Genomes, Genetic Variation & Mutations Flashcards
what is significant about eukaryotic genomes?
are large
arranged as linear chromosomes
mitochondrial genome
What are exons?
only a small part of the genome
lots of the sections of the chromosome are non-coding DNA
protein coding regions only 1.5%
What are transposons?
45% transposons of human genome
can replicate and insert into other parts of the genome
discovered in 1940s in maize
some transpose via mRNA
What are the 2 cateogories of transposons?
DNA transposons (Class2)
Retrotransposons (Class1)
What are DNA transposons?
move via a DNA intermediate
via a cut and paste mechanism
can insert into different sections
most mobile elements in bacteria
What are retrotransposons?
move via an RNA intermediate phase
most mobile elements in eukaryotes
most common type in human genome
inserted by an enzyme coded by the RNA
or by different type of reverse transcription
Eukaryotic genomes
highly variable in size
variability attributed to repeated sequences & non-coding DNA
transposons can insert copies elsewhere in the genome
retrotransposons transpose via RNA
How are genomes sequenced?
- sequence many small fragments
- assemble sequence in silico (bioinformatics)
fragments held together by overlapping sections
First generation sequencing
very easy and advantageous
wouldn’t use to sequence a genome now
second generation sequencing
creates short fragments
high throughput
cost effective
often doesn’t get a complete genome
third generation sequencing
single molecule sequencing
produce long sequences
flow cell pores full of DNA molecules
pores detect current as DNA passes through
Genome Sequencing
allows rapid sequencing of non-repetitive parts of genomes
sequence repeated sections also required single molecule sequencing
types of genetic variation (4)
single nucleotide polymorphism (SNPs)
indwells (insertions and deletions)
copy number variations (CNVs)
Structural rearrangements
What is an allele?
term to describe alternative forms of a heritable trait
What is polymorphism?
variation within a population of a given trait
What is a single nucleotide polymorphism?
variation that occurs in a single nucleotide
e.g. A->T to T -> A
When was the first genome published?
2001
genome sequence in 2007 was less than $1million
0.1% of genome was different at snip level to reference genome
What is an INDEL?
insertion / deletion
small scale of inserting or deleting a base pair
disrupts reading frame
many different insertion types so polymorphic
multi allelic so useful in genetic profiling
What are the effect of base substitutions in coding regions?
degenerate
- changes in 3rd nucleotide often has no effect
silent
- no change in amino acid
missense
- changes amino acid completely
nonsense
- translates for a stop codon
can cause frameshifts and non-functional proteins
What is a base pair transition?
changes from pyrimidine to pyrimidine or purine to purine
what is a base pair transversion?
changes from pyrimidine to purine
what is the term for the normal allele?
wild type
What mechanisms to cells have to prevent and correct mutations?
proofreading by DNA polymerases
post-replication mismatch repair
DNA repair by homologous recombination
cell cycle checkpoints
What is an intercalating agent?
chemical mutagen inserted between base pairs
causing a frameshift mutation
what is a base analogue?
chemical mutagen incorporated into DNA in place of a normal base
causing a mispair and base substitutions
what are base modifying agents?
chemical mutagen
covalently alter a base causing the base to mislaid
base substitution
what is the structure of an intercalating agent?
planar molecule
intercalate between base pairs
get between DNA and cause issues with replication
What is the structure of base analogues?
analogue of thyme
also pair with guanine
mimic bases and become integrated in DNA
what is the structure of base modifying agents?
covalently alter a base
delaminating agents remove amino groups
hydroxylating agents add hydroxyl groups
alkylating agents add alkyl groups
What is a delaminating agent?
remove amino groups
cytosine can lose an amino group and become uracil
What is an alkylating agent?
add alkyl groups
What is replication slippage?
DNA strand separation and rejoicing at different places
may have looping out
more likely with repeating strands
if in synthesised, results in addition of repair unit
if in template, deletion of unit
What is mutant selection?
selection of mutant by geneticists to isolate rare mutants
what did the Lederberg Experiment demonstrate?
mutations occurred before selection - colonies that survived were in the same position
mutations are random
