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96-538: The cause of WPW is typically unknown and is likely due to a combination of chance and genetic factors. A small number of cases are due to a mutation of the PRKAG2 gene which may be inherited in an autosomal dominant fashion. The underlying mechanism involves an accessory electrical conduction pathway between the atria and the ventricles . It is associated with other conditions such as Ebstein anomaly and hypokalemic periodic paralysis . The diagnosis of WPW occurs with

192-433: A butterfly may produce offspring with new mutations. The majority of these mutations will have no effect; but one might change the colour of one of the butterfly's offspring, making it harder (or easier) for predators to see. If this color change is advantageous, the chances of this butterfly's surviving and producing its own offspring are a little better, and over time the number of butterflies with this mutation may form

288-406: A combination of palpitations and when an electrocardiogram (ECG) show a short PR interval and a delta wave. It is a type of pre-excitation syndrome . WPW syndrome may be monitored or treated with either medications or an ablation (destroying the tissues) such as with radiofrequency catheter ablation . It affects between 0.1 and 0.3% in the population. The risk of death in those without symptoms

384-729: A group of expert geneticists and biologists , who have the responsibility of establishing the standard or so-called "consensus" sequence. This step requires a tremendous scientific effort. Once the consensus sequence is known, the mutations in a genome can be pinpointed, described, and classified. The committee of the Human Genome Variation Society (HGVS) has developed the standard human sequence variant nomenclature, which should be used by researchers and DNA diagnostic centers to generate unambiguous mutation descriptions. In principle, this nomenclature can also be used to describe mutations in other organisms. The nomenclature specifies

480-413: A healthy, uncontaminated cell. Naturally occurring oxidative DNA damage is estimated to occur 10,000 times per cell per day in humans and 100,000 times per cell per day in rats . Spontaneous mutations can be characterized by the specific change: There is increasing evidence that the majority of spontaneously arising mutations are due to error-prone replication ( translesion synthesis ) past DNA damage in

576-429: A history of syncope, but risk stratification is best performed by assessing how frequently a pathway can conduct impulse to the ventricles, usually via programmed electrical stimulation (PES) in the cardiac electrophysiology laboratory. This is an invasive but generally low-risk procedure during which the atria are stimulated to try to induce tachycardia. If a tachycardia involving the accessory pathway can be triggered,

672-1018: A larger percentage of the population. Neutral mutations are defined as mutations whose effects do not influence the fitness of an individual. These can increase in frequency over time due to genetic drift . It is believed that the overwhelming majority of mutations have no significant effect on an organism's fitness. Also, DNA repair mechanisms are able to mend most changes before they become permanent mutations, and many organisms have mechanisms, such as apoptotic pathways , for eliminating otherwise-permanently mutated somatic cells . Beneficial mutations can improve reproductive success. Four classes of mutations are (1) spontaneous mutations (molecular decay), (2) mutations due to error-prone replication bypass of naturally occurring DNA damage (also called error-prone translesion synthesis), (3) errors introduced during DNA repair, and (4) induced mutations caused by mutagens . Scientists may sometimes deliberately introduce mutations into cells or research organisms for

768-497: A major source of raw material for evolving new genes, with tens to hundreds of genes duplicated in animal genomes every million years. Most genes belong to larger gene families of shared ancestry, detectable by their sequence homology . Novel genes are produced by several methods, commonly through the duplication and mutation of an ancestral gene, or by recombining parts of different genes to form new combinations with new functions. Here, protein domains act as modules, each with

864-502: A minor effect. For instance, human height is determined by hundreds of genetic variants ("mutations") but each of them has a very minor effect on height, apart from the impact of nutrition . Height (or size) itself may be more or less beneficial as the huge range of sizes in animal or plant groups shows. Attempts have been made to infer the distribution of fitness effects (DFE) using mutagenesis experiments and theoretical models applied to molecular sequence data. DFE, as used to determine

960-565: A number of beneficial mutations as well. For instance, in a screen of all gene deletions in E. coli , 80% of mutations were negative, but 20% were positive, even though many had a very small effect on growth (depending on condition). Gene deletions involve removal of whole genes, so that point mutations almost always have a much smaller effect. In a similar screen in Streptococcus pneumoniae , but this time with transposon insertions, 76% of insertion mutants were classified as neutral, 16% had

1056-404: A particular and independent function, that can be mixed together to produce genes encoding new proteins with novel properties. For example, the human eye uses four genes to make structures that sense light: three for cone cell or colour vision and one for rod cell or night vision; all four arose from a single ancestral gene. Another advantage of duplicating a gene (or even an entire genome)

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1152-413: A regular narrow complex tachycardia may be managed similarly to other regular narrow complex supraventricular tachycardias: first with vagal maneuvers followed by a trial of adenosine (first-line therapy). The 2015 ACC/AHA/HRS guidelines recommend beta-blockers or calcium channel blockers as second-line agents, electric cardioversion is reserved for refractory arrhythmias. However, if there is any doubt about

1248-460: A significantly higher rate than the AV node. For instance, in the example above, if an individual had an atrial rate of 300 beats per minute, the accessory bundle may conduct all the electrical impulses from the atria to the ventricles, causing the ventricles to contract at 300 beats per minute. Extremely rapid heart rates such as this may result in hemodynamic instability or cardiogenic shock . In some cases,

1344-486: A significantly reduced fitness, but 6% were advantageous. This classification is obviously relative and somewhat artificial: a harmful mutation can quickly turn into a beneficial mutations when conditions change. Also, there is a gradient from harmful/beneficial to neutral, as many mutations may have small and mostly neglectable effects but under certain conditions will become relevant. Also, many traits are determined by hundreds of genes (or loci), so that each locus has only

1440-468: A whole. Changes in DNA caused by mutation in a coding region of DNA can cause errors in protein sequence that may result in partially or completely non-functional proteins. Each cell, in order to function correctly, depends on thousands of proteins to function in the right places at the right times. When a mutation alters a protein that plays a critical role in the body, a medical condition can result. One study on

1536-473: Is a condition that is difficult to fully reverse even with an early diagnosis. However, early initiation of treatment may improve outcomes. Care should also be directed to any other organs that are affected by this lack of blood flow (e.g., dialysis for the kidneys, mechanical ventilation for lung dysfunction). Mortality rates for cardiogenic shock are high but have been decreasing in the United States. This

1632-415: Is a major pathway for repairing double-strand breaks. NHEJ involves removal of a few nucleotides to allow somewhat inaccurate alignment of the two ends for rejoining followed by addition of nucleotides to fill in gaps. As a consequence, NHEJ often introduces mutations. Induced mutations are alterations in the gene after it has come in contact with mutagens and environmental causes. Induced mutations on

1728-585: Is a slurred upstroke in the QRS complex that is associated with a short PR interval. The short PR interval and slurring of the QRS complex are reflective of the impulse making it to the ventricles early (via the accessory pathway) without the usual delay experienced in the AV node. If a person with WPW experiences episodes of atrial fibrillation, the ECG shows a rapid polymorphic wide-complex tachycardia (without torsades de pointes ). This combination of atrial fibrillation and WPW

1824-465: Is about 0.5% per year in children and 0.1% per year in adults. In some cases, non-invasive monitoring may help to more carefully risk stratify patients into a lower risk category. In those without symptoms ongoing observation may be reasonable. In those with WPW complicated by atrial fibrillation , cardioversion or the medication procainamide may be used. The condition is named after Louis Wolff , John Parkinson , and Paul Dudley White who described

1920-468: Is accepted that the majority of mutations are neutral or deleterious, with advantageous mutations being rare; however, the proportion of types of mutations varies between species. This indicates two important points: first, the proportion of effectively neutral mutations is likely to vary between species, resulting from dependence on effective population size ; second, the average effect of deleterious mutations varies dramatically between species. In addition,

2016-444: Is called a de novo mutation . A change in the genetic structure that is not inherited from a parent, and also not passed to offspring, is called a somatic mutation . Somatic mutations are not inherited by an organism's offspring because they do not affect the germline . However, they are passed down to all the progeny of a mutated cell within the same organism during mitosis. A major section of an organism therefore might carry

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2112-400: Is capable of slowing the rate of conduction of electrical impulses to the ventricles, whereas the bundle of Kent lacks this capability. When an aberrant electrical connection is made via the bundle of Kent, tachydysrhythmias may therefore result. WPW is commonly diagnosed on the basis of the electrocardiogram in an asymptomatic individual. In this case, it is manifested as a delta wave, which

2208-507: Is considered dangerous, and most antiarrhythmic drugs are contraindicated. When an individual is in normal sinus rhythm , the ECG characteristics of WPW are a short PR interval (less than 120 milliseconds in duration), widened QRS complex (greater than 120 milliseconds in duration) with slurred upstroke of the QRS complex, and secondary repolarization changes (reflected in ST segment - T wave changes). In individuals with WPW, electrical activity that

2304-427: Is due to damage to the heart muscle , most often from a heart attack or myocardial contusion . Other causes include abnormal heart rhythms , cardiomyopathy , heart valve problems, ventricular outflow obstruction (i.e. systolic anterior motion in hypertrophic cardiomyopathy ), or ventriculoseptal defects. It can also be caused by a sudden decompressurization (e.g. in an aircraft), where air bubbles are released into

2400-417: Is eponymously named for British physiologist Albert Frank Stanley Kent (1863–1958), who described lateral branches in the atrioventricular groove of the monkey heart (erroneously believing these constituted the normal atrioventricular conduction system). In 1915, Frank Norman Wilson (1890–1952) became the first to describe the condition later called Wolff–Parkinson–White syndrome. Alfred M. Wedd (1887–1967)

2496-478: Is important in animals that have a dedicated germline to produce reproductive cells. However, it is of little value in understanding the effects of mutations in plants, which lack a dedicated germline. The distinction is also blurred in those animals that reproduce asexually through mechanisms such as budding , because the cells that give rise to the daughter organisms also give rise to that organism's germline. A new germline mutation not inherited from either parent

2592-405: Is important to note, however, that none of these devices are permanent solutions but rather are a bridge to a more definitive therapy such as a heart transplantion . An intra-aortic balloon pump is a device placed by a cardiac surgeon into the descending aorta . It consists of a small balloon filled with helium that helps the heart to pump blood by inflating during diastole (the resting phase of

2688-445: Is in a coding or non-coding region . Mutations in the non-coding regulatory sequences of a gene, such as promoters, enhancers, and silencers, can alter levels of gene expression, but are less likely to alter the protein sequence. Mutations within introns and in regions with no known biological function (e.g. pseudogenes , retrotransposons ) are generally neutral , having no effect on phenotype – though intron mutations could alter

2784-459: Is initiated in the SA node travels through the accessory pathway, as well as through the AV node to activate the ventricles via both pathways. Since the accessory pathway does not have the impulse slowing properties of the AV node, the electrical impulse first activates the ventricles via the accessory pathway, and immediately afterwards via the AV node. This gives the short PR interval and slurred upstroke of

2880-429: Is likely due to its rapid identification and treatment in recent decades. Some studies have suggested that this is possibly related to new treatment advances. Nonetheless, the mortality rates remain high and multi-organ failure in addition to cardiogenic shock is associated with higher rates of mortality. The presentation is the following: Cardiogenic shock is caused by the failure of the heart to pump effectively. It

2976-439: Is linked to ventricular fibrillation, and thus may be worse than procainamide. AV node blockers should be avoided in atrial fibrillation and atrial flutter with WPW or history of it; this includes adenosine , diltiazem , verapamil , other calcium channel blockers , and beta blockers . They can exacerbate the syndrome by blocking the heart's normal electrical pathway (therefore favoring 1:1 atrial to ventricle conduction through

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3072-521: Is most commonly precipitated by a heart attack . Treatment of cardiogenic shock depends on the cause with the initial goals to improve blood flow to the body. If cardiogenic shock is due to a heart attack, attempts to open the heart's arteries may help. Certain medications, such as dobutamine and milrinone, improve the heart's ability to contract and can also be used. When these measures fail, more advanced options such as mechanical support devices or heart transplantation can be pursued. Cardiogenic shock

3168-464: Is sometimes associated with Leber's hereditary optic neuropathy , a form of mitochondrial disease . WPW carries a small risk of sudden death, presumably due to rapidly conducted atrial fibrillation causing ventricular fibrillation. While the overall risk is approximately 2.4 per 1000 person years, the risk in an individual is dependent on the properties of the accessory pathway causing pre-excitation. A higher risk accessory pathway may be suggested by

3264-406: Is that this increases engineering redundancy ; this allows one gene in the pair to acquire a new function while the other copy performs the original function. Other types of mutation occasionally create new genes from previously noncoding DNA . Changes in chromosome number may involve even larger mutations, where segments of the DNA within chromosomes break and then rearrange. For example, in

3360-422: Is that when they move within a genome, they can mutate or delete existing genes and thereby produce genetic diversity. Nonlethal mutations accumulate within the gene pool and increase the amount of genetic variation. The abundance of some genetic changes within the gene pool can be reduced by natural selection , while other "more favorable" mutations may accumulate and result in adaptive changes. For example,

3456-429: Is unclear whether invasive risk stratification (with PES) is necessary in the asymptomatic individual. While some groups advocate PES for risk stratification in all individuals under 35 years old, others only offer it to individuals who have history suggestive of a tachydysrhythmia, since the incidence of sudden cardiac death is so low (less than 0.6% in some reports). Other methods of risk stratification include observing

3552-530: The Homininae , two chromosomes fused to produce human chromosome 2 ; this fusion did not occur in the lineage of the other apes , and they retain these separate chromosomes. In evolution, the most important role of such chromosomal rearrangements may be to accelerate the divergence of a population into new species by making populations less likely to interbreed, thereby preserving genetic differences between these populations. Sequences of DNA that can move about

3648-429: The endocardium at the apex of the heart, then finally to the ventricular myocardium . The AV node serves an important function as a "gatekeeper", limiting the electrical activity that reaches the ventricles. In situations where the atria generate excessively rapid electrical activity (such as atrial fibrillation or atrial flutter ), the AV node limits the number of signals conducted to the ventricles. For example, if

3744-409: The product of a gene , or prevent the gene from functioning properly or completely. Mutations can also occur in non-genic regions . A 2007 study on genetic variations between different species of Drosophila suggested that, if a mutation changes a protein produced by a gene, the result is likely to be harmful, with an estimated 70% of amino acid polymorphisms that have damaging effects, and

3840-429: The "Delicious" apple and the "Washington" navel orange . Human and mouse somatic cells have a mutation rate more than ten times higher than the germline mutation rate for both species; mice have a higher rate of both somatic and germline mutations per cell division than humans. The disparity in mutation rate between the germline and somatic tissues likely reflects the greater importance of genome maintenance in

3936-470: The DFE also differs between coding regions and noncoding regions , with the DFE of noncoding DNA containing more weakly selected mutations. In multicellular organisms with dedicated reproductive cells , mutations can be subdivided into germline mutations , which can be passed on to descendants through their reproductive cells, and somatic mutations (also called acquired mutations), which involve cells outside

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4032-474: The DFE of advantageous mutations may lead to increased ability to predict the evolutionary dynamics. Theoretical work on the DFE for advantageous mutations has been done by John H. Gillespie and H. Allen Orr . They proposed that the distribution for advantageous mutations should be exponential under a wide range of conditions, which, in general, has been supported by experimental studies, at least for strongly selected advantageous mutations. In general, it

4128-422: The DNA. Ordinarily, a mutation cannot be recognized by enzymes once the base change is present in both DNA strands, and thus a mutation is not ordinarily repaired. At the cellular level, mutations can alter protein function and regulation. Unlike DNA damages, mutations are replicated when the cell replicates. At the level of cell populations, cells with mutations will increase or decrease in frequency according to

4224-434: The ECG findings in 1930. People with WPW are usually asymptomatic when not having a fast heart rate. However, individuals may experience palpitations , dizziness , shortness of breath , or infrequently syncope (fainting or near fainting) during episodes of supraventricular tachycardia . WPW is also associated with a very small risk of sudden death due to more dangerous heart rhythm disturbances. Electrical activity in

4320-497: The Impella devices being some of the most common. This device is placed by a cardiac surgeon into the left ventricle of the heart and essentially acts as a pump, drawing blood from the left ventricle and pushing it out into the aorta so that it could be delivered to the rest of the body. Unlike intra-aortic balloon pumps, the Impella acts independently from the cardiac cycle. It can be adjusted to pump at faster rates to take blood out of

4416-638: The QRS complex known as the delta wave. In case of type A pre-excitation (left atrioventricular connections), a positive R wave is seen in V1 ("positive delta") on the precordial leads of the electrocardiogram, while in type B pre-excitation (right atrioventricular connections), a predominantly negative delta wave is seen in lead V1 ("negative delta"). People with WPW may have more than one accessory pathway – in some cases, as many as eight abnormal pathways have been found. This has been seen in individuals with Ebstein's anomaly . Wolff–Parkinson–White syndrome

4512-505: The accessory pathway. According to the ACLS protocol, people with WPW who are experiencing rapid abnormal heart rhythms ( tachydysrhythmias ) may require synchronized electrical cardioversion if they are demonstrating severe signs or symptoms (for example, low blood pressure or lethargy with altered mental status ). If they are relatively stable, medication may be used. WPW pattern with hemodynamically stability and orthodromic AVRT leading to

4608-492: The adaptation rate of organisms, they have some times been named as adaptive mutagenesis mechanisms, and include the SOS response in bacteria, ectopic intrachromosomal recombination and other chromosomal events such as duplications. The sequence of a gene can be altered in a number of ways. Gene mutations have varying effects on health depending on where they occur and whether they alter the function of essential proteins. Mutations in

4704-518: The appearance of skin cancer during one's lifetime is induced by overexposure to UV radiation that causes mutations in the cellular and skin genome. There is a widespread assumption that mutations are (entirely) "random" with respect to their consequences (in terms of probability). This was shown to be wrong as mutation frequency can vary across regions of the genome, with such DNA repair - and mutation-biases being associated with various factors. For instance, Monroe and colleagues demonstrated that—in

4800-437: The atria to electrical activation of the ventricles ), which is usually shortened to less than 120 milliseconds in duration. Individuals with WPW have an accessory pathway that communicates between the atria and the ventricles, in addition to the AV node. This accessory pathway is known as the bundle of Kent. This accessory pathway does not share the rate-slowing properties of the AV node and may conduct electrical activity at

4896-491: The atria are electrically activated at 300 beats per minute, half those electrical impulses may be blocked by the AV node, so that the ventricles are stimulated at only 150 beats per minute – resulting in a pulse of 150 beats per minute. Another important property of the AV node is that it slows down individual electrical impulses. This is manifested on the electrocardiogram as the PR interval (the time from electrical activation of

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4992-413: The blood cells) as well as the formation of lesions on the heart valve, namely the mitral or aortic valves . Contraindications to an Impella device insertion include aortic dissection, the presence of a mechanical aortic valve, and the presence of a blood clot in the left ventricle. Venous-arterial extra-corporeal membrane oxygenation is a circuit support system that is meant to replace the function of

5088-399: The bloodstream ( Henry's law ), causing heart failure . An electrocardiogram helps to establish the exact diagnosis and guides treatment, it may reveal: Echocardiography may show poor ventricular function, signs of PED, rupture of the interventricular septum , an obstructed outflow tract or cardiomyopathy. The Swan–Ganz catheter or pulmonary artery catheter may assist in

5184-448: The cardiac cycle) and deflating during systole (the contracting phase of the cardiac cycle). Intra-aortic balloon pumps do not directly increase cardiac output, but importantly, they decrease the amount of pressure that the heart has to pump against, thereby allowing for more blood flow and oxygen to be delivered to the heart muscles. Intra-aortic balloon pumps have been around for several decades and are most commonly used first-line of

5280-673: The cardiologist can then assess how rapidly the accessory pathway is able to conduct. The faster it can conduct, the higher the likelihood the accessory pathway can conduct fast enough to trigger a lethal tachycardia. High-risk features that may be present during PES include an effective refractory period of the accessory pathway less than 250 ms, multiple pathways, septal location of pathway, and inducibility of supraventricular tachycardia ( AVRT , atrial fibrillation). Individuals with any of these high-risk features are generally considered at increased risk for SCD or symptomatic tachycardia, and should be treated accordingly (i.e.: catheter ablation). It

5376-439: The category of by effect on function, but depending on the specificity of the change the mutations listed below will occur. In genetics , it is sometimes useful to classify mutations as either harmful or beneficial (or neutral ): Large-scale quantitative mutagenesis screens , in which thousands of millions of mutations are tested, invariably find that a larger fraction of mutations has harmful effects but always returns

5472-421: The combination of an accessory pathway and abnormal heart rhythms can trigger ventricular fibrillation , a leading cause of sudden cardiac death. WPW may be associated with PRKAG2 , a protein kinase enzyme encoded by the PRKAG2 gene . The bundle of Kent is an abnormal extra or accessory conduction pathway between the atria and ventricles that is present in a small percentage (between 0.1 and 0.3%) of

5568-404: The combination of both an Impella device and Venous-arterial extra-corporeal membrane oxygenation may decrease the heart's pulmonary capillary wedge pressure , thereby decreasing the amount of stress on the cardiac muscles. Because Venous-arterial extra-corporeal membrane oxygenation is a very invasive procedure, it is not usually the first-line chosen device for patients in cardiogenic shock and

5664-438: The comparatively higher frequency of cell divisions in the parental sperm donor germline drive conclusions that rates of de novo mutation can be tracked along a common basis. The frequency of error during the DNA replication process of gametogenesis , especially amplified in the rapid production of sperm cells, can promote more opportunities for de novo mutations to replicate unregulated by DNA repair machinery. This claim combines

5760-544: The comparison of genes between different species of Drosophila suggests that if a mutation does change a protein, the mutation will most likely be harmful, with an estimated 70 per cent of amino acid polymorphisms having damaging effects, and the remainder being either neutral or weakly beneficial. Some mutations alter a gene's DNA base sequence but do not change the protein made by the gene. Studies have shown that only 7% of point mutations in noncoding DNA of yeast are deleterious and 12% in coding DNA are deleterious. The rest of

5856-407: The complementary undamaged strand in DNA as a template or an undamaged sequence in a homologous chromosome if it is available. If DNA damage remains in a cell, transcription of a gene may be prevented and thus translation into a protein may also be blocked. DNA replication may also be blocked and/or the cell may die. In contrast to a DNA damage, a mutation is an alteration of the base sequence of

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5952-404: The dedicated reproductive group and which are not usually transmitted to descendants. Diploid organisms (e.g., humans) contain two copies of each gene—a paternal and a maternal allele. Based on the occurrence of mutation on each chromosome, we may classify mutations into three types. A wild type or homozygous non-mutated organism is one in which neither allele is mutated. A germline mutation in

6048-468: The diagnosis by providing information on the hemodynamics . When cardiomyopathy is suspected as the cause of cardiogenic shock, a biopsy of heart muscle may be needed to make a definite diagnosis . If the cardiac index falls acutely below 2.2 L/min/m , the person may be in cardiogenic shock. Initial management of cardiogenic shock involves medications to augment the heart's function. Certain medications, such as dobutamine or milrinone , enhance

6144-468: The diagnosis of orthodromic AVRT or if aberrant conduction leading to a wide complex QRS is observed, it may be prudent to manage as undifferentiated wide complex tachycardia. People with atrial fibrillation and rapid ventricular response may be treated with amiodarone or procainamide to stabilize their heart rate. Procainamide and cardioversion are accepted treatments for conversion of tachycardia found with WPW. Amiodarone in atrial fibrillation with WPW,

6240-431: The distribution of fitness effects was done by Motoo Kimura , an influential theoretical population geneticist . His neutral theory of molecular evolution proposes that most novel mutations will be highly deleterious, with a small fraction being neutral. A later proposal by Hiroshi Akashi proposed a bimodal model for the DFE, with modes centered around highly deleterious and neutral mutations. Both theories agree that

6336-435: The effects of the mutations on the ability of the cell to survive and reproduce. Although distinctly different from each other, DNA damages and mutations are related because DNA damages often cause errors of DNA synthesis during replication or repair and these errors are a major source of mutation. Mutations can involve the duplication of large sections of DNA, usually through genetic recombination . These duplications are

6432-408: The general population. This pathway may communicate between the left atrium and the left ventricle, in which case it is termed a "type A pre-excitation", or between the right atrium and the right ventricle, in which case it is termed a "type B pre-excitation" in old, currently abandoned classification. Problems arise when this pathway creates an electrical circuit that bypasses the AV node. The AV node

6528-455: The genome, such as transposons , make up a major fraction of the genetic material of plants and animals, and may have been important in the evolution of genomes. For example, more than a million copies of the Alu sequence are present in the human genome , and these sequences have now been recruited to perform functions such as regulating gene expression . Another effect of these mobile DNA sequences

6624-399: The germline than in the soma. In order to categorize a mutation as such, the "normal" sequence must be obtained from the DNA of a "normal" or "healthy" organism (as opposed to a "mutant" or "sick" one), it should be identified and reported; ideally, it should be made publicly available for a straightforward nucleotide-by-nucleotide comparison, and agreed upon by the scientific community or by

6720-515: The hands of an experienced electrophysiologist. Findings from 1994 indicate success rates of as high as 95% in people treated with radiofrequency catheter ablation for WPW. If radiofrequency catheter ablation is successfully performed, the condition is generally considered cured. Recurrence rates are typically less than 5% after a successful ablation. Some patients, such as the ones with underlying Ebstein's anomaly and inherited cardiomyopathies , may have multiple accessory pathways. The bundle of Kent

6816-402: The heart as it heals or awaits a more definitive treatment. It consists of a circuit that essentially drains blood from a patient's venous system, runs that blood through a circulator which adds oxygen and removes carbon dioxide, and ultimately returns blood back into the patient's arterial system where the newly oxygenated blood can be delivered to the person's organs. Some evidence suggests that

6912-517: The heart's pumping function and are often used first-line to improve the low blood pressure and delivery of blood to the rest of the body. Patients who have cardiogenic shock unresponsive to medication therapy may be candidates for more advanced options such as a mechanical circulatory support device. There are several types of mechanical circulatory support devices, the most common being intra-aortic balloon pumps, left ventricular assist devices, and venous-arterial extra-corporeal membrane oxygenation. It

7008-470: The left ventricle and into the aorta more quickly, thereby decreasing the amount of work that the left ventricle has to do. While the Impella is commonly used in settings of cardiogenic shock, some evidence suggests that it placing an Impella device in an acute cardiogenic shock setting, where the heart fails to pump suddenly, may not necessarily guarantee increased survival. Potential complications specific to an Impella device include hemolysis (shearing of

7104-482: The mechanical circulatory support devices. However, it is not without its potential complications. Potential complications include injury upon insertion of the device to arteries supplying the spinal cord as well as risks with any procedure such as bleeding and infection. Contraindications to intra-aortic balloon pumps include aortic dissection, an abdominal aortic aneurysm, and irregularly fast heart beats. There are several types of left ventricular assist devices, with

7200-549: The molecular level can be caused by: Whereas in former times mutations were assumed to occur by chance, or induced by mutagens, molecular mechanisms of mutation have been discovered in bacteria and across the tree of life. As S. Rosenberg states, "These mechanisms reveal a picture of highly regulated mutagenesis, up-regulated temporally by stress responses and activated when cells/organisms are maladapted to their environments—when stressed—potentially accelerating adaptation." Since they are self-induced mutagenic mechanisms that increase

7296-532: The mutations are either neutral or slightly beneficial. Cardiogenic shock Cardiogenic shock is a medical emergency resulting from inadequate blood flow to the body's organs due to the dysfunction of the heart . Signs of inadequate blood flow include low urine production (<30 mL/hour), cool arms and legs, and decreased level of consciousness. People may also have a severely low blood pressure and heart rate. Causes of cardiogenic shock include cardiomyopathic , arrhythmic, and mechanical. Cardiogenic shock

7392-464: The normal human heart begins when a cardiac action potential arises in the sinoatrial (SA) node, which is located in the right atrium . From there, the electrical stimulus is transmitted via internodal pathways to the atrioventricular (AV) node. After a brief delay at the AV node, the stimulus travels through the bundle of His to the left and right bundle branches and then to the Purkinje fibers and

7488-513: The observable characteristics ( phenotype ) of an organism. Mutations play a part in both normal and abnormal biological processes including: evolution , cancer , and the development of the immune system , including junctional diversity . Mutation is the ultimate source of all genetic variation , providing the raw material on which evolutionary forces such as natural selection can act. Mutation can result in many different types of change in sequences. Mutations in genes can have no effect, alter

7584-470: The observed effects of increased probability for mutation in rapid spermatogenesis with short periods of time between cellular divisions that limit the efficiency of repair machinery. Rates of de novo mutations that affect an organism during its development can also increase with certain environmental factors. For example, certain intensities of exposure to radioactive elements can inflict damage to an organism's genome, heightening rates of mutation. In humans,

7680-401: The pre-excitation pathway, potentially leading to unstable ventricular arrhythmias). The definitive treatment of WPW is the destruction of the abnormal electrical pathway by catheter ablation . Two main types of catheter ablation include radiofrequency ablation with heat or cryoablation with cold energy. This procedure is performed by cardiac electrophysiologists and has high success rate in

7776-479: The protein product if they affect mRNA splicing. Mutations that occur in coding regions of the genome are more likely to alter the protein product, and can be categorized by their effect on amino acid sequence: A mutation becomes an effect on function mutation when the exactitude of functions between a mutated protein and its direct interactor undergoes change. The interactors can be other proteins, molecules, nucleic acids, etc. There are many mutations that fall under

7872-415: The relative abundance of different types of mutations (i.e., strongly deleterious, nearly neutral or advantageous), is relevant to many evolutionary questions, such as the maintenance of genetic variation , the rate of genomic decay , the maintenance of outcrossing sexual reproduction as opposed to inbreeding and the evolution of sex and genetic recombination . DFE can also be tracked by tracking

7968-487: The remainder being either neutral or marginally beneficial. Mutation and DNA damage are the two major types of errors that occur in DNA, but they are fundamentally different. DNA damage is a physical alteration in the DNA structure, such as a single or double strand break, a modified guanosine residue in DNA such as 8-hydroxydeoxyguanosine , or a polycyclic aromatic hydrocarbon adduct. DNA damages can be recognized by enzymes, and therefore can be correctly repaired using

8064-431: The reproductive cells of an individual gives rise to a constitutional mutation in the offspring, that is, a mutation that is present in every cell. A constitutional mutation can also occur very soon after fertilization , or continue from a previous constitutional mutation in a parent. A germline mutation can be passed down through subsequent generations of organisms. The distinction between germline and somatic mutations

8160-453: The sake of scientific experimentation. One 2017 study claimed that 66% of cancer-causing mutations are random, 29% are due to the environment (the studied population spanned 69 countries), and 5% are inherited. Humans on average pass 60 new mutations to their children but fathers pass more mutations depending on their age with every year adding two new mutations to a child. Spontaneous mutations occur with non-zero probability even given

8256-413: The same mutation. These types of mutations are usually prompted by environmental causes, such as ultraviolet radiation or any exposure to certain harmful chemicals, and can cause diseases including cancer. With plants, some somatic mutations can be propagated without the need for seed production, for example, by grafting and stem cuttings. These type of mutation have led to new types of fruits, such as

8352-657: The single-stranded human immunodeficiency virus ), replication occurs quickly, and there are no mechanisms to check the genome for accuracy. This error-prone process often results in mutations. The rate of de novo mutations, whether germline or somatic, vary among organisms. Individuals within the same species can even express varying rates of mutation. Overall, rates of de novo mutations are low compared to those of inherited mutations, which categorizes them as rare forms of genetic variation . Many observations of de novo mutation rates have associated higher rates of mutation correlated to paternal age. In sexually reproducing organisms,

8448-408: The skewness of the distribution of mutations with putatively severe effects as compared to the distribution of mutations with putatively mild or absent effect. In summary, the DFE plays an important role in predicting evolutionary dynamics . A variety of approaches have been used to study the DFE, including theoretical, experimental and analytical methods. One of the earliest theoretical studies of

8544-416: The structure of genes can be classified into several types. Large-scale mutations in chromosomal structure include: Small-scale mutations affect a gene in one or a few nucleotides. (If only a single nucleotide is affected, they are called point mutations .) Small-scale mutations include: The effect of a mutation on protein sequence depends in part on where in the genome it occurs, especially whether it

8640-565: The studied plant ( Arabidopsis thaliana )—more important genes mutate less frequently than less important ones. They demonstrated that mutation is "non-random in a way that benefits the plant". Additionally, previous experiments typically used to demonstrate mutations being random with respect to fitness (such as the Fluctuation Test and Replica plating ) have been shown to only support the weaker claim that those mutations are random with respect to external selective constraints, not fitness as

8736-425: The template strand. In mice , the majority of mutations are caused by translesion synthesis. Likewise, in yeast , Kunz et al. found that more than 60% of the spontaneous single base pair substitutions and deletions were caused by translesion synthesis. Although naturally occurring double-strand breaks occur at a relatively low frequency in DNA, their repair often causes mutation. Non-homologous end joining (NHEJ)

8832-756: The type of mutation and base or amino acid changes. Mutation rates vary substantially across species, and the evolutionary forces that generally determine mutation are the subject of ongoing investigation. In humans , the mutation rate is about 50–90 de novo mutations per genome per generation, that is, each human accumulates about 50–90 novel mutations that were not present in his or her parents. This number has been established by sequencing thousands of human trios, that is, two parents and at least one child. The genomes of RNA viruses are based on RNA rather than DNA. The RNA viral genome can be double-stranded (as in DNA) or single-stranded. In some of these viruses (such as

8928-451: The vast majority of novel mutations are neutral or deleterious and that advantageous mutations are rare, which has been supported by experimental results. One example is a study done on the DFE of random mutations in vesicular stomatitis virus . Out of all mutations, 39.6% were lethal, 31.2% were non-lethal deleterious, and 27.1% were neutral. Another example comes from a high throughput mutagenesis experiment with yeast. In this experiment it

9024-423: The ventricular rate during spontaneous atrial fibrillation on a 12-lead ECG. RR intervals of less than 250 ms suggest a higher risk pathway. During exercise testing, abrupt loss of pre-excitation as heart rate increases also suggest a lower risk pathway. However, this approach is hampered by the normal improvement in AV node conduction during exercise which can also mask pre-excitation despite ongoing conduction down

9120-432: Was shown that the overall DFE is bimodal, with a cluster of neutral mutations, and a broad distribution of deleterious mutations. Though relatively few mutations are advantageous, those that are play an important role in evolutionary changes. Like neutral mutations, weakly selected advantageous mutations can be lost due to random genetic drift, but strongly selected advantageous mutations are more likely to be fixed. Knowing

9216-1032: Was the next to describe the condition in 1921. Cardiologists Louis Wolff (1898–1972), John Parkinson (1885–1976) and Paul Dudley White (1886–1973) are credited with the definitive description of the disorder in 1930. Mutation In biology , a mutation is an alteration in the nucleic acid sequence of the genome of an organism , virus , or extrachromosomal DNA . Viral genomes contain either DNA or RNA . Mutations result from errors during DNA or viral replication , mitosis , or meiosis or other types of damage to DNA (such as pyrimidine dimers caused by exposure to ultraviolet radiation), which then may undergo error-prone repair (especially microhomology-mediated end joining ), cause an error during other forms of repair, or cause an error during replication ( translesion synthesis ). Mutations may also result from substitution , insertion or deletion of segments of DNA due to mobile genetic elements . Mutations may or may not produce detectable changes in

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