Glossary of 9-1-05 Molecular medicine
Other Decks By This User
- A DNA sequence variation may or may not be pathogenic
- an allele present in more than 1% of the general population
- G2983>A means what?
- a nucleotide exchange of guanine for adenine at position 2983
- What does C282Y mean?
- a missense mutation C is original amino acid, the position, and the new amino acid (tyrosin)
- What does W1282X mean?
- nonsense mutation original, position, folowed by X
- what does 711+1G->T
- mutation in intron/splicing site 1 is the 5' donor splice site
- What is a point mutation?
- a single base pair change in DNA
- What is missense mutation?
- changes in amino acid.
- What is silent mutation?
- does not change Amino acid
- what is conservative?
- changes to an amino acid with simliar properties
- What is a nonsense mutation?
- creates a stop codon Very deletarious to the protein!
- What are RNA splicing mutations?
- they disrupt the consensus sequences from splicing, or create alternative sites (pathogenic)
- What are small insertions/deletions?
- Will change reading frame (frameshift) if not in multiples of 3. (pathogenic)
- What is loss of function?
- reduces or eliminates the amount of funstional protein. ie. CF
- What is gain of function?
- increases production of a normal protein ie Anchondroplasia
- What are novel property mutations?
- changes function of the protein ie sickle cell anemia no effect on O2 transport, Huntington disease
- What is dominant negative?
- An allele that disrupts the function of the wild type allele in the same cell. Its worse than having none. Osteogenesis imperfecta.
- What are triplet repeat expansions?
- unstable mutations in which have expansion of a segment of DNA that contains 3 nucleotides
-lead to abnormalities of gene expressionandfunction
-repeats can be anywhere in gene even in intron
Huntington, fragile X, spinal cerebellar ataxis, Freidreichs ataxias, myotonic dystrophy
- What is anticipation?
- degree of expressivity or penetrance changes, usually increases, from one generation to the next
- What is parental bias?
- tenedency for a repeat to expand differs from a male vs. female
- important concepts of mitochondrial genetics
- -own genome
high mutation rate
-variable inheritance and expression (diff phenotypes even in same family)
-heteroplasmy (diff tissue have diff levels)
-segregate as mendelian traits
- Couple key ideas about Real time PCR
- very rapid and sensitive 1/100,000
-use melting point analysis mutation destablizes and reduces melting point. Heterozygotes have 2 Tm's.
- What is RFLP?
- Restriction fragment length polymorphism use restriction enzymes to cut DNA at specific sites palindromic sequences
-good if mutation adds or deletes a site so get change in pattern
- What are "ARMS"?
- -Allele specific PCR amplification
-good if mutation doesnt change restiction site
-faster than PCR RFLP
-design primers specific to mildtype and mutated sequence
-needs 3' end to add and wildtype primer will extend
-score for absence/presence of a band)
- What is ASO or Dot Blot?
- -allele specificoligonucleotide hybridization
-short probes if perfect match will hybridize
-useful if no informative restriction site
-if probe binds you get color
-can be adapted for high throughput by spotting oliogos and probing patients labelled DNA (reverse dot blot)
- What is microarray?
- ASO for known mutations probes can be spotted onto chip, fluoresce labeled patient DNA will bind to mutant or WT or both. Mismatches wont bind.
- Southern Blotting +/-/
- can see large scale duplications and deletions expansions
-disadvantages: takes forever , expensive
- DNA sequencing
- incorporates random ddNTPs that dont allow pol to extend
+speels out DNA seq (gold standard)
- Newer DNA sequencing
- automated, uses fluorescence read by laser/CCD camera
should be 1 peak/position.
overlapping (go over)
- What are microsatellites?
- short tandem repeats
-maternal cell conamination
- What is locus heterogeneity?
- more than one locus associated with a specific clinical phenotype (lots genes, 1 disease)
- Modifier gene
- gene that alters phenotype associated with mutations in a non allelic gene (thalassemia and sickle cell interaction)
- Clinical or Phenotype heterogeneity
- association of more than one phentype with mutations at a single locus. 1 gene, variable disease CF)
- Allelic heterogeneity
- multiple alleles at a locus ( many possible mutations in 1 gene, CF)
- Diagnostic Testing
- having a diagnosis is important to know recurrence risk, access support groups, avoid other invasive $$ procedures
- Predictive testing
- asymptomatic patients want to know. Counseling
- Carrier testing
- most informative when familial mutation is known disouraged in children
- Prenatal testing
- familys specific mutation should be known before testing offered
- ______ is used for biochemical disorder testing
- enzyme assay
- When family history of a disease, should______________
then subsequent at risk people can have very informative test for only that mutation
- Affected person tested
CF carrier screening,ehthnicity matters!
You must Login or Register to add cards