Term
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Definition
| methylation of DNA in a genome hotspot silences a gene; histone modification of a protein may alter its activity |
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Term
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Definition
| do not encode proteins but inhibit gene expression |
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Term
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Definition
| silences genes for high cholesterol, etc. |
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Term
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Definition
| areas of DNA w/ triplet nucleotide repeats that are unstable past a certain number of repeats; repeats expand per generation. |
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Term
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Definition
| "at a single locus, an allele is either active or inactive depending on the parent from which that allele was inherited" - increased risk in assisted reproductive technologies. maternal/paternal must both become one or the other when the offspring grows up and gives genes to their offspring. if not, results in badness |
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Term
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Definition
| both members of a chromosome pair or segments of a chromosome pair are inherited from one parent and neither is inherited from the other parent |
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Term
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Definition
| increased severity of phenotype in successive generations (like increased triplet expansions) |
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Term
| fragile x presentation, inheritance, treatment |
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Definition
| joint laxity, mitral valve prolapse, patulous eustachain tubes / recurrent OM (big ears that accumulate fluid), macro-orchidism onset during puberty (big balls). moderate to severe intellectual disability, hyperactivity, depression, unusual speech pattern, temper tantrums. "can i have the blood back now". / worse in boys than girls. repeat disorder (on X chromosome) - CGG repeats result in epigenetic change that leads to suppression of a gene and reduction of protein that's important in testis+brain development. counseling - mothers have 50% chance of having an affected child w/ fragile x. mGluR inhibitors = treatment. mGluR causes long-term depression in mice. fragile x is a disease of excess |
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Term
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Definition
| = CGG repeats. unmethylated regions of genome that are associated with the 5' ends of most housekeeping and many regulatory genes. methylation hotspots (methylation is thought to be the principal mechanism behind x-chromosome inactivation and imprinting). |
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Term
| categories of CGG repeats |
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Definition
| 0-45 normal, 46-54 grey zone, 55-199 premutation, >200 full mutation |
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Term
| pre-mutation carrier w/ 103 repeats on one X and 30 on another has _% chance of having an affected child with fragile X |
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Definition
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Term
| why do females usually have less severe fragile x than males |
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Definition
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Term
| premature ovarian failure |
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Definition
| 21% risk in female premutation carriers |
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Term
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Definition
| fragile x-associated tremor-ataxia syndrome - affects male pre-mutation carriers |
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Term
| prader-willi syndrome presentation, inheritance and treatment |
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Definition
| floppy and underweight as a baby, and then hyperphagia begins. cognitive delay, behavioral problems, temperature instability, short stature, esotropia (eyes turn in). decreased ability to vomit, high pain threshold, hypogonadism, unusual skills with jigsaw puzzles, speech, skin picking, early puberty (premature adrenarche). obsessive-compulsive behavior worsens with age in adolescence. adult problems - DMII, obesity, CVD, early demise. FISH or methylation analysis (maternal pattern only) diagnoses the deletion in PATERNAL chromosome 70% of the time. 25% = uniparental maternal disomy. 2% imprinting defect. (if this happens there is a high recurrence risk). treatment: GH, testosterone, rigid diet modification, behavior therapy. |
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Term
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Definition
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Term
| Angelman Syndrome presentation, inheritance, treatment |
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Definition
| "happy puppet" always laughing, severe MR so that don't talk, seizures. inherited by same deletion as PWS, but MATERNAL chromosome deletion. |
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Term
| effects of GH therapy in children with PWS (6) |
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Definition
| increased height velocity and final height, decreased fat mass/distribution, increased bone mineral density, improved muscle tone, improved respiratory function and physical performance, changes in body habitus with loss of many PWS characteristics |
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Term
| imprinting / when are there more errors |
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Definition
| hypomethylate = turn ON a gene. imprinting = genetic modifications that are erased during meiosis I and re-done during meiosis II (which happens before fertilization in males and after fertilization in females). more risk of maternal imprinting errors in assisted reproductive technology. |
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Term
| side effects of GH therapy |
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Definition
| early reports of death due to tonsillar hypertrophy |
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Term
| hypogonadism / treatment / what test would you send for it |
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Definition
| FSH and LH deficiencies, small penis, hypoplastic labia minora in 90% of PWS cases, cryptorchidism. / in adolescence treatment with testosterone or estrogen may be helpful in improving bone density, altering behavior, bringing on secondary sex characteristics. / methylation study for Angelman syndrome (or FISH if asked on boards) |
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Term
| mitochondria are inherited from the _ of the _ |
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Definition
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Term
| t/f mitochondrial dna encodes all genes for mitochondrial proteins |
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Definition
| false - encodes for 37 genes. the rest are in the cytoplasm, and resultant proteins are transported back to the mito. "maternally inherited mitochondrial disease" refers to a change in the 37 genes. |
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Term
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Definition
| polypeptides, rRNAs and tRNAs as well as a control region |
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Term
| t/f 95% of mito goes to making ATP |
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Definition
| f - only 5%. 95% does other stuff specific for a differentiated cell |
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Term
| mitochondrial duties stay the same in embryos and adults t/f |
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Definition
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Term
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Definition
| build, breakdown and recycle a cell's molecular building blocks. contain rate-limiting enzymes for pyrimidine biosynthesis (dihydroorotate dehydrogenase). in the liver, mito specifically detox ammonia in urea cycle. required for cholesterol metabolism, est/test metabolism, NT metabolism, free radical production and detox. |
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Term
| maternal mitochondrial genetics (4) |
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Definition
| asexual (high recurrence risk from mom), heteroplasmy (mitos in different areas of the body have different mutations), bottleneck (different amounts of mutant mito in different oocytes), threshold (some tissues need more energy than others; the ones that need more malfunction first when there's not enough ATP) |
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Term
| maternal mitochondrial pedigrees |
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Definition
| everyone inherits stuff from females but not males |
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Term
| most common mitochondrial Dz (3) |
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Definition
| bowel dz, migraine, depression |
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Term
| what to ask for in a family history of mito disease (3) |
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Definition
| psych/neuro problems, migraines, bowel dysmobility, diabetes, deafness, failure to thrive, cardiac problems, degenerative disease. use all relatives (unaffected are controls), ask whether any men w/ symptoms have children w/ symptoms (in maternal mito dz they would not) |
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Term
| clinical course w. multiple systems and no other explanations |
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Definition
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Term
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Definition
| lactic acid, urine organic acid intermediates from kreb cycle |
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Term
| muscle biopsy / how does it change treatment |
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Definition
| 50% yield because of heteroplasmy, but tests for mitochondrial dysfunction in all complexes (or at least 1-4) of electron transport chain. / it doesn't really change treatment - lots of false positives, should try noninvasive testing first. |
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Term
| treatment for mitochondrial dz |
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Definition
| vitamin cocktails unproven. avoid stress/fasting; take fluids w/ sugars; preventative approach |
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Term
| mitochondrial dz is often misdiagnosed as (2) |
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Definition
| fibromyalgia, because of thinness, depression, hearing loss. eye movements, eyelid sagging. OR as vaccine causing autism - quick degeneration due to the STRESS of the shots, but would have developed anyway. compromise- space out the shots |
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Term
| examples of multifactorial inheritance |
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Definition
| hypertension, asthma, autism, diabetes, neural tube defects (take folate!), isolated cleft lip and palate, schizophrenia, cancer, pyloric stenosis |
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Term
| characteristics of multifactorial disorders (3) / recurrence risk |
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Definition
| familial concentration without a set pattern of inheritance; considerable variation in severity and expression of the phenotype; often sex differences in the frequency of occurrence (more males with pyloric stenosis) / 3-5% |
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Term
| recurrence risks in multifactorial disorders are based upon |
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Definition
| empiric risks = statistics |
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Term
| friedrich ataxia presentation, inheritance, treatment |
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Definition
| muscle weakness, loss of coordination in arms and legs (ataxia), vision impairment, hearing loss and slurred speech, aggressive scoliosis, diabetes, hypertrophic cardiomyopathy / trinucleotide repeat expansion > insufficient levels of frataxin, a mitochondrial iron chaperone that shields iron from ROS and renders it bioavailable. / EKG |
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Term
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Definition
| a mitochondrial iron chaperone that shields iron from ROS and renders it bioavailable. participates in the synthesis and maintenance of the iron-sulfur clusters present in complexes I-III of the respiratory chain, and aconitate in the Krebs cycle. friedreich ataxia results in mitochondrial iron overload, leading to mito dysfunction |
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Term
| neurodegenerative disorders with mito components (4) / treatment |
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Definition
| FA, Alzheimer's, Parkinson, amyotrophic lateral sclerosis / clinical trials with anti-oxidant therapy are in progress |
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