Term
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Definition
| study of single gene function |
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Term
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Definition
| study of interaction of all genes |
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Term
| Altered transcription causes |
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Definition
| alterations in binding site of promoter or of the regulatory proteins that modify txn |
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Term
| Cause of altered splicing |
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Definition
| change in splice site recognition sequences |
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Term
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Definition
| splicing of exons together in different combos allows multiple proteins to be created from a single gene |
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Term
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Definition
| newly formed proteins are frequently modified by hydroxylation, phosphorylation, disulfide bonds or addition of glycoproteins or lipoproteins |
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Term
| Postranslational localization |
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Definition
| result of posttrans mods and disruptions may alter transport of the protein |
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Term
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Definition
| specific mutation that commonly occurs in the population and is not associated with a disease phenotype |
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Term
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Definition
| change a single base that does not result in an AA change |
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Term
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Definition
| mutations that change a base pair and results in an AA change |
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Term
| loss of function mutations |
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Definition
| produce either a reduced amount or a reduced activity of the gene product and usually have a minimal effect on the phenotype unless both alleles are affected |
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Term
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Definition
| indicates no product or function results from an allele |
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Term
| Null allele in heterozygotes |
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Definition
| have one good allele so may have a sufficient product level for normal function |
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Term
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Definition
| a 50% product level results in an altered phenotype caused by a mutation in only one gene (a dominant phenotype) resulting in no actual product in cell because the remaining good gene is not sufficient to maintain phenotype in the absence of the mutated gene |
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Term
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Definition
| In a heterzygote when the normal function of the product is lost and the abnormal product interferes with the product of the normal allele ie no good product |
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Term
| Gain of function mutation |
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Definition
| produce either an increased amount or increased activity of the product |
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Term
| Simple Human genetic diseases |
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Definition
| exhibit mendelian inheritance ie marfan syndrome |
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Term
| Example of complex inheritance disease |
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Definition
| hypertrophic cardiomyopathy |
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Term
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Definition
1.tall
2.slender
3.loose jointed
4. results in longer bones ie arachnodactyly
5.narrow face
6.crowded teeth
7. slight kyphosis |
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Term
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Definition
| may experience dislocation of one or both lenses of the eye as well as retinal detachment, glaucoma, and cataracts |
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Term
| Marfan is a disorder of the |
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Definition
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Term
| Marfan heart and blood vessel symptoms |
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Definition
| abnormalities due to loss of fibrillin-1 resulting in a weakened stretched aorta wall, a process called aortic dilatation |
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Term
| Marfan cardiac valve problems |
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Definition
1.Mitral valve prolapse
2.Aortic valve incompetence due to cystic medionecrosis |
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Term
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Definition
| lack of connective tissue causes a loss of medial wall support resulting in the dilation of the aortic valve ring and root of aorta causing valvular incompetence |
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Term
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Definition
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Term
| Percentage of familial autosomal dominant inheritance cases |
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Definition
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Term
| Marfan syndrome results from |
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Definition
| inherited defect in an extracellular glycoprotein called fibrillin 1 |
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Term
| Marfan mutations in exons 24-32 |
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Definition
| primarily (60%) involve a cysteine |
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Term
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Definition
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Term
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Definition
| modular structure w/ 47 repeats of six cysteine epidermal growth factor (EGF)-like motifs 43 of which are of the calcium binding type |
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Term
| Fibrillin 1 functional determinant |
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Definition
| monomers associate to form complex extracellular macroaggregates termed microfibrils which are important for the integrity and homeostasis of both elastic and nonelastic tissues |
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Term
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Definition
| composes the elastic fibers, microfibrils, (elastin) that attach to the contractile units in the aortic smooth muscle cells |
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Term
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Definition
| functions as latent TGFbeta Binding protein 1 (LTBP-1) which when bound inactivates TGFbeta |
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Term
| Effect of Fibrillin 1 mutation on TGFbeta |
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Definition
| LTBP-1 activity of Fibrillin1 is lost so get increased TGFbeta activity |
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Term
| Large latent TGFbeta complex |
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Definition
inactivated extracellular matrix storage complex consisting of
1.TGFbeta homodimer bound to LAP
2.Latency associated peptide (LAP) bound to
3.LTBP1 |
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Term
| Increased activation of TGFbeta leads to |
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Definition
| altered txn of TGFbeta responsive genes causing inflammation, ECM degradation, apoptosis resulting in medial degeneration leading to aneurysms and dissections |
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Term
| Loss of fibrillin 1 results in an what effect on the aorta |
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Definition
| inability of the aorta to recoil due to reduced elastic properties of teh tissue leading to a permanently distended and weakened aortic wall |
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Term
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Definition
T=(Pxr)/w ie wall tension = (P x radius)/wall thickness
so aneurysm causes expansion increasing the radius and thining the wall both of which increase the wall tension |
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Term
| Heart failure characteristic |
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Definition
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Term
| Hypertrophic cardiomyopathy characteristics of heart wall |
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Definition
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Term
| hypertrophic cardiomyopathy: fiber description |
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Definition
| exhibit myocardial fiber disarray going in all directions |
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Term
| HCM clinical and phys features |
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Definition
1. systolic ejection murmur
2. angina
3.exertion related dyspnea/impaired consiousness
4. variety of heart problems
5. can be asymptomatic
6. common cause of sudden death in young athletes |
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Term
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Definition
| harsh systolic ejection murmur caused by ventricular outflow obstruction as the anterior mitral leaflet moves toward the ventricular septum during systole |
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Term
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Definition
| due to high left ventricular chamber pressure resulting in focal myocardial ischemia |
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Term
| Other heart problems in HCM |
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Definition
1. Atrial fibrillation w/ thrombus formation and possible embolization
2. infective endocarditis of the mitral valve
3. intractable cardiac failure
4. ventricular arrhythimias and sudden death |
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Term
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Definition
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Term
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Definition
| variable with differing ages of onset, distribution and clinical presention |
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Term
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Definition
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Term
| HCM is primarily a disease of what |
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Definition
| sarcomere (60%) of patients |
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Term
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Definition
B-myosin heavy chain-44%
myosin binding protein c-35% |
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Term
| Effects of cardiac myosin heavy chain mutation on mouse |
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Definition
1.hyper dynamic ejection
2.reduced diastolic filling
3.impaired relaxation
4.pressure gradient btwn ventricular and aortic pressures
5.delayed pressure relaxation and rapid pressure acceleration |
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