CMMB final material Flashcards
The human genome main
- two copies in every somatic cell
- one copy in gametes
- 22 autosomes and 2 sex chromosomes
Genetic variation in normal populations
a) chromosomal level
b) CNV/person
c) single nucleotide level
Genetic variation also causes disease
a) whole chromosome (aneuploidy) Trisomy 21 (Down’s Syndrome)
b) Partial chromosome imbalance: seen by FISH
c) single nucleotide substitutions= Achondroplasia (little people)
polymorphism
any change within a popualtion thats >1%
-rare variant- anything less than 1%
Types of DNA polymorphisms
- single nucleotide insertion/deletion
- microsatellite
- minisatellite
- copy number variant (CNV)
- single nucleotide variant (SNV)
single nucleotide insertion/deletion
- many in the genome, unstable through generations
- unstable because DNA reproduces a second strand that can slip causing gain/lost od nucleotides
Microsatellites
- repeat units are 2-5 nucleotides in length
- also called Short Tandem Repeat (STR)
- certain number of repeats= many alleles in normal populations
Microsatellite uses
- DNA fingerprinting (everyone has different number of repeats)
- also half are passed off to kids
- disease: finding where those genes are located
Minisatellites
- repeat units are 10-100 nucleotides in length
- also called VNTR–> variable number of tandem repeat units
- Southern blot used
Copy Number Variation
- deletions and duplications
- range from 200 to >2000000 nucleotides
- usually 0-4 copies
Single nucleotide variants (SNVs)
- most common type of sequence variation
- more than 3000000/person
- many different effects: benign to disease-causing
Origins of Sequence Variation/Mutations
- replication errors
- DNA damage (deamination, depurination, demethylation) also by mutagens
Large deletion/duplication mechanisms
- more likely to happen in repetitive sequences
- if homologous sequences are very similar wrong ones can align together
CMT1a
Charcot-Marie-Tooth
- duplication
- progressive peripheral motor and sensory neuropathy (numbness/weakness)
HNPP
- Hereditary Neuropathy with Liability to Pressure Palsies
- peripheral nerves are unusally sensitive to pressure and results in numbness, tingling, and/or loss of muscle function
-deletion
Haemophilia A
- inverted repeats
- found in 45% of patients
normal is
1-21,22,23
affected
22, 21-1, 23
Translation refresher
a codon= 2 base pairs (total=64 codons)
-each codon= 1 amino acid
20AA
3 STOP: UGA, UAA, UAG
1 START: AUG (met)
Nomenclature (DNA level)
nucleotide #1: A in ATG (start)
upstream nucleotides are negative eg) 2 bps to the left= -2
downstream coding nucleotides numbered normally–> introns are skipped
amino acids numbered starting with the start codon=1
Mutation Types
A) Nucleotide Substitutions -AA effect: synonymous (silent) non synonymous (missense) nonsense splicing effects
B) duplication/deletion
- small
- large (one or more exons)
C) dynamic mutations
Synonymous (silent)
-DNA sequence change doesnt change the actual AA that is coded
Non-synonymous (missense)
-DNA sequence change; CHANGES the AA
Nonsense
premature stop codon
-ie) CTA–> CTG both are LEU
if this is found as the 325th AA in a protein how would you write that?
p.Leu325Leu
CTG–>CCG (LEU–> PRO)
if this as the 112th AA in a protein how would you write that?
p.Leu112Pro