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22 Cards in this Set
- Front
- Back
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What are some causes of epigenetic differences?
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Differing expression of genes can be caused by methylation - silence a gene hotspot
Histone modification microRNAs (inhibit gene expression - account for 2% of human genome) |
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What is caused by overactive PCSK9 protein, and what is one way production could be decreased?
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leads to dangerously high levels of cholesterol
RNAi against PCSK9 was shown to reduce levels of bad cholesterol up to 60% |
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What is the sequence of gene silencing causing by RNAi?
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dsRNA binds to DICER complex
DICER cleaves dsRNA into smaller fragments RNA strand loaded into RISC, and linked to mRNA by base pairing mRNA cleaved by RISC |
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Describe the phenotypic (physical and personality) features of Fragile X
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Physical:
Mildly dysmorphic facial features - long thin face, prominent forehead and jaw, large ears Connective tissue abnormalities Mitral valve prolapse Patulous Eustachian tubes Joint Laxity Marco-orchidism Personality: Moderate to severe intellectual disabillity Autistic like behavior, temper tantrums, hyperactivity, hyperacusis ( sound sensitivity), impulsiveness, unusual speech pattern, depression |
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What causes Fragile X?
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excessive CGG repeats lead to methylation of the FMR1 gene and failure of expression
>200 repeats is the full mutation 55-199 is premutation - some symptoms and at risk for Fragile X child. FMR1 not methylated 50-55: grey zone - potential risk controversial 0-49: normal |
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What are CpG islands?
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unmethylated CGG repeat regions at the 5' ends of many genes
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What is Martin-Bell's Pedigree?
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Pedigree for Fragile X-
CGG repeats can expand in female meiosis but not significantly in male meiosis |
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What abnormalities are exhibited in pre-mutation carriers of Fragile X?
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Males: FXTAS (Fragile X associated tremor ataxia syndrome)
Females: Premature Ovarian Failure (21% risk in these carriers) |
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What pathway is being exploited as a potential FMR-1 therapy?
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Metabotrobic glutamate receptor 5 pathway antagonists have demonstrated benefits in reducing seizures, improving behavior and cognition
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Define Triplet Instability
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Areas of DNA with triplet nucleotide repeats that are unstable past a certain number of repeats (expansion is possible)
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What causes Prader Willi and how can Prader Willi Syndrome be detected?
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Prophase banding - paternal del 15q11.2 in 60% of patients with PWS
(use FISH) |
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What are the symptoms of Prader-Willi?
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Neonatal Hypotonia
Hyperphagia/obesity short stature moderate intellectual disability hypogonadism small hands and feet characteristic faces esotropia temp instability dec ability to vomit and high pain threshold viscous saliva speech articulation defects coronary artery disease |
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What causes Angelman syndrome?
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Deletion of 15q.11.2 in maternal chromosome
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What are the symptoms of Angelman Syndrome?
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Severe intellectual disability
seizures absent speech paroxysms of laughter tongue protrusion stiff ataxic gait characteristic faces |
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What causes differing expression of genes on maternal vs paternal chromosomes? Which chromosomes can this occur on?
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Caused by imprinting (as in Angelman and Prader-Willi syndrome)
Only occurs on certain chromosomes: 6,7,11,15 |
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How does epigenetic reprogramming occur?
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Epigenetic imprints are erased when primordial germ cells enter the gonads, and imprinting occurs during different stages of gametogenesis in male and female
Male: haploid (meiotic phase) on spermatogenesis Females: likelly occurs during postnatal growth phase while oocytes are still arrested in diplotene of prophase I. |
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What are the genes affected by deletion or imprinting that result in Prader Willi?
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Paternal expression has active SNURF/SNRPN and methylated UBE3A.
Deletion gets rid of SNURF/SNRP, leaving only maternal expression in of UBE3A Uniparental Maternal Disomy results from incorrect methylation of paternal chromosome - SNURF/SNRPN is methylated and UBE3A is not |
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What are possible therapies for PWS?
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Growth Hormone, testosterone, rigid diet, behavioral therapy
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What are possible therapies for Angelman?
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Physical therapy and adaptive devices to help with gait/balance problems. Speech therapy
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3 Other imprinting disorders
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Transient Neonatal Diabetes Mellitus
Silver Russel Syndrome Beckwith Wiedmann Syndrome |
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Define Uniparental Disomy
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Both members of a chromosome pair or segment of a chromosome pair are inherited from one parent and neither is inherited from the other parent
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What is trisomy rescue
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Poorly understood decrease from trisomy to disomy - can cause uniparental disomy
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