MTM WK6 - MUTATIONS & GENETIC DISEASES Flashcards
(28 cards)
GENOME VARIATION
changes in number or structure of chromosomes e.g. DNA substitution or deletion
PATHOGENIC GENE VARIATION
variation that disrupts gene function
CAUSES OF MUTATIONS (4)
- errors in DNA rep.
- UV - covalently binds 2 adjacent thymines (BAD)
- ionising radiation - breaks in DNA
- chemicals - breaks in DNA
POLYMORPHISMS
non-harmful mutations e.g. silent or substitution
SINGLE NUCLEOTIDE POLYMORPHISM (SNP)
change in single base at particular position e.g. most ppl have C at one place but some have T (>1%)
DNA SEQUENCING (used to look for bases)
- amplify tiny amounts of target DNA & use DNA as template to generate set of fragments that differ in length from each other then sequence fragments by size, identify bases at end & recreate original DNA sequence
- determine exact location & type of mutation
ENDOGENOUS (inside) MECHANISMS CAUSING DNA DAMAGE (3)
- DEPURINATION (deletion mutation of A or G due to splitting of purine-sugar bond)
- DEAMINATION (cytosine randomly deaminated to uracil)
- CYTOSINE METHYLATION (cytosine deaminate to form thymine)
GERMLINE MUTATION
mutations in egg/sperm which are heritable
SOMATIC MUTATIONS
non-heritable mutations in non-germline tissues
CHECKS FOR DNA REPLICATION SUCCESS (3)
- G2 checkpoint checks DNA
- DNA polymerase checks for issues as it adds bases
- mismatch proteins (excise newly synthesised mismatch & use template strand to re-synthesise new one)
REPAIRING OF DOUBLE-STRANDED DNA BREAK
use ligands to pair ends of broken strands (leads to deletion of some nucleotides)
MISSENSE MUTATION
substitution where new code codes for different amino so dif. primary so dif. tertiary
NONSENSE MUTATION
substitution mutation which codes for stop codon
SPLICE-SITE MUTATION
occur where splicing is meant to occur (leads to altered RNA sequence)
COPY NUMBER MUTATIONS
insertion/deletion caused by unequal crossing over between repeat sequences (as there are too many repeats)
LIGHT VS DARK BANDS OF CHROMOSOME
light replicates earlier & has less condensed chromatin
WAYS WE EXAMINE CHROMOSOMES (3)
Karyotype, FISH, array CGH
KARYOTYPE (lowest resolution)
get sample of blood –> separate RBC –> add cultured medium to suspension –> incubate for 3 days at 37 –> add something that stops cell division –> fix cells –> stain cells –> photograph cells –> organise cells into karyotype –> examine chromosomes for errors
FISH
create fluorescent probes to hybridise specific area of chromosome then hybridise patient DNA & look for fluorescent markers (e.g. light up if chromosome present)
ARRAY CGH
- hybridise both the test genomic DNA & normal reference DNA in DNA microarray containing probes representing genomic regions of interest (DNAs compete for same probe site on microarray)
- if reference & test DNA are same then you get one middle colour but if patient doesn’t have chromosome in a part, it fluoresces
KARYOTYPE NOMENCLATURE OF ABNORMALITIES
number of chromosomes —– sex chromosomes —- abnormality e.g. 47,XX,+21 (down syndrome as 1 extra chromosome & +21)
NON DISJUNCTION
cell doesn’t divide properly so one daughter has 2 copies of chromosome & one daughter has 0
ANEUPLOIDY
change in number of a specific chromosome (trisomy = 3 copies of chromosome) (monosomy = 1 copy (1 less than usual)
POLYPLOIDY
change in overall chromosome number (triploidy = extra set of chromosomes (3 sets)) (tetraploidy = 2 extra sets of chromosomes (4sets/92 pair)
