Term
|
Definition
| Disease severity increases or age of onset decreases from one generation to the next |
|
|
Term
| Classification of alleles in tandem repeat expansions |
|
Definition
Mutable: Do not cause disease but show meiotic instability(Sex specific)
Slipping back, expand.(looping out of okazaki fragments.)
Slipping forward(looping out of template strand = Contraction.
Intra-strand hairpins is the key to dynamic instability |
|
|
Term
Repeat Disorders
Fragile X:
Freidreich Ataxia:
Huntington, SCA:
Freidrecih Ataxia:
Myotonic Dystrophy: |
|
Definition
Fragile X: CGG 5'utr, Maternal.
Huntington, SCA: CAG coding paternal
Freidreich Ataxia: GAA Intron
Myotnic Dystrophy: CTG(I)Coding
or CCTG(II) Intron
maternal |
|
|
Term
| Dna testing for Dynamic Mutations |
|
Definition
(NNN) 6-200 PCR
(NNN) > 200 southern blot |
|
|
Term
| Cytogenetic diagnosis of Fragil X |
|
Definition
Non staining constriction near the distal end of Q
Heavy amount of methylation on repeat expansion causes lack of staining.
Probe 5' region of FMR1 gene.
CGG repeats methylated. MeCP2 binds, recruits HDACs. Chromatin condensation |
|
|
Term
| FRAXAS and Fredreich Ataxia |
|
Definition
Mutation may be due to triplet expansion or missense mutation/deletion.
Both diseases are null mutation.
Associated tremors in FRAXAS(late in life) are due to altered RNA function. |
|
|
Term
| Pathogenetic Mechanism of CTG repeats in DM1 and DM2 |
|
Definition
| DM1 and DM2 mRNA is CUG. CUG repeats titrate out an RNA binding protein necessary for correct splicing of other mRNAs. |
|
|
Term
| Pathogenesis of polyglutamine diseases |
|
Definition
Huntingtons and SCA.
Insoluble aggregates or inclusions from protein.
Inclusions are protective.
Selective pathogenesis of htt.
Rhes is only expressed in Cerebral cortex.
Rhes binds mHTT and promotes sumolyation.
Aggregate -> soluble by SUMO. Solubule is cytotoxic. |
|
|
Term
| Male and Female differentiation |
|
Definition
SRY -> SOX9 SOX9 inhibits female WNT4.
WNT4 -> DAX1 inhibits SOX9 |
|
|
Term
|
Definition
| Acts as mRNA. Only enough for 1 x chromosome is produced. |
|
|
Term
| Huntington and SCA diagnosis |
|
Definition
|
|
Term
| Pathogensis polyglutamine diseases |
|
Definition
| • Pathogenesis of polyglutamine diseases is not through the cellular inclusion formation but through interference with transcriptional regulation of key cell cycle regulator genes |
|
|
Term
|
Definition
Loss of function. Half is not enough
Generally, all(different) mutations in a gene result in same phenotype.
Nail Patella Syndrome |
|
|
Term
Gain of function.
Autosomal Dominant mechanism |
|
Definition
Up-regulation, novel function.
Normally Missense
Different mutations in same gene may
Null gives opposite disease.
FGFR3 |
|
|
Term
|
Definition
Mutant protein interferes with normal protein (collagenopathies)
Different mutations in same gene -> same phenotype
Null gives milder disease |
|
|
Term
|
Definition
Type 1: Null mutations, haploinsufficiency
Type 2-4: missense, dominant negative |
|
|
Term
| Premature termination codon |
|
Definition
End result is no protein made.
Null mutation |
|
|
Term
| Disorders due to gross changes in DNA. |
|
Definition
usually recombination between non-homologous repeat sequences
22q11 deletion syndrome
a-thalassaemia
Williams-Beuren Syndrome
Smith-Magenis
Deletion usually worse then duplication |
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