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Effects of Inbreeding in Animals and Humans

Genetics is the branch in biology which studies the origin, transmission and expression of genetic information, and the variation it causes amongst species. In this essay I will talk particularly about inbreeding in animals and humans, and the effect of this on their population.
As described by the famous naturalist Charles Darwin, natural selection works by selecting those individuals amongst species with the traits and characteristics that will make them more likely to survive in the environment in which they live, compared to other members of the same species. This gives those individuals a reproductive advantage. Therefore these individuals will pass on their genes to the following generations. This process hence eliminates alleles of traits from the gene pool that cause an individual to be less fit to live compared to the other members of their species population.
Inbreeding occurs when two individuals from the same species mate, which are more closely related than if you had selected them randomly from the whole population. In simple terms it means mating between individuals that are related to one another. Within animals this can mean mating between brothers and sisters, father and daughter or mother and son, although this degree of inbreeding is rarely seen in humans, it can also observed and is usually seen as mating between cousins etc.
Naturally animals do not voluntarily inbreed with their close relatives, and we can see some mechanisms in animal behaviour which prevents this from happening. For instance animals which live in a pack for example prairie dogs usually kick out their young males to prevent them from inbreeding with their female relatives. Additionally the reluctance of females to copulate with closely related males prevents this further (Hoogland 1982). Nevertheless natural inbreeding can be observed in some mammals. These include the meadow vole and the American pika, where inbreeding has become their normal reproductive path.
However in humans inbreeding is a voluntary action of the individuals itself, which can be influenced by environmental pressures and mental isolation (individual chooses mate from a certain culture, background etc). A prominent example is where the pharaoh frequently married his sisters to carry on the family name and keep the royalty to one family. As I will discuss, this brings an explanation to the large numbers of infant mummies, at the burial places.
Humans frequently and deliberately inbreed animals to fix traits into a breed and for many other reasons this is called ‘selective inbreeding’ and the purposes of this include; scientific research, food supply, and as pets.
A common example of this is the selective inbreeding of mice, used for scientific research purposes. Repeated inbreeding produces mice that are completely uniform, as their genome becomes homozygous (identical alleles at a given gene loci) at virtually all of their gene loci. This property offers numerous advantages over outbred mice, which are mice that have been bred from parents that are not closely related.
The uniformity of the inbred strains reduces the number of mice needed for experiments, because the experimental variability in the phenotype is limited to variations to epigenetic, extra genetic and/or varying uncontrolled environmental factors.(Hedrich 2004) The use of inbreeding in this way has indirect beneficial effects to both the animal and human population, as the results obtained from such experiments contribute to our understanding of health, which will further be inflicted onto the population for a better living.
Figure 1 shows the cross between mice. It illustrates the pairing of a gene allele annotated ‘D’ for the dominant allele, and ‘d’ for the recessive allele during inbreeding between brothers and sisters. We can see that over time the chromosome locus for the gene becomes homologous. Considering this happens for the rest of the gene loci, a pure inbreed line is produced. Although not shown or mentioned in the diagram, many mice die during the inbreeding process due to the allele rearrangement bringing together defective alleles, which leads to the mice dying. This hence leaves behind healthy inbred mice, which are said to have shed their genetic load (the number of deleterious alleles in a heterozygous condition present in an individuals genome).
Therefore the first evident consequence of inbreeding on a population is the reduction in genetic diversity due to loss of alleles from mortality, and as a result there is increased homozygosity.
Reduction in genetic diversity also referred to as genetic erosion explains the fact that as you inbreed animals and humans the alleles at corresponding chromosomal loci become identical and therefore reducing the diversity within the genome and hence within the population. But how would genetic erosion effect the population? The first reason is that it can result in a loss of potentially valuable and useful alleles from the gene pool, thus reducing the capability of the population to adapt to varying environmental conditions e.g. climate change, new pathogens etc, which increases their risk of extinction. This is particularly important especially in the animal populations.
Genetic diversity is measured by using a technique that analyses short tandem repeats (STR) also known as microsatellites in the genome. The STR consists of short DNA sequences repeated a variable number of times, the number of repeats of this sequence vary within individuals, and so measuring the length of these variable sequences represents the variation within individuals which therefore reflects the genetic diversity.
We can further work out the association of genetic diversity to a particular ancestor. The inbreeding coefficient is used to estimate probability that two alleles at a locus in an individual are identical by descent from a common ancestor (Klug 2010). For example inbreeding coefficient for second cousins is 1/64 and for third cousins is 1/256. The inbreeding coefficient is inversely related to the frequency of heterozygotes in the population. It can be calculated by the following equation:
In the equation N is the number of loops seen in a pedigree, whilst n is the number of ancestors in each loop. Using the example in figure 2 which shows the inbreeding between first cousins;
N = 2
n = 5
F = 2 ( ½ )^5
Therefore the inbreeding coefficient between first cousins is;
F = 1/16,
Genetic drift is the random variation in allele frequency from generation to generation. Inbreeding has very similar effects to genetic drift in small populations. In both cases heterozygosity decreases and homozygosity increases. In the case of inbreeding in large populations however, allele frequency stays relatively the same as homozygosity increases. Genetic drift causes only small departures from the Hardy-Weinberg; where as those caused by inbreeding can be extreme.
An adverse effect in inbreeding can be observed if the chromosome locus which is becoming homozygous is actually defective or lethal. Within the population the alleles are randomly dispersed so that nearly everyone will carry at least one defective recessive allele for a given trait in their genome, and the expression of this allele is seen more frequently when you mate with someone that has a very similar genome to yours i.e. inbreeding. The severity of the situation depends on the trait being influenced by this inheritance.
This is what leads to inbreeding depression. Inbreeding itself doesn’t cause inbreeding depression; it is only when the increased homozygosity leads to an increase in the proportion of deleterious recessive alleles in a population compared to previous generation, and so leads to the more frequent occurrence of rare recessive alleles in a homozygous condition. This increases the occurrence of aberrant phenotypes which would have normally been masked in the heterozygous state. So there is a concomitant reduction in the overall fitness in the population. Here fitness will be defined as the relative reproductive success and is estimated with the component of fitness such as viability or fecundity (Hartl and Clark 1989).
The second important consequence of genetic erosion is a reduction in the levels of heterozygosity and the consequences this leads to. As when mating with members of the population with a similar genome, will cause the individuals to become homozygous at many of there chromosome loci.

We can see the increase in homozygosity being represented by graph 1. This additionally demonstrates the closer the kinship within individuals then the more chance there is that their gene loci are going to end up being homozygous. This is because the closer they are related the more similar their genome will be therefore will reach homozygosity quicker than less related individuals.
Many studies have reported associations between individual heterozygosity for protein polymorphisms and viability, one of these studies was the theory of the heterozygote advantage.
Heterozygote advantage describes the situation in which an individual with a heterozygote genotype has a greater relative fitness than either the individuals with homozygote dominant or homozygote recessive genotype. This selection which prefers the heterozygote is one of the mechanisms that maintain polymorphism and helps to explain some kinds of genetic variability.
This theory has been demonstrated on many organisms but was initially experimented with the Drosophila melanogaster which is a classic model organism for research in genetics. It was demonstrated that a mutation was advantageous when in heterozygous state but is disadvantageous when in a homozygous state. This mutant allele was an autosomal gene that expressed an ebony body color. When the fruit fly inherited both copies of the allele, it expressed the dark ebony colour but was very weak which placed it in a reproductive disadvantage. When the organism was heterozygous for the allele it was healthy and had an improved viability.
Heterozygosity is also seen as advantageous in many situations within the human population as well. In particular an example which is well known is which in being heterozygote for the sickle cell anemia trait provides resistance for the infectious disease frequently seen in Africa; malaria. When an individual is affected by sickle cell anemia, their red blood cells lose their distinct round shape and become sickle-shaped when exposed to low-oxygen conditions. This deformation of the cells can cause them to become wedged in capillaries, which deprives other parts of the body of oxygen.
Those individuals who are heterozygote for this trait do not suffer from the adverse phenotypical symptoms but have some sickle shaped red blood cells mixed along side their healthy ones. For this reason they are genetically able to live healthily but also have an environmental advantage against malaria. This is because it is difficult for the malaria pathogen plasmodium to survive in the defective red blood cells due to its shape. As this is the plasmodiums main site of reproduction it can not lead to cause malaria. Therefore evolution plays its role by selecting those individuals with this heterozygous genotype, who are better fit to survive in the malaria prone environment than others. They hence pass on their genes to the next generation. This process enables the sickle cell allele to remain in dynamic equilibrium within these populations.
By applying our knowledge of inbreeding, we can see how being homozygous at this loci would reduce this population’s fitness for survival especially in those parts of the world where malaria is persistent e.g. sub-Saharan Africa. As inbreeding will increase the chance that this allele will become heterozygous and the individuals will lose their environmental advantage.
Whilst studying the involvement of genes in cancer formation, it was noticed inbreeding also plays a part in the number of cancer cases observed. Island populations have higher number of inbreeding number compared to larger populations. This is due to the lower number of diverse mating partners. Anthropological research which lasted over three decades was carried out on island populations in Middle Dalmatia and Croatia. Using data taken from the Croatia Cancer registry as control data, the results of the experiment showed that there was a clear trend in the occurrence of cancer and inbreeding rate (Rudan I 1999). This therefore proved that genes too account for the reason cancerous cells occur, but more importantly to realise is that inbreeding increases this chance by bringing together these rare alleles of genes that would have normally remained on its own and hence disguised. Therefore inbreeding can be said to play a significant role in the occurrence cancer.
Inbreeding has many advantages in scientific research in controlled laboratory environments, but uncontrolled inbreeding in the population has many adverse effects. It can be therefore concluded that the effects of inbreeding leads to more disadvantageous situation that it does to advantageous considering the evidence seen from reduced fitness due to homozygosity and heterozygous advantage studies. Although this depends largely on the trait being inherited due to similar allele pairings. Nevertheless populations which have shed their genetic load can survive healthily by using inbreeding as their normal reproductive path, but then again it is suggested that where possible inbreeding should be avoided.

Migraine Headaches: Causes, Symptoms and Treatments

A migraine headache(1) is a type of vascular headache.it is caused by Vassodillation.In it release of chemicals from nerve fibers occurs which coil around the large arteries of brain. Sympathetic nervous system is usually activated by migraine attacks, which controls responses that cause pain and strees. The oral medicine which are taken to treat migraine headaces,their impaired absorption is a main reason for the ineffectivness of medicines.Migraine has influenced 28 lack Americans, and among them females are suffering more frequently(17%)than males(6%). Nausea, vomiting, diarrhae, facial pallor, cold hands and cold feet and sensitivity to light comonly are the symptoms of migraine headaches.A typical attack lasts b/w 4-72 hours.It is estimated that 20% of migraine headaches are linked with an aura(3).Some migraines are accompanied by neurological dysfunction these are some complicated migraines(4).When symptoms are clear then migraine headaches are diagnosed.Migraines normally begin in early days. It can also occur in a person beyond the age 50,advancing ages make other types of headaches.Migraine(5) is often remained under diagnosed and under treated.Migraine headache is incurable until now.
A migraine headache is a type of vascular headache.
A typical attack lasts b/w 4-72 hours.
Migraine attacks activate the sympethetic nervous system of the body.
INTRODUCTION Migraine headache is a type of vascular headache. It is caused by vassodillation. In it release of chemical from nerve fibers(8) occurs, which coil around the large arteries of brain. These large sized blood vessels stretch the nerves that coil around the blood vessels and cause the nerves to release chemicals.
These chemicals cause inflammation, pain and more large size of the arteries.(9)
Which cause more severe pain. Sympathetic nervous system is usually activated by migraine attacks(10),which controls responses that cause pain and stress.Many other symptoms are also caused by this activation,for example the increased activity of sympethetic nervous system in the intestine causes nausea,vomiting and diarrhea.
The oral medicine which are taken to treat migraine headaces,their impaired absorption is a main reason for the ineffectivness of medicines.Ciculation of blood is also decreased due to increased activity of sympathetic nervous system and that leads to cold hands and feet and pallor of the skin.
The increased activity of sympethetic nervous system activity also causes the sensitivity of light and sound (11) as well as blurred vissions.
Migraine has influenced 28 lack Americans, and among them females are suffering more frequently (17%) than males (6%). Anyhow migraine is largely under diagnosed and under treated till now.
SYMPTOMS Most migraine attacks are correlated with headaches.(12)
sometime the pain is usually in the forehead, near the eye, or at the back side of head
Pain is usually on one side of head and sometime it is on the both sides of head
The one side headache usually change from one side to another ,in case of the same side headache it should alert the doctor to consider a sec. headache caused by a brain tumor.
It is usually increased by daily activities such as walking upstairs
Nausea, vomiting, diarrhae, facial pallor, cold hand and cold feet and sensitivity to light commonly are the symptoms of migraine headaches.
A migraine sufferer usually wants to sit in loneliness
A typical attack lasts b/w 4-72 hours.
The symptoms may also involve
sleeping
irritability(13)
fatigue(14)
depression(15)
yawing(16)
MIGRAINE TRIGGERS It is a factor relating to environment or physiological conditions which lead to headaches in those persons who are prone to migraine headaches.Only a few migraine sufferers,can clearly identify these triggers. Examples include:
Stress
Sleep disturbances
Fasting
Hormones
bright or flickering lights
Odors,
Cigarette smoke
Alcohol
Aged cheeses
Chocolate
Monosodium glutamate
Nitrites
Aspartame and caffeine
In some women, the decrease in the level of estrogen during the onset of puberty is a trigger for migraine headaches which is referred to as menstrual migraines.
Migraine and Female hormones Some women suffer from migraine headaches around the time of their menstrual cycles. And some other women suffer from migraine headaches only at the time of menstrual cycle.”Menstrual migraine” is a term whish is used mainly to describe migraines that occur in those women who have all of their headaches before two days and after one day of their menstrual cycles. Decreasing levels of estrogen at the onset of menses is the main cause of menstrual migraines.
MIGRAINE AURA It is estimated that 20% of migraine headaches are linked with an aura, frequently the aura causes the headaches, even though sometimes it may occur at the same time with the headache.
The most frequent auras are;
Flashing, bright lights in zigzag pattern, starting in the middle and moving outward,
A gap in the visual field which is known as a blind spot.
Some old migraine suffering patients may practice only the visual aura, without the headache.A less common aura consists of pins-and-needle sensation in the hand and on the arm and also around mouth and near nose.
Other types of auras include aural abnormalities and irregular tastes and smell.
Approximately after 24 hours of migraine attacks the sufferer may feel lack of energy and may practice a low grade headache.
Retinal or visual migraines are rare (17) types of attacks and are characterized by repetitive instances of sightlessness on one side lasting one hour that can be linked with headache.
SOME VARIANTS OF HEADACHE Some migraines are accompanied by neurological dysfunction these are some complicated migraines. The brain determines the part of the body that is affected by dysfunction, and is responsible for headache.
Verterobasilor migraines These are involved in the dysfunction of the lower brain that controls the automatic activities like awareness and sense of balance.
The symptoms include
fainting as an aura
giddiness (wooziness in which the environment seems to be rotating)
double visualization
Hemiplegics migraines These include paralysis or fault of one side of the body,
Mimicking a stroke.
The paralysis or fault is typically momentary, but from time to time it can last for many days.
MIGRAINE HEADACHE DIAGNOSE When symptoms are clear then migraine headaches are dignosed.Migraines normally initiate in early days.(19)It can also occur in a person beyond the age 50,but as the age increases it makes other types of headaches.
In this a family history is also involved,this disease may be transfered from parents to their children geneticaly.
Patients who have the first headache ever,a significant change in their chracteristics of headach or an connection of the headache with nervous system symptoms, like visual or hearing or sensory loss may have need of extra tests to take out the diseases other than migraine.
There are some tests which are used to diagnose the headaches which include blood testing and scanning that is CT or MRI.
TREATMENT OF MIGRAINES There are two types of treatment.(20)
Non-medication therapies for migraine
Medication for migraine
Non-medication therapy for migraine The therapy can be a preventive or non medicated therapy that does not involve medication.
a – by using ice, biofeedback, and relaxing techniques headaches can be stopped.
b – sleep can be the best medicine.
c – by avoiding smoking the effect of migraine can also be minimized.
d – by avoiding convinced foods specially those which are high in thyramine like sharp cheese or those which contain sulfites (wines) or nitrates (nuts, pressed meats) migraine headache can be stopped.
Commonly, a healthy life-style with good diet, an sufficient ingestion of liquids, adequate sleep and exercise can be useful therapy. Acupuncture has been recommended as a useful therapy.
Medication for migraine Some individuals suffering from migraine generally treat themselves with over-the-counter (OTC) or non prescription pain relievers. Many types of OTC analgesics(21) or pain relievers are accessible. These are efficient for short interval of time only. When used according to informations on labels.
Two types of analgesics are:
Acetaminophen(22)
Non-steroidal anti-inflammatory drugs(NSAIDS)(23)
Acetaminophen It acts on the pain centers in the brain and reduces pain and fever.It is well tolerated by the stomach and normally is considered easier on the stomach than NSAIDS, when it is taken in large doses it can also damage kidney, and it can also effect liver.
NSAIDS There are two types of NSAIDS
aspirin
non aspirin
Ibuprofen and naproxen are the examples of non aspirin NSAIDS.Some NSAIDS are accessible by only prescription.To treat arthritis and other inflammatory conditions prescription NSAIDS are usually prescribed. The amount of active ingredient in each pill is the main difference between OTC NSAIDS and prescription NSAIDS.
The pain can be relieved by the action of NSAIDS on the inflammation that causes the pain.Although carticosteroids are valuable in inflammation but when used for long interval of time these have very toxic side effects.
Aspirin, aleve, motrin and advil all are NSAIDS and have similar effects in relieving pain and fever.
Their effect on platelets is the main difference between aspirin and non aspirin NSAIDS, platelets are the small particles in blood that cause blood clots, and aspirin inhibit the action of platelets. The non aspirin NSAIDS also inhibit the action of platelets but their action is not as long as aspirin.
Precautions while using OTC analgesics Following precautions should be observed with OTC analgesics;
Children and teenagers should avoid aspirin for the cure of headache because of its dangerous side effects of developing Reye’s syndrome that can lead to comma or even death.
People who are suffering with balance disorder should not use aspirin.
Because of the increased risk of bleeding people who are suffering from ulcers of stomach and duodenoum should not use aspirin and non aspirin NSAIDS.
People who are suffering with liver diseases should also not take aspirin because it may affect the kidney and liver’s functions.
OTC and prescription analgesic should not be overused, because their overuse can cause development of tolerance of these analgesics means increasing ineffectiveness of the analgesics.
TREATMENT FOR MODERATE TO SEVERE ATTACK Specific migraine futile medicines are used for the treatment of moderate to severe attackBecause they not only relief the headache but also terminate the headache.
Examples include Triptans and Ergot preprations.
Triptans
The triptans (24) constricts the blood vessels and reduce the inflammation by attaching to the serotonin receptors which surround the blood vessels. This aborts the headache, in past it was used with the name of somatript,the new form of it is zolimtriptan that are available as tablets in market.
Side effects of triptans
Facial flushing, tingling of skin and a sense of tightness around chest and neck are the most common side effects of triptans.Other side effects which are not more common are drowsiness, fatigue and dizziness. The most serious side effects are heart attacks and strokes, because these can narrow arteries in brain as well as in the heart.
Ergots
The effect of ergots is like triptans that terminate migraine headaches.These are in the combined form with caffeine and other pain reliefers.Ergotaminepreprations(ergomar,wigraine,cafergot) and dihydroergotamine preprations(DHE45,Migranal) are the examples of ergots. Ergots constrict the blood vessels which is more dangerous for heart.
Midrin
It is used to terminate migraine and tension causing headaches. It is a combined product of isometheptene (a blood vessel constrictor), acetaminophen (a pain reliever), and dichloralphenazone (a mild sedative). It acts more effectively if it is used early during a headache.
PREVENTIONS
There are two ways to prevent migraine headache,(14)
By avoiding the headache causing factors
By preventing headaches by taking medicines
PROPHYLACTIC MEDICATIONS FOR MIGRAINE HEADACHES
These are medicines which are taken daily to mininmize the duration of headaches.When a headache has begun then these are not taken at once. Several types of prophylactic medications are there
beta blockers
calcium channel blocker
tricyclic anti depresants
anti serotonin agents
anti convulsants
The doctor should take into account the side effects of the drug, drug-drug interactions and co-existing conditions such as diabetes, heart diseases and high blood pressure while choosing prophylactic medication for a patient.
PROPER WAY TO USE PREVNTIVE MEDICATIONS
The medications should be prescribed by the doctor who is familiar with treatment.
Decisions about to take medicines based on their side effects
Propranolal is used first,but it is not provided to the individuals who have asthma or heart disease.
These begin at low doses and steadily increase to higher doses.
CONCLUSIONS Migraine is often remained underdiagnosed and under treated. There is no cure for migraine, there are many measures for the better life of migraine sufferers(25).Pharmacists are trying their best to invent a new drug for the cure of migraine.Individulizing treatment is essential for better results.

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