Term
| What is locus heterogeneity? What is allelic heterogeneity? Phenotypic heterogeneity? |
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Definition
locus heterogeneity: the same disease can arise from mutations in different genes
allelic heterogeneity: different mutations occuring at the same gene
phenotypic heterogeneity: variation of phenotype that occurs in patients with mutations in a specific gene |
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Term
| What is the (MOI) of Hemophilia A? |
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Definition
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Term
| What is the (MOI) of cystic fibrosis (CF)? |
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Definition
autosomal recessive;
affects the entire body, causing progressive disability and often early death.
The name cystic fibrosis refers to the characteristic scarring (fibrosis) and cyst formation within the pancreas, first recognized in the 1930s.[1] Difficulty breathing is the most serious symptom and results from frequent lung infections that are treated with, though not cured by, antibiotics and other medications. A multitude of other symptoms, including sinus infections, poor growth, diarrhea, and infertility result from the effects of CF on other parts of the body.
CF is caused by a mutation in the gene for the protein cystic fibrosis transmembrane conductance regulator (CFTR). This gene is required to regulate the components of sweat, digestive juices, and mucus. Although most people without CF have two working copies of the CFTR gene, only one is needed to prevent cystic fibrosis. CF develops when neither gene works normally and therefore has autosomal recessive inheritance |
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Term
| What is the (MOI) of alpha-1-antitrypsin deficiency? |
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Definition
autosomal recessive;
caused by defective production of alpha 1-antitrypsin (A1AT), leading to decreased A1AT activity in the blood and lungs, and deposition of excessive abnormal A1AT protein in liver cells.[1][2] There are several forms and degrees of deficiency, principally depending on whether the sufferer has one or two copies of the affected gene. Severe A1AT deficiency causes panacinar emphysema or COPD in adult life in many people with the condition (especially if they are exposed to cigarette smoke), as well as various liver diseases in a minority of children and adults, and occasionally more unusual problems.[3] It is treated by avoidance of damaging inhalants, by intravenous infusions of the A1AT protein, by transplantation of the liver or lungs, and by a variety of other measures, but it usually produces some degree of disability and reduced life expectancy. |
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Term
| What is the (MOI) of Duchenne muscular dystrophy (DMD)? |
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Definition
X-linked recessive;
which results in muscle degeneration, difficulty walking, breathing, and death. The incidence is 1 in 3,000.[1] Females and males are affected, though females are rarely affected and are more often carriers. The disorder is caused by a mutation in the dystrophin gene, located in humans on the X chromosome (Xp21). The dystrophin gene codes for the protein dystrophin, an important structural component within muscle tissue. Dystrophin provides structural stability to the dystroglycan complex (DGC), located on the cell membrane.
Symptoms usually appear in male children before age 5 and may be visible in early infancy. Progressive proximal muscle weakness of the legs and pelvis associated with a loss of muscle mass is observed first. Eventually this weakness spreads to the arms, neck, and other areas. Early signs may include pseudohypertrophy (enlargement of calf and deltoid muscles), low endurance, and difficulties in standing unaided or inability to ascend staircases. As the condition progresses, muscle tissue experiences wasting and is eventually replaced by fat and fibrotic tissue (fibrosis). By age 10, braces may be required to aid in walking but most patients are wheelchair dependent by age 12. Later symptoms may include abnormal bone development that lead to skeletal deformities, including curvature of the spine. Due to progressive deterioration of muscle, loss of movement occurs, eventually leading to paralysis. Intellectual impairment may or may not be present but if present, does not progressively worsen as the child ages. The average life expectancy for patients afflicted with DMD varies from late teens to early to mid 20s. |
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Term
| What is the (MOI) of Tay Sachs disease? |
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Definition
autosomal recessive;
In its most common variant, known as infantile Tay–Sachs disease, it causes a relentless deterioration of mental and physical abilities that commences around six months of age and usually results in death by the age of four.[1]
It is caused by a genetic defect in a single gene with one defective copy of that gene inherited from each parent. The disease occurs when harmful quantities of gangliosides accumulate in the nerve cells of the brain, eventually leading to the premature death of those cells. There is currently no cure or treatment. Tay–Sachs disease is rare, and other autosomal recessive disorders, such as cystic fibrosis and sickle cell anemia, are far more common |
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Term
| What is the (MOI) of Sickle cell disease? |
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Definition
autosomal recessive;
Sickle-cell disease (SCD), or sickle-cell anaemia (or anemia; SCA) or drepanocytosis, is an autosomal recessive genetic blood disorder with incomplete dominance, characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickling decreases the cells' flexibility and results in a risk of various complications. The sickling occurs because of a mutation in the haemoglobin gene. Life expectancy is shortened, with studies reporting an average life expectancy of 42 in males and 48 in females.[1]
Sickle-cell disease, usually presenting in childhood, occurs more commonly in people (or their descendants) from parts of tropical and sub-tropical regions where malaria is or was common. One-third of all indigenous inhabitants of Sub-Saharan Africa carry the gene,[2] because in areas where malaria is common, there is a fitness benefit in carrying only a single sickle-cell gene (sickle cell trait). Those with only one of the two alleles of the sickle-cell disease, while not totally resistant, are more tolerant to the infection and thus show less severe symptoms when infected |
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Term
| What is the (MOI) of Alpha and Beta Thalassemia? |
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Definition
autosomal recessive;
blood disease that originated in the Mediterranean region. In thalassemia the genetic defect, which could be either mutation or deletion, results in reduced rate of synthesis or no synthesis of one of the globin chains that make up hemoglobin. This can cause the formation of abnormal hemoglobin molecules, thus causing anemia, the characteristic presenting symptom of the thalassemias.
Thalassemia is a quantitative problem of too few globins synthesized, whereas sickle-cell disease (a hemoglobinopathy) is a qualitative problem of synthesis of an incorrectly functioning globin. Thalassemias usually result in underproduction of normal globin proteins, often through mutations in regulatory genes. Hemoglobinopathies imply structural abnormalities in the globin proteins themselves.[1] The two conditions may overlap, however, since some conditions that cause abnormalities in globin proteins (hemoglobinopathy) also affect their production (thalassemia). Thus, some thalassemias are hemoglobinopathies, but most are not. Either or both of these conditions may cause anemia. |
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Term
| What is the (MOI) of Fragile X Syndrome? |
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Definition
X-linked recessive
Fragile X syndrome (FXS), Martin–Bell syndrome, or Escalante's syndrome (more commonly used in South American countries), is a genetic syndrome that is the most commonly known single-gene cause of autism and the most common inherited cause of intellectual disability.[1][2] It results in a spectrum of characteristic physical and intellectual limitations and emotional and behavioral features which range from severe to mild in manifestation.
The syndrome is associated with the expansion of a single trinucleotide gene sequence (CGG) on the X-chromosome, and results in a failure to express the protein coded by the FMR1 gene, which is required for normal neural development. There are four generally accepted states of the chromosome region involved in Fragile X syndrome which relate to the length of the repeated CGG sequence; Normal (29–31 CGG repeats) (not affected by the syndrome), Premutation (55–200 CGG repeats)(not affected by the syndrome), Full Mutation (more than 200 CGG repeats)(affected), and Intermediate or Gray Zone Alleles (40–60 repeats) |
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Term
| What is the (MOI) of Huntington's Disease (HD)? |
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Definition
autosomal dominant;
is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and dementia. It typically becomes noticeable in middle age. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea. It is much more common in people of Western European descent than in those of Asian or African ancestry. The disease is caused by an autosomal dominant mutation on either of an individual's two copies of a gene called Huntingtin, which means any child of an affected parent has a 50% risk of inheriting the disease. In the rare situations where both parents have an affected copy, the risk increases to 75%, and when either parent has two affected copies, the risk is 100% (all children will be affected). Physical symptoms of Huntington's disease can begin at any age from infancy to old age, but usually begin between 35 and 44 years of age. About 6% of cases start before the age of 21 years with an akinetic-rigid syndrome; they progress faster and vary slightly. The variant is classified as juvenile, akinetic-rigid or Westphal variant HD.
The Huntingtin gene normally provides the genetic information for a protein that is also called "Huntingtin". The mutation of the Huntingtin gene codes for a different form of the protein, whose presence results in gradual damage to specific areas of the brain. The exact way this happens is not fully understood. Genetic testing can be performed at any stage of development, even before the onset of symptoms. This fact raises several ethical debates: at what age is an individual considered mature enough to choose testing, do parents have the right to have their children tested, and managing confidentiality and disclosure of test results. Genetic counseling has developed to inform and aid individuals considering genetic testing and has become a model for other genetically dominant diseases.
Symptoms of the disease can vary between individuals and among affected members of the same family, but the symptoms progress predictably for most individuals. The earliest symptoms are a general lack of coordination and an unsteady gait. As the disease advances, uncoordinated, jerky body movements become more apparent, along with a decline in mental abilities and behavioral and psychiatric problems. Physical abilities are gradually impeded until coordinated movement becomes very difficult. Mental abilities generally decline into dementia. Complications such as pneumonia, heart disease, and physical injury from falls reduce life expectancy to around twenty years after symptoms begin. There is no cure for HD, and full-time care is required in the later stages of the disease. Emerging treatments can relieve some of its symptoms |
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Term
| What determines whether an allele is dominant or recessive? |
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Definition
| Whether 50% of the gene product is enough (recessive) or not (dominant) |
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Term
| For determining carrier risk for autosomal recessive gene, how is the carrier risk altered when the child is born and healthy? |
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Definition
1/2---> 2/3
For any autosomal recessive disorder, the probability of the child being a carrier is 50%, healthy is 25%, and affected is 25%. Once the child is born and is healthy, we now know that one of the possibilities is removed. Of the remaining possibilities, 2 of the 3 would result in the child being a carrier. |
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