Genomes, Genetic Variation & Mutations

Question 1

what is significant about eukaryotic genomes?

Answer 1

are large
arranged as linear chromosomes

mitochondrial genome

Question 2

What are exons?

Answer 2

only a small part of the genome
lots of the sections of the chromosome are non-coding DNA
protein coding regions only 1.5%

Question 3

What are transposons?

Answer 3

45% transposons of human genome

can replicate and insert into other parts of the genome
discovered in 1940s in maize
some transpose via mRNA

Question 4

What are the 2 cateogories of transposons?

Answer 4

DNA transposons (Class2)
Retrotransposons (Class1)

Question 5

What are DNA transposons?

Answer 5

move via a DNA intermediate
via a cut and paste mechanism
can insert into different sections
most mobile elements in bacteria

Question 6

What are retrotransposons?

Answer 6

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

Question 7

Eukaryotic genomes

Answer 7

highly variable in size
variability attributed to repeated sequences & non-coding DNA
transposons can insert copies elsewhere in the genome
retrotransposons transpose via RNA

Question 8

How are genomes sequenced?

Answer 8

1. sequence many small fragments
2. assemble sequence in silico (bioinformatics)
   fragments held together by overlapping sections

Question 9

First generation sequencing

Answer 9

very easy and advantageous
wouldn’t use to sequence a genome now

Question 10

second generation sequencing

Answer 10

creates short fragments
high throughput
cost effective
often doesn’t get a complete genome

Question 11

third generation sequencing

Answer 11

single molecule sequencing
produce long sequences
flow cell pores full of DNA molecules
pores detect current as DNA passes through

Question 12

Genome Sequencing

Answer 12

allows rapid sequencing of non-repetitive parts of genomes
sequence repeated sections also required single molecule sequencing

Question 13

types of genetic variation (4)

Answer 13

single nucleotide polymorphism (SNPs)
indwells (insertions and deletions)
copy number variations (CNVs)
Structural rearrangements

Question 14

What is an allele?

Answer 14

term to describe alternative forms of a heritable trait

Question 15

What is polymorphism?

Answer 15

variation within a population of a given trait

Question 16

What is a single nucleotide polymorphism?

Answer 16

variation that occurs in a single nucleotide

e.g. A->T to T -> A

Question 17

When was the first genome published?

Answer 17

2001

genome sequence in 2007 was less than $1million

0.1% of genome was different at snip level to reference genome

Question 18

What is an INDEL?

Answer 18

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

Question 19

What are the effect of base substitutions in coding regions?

Answer 19

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

Question 20

What is a base pair transition?

Answer 20

changes from pyrimidine to pyrimidine or purine to purine

Question 21

what is a base pair transversion?

Answer 21

changes from pyrimidine to purine

Question 22

what is the term for the normal allele?

Answer 22

wild type

Question 23

What mechanisms to cells have to prevent and correct mutations?

Answer 23

proofreading by DNA polymerases
post-replication mismatch repair
DNA repair by homologous recombination
cell cycle checkpoints

Question 24

What is an intercalating agent?

Answer 24

chemical mutagen inserted between base pairs
causing a frameshift mutation

Question 25

what is a base analogue?

Answer 25

chemical mutagen incorporated into DNA in place of a normal base causing a mispair and base substitutions

Question 26

what are base modifying agents?

Answer 26

chemical mutagen covalently alter a base causing the base to mislaid base substitution

Question 27

what is the structure of an intercalating agent?

Answer 27

planar molecule intercalate between base pairs get between DNA and cause issues with replication

Question 28

What is the structure of base analogues?

Answer 28

analogue of thyme also pair with guanine mimic bases and become integrated in DNA

Question 29

what is the structure of base modifying agents?

Answer 29

covalently alter a base delaminating agents remove amino groups hydroxylating agents add hydroxyl groups alkylating agents add alkyl groups

Question 30

What is a delaminating agent?

Answer 30

remove amino groups cytosine can lose an amino group and become uracil

Question 31

What is an alkylating agent?

Answer 31

add alkyl groups

Question 32

What is replication slippage?

Answer 32

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

Question 33

What is mutant selection?

Answer 33

selection of mutant by geneticists to isolate rare mutants

Question 34

what did the Lederberg Experiment demonstrate?

Answer 34

mutations occurred before selection - colonies that survived were in the same position mutations are random