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33 Cards in this Set
- Front
- Back
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Disorders which show and earlier age of onset and increased severity with successive generations are called _____.
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Anticipation
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What causes unstable mutations?
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Genes with an abnormal number of multiple tandem repeats are unstable.
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During DNA replication what causes Genes with abnormal number of multiple tandem repeats to have further repeats occur?
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Slipped mispairing at the replication fork during DNA synthesis.
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Describe the slipped mispairing at replication fork which leads to increased repeats (results in an unstable mutation).
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The DNA at the replication fork becomes single-stranded briefly, then aligns out of register within the repeat region as synthesis continues
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How does instability (an increase in repeats) affect the phenotype of the disease (two ways)?
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Protein sequence alteration
Alteration of mRNA stability, translatability or splicing |
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Name three diseases caused by unstable mutations.
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Huntington Disease
Fragile X syndrome Myotonic dystrophy |
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What is the symptoms of myotonic dystrophy?
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Delayed skeletal muscle relaxation following volutnary contraction
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What is the molecular basis for myotonic sytrophy?
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Splicing errors result in a mature mRNA encoding a non-functional protein. Lack of this chloride channel affects ion conductance in skeletal muscle and probably leads to the myotonia.
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Define this term: Process which equalizes the relative contribution of the X chromosome in females and males.
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Dosage compensation (or X inactivation)
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Where is the inactive X genes stored?
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In condensed chromatin located in the Barr Body.
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How does X-inactivation affec the clinical presentation of X-linked mutations?
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May be present as a continum due to random inactivation
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What is the clinical presentation of Fragile X syndrome?
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Cytologicall an unstained gap on the long arm of the X chromosome.
Behavioral problems Moderate to sever mental retaration Delayed moto an speech skills |
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What is the molecular basis for Fragile X?
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A normal allelee contains 6-52 CGG triplets. in Fragile X syndrome when the repeats increase beyond 230 this region becomes hypermehtylated and transcription of this allele is shut off leading to manifestation of the disease.
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What are normal transmitting males in reference to Fragile X syndrome?
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Males having an intermediate number of repeats (50-230).
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Define: Repeats whichare unstable in meiosis in females causing an increase in the number of repeats and potentially leading to Fragile X syndrome?
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Premutations
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Do normal transmitting males have unstable mutations within the repeat region?
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No, therefore the children will not develop Fragile X syndrome.
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Name the disease: Characterized by
Sudden jerky, involuntary movements Sever problems with balance and coordination Difficulty shifitng your gaze without moving your head Hesitant, halting or slurred speech Swallowing problems Dementia. |
Huntington Disease
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What is the biochemical basis for Huntington disease?
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Cag repeat expansion in huntingtin gene's coding region resulting in a toxic gain of function effect
Autosomal dominant. |
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Is the mitochondrial genome circular or linear?
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Circular
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What are the three types of coding products (with numbers) in the mitochondrial genome?
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2 ribosomal RNAs
22 tRNAs 13 proteins involved in oxidative phosphorylation |
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What is the mode of inheritance in mitochondrial DNA.
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Mendelian but always inherited from the mother.
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Give an example of a maternal mitochondria gene disease.
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Leber hereditary Optic neuropathy.
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Name the disease:
Characterized by optic nerve degeneration Missense mutations in any of the three genes encoding respiratory enzymes. |
LHON (leber Hereditary Optic Neuropathy)
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Define: The presence of more than one type of mitochondrial DNA.
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Heteroplasmy
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How does heteroplasmy affect the clinical presentation of mitochnodrial disorders>
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Different proportions of Wild type and normal mitochondria result in many different phenotypes
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describe the three major features of mitochnodrial behavior and function which result in a wide range of clinical phenotypes.
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Heteroplasmy
Different tissue requirements for oxidative phhosphorylation Oxidative phosphorylation in general declines with age so mitochnodrial disease may become more symptomtatic in older patients. |
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Define: The phenomenon of parent-of origin gene expression.
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Genomic imprinting
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What is the molecular basis for genomic imprinting?
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Some genes are expressed from a maternally inherited chromosome and some are silenced on the paternal chromosome while other genese sho the opposite expression pattern and are only expressed from a paternally inherited chromosome.
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What is the biochemical basis for PWS and Angelman syndrome?
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A deletion in either the paternal or materanal chromosome results in the genes not being inactivated.
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Name this disease:
Hypotonia Initial failure to thrive Distinctive facial features Mild to moderate mental retardation Hypogonadism Eating disorder (obesity) |
Prader-Willi syndrome
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Name this disease:
Characterized by Hypotonia Seizures Jerky, uncoordinated Movements Severe Mental retardation Unprovoked smiling/laughter lack of speech |
Angelman Syndrome
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What does Prader-Willi Syndrome result from? (What deletion where?)
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Deletion on Paternal 15
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Where does the deletion occur for Angelman syndrome?
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Deletion on maternal 15
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