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47 Cards in this Set
- Front
- Back
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in an X-linked recessive disease, how could a dad with the disease pass it on to a son?
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Uniparental Disomy
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what's uniparental disomy?
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Inherit both homologs of a chromosome pair from the same parent
*trisomic resuce |
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what's trisomic rescue?
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Presume that the fetus was originally trisomic with loss of a chromosome leading to a “normal” disomic state
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where's the mess up in uniparental heterodisomy?
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Meiosis I
two different homologs of the same chromosome (nondisjunction ) |
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where's the mess up in uniparental isodisomy?
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Meiosis II
two copies of the same homolog (nondisjunction) |
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what are exs of uniparental disomy?
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CF w/ only 1 parent is known carrier
Hemophilia A: father to son transmission |
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what's differential expression of two alleles of a gene in somatic cells?
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genomic imprinting: one allele is “on”, the other is imprinted (“off”), usually due to hypermethylation of the DNA
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what type of gene inactivation is genomic imprinting?
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Reversible form of gene inactivation, not due to a mutation
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what's the effect of parent of origin of gametes in imprinting?
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The genomes we inherit from our mothers and fathers are not functionally equivalent
~0.1% of genes are imprinted |
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what are the symptoms of Prader-Willi syndrome?
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Mild to moderate mental retardation
Short stature Small hands and feet Palpebral fissures almond shaped (+/- upslanting) Small external genitalia Hypotonia and poor feeding (infancy) Compulsive overeating (hyperphagia) and obesity beginning at about 2 years Many with fair hair and skin color *Stomach rupture the most common cause of death |
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what mutation causes Prader-Willi syndrome?
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Deletion on paternally derived chromosome 15 in 70% of cases:
PRADER deleted PATernal! |
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what mutation causes Angelman syndrome?
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deletion on maternally derived chromosome 15 in 70% cases:
AngelMAN deleted MOM! |
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what are the symptoms of Angelman syndrome?
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Severe mental retardation
Inappropriate laughter Seizures Jerky gait “Happy puppet” syndrome |
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genomic imprinting is an ________ modification of DNA resulting in: ______
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Genomic imprinting is an epigenetic modification of DNA resulting in the monoallelic and parent-of-origin specific expression of certain genes: 1 allele makes protein
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when does genomic imprinting occur?
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Occurs during gametogenesis before fertilization and marks genes as having come from either the mother or father
After conception, the imprint suppresses expression of the imprinted allele in some or all of the somatic tissue of the embryo |
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what are some genes that are maternally and paternally imprinted?
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maternally: ZNF127, NDN, SNRPN, IPW
paternally: E6-AP, ATP10C |
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Why are kids w/ Prader willi so fair?
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melanin gene (P) deleted
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what are the other causes of Prader-Willi?
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uniparental disomy: 25%
other: 5% ex: imprinting center error - regulates imprinting switch in gametes |
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is an imprinted allele expressed or silenced?
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silenced b/c hypermethylated
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is chromosome 15 imprinted only in ppl w/ Angelman and Prader Willi?
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no in everyone- these kids just happen to have deletions in the part of genes that are supposed to be expressed- have missing genes
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what is an imprinting center mutation?
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Imprinting center region that controls the imprint switching during gametogenesis
Mutation disrupts regulation of imprinting switch |
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what are the causes of Angelman syndrome?
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Deletion on maternally derived chromosome 15 - 70%
Uniparental disomy <5% Other 20-30% Imprinting center error Mutation in E6-AP (UBE3A) Causative gene |
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what's the problem with Angelman syndrome: uniparental disomy?
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Inherited both chromosome 15’s from father
Both alleles are imprinted (off) So no gene product is produced |
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what gene's affected by mutations in E6-AP (UBE3A)? what's bad about mutation?
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Ubiquitin-protein ligase gene
Normally expressed only from the maternal allele in the central nervous system Tissue-specific imprinted gene that may contribute to the severe mental retardation seen in these patients |
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who passes on disease with mitochondrial disease?
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mom
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what are the symptoms in MERRF: myoclonic epilepsy with ragged red fibers? how does disease change over time?
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Myoclonic epilepsy and mitochondrial myopathy with ragged-red fibers
Onset generally can be from childhood to late adulthood Course can be slowly progressive or rapidly downhill May also develop other symptoms: sensory neural hearing loss, ataxia, diabetes, cardiomyopathy and dementia |
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what are 90% mutations of MERRF from?
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mitochondrial tRNAlys gene
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what are the mitochondrial funcs?
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energy production!! any organ that has a high need for energy are more likely to be mutated
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how many genes does mitochondrial DNA have?
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37 genes
2 rRNAs 22 tRNAs 13 mito protein subunits |
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nuclear DNA codes for hundreds of proteins important to mitochondrial struc and func:
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All replication factors are nucleus-derived
Inter-genomic communication |
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how many basepairs does mitochondrial DNA have?
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16,569 nucleotide base pairs (versus 3 billion in nuclear DNA)
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why is mutation rate the way it is for mitochondria?
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Lack proof-reading and significant DNA-repair mechanisms
Mutation rate 10-100 times greater than that of nuclear DNA |
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how many mitochondria in ea cell? how many copies of mtDNA in ea mitochondria?
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100’s of mitochondria in each cell
2-10 copies of mtDNA in each mitochondrion |
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how do mitochondria divide?
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by simple fission and each mtDNA molecule divides within the mitochondria.
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how do mtDNA molecules sort themselves in mitochondria?
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randomly among the new mitochondria and the mitochondria distribute randomly between the two new daughter cells – Replicative Segregation.
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what's the presence of more than one type of mitochondrial DNA in the mitochondria of a single individual?
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heteroplasmy
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what's the presence of only one type of mitochondrial DNA in the mitochondria of a single individual?
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homoplasmy
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how is mitochondrial mutation phenotypically expression?
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Dependent on the proportion of normal to mutant mtDNA in the cells of different tissues
Can vary according to the dependence of the tissue on oxidative energy production Therefore, reduced penetrance, variable expression and pleiotropy are all features of mito disorders! |
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where is mitochondrial dysfunction most evident?
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in tissues that are most dependent on aerobic energy production
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when does mitochondrial dysfunction show itself?
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Tissue/mutation-specific threshold effect
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what is mitochondrial dysfunction modified by? may occur at?
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Modified by proportion of abnormal mitochondria
May occur at different times in clinical course |
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why is mitochondrial inheritance maternal? who carries on gene?
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Maternal inheritance - abundance of mito in ovum (~200,000), few in sperm (~10) and those few do not persist in offspring, therefore inherit all mtDNA from mom
Daughters transmit mtDNA, but sons do not |
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describe genetic bottleneck:
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1) Heteroplasmic females usually transmit some mutant mtDNAs
2) The number of mtDNA within each oocyte is reduced before being amplified in the mature oocyte - mitochondrial “genetic bottleneck” leads to variability in the percentage of mutant mtDNA seen in offspring 3) Mothers with a high proportion of mutant mtDNA molecules are more likely to have clinically affected offspring than those mothers with a lower proportion |
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what's the inheritance pattern of mtDNA?
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Maternal (deletions, point mutations, duplications)
Sporadic (deletions, point mutations) |
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what's the nuclear inheritance pattern?
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Autosomal dominant
Autosomal recessive X-linked |
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mitochondrial diseases involve what components of nervous system?
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Mitochondrial disease involves one or more components of the nervous system in combination with that of other organ systems
Mitochondrial disease is an under-recognized cause of neurologic dysfunction in children and adults |
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how are mitochondrial diseases inherited?
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Mitochondrial diseases may be inherited either in Mendelian or non-Mendelian fashion; important implications for genetic counseling
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