove|major groove]] is much wider than the [[Minor groove|minor groove]] and this means that specific [[DNA-protein interactions|DNA-protein interactions]] can take place on the major groove due to the backbone not being in the way. The specific [[Nucleotides|nucleotides]] that face into the major groove are the N7 and C6 groups of [[Purines|purines]] and the C4 and C5 groups of [[Pyrimidines|pyrimidines]], which accept hydrogen ions from the [[Amino acids|amino acids]] in the [[Proteins|protein]] to form [[Hydrogen bonds|hydrogen bonds]]<ref>Delmar Larsen (N.d.), 'B-Form, A-Form, Z-Form of DNA', Available at: http://biowiki.ucdavis.edu/Genetics/Unit_I%3A_Genes,_Nucleic_Acids,_Genomes_and_Chromosomes/Chapter_2._Structures_of_nucleic_acids/B-Form,_A-Form,_Z-Form_of_DNA, Accessed: 25th November 2014</ref>.

Due to the [[Double helix|double helical]] structure of DNA, the [[Nitrogenous base|nitrogenous bases]] are found on the inside of the structure, forming a [[Hydrophobic|hydrophobic]] interior. The negative charge from the [[Phosphate group|phosphate groups]] gives the [[Sugar phosphate backbone|sugar-phosphate backbone]] of DNA a negative charge, which repels [[Nucleophile|nucleophiles]], including [[Water|water]]. This makes DNA less vulnerable to nucleophilic attack, thus DNA is considered to be a very stable molecule. DNA is much more stable then [[RNA|RNA]] since [[RNA|RNA]] is only single-stranded - the [[Nitrogenous base|nitrogenous bases]] are left exposed to attack by [[Nucleophile|nucleophiles]] on one side.

In 1953, despite many other theories, [[James watson|James Watson]] and [[Francis Crick|Francis Crick]] discovered the true structure of a double stranded DNA molecule to be a 'Double Helix'. This was solved as a result of 'stick-and-ball' models they created, along with utilising the work of fellow scientists [[Rosalind Franklin|Rosalind Franklin]] and [[Maurice Wilkins|Maurice Wilkins]] on [[X-ray crystallography|X-ray crystallography]]<ref>http://nobelprize.org/educational/medicine/dna_double_helix/readmore.html</ref> . The [[X-ray diffraction|X-ray diffraction]] photographs obtained from [[DNA|DNA]] fibres, displayed a unique X-shape, which illustrates a helical stucture, although they indicated a repeating structure of 3.4 Å apart per turn of the helix, each base is rotated 36 degrees from the next one. The diameter of the helix is 23.7 Å. They found that the sugar-phosphate backbone was on the outside and the bases are positioned on the inside of the helix<ref>http://www.chm.bris.ac.uk/motm/dna/dna.htm</ref><ref>J.Berg, J.Tymoczko, L.Stryer;, 113-115, 2012 Freeman; Biochemistry</ref>.

The above information described the B-form of DNA. DNA is also found in A- and Z-forms<ref>Berg, J.M., Tymoczko, J.L. and Stryer, L. (2011) Biochemistry. Seventh Edition. Basingstoke: Basingstoke : Palgrave Macmillan. p20</ref>. When the DNA becomes dehydrated, the A-form is seen<ref>Ferrier, D.R. (2014) Biochemistry. Baltimore, Md. ; London: Baltimore, Md. ; London : Lippincott Williams and Wilkins. p398</ref>. It is also right-handed, but there are 11 bases per turn and the helix is broader. The diameter is 25.5 Å. Another difference is that the tilt of the base pairs increases by 18o, to 19o from perpendicular to the helix axis.

The Z-form is differs far more as it is a left-handed double helix. This form is rarely seen without the help of high salt concentrations<ref>Bae, S., Kim, D., Kim, K.K., Kim, Y.-g., Hohng, S. and Kim, Y.-G. (2011) 'Intrinsic Z- DNA is stabilized by the conformational selection mechanism of Z- DNA-binding proteins', Journal of the American Chemical Society, 133(4), p. 668.</ref>. The bonds are zigzagged as the bonds are alternating anti and syn (whereas A- and B-forms are anti only). The Z-form is narrower, having a diameter of only 18.4 Å, but there is a 3.8 Å rise per base pair. It is thought that transitions between the B and Z forms of DNA may be involved in the regulation of gene regulation.

The DNA of the Indian muntjac which is an Asiatic deer has the longest length (approximately 3 billion nucleotides) among all the known DNA molecules of other organisms<ref name="null">Berg, J.M, Biochemistry, 7th ed, 2012:117</ref>.

DNA is negatively charged due to the negativley charged [[Inorganic phosphate|phosphate ions in]] the [[Sugar-phosphate backbone|sugar-phosphate backbone]] hence it can be used for [[Gel electrophoresis|gel electrophoresis]] to identify different lengths of DNA. The negative charge of the backbone, along with the [[OH group|OH-groups on]] the [[Deoxyribose sugar|deoxyribose sugar]], means that the backbone is [[Hydrophillic|Hydrophillic]] as [[Water|water can]] form [[Hydrogen bonds|hydrogen bonds with]] it. The centre of the DNA molecule is [[Hydrophobic|hydrophobic]] due to the lack of charge in [[DNA bases|DNA bases]]. The [[Hydrophillic|hydrophillic outer]] and [[Hydrophobic|hydrophobic inner]] of the DNA molecule means that it is [[Soluble|soluble in]] water<ref>Ruvolo M, Hartl, DL (2012) Genetics : analysis of genes and genomes, 8th ed, Burlington, MA : Jones and Bartlett Learning</ref>.

=== Replication ===

The double stranded nature of DNA is important to the "semi-conservative replication" method of DNA replication. In this process, the e[[Enzyme|nzyme]] DNA [[DNA helicase|helicase]] unwinds the double helix by breaking the hydrogen bonds between the complementary bases on each strand revealing the 2 seperate strands. On these strands are the revealed bases, which attract complementary bases on free [[Nucleotide|nucleotides]]. The free [[Nucleotide|nucleotides]] are joined together by an e[[Enzyme|nzyme]] [[DNA polymerase|DNA polymerase]]. Deoxynucletotriphosphates (dNTPs) are added onto the 3' hydroxyl group on the growing strand through the 5' triphosphate group on the incoming dNTP in a esterification reaction<ref>Berg JM, Tymoczko JL, Gatto GJ jr, Stryer L. Biochemistry. 8th ed. New York: W.H. Freeman and Company. 2015. P107-111</ref>. The joining of nucleotides forms a new strand of DNA which is identical to the other double strand of DNA, as it uses one of the original strands as a template for replication. Each daughter double strand of DNA is made up of a parent strand and a newly sythesised strand.

Even though both strands in the parental DNA molecule are copied to form identical products, the two strands are copied in a slightly different manner from each other. This is due to the fact that DNA is always synthesised in a 5' to 3' direction. The 3' to 5' strand, known as the leading strand, is copied continuously by DNA polymerase. The other strand is called the lagging strand, as it is replicated more slowly. To replicate the [[Lagging strand|lagging strand]], RNA [[Primers|primers]] are placed on several points along the lagging strand by an enzyme called primase. The gaps on the lagging strand between the RNA primers are replicated by DNA polymerase, and the short fragments of replicated DNA are known as Okazaki fragments. However, in order to complete the replication of the lagging strand, RNA primers must be replaced by DNA sequences. Another DNA polymerase removes the RNA primers and synthesises DNA fragments to replace them. The [[Okizaki fragment|Okazaki fragments]] and the RNA primer replacements are still not joined, so [[DNA ligase|DNA ligase]] comes in an ligates all the fragments of DNA together<ref>Hartl, D. L. and Ruvolo, M., 2012. Genetics: Analysis of Genes and Genomes. 8th ed. Burlington: Jones and; Bartlett Learning. Pages 205-210</ref>.

The theory of [[Semi-conservative replication|semi-conservative replication]] was proven to be correct by the Messelson-Stahl experiment. In this experiment, [[Escherichia coli|''E.coli'']] were grown in a medium containing 15-N for a number of generations. The bacteria were then transferred to a medium containing 14-N. After one replication cycle DNA was extracted from the bacteria and [[Centrifugation|centrifuged]]. The centrifugation separated the DNA by density, producing one band with density between that of 15-N DNA and 14-N DNA. This showed that one strand came from the parent (15-N) and one strand was newly synthesised from free nucleotides (14-N)<ref>Berg J.M, Tymoczko J.L, Stryer L, Biochemistry, 7th ed. 2012:123, New York: W.H Freeman and Company</ref>.

=== References ===

<references />

DNA

2017-12-05T22:20:59Z

170057943:

[[Image:BASE PAIRINGS.png|left|DNA Helix]]

DNA (deoxyribonucleic acid) is the genetic information found in the [[Nucleus|nuclei]] of most [[Organism|organisms]]. It is arranged into structures called [[Chromosome|chromosomes]]. The structure of DNA was first identified as having a [[Double helix|'double-helix' structure]] by [[Watson|Watson]] and [[Crick|Crick]] in 1953. DNA is composed of 4 [[Base|bases]]: the [[Purine|purines]], [[Adenine|adenine]] (A) and [[Guanine|guanine]] (G) and [[Pyrimidine|pyrimidines]] ,[[Thymine|thymine]] (T) and [[Cytosine|cytosine]] (C)<ref>HARTL AND JONES,2009:41, GENETICS : ANALYSIS OF GENES AND GENOMES SEVENTH EDITION.</ref>. These form complementary base pairs of A-T and G-C. DNA also contains a [[Phosphate|phosphate]] group connected to a [[Deoxyribose sugar|deoxyribose sugar]]. The phosphate group is attached to the sugar through a [[Phosphodiester bond|phosphodiester bond]]. Humans have 99.5% similarities with other humans in their DNA.

=== Structure of DNA ===

DNA ([[Deoxyribonucleic acid|deoxyribonucleic acid]]) is a chain of [[Monomers|monomers]] (repeating units) called "[[Nucleotides|nucleotides]]". A [[Nucleotide|nucleotide]] consists of: a [[Deoxyribose|2` deoxyribose sugar]] (A five-carbon [[Pentose sugar|pentose similar]] to that of [[Ribose|ribose]] [[Sugar|sugar found]] in [[RNA|RNA]]. Its chemical formula is C5H10O4), a [[Phosphate group|phosphate group]] (which forms a [[Phosphodiester bond|phosphodiester bond]]: connecting 2 [[Deoxyribose|deoxyribose sugars]] together) and a [[Nitrogenous base|nitrogenous base]] (one from [[Adenine|A]], [[Cytosine|C]], [[Guanine|G or]] [[Thymine|T]], which forms a side chain branching from the 1' carbon of the 2` [[Deoxyribose sugar|deoxyribose sugar]]).

The [[Deoxyribose sugar|deoxyribose sugar]]/[[Phosphate group|phosphate group]] region is regarded as the [[Sugar-phosphate backbone|'backbone']] of DNA strands due to its structural purpose and the sequence of [[DNA bases|bases carries]] the [[Genetics|gentic information]]. In order to produce a double-stranded DNA structure, interactions occur between [[Complementary base pairs|complementary bases.]] The [[Complementary base pairs|complementary base pairs]] in DNA interact with one another via [[Hydrogen bonds|hydrogen bonds]]: A-T interactions consist of 2 intermolecular [[Hydrogen bonds|hydrogen bonds]], whereas G-C interactions consist of 3 intermolecular [[Hydrogen bonds|hydrogen bonds]]. In between these bases are hydrophobic interactions known as van der Waal forces. These interactions form bridges between two DNA chains, thus creating a double-stranded 'ladder' shaped structure. Each strand acts as a template for the other one in DNA replication. DNA is copied into [[MRNA|mRNA]] (messenger RNA) which carries the information from the original DNA template strand to be involved in [[Protein synthesis|protein synthesis]]. The process of DNA being copied into mRNA is termed [[Transcription|transcription]]. The transcribed mRNA is then translated to a [[Polypeptide|polypeptide in]] a process called [[Translation|translation]] by [[TRNA|tRNA]].

In the DNA [[Double helix|double helix]] the strands of the [[Sugar phosphate backbone|backbone]] are closer together on one side of the [[Helix|helix]] than they are on the other. This leads to the formation of major and minor grooves<ref name="null">Boston University (N.d.) 'Major and Minor Grooves', Available at: https://tandem.bu.edu/knex/knex.pdf</ref>. The [[Major groove|major groove]] is much wider than the [[Minor groove|minor groove]] and this means that specific [[DNA-protein interactions|DNA-protein interactions]] can take place on the major groove due to the backbone not being in the way. The specific [[Nucleotides|nucleotides]] that face into the major groove are the N7 and C6 groups of [[Purines|purines]] and the C4 and C5 groups of [[Pyrimidines|pyrimidines]], which accept hydrogen ions from the [[Amino acids|amino acids]] in the [[Proteins|protein]] to form [[Hydrogen bonds|hydrogen bonds]]<ref>Delmar Larsen (N.d.), 'B-Form, A-Form, Z-Form of DNA', Available at: http://biowiki.ucdavis.edu/Genetics/Unit_I%3A_Genes,_Nucleic_Acids,_Genomes_and_Chromosomes/Chapter_2._Structures_of_nucleic_acids/B-Form,_A-Form,_Z-Form_of_DNA, Accessed: 25th November 2014</ref>.

Due to the [[Double helix|double helical]] structure of DNA, the [[Nitrogenous base|nitrogenous bases]] are found on the inside of the structure, forming a [[Hydrophobic|hydrophobic]] interior. The negative charge from the [[Phosphate group|phosphate groups]] gives the [[Sugar phosphate backbone|sugar-phosphate backbone]] of DNA a negative charge, which repels [[Nucleophile|nucleophiles]], including [[Water|water]]. This makes DNA less vulnerable to nucleophilic attack, thus DNA is considered to be a very stable molecule. DNA is much more stable then [[RNA|RNA]] since [[RNA|RNA]] is only single-stranded - the [[Nitrogenous base|nitrogenous bases]] are left exposed to attack by [[Nucleophile|nucleophiles]] on one side.

In 1953, despite many other theories, [[James watson|James Watson]] and [[Francis Crick|Francis Crick]] discovered the true structure of a double stranded DNA molecule to be a 'Double Helix'. This was solved as a result of 'stick-and-ball' models they created, along with utilising the work of fellow scientists [[Rosalind Franklin|Rosalind Franklin]] and [[Maurice Wilkins|Maurice Wilkins]] on [[X-ray crystallography|X-ray crystallography]]<ref>http://nobelprize.org/educational/medicine/dna_double_helix/readmore.html</ref> . The [[X-ray diffraction|X-ray diffraction]] photographs obtained from [[DNA|DNA]] fibres, displayed a unique X-shape, which illustrates a helical stucture, although they indicated a repeating structure of 3.4 Å apart per turn of the helix, each base is rotated 36 degrees from the next one. The diameter of the helix is 23.7 Å. They found that the sugar-phosphate backbone was on the outside and the bases are positioned on the inside of the helix<ref>http://www.chm.bris.ac.uk/motm/dna/dna.htm</ref><ref>J.Berg, J.Tymoczko, L.Stryer;, 113-115, 2012 Freeman; Biochemistry</ref>.

The above information described the B-form of DNA. DNA is also found in A- and Z-forms<ref>Berg, J.M., Tymoczko, J.L. and Stryer, L. (2011) Biochemistry. Seventh Edition. Basingstoke: Basingstoke : Palgrave Macmillan. p20</ref>. When the DNA becomes dehydrated, the A-form is seen<ref>Ferrier, D.R. (2014) Biochemistry. Baltimore, Md. ; London: Baltimore, Md. ; London : Lippincott Williams and Wilkins. p398</ref>. It is also right-handed, but there are 11 bases per turn and the helix is broader. The diameter is 25.5 Å. Another difference is that the tilt of the base pairs increases by 18o, to 19o from perpendicular to the helix axis.

The Z-form is differs far more as it is a left-handed double helix. This form is rarely seen without the help of high salt concentrations<ref>Bae, S., Kim, D., Kim, K.K., Kim, Y.-g., Hohng, S. and Kim, Y.-G. (2011) 'Intrinsic Z- DNA is stabilized by the conformational selection mechanism of Z- DNA-binding proteins', Journal of the American Chemical Society, 133(4), p. 668.</ref>. The bonds are zigzagged as the bonds are alternating anti and syn (whereas A- and B-forms are anti only). The Z-form is narrower, having a diameter of only 18.4 Å, but there is a 3.8 Å rise per base pair. It is thought that transitions between the B and Z forms of DNA may be involved in the regulation of gene regulation.

The DNA of the Indian muntjac which is an Asiatic deer has the longest length (approximately 3 billion nucleotides) among all the known DNA molecules of other organisms<ref name="null">Berg, J.M, Biochemistry, 7th ed, 2012:117</ref>.

DNA is negatively charged due to the negativley charged [[Inorganic phosphate|phosphate ions in]] the [[Sugar-phosphate backbone|sugar-phosphate backbone]] hence it can be used for [[Gel electrophoresis|gel electrophoresis]] to identify different lengths of DNA. The negative charge of the backbone, along with the [[OH group|OH-groups on]] the [[Deoxyribose sugar|deoxyribose sugar]], means that the backbone is [[Hydrophillic|Hydrophillic]] as [[Water|water can]] form [[Hydrogen bonds|hydrogen bonds with]] it. The centre of the DNA molecule is [[Hydrophobic|hydrophobic]] due to the lack of charge in [[DNA bases|DNA bases]]. The [[Hydrophillic|hydrophillic outer]] and [[Hydrophobic|hydrophobic inner]] of the DNA molecule means that it is [[Soluble|soluble in]] water<ref>Ruvolo M, Hartl, DL (2012) Genetics : analysis of genes and genomes, 8th ed, Burlington, MA : Jones and Bartlett Learning</ref>.

=== Replication ===

The double stranded nature of DNA is important to the "semi-conservative replication" method of DNA replication. In this process, the e[[Enzyme|nzyme]] DNA [[DNA helicase|helicase]] unwinds the double helix by breaking the hydrogen bonds between the complementary bases on each strand revealing the 2 seperate strands. On these strands are the revealed bases, which attract complementary bases on free [[Nucleotide|nucleotides]]. The free [[Nucleotide|nucleotides]] are joined together by an e[[Enzyme|nzyme]] [[DNA polymerase|DNA polymerase]]. Deoxynucletotriphosphates (dNTPs) are added onto the 3' hydroxyl group on the growing strand through the 5' triphosphate group on the incoming dNTP in a esterification reaction<ref>Berg JM, Tymoczko JL, Gatto GJ jr, Stryer L. Biochemistry. 8th ed. New York: W.H. Freeman and Company. 2015. P107-111</ref>. The joining of nucleotides forms a new strand of DNA which is identical to the other double strand of DNA, as it uses one of the original strands as a template for replication. Each daughter double strand of DNA is made up of a parent strand and a newly sythesised strand.

Even though both strands in the parental DNA molecule are copied to form identical products, the two strands are copied in a slightly different manner from each other. This is due to the fact that DNA is always synthesised in a 5' to 3' direction. The 3' to 5' strand, known as the leading strand, is copied continuously by DNA polymerase. The other strand is called the lagging strand, as it is replicated more slowly. To replicate the [[Lagging strand|lagging strand]], RNA [[Primers|primers]] are placed on several points along the lagging strand by an enzyme called primase. The gaps on the lagging strand between the RNA primers are replicated by DNA polymerase, and the short fragments of replicated DNA are known as Okazaki fragments. However, in order to complete the replication of the lagging strand, RNA primers must be replaced by DNA sequences. Another DNA polymerase removes the RNA primers and synthesises DNA fragments to replace them. The [[Okizaki fragment|Okazaki fragments]] and the RNA primer replacements are still not joined, so [[DNA ligase|DNA ligase]] comes in an ligates all the fragments of DNA together<ref>Hartl, D. L. and Ruvolo, M., 2012. Genetics: Analysis of Genes and Genomes. 8th ed. Burlington: Jones and; Bartlett Learning. Pages 205-210</ref>.

The theory of [[Semi-conservative replication|semi-conservative replication]] was proven to be correct by the Messelson-Stahl experiment. In this experiment, [[Escherichia coli|''E.coli'']] were grown in a medium containing 15-N for a number of generations. The bacteria were then transferred to a medium containing 14-N. After one replication cycle DNA was extracted from the bacteria and [[Centrifugation|centrifuged]]. The centrifugation separated the DNA by density, producing one band with density between that of 15-N DNA and 14-N DNA. This showed that one strand came from the parent (15-N) and one strand was newly synthesised from free nucleotides (14-N)<ref>Berg J.M, Tymoczko J.L, Stryer L, Biochemistry, 7th ed. 2012:123, New York: W.H Freeman and Company</ref>.

=== References ===

<references />

DNA

2017-12-05T22:20:23Z

170057943:

[[Image:BASE PAIRINGS.png|left|DNA Helix]]

DNA (deoxyribonucleic acid) is the genetic information found in the [[Nucleus|nuclei]] of most [[Organism|organisms]]. It is arranged into structures called [[Chromosome|chromosomes]]. The structure of DNA was first identified as having a [[Double helix|'double-helix' structure]] by [[Watson|Watson]] and [[Crick|Crick]] in 1953. DNA is composed of 4 [[Base|bases]]: the [[Purine|purines]], [[Adenine|adenine]] (A) and [[Guanine|guanine]] (G) and [[Pyrimidine|pyrimidines]] ,[[Thymine|thymine]] (T) and [[Cytosine|cytosine]] (C)<ref>HARTL AND JONES,2009:41, GENETICS : ANALYSIS OF GENES AND GENOMES SEVENTH EDITION.</ref>. These form complementary base pairs of A-T and G-C. DNA also contains a [[Phosphate|phosphate]] group connected to a [[Deoxyribose sugar|deoxyribose sugar]]. The phosphate group is attached to the sugar through a [[Phosphodiester bond|phosphodiester bond]]. Humans have 99.5% similarities with other humans in their DNA.

=== Structure of DNA ===

DNA ([[Deoxyribonucleic acid|deoxyribonucleic acid]]) is a chain of [[Monomers|monomers]] (repeating units) called "[[Nucleotides|nucleotides]]". A [[Nucleotide|nucleotide]] consists of: a [[Deoxyribose|2` deoxyribose sugar]] (A five-carbon [[Pentose sugar|pentose similar]] to that of [[Ribose|ribose]] [[Sugar|sugar found]] in [[RNA|RNA]]. Its chemical formula is C5H10O4), a [[Phosphate group|phosphate group]] (which forms a [[Phosphodiester bond|phosphodiester bond]]: connecting 2 [[Deoxyribose|deoxyribose sugars]] together) and a [[Nitrogenous base|nitrogenous base]] (one from [[Adenine|A]], [[Cytosine|C]], [[Guanine|G or]] [[Thymine|T]], which forms a side chain branching from the 1' carbon of the 2` [[Deoxyribose sugar|deoxyribose sugar]]).

The [[Deoxyribose sugar|deoxyribose sugar]]/[[Phosphate group|phosphate group]] region is regarded as the [[Sugar-phosphate backbone|'backbone']] of DNA strands due to its structural purpose and the sequence of [[DNA bases|bases carries]] the [[Genetics|gentic information]]. In order to produce a double-stranded DNA structure, interactions occur between [[Complementary base pairs|complementary bases.]] The [[Complementary base pairs|complementary base pairs]] in DNA interact with one another via [[Hydrogen bonds|hydrogen bonds]]: A-T interactions consist of 2 intermolecular [[Hydrogen bonds|hydrogen bonds]], whereas G-C interactions consist of 3 intermolecular [[Hydrogen bonds|hydrogen bonds]]. In between these bases are hydrophobic interactions known as van der Waal forces.<references /> These interactions form bridges between two DNA chains, thus creating a double-stranded 'ladder' shaped structure. Each strand acts as a template for the other one in DNA replication. DNA is copied into [[MRNA|mRNA]] (messenger RNA) which carries the information from the original DNA template strand to be involved in [[Protein synthesis|protein synthesis]]. The process of DNA being copied into mRNA is termed [[Transcription|transcription]]. The transcribed mRNA is then translated to a [[Polypeptide|polypeptide in]] a process called [[Translation|translation]] by [[TRNA|tRNA]].

In the DNA [[Double helix|double helix]] the strands of the [[Sugar phosphate backbone|backbone]] are closer together on one side of the [[Helix|helix]] than they are on the other. This leads to the formation of major and minor grooves<ref name="null">Boston University (N.d.) 'Major and Minor Grooves', Available at: https://tandem.bu.edu/knex/knex.pdf</ref>. The [[Major groove|major groove]] is much wider than the [[Minor groove|minor groove]] and this means that specific [[DNA-protein interactions|DNA-protein interactions]] can take place on the major groove due to the backbone not being in the way. The specific [[Nucleotides|nucleotides]] that face into the major groove are the N7 and C6 groups of [[Purines|purines]] and the C4 and C5 groups of [[Pyrimidines|pyrimidines]], which accept hydrogen ions from the [[Amino acids|amino acids]] in the [[Proteins|protein]] to form [[Hydrogen bonds|hydrogen bonds]]<ref>Delmar Larsen (N.d.), 'B-Form, A-Form, Z-Form of DNA', Available at: http://biowiki.ucdavis.edu/Genetics/Unit_I%3A_Genes,_Nucleic_Acids,_Genomes_and_Chromosomes/Chapter_2._Structures_of_nucleic_acids/B-Form,_A-Form,_Z-Form_of_DNA, Accessed: 25th November 2014</ref>.

Due to the [[Double helix|double helical]] structure of DNA, the [[Nitrogenous base|nitrogenous bases]] are found on the inside of the structure, forming a [[Hydrophobic|hydrophobic]] interior. The negative charge from the [[Phosphate group|phosphate groups]] gives the [[Sugar phosphate backbone|sugar-phosphate backbone]] of DNA a negative charge, which repels [[Nucleophile|nucleophiles]], including [[Water|water]]. This makes DNA less vulnerable to nucleophilic attack, thus DNA is considered to be a very stable molecule. DNA is much more stable then [[RNA|RNA]] since [[RNA|RNA]] is only single-stranded - the [[Nitrogenous base|nitrogenous bases]] are left exposed to attack by [[Nucleophile|nucleophiles]] on one side.

In 1953, despite many other theories, [[James watson|James Watson]] and [[Francis Crick|Francis Crick]] discovered the true structure of a double stranded DNA molecule to be a 'Double Helix'. This was solved as a result of 'stick-and-ball' models they created, along with utilising the work of fellow scientists [[Rosalind Franklin|Rosalind Franklin]] and [[Maurice Wilkins|Maurice Wilkins]] on [[X-ray crystallography|X-ray crystallography]]<ref>http://nobelprize.org/educational/medicine/dna_double_helix/readmore.html</ref> . The [[X-ray diffraction|X-ray diffraction]] photographs obtained from [[DNA|DNA]] fibres, displayed a unique X-shape, which illustrates a helical stucture, although they indicated a repeating structure of 3.4 Å apart per turn of the helix, each base is rotated 36 degrees from the next one. The diameter of the helix is 23.7 Å. They found that the sugar-phosphate backbone was on the outside and the bases are positioned on the inside of the helix<ref>http://www.chm.bris.ac.uk/motm/dna/dna.htm</ref><ref>J.Berg, J.Tymoczko, L.Stryer;, 113-115, 2012 Freeman; Biochemistry</ref>.

The above information described the B-form of DNA. DNA is also found in A- and Z-forms<ref>Berg, J.M., Tymoczko, J.L. and Stryer, L. (2011) Biochemistry. Seventh Edition. Basingstoke: Basingstoke : Palgrave Macmillan. p20</ref>. When the DNA becomes dehydrated, the A-form is seen<ref>Ferrier, D.R. (2014) Biochemistry. Baltimore, Md. ; London: Baltimore, Md. ; London : Lippincott Williams and Wilkins. p398</ref>. It is also right-handed, but there are 11 bases per turn and the helix is broader. The diameter is 25.5 Å. Another difference is that the tilt of the base pairs increases by 18o, to 19o from perpendicular to the helix axis.

The Z-form is differs far more as it is a left-handed double helix. This form is rarely seen without the help of high salt concentrations<ref>Bae, S., Kim, D., Kim, K.K., Kim, Y.-g., Hohng, S. and Kim, Y.-G. (2011) 'Intrinsic Z- DNA is stabilized by the conformational selection mechanism of Z- DNA-binding proteins', Journal of the American Chemical Society, 133(4), p. 668.</ref>. The bonds are zigzagged as the bonds are alternating anti and syn (whereas A- and B-forms are anti only). The Z-form is narrower, having a diameter of only 18.4 Å, but there is a 3.8 Å rise per base pair. It is thought that transitions between the B and Z forms of DNA may be involved in the regulation of gene regulation.

The DNA of the Indian muntjac which is an Asiatic deer has the longest length (approximately 3 billion nucleotides) among all the known DNA molecules of other organisms<ref name="null">Berg, J.M, Biochemistry, 7th ed, 2012:117</ref>.

DNA is negatively charged due to the negativley charged [[Inorganic phosphate|phosphate ions in]] the [[Sugar-phosphate backbone|sugar-phosphate backbone]] hence it can be used for [[Gel electrophoresis|gel electrophoresis]] to identify different lengths of DNA. The negative charge of the backbone, along with the [[OH group|OH-groups on]] the [[Deoxyribose sugar|deoxyribose sugar]], means that the backbone is [[Hydrophillic|Hydrophillic]] as [[Water|water can]] form [[Hydrogen bonds|hydrogen bonds with]] it. The centre of the DNA molecule is [[Hydrophobic|hydrophobic]] due to the lack of charge in [[DNA bases|DNA bases]]. The [[Hydrophillic|hydrophillic outer]] and [[Hydrophobic|hydrophobic inner]] of the DNA molecule means that it is [[Soluble|soluble in]] water<ref>Ruvolo M, Hartl, DL (2012) Genetics : analysis of genes and genomes, 8th ed, Burlington, MA : Jones and Bartlett Learning</ref>.

=== Replication ===

The double stranded nature of DNA is important to the "semi-conservative replication" method of DNA replication. In this process, the e[[Enzyme|nzyme]] DNA [[DNA helicase|helicase]] unwinds the double helix by breaking the hydrogen bonds between the complementary bases on each strand revealing the 2 seperate strands. On these strands are the revealed bases, which attract complementary bases on free [[Nucleotide|nucleotides]]. The free [[Nucleotide|nucleotides]] are joined together by an e[[Enzyme|nzyme]] [[DNA polymerase|DNA polymerase]]. Deoxynucletotriphosphates (dNTPs) are added onto the 3' hydroxyl group on the growing strand through the 5' triphosphate group on the incoming dNTP in a esterification reaction<ref>Berg JM, Tymoczko JL, Gatto GJ jr, Stryer L. Biochemistry. 8th ed. New York: W.H. Freeman and Company. 2015. P107-111</ref>. The joining of nucleotides forms a new strand of DNA which is identical to the other double strand of DNA, as it uses one of the original strands as a template for replication. Each daughter double strand of DNA is made up of a parent strand and a newly sythesised strand.

Even though both strands in the parental DNA molecule are copied to form identical products, the two strands are copied in a slightly different manner from each other. This is due to the fact that DNA is always synthesised in a 5' to 3' direction. The 3' to 5' strand, known as the leading strand, is copied continuously by DNA polymerase. The other strand is called the lagging strand, as it is replicated more slowly. To replicate the [[Lagging strand|lagging strand]], RNA [[Primers|primers]] are placed on several points along the lagging strand by an enzyme called primase. The gaps on the lagging strand between the RNA primers are replicated by DNA polymerase, and the short fragments of replicated DNA are known as Okazaki fragments. However, in order to complete the replication of the lagging strand, RNA primers must be replaced by DNA sequences. Another DNA polymerase removes the RNA primers and synthesises DNA fragments to replace them. The [[Okizaki fragment|Okazaki fragments]] and the RNA primer replacements are still not joined, so [[DNA ligase|DNA ligase]] comes in an ligates all the fragments of DNA together<ref>Hartl, D. L. and Ruvolo, M., 2012. Genetics: Analysis of Genes and Genomes. 8th ed. Burlington: Jones and; Bartlett Learning. Pages 205-210</ref>.

The theory of [[Semi-conservative replication|semi-conservative replication]] was proven to be correct by the Messelson-Stahl experiment. In this experiment, [[Escherichia coli|''E.coli'']] were grown in a medium containing 15-N for a number of generations. The bacteria were then transferred to a medium containing 14-N. After one replication cycle DNA was extracted from the bacteria and [[Centrifugation|centrifuged]]. The centrifugation separated the DNA by density, producing one band with density between that of 15-N DNA and 14-N DNA. This showed that one strand came from the parent (15-N) and one strand was newly synthesised from free nucleotides (14-N)<ref>Berg J.M, Tymoczko J.L, Stryer L, Biochemistry, 7th ed. 2012:123, New York: W.H Freeman and Company</ref>.

=== References ===

<references />