Genetics and DNA Flashcards
Heterochromatin (3)
Smallest amount of interphase chromatin: highly condensed state of chromatin that contains tightly wound DNA
This prevents any transcription or DNA replication from undergoing.
Stained darker in an electron micrograph
Euchromatin
Largest amount of interphase chromatin: Loosely wound DNA that allows transcription and DNA replication.
Euchromatin is stained lighter in in electron micrographs.
Main functions of DNA that is related to its structures.
Large macromolecule that is able to store information for organism synthesis, through complementary base pairing.
Allows accurate replication of DNA through complementary base pairing.
Allows beneficial mutations to be selected for.
Genome’s relation to disease susceptibility.
Disease can be caused by a single gene: Monogenic. A change in this gene cause loss/ gain in function of a protein.
DIsease can be caused by polygenic genes: More than one gene influence the presence of a disease.
Diseases can also be initiated by the interaction between environmental and genetic factors.
Huntington’s disease.
Neurodegenerative disease inherited in an autosomal dominant fashion.
Causes damage in the nerve cells in areas of the brain.
Caused by the increase of CAG trinucleotide repeats in Huntingtin gene (HTT), in chromosome 4 .
An increase in CAG (insertion), which codes for glutamine, create a gain in function.
Polyglutamine creates a toxic product which kills neurones.
Nucleosome
Compose of DNA, negatively charges, wound around positively charged histones.
DNA is wound around an octamer, composed of 8 histones, two of each: H2A, H3, H2B, H4.
Core histones are linked with linker DNA.
Single nucleotide polymorphism.
Single base change in the DNA sequence.
It can either change the amino acid sequence (non-synonymous) or not , (synonymous) .
How can mutations be characterised? (3)
- Effect on heritability:
Germ line or somatic. - Scale of mutation:
Chromosomal or single nucleotide polymorphism. - Effect on normal function:
Loss, gain or no effect
Describe the appearance of a metaphase chromosome
Short arm and long arm. The length of the chromosomes before and after the centromere.
Telomere: Repetitive sequence of DNA usually at the end of the chromosome.
Centromere: Separates chromosome into long arm and short arm. SIte of attach for sister chromatids.
Kinetochore: Complex proteins attached to the centromere where spindle microtubules attach to during metaphase and anaphase.
Prophase
Chromosomes condenses
Mitoic spindle fibres start to form from centrosomes
Prometaphase
Nuclear membrane and envelope disintegrates.
Spindle fibres from centromeres attach to the kinetochores of the chromosomes
Metaphase
Chromosomes are aligned across the centre of the equator using spindle fibres which are oriented at opposite ends of the cell.
Anaphase
Spindle microtubule contracts and shortens
Pulls the chromosomes apart at the centromere towards spindle poles.
Chromosome is separated into sister chromatids.
Telophase
Chromosomes arrive at opposite poles.
Nuclear envelope forms around chromosomes.
Cytokinesis
Contractile ring creates a cleavage furrow
Causes cytoplasm to divide into two genetically identical cells.
Cell cycle checkpoints
Controlled by cyclins and protein kinases
Controls whether cells die, wait or continue the cell cycle
Checks for:
Damaged DNA
Unfavourable extracellular environments
Improper attachment of chromosome to mitotic spindle fibre
P53 regulator
Cell cycle checkpoint located at G1 which checks for damaged DNA
Around 50% of cancers have mutations in this reglator
Enzymes involved in DNA replication
DNA helicase:
Breaks hydrogen bonds between base pairs and allows the formation of replication forks.
DNA primase:
Works on lagging strand by adding short sequence of nucleotides to allow DNA polymerase to start replication.
DNA polymerase:
Adds nucleotides to temple DNA, forms phosphodiester bonds between nucleotides.
DNA ligase:
Seals up okazaki fragments
DNA binding proteins:
Keep DNA straight and stable during replication by preventing double helix from reforming.
Werner syndrome
Condition caused by the mutation to DNA helicase
Causes DNA helicase from being efficient and fast enough
Symptoms:
Premature aging
Increased risk in conditions seen in older people at a young age:
osteoporosis, atherosclerosis and cataracts.
How are mutations in DNA prevented during the cell cycle?
DNA polymerase proof reads the DNA sequence during S phase
Excision repair systems act throughout the cell life cycle
Excision repair system
When an error occurs in DNA:
- DNA nuclease cuts out the wrong base pair.
- DNA polymerase inserts the correct base pair.
- DNA ligase seals up the new base pair back into the DNA sequence
Sources of DNA damage
Internal:
Caused from errors in normal cell function, like error in DNA replication.
External:
Mutagens
UV
Ionising radiation.
How is DNA packaged into chromatin
Using histones to form a nucleosome:
DNA wrap around a histone complex (histone octamer) composed of two copies of; H2A, H2B, H3, H4.
H1, histone 1, binds to linker DNA which connects nucleosomes together and compacts them.
Chromatin remodelling complexes
Protein complexes that attach to the histone octamer and DNA
Alters the shape of the nucleosome by making it tighter/ looser.
It is inactive in mitosis as this prevents chromosomes from being looser and unwinding
Histone modifying enzymes
Enzymes that allows chromatin remodelling:
Acetyl, phosphate or methyl groups can be added/ removed from histone chains.
Changes the hydrophobic and hydrophilic tendencies of histone, which causes chromatin to be looser or tighter.
Homologous recombination
Occurs in prophase 1:
Homologous chromosomes and their non-sister chromatid cross over alleles at the same genes by forming chiasmas.
Separated when anaphase occurs.
Benefits of sexual reproduction
Increases genetic variation by combining genes.
Allows deleterious combination of genes to be removed.
This prevents the population from being less susceptible to changes in the environment.
Haemophilia A
Recessive X-linked genetic condition:
Lack of clotting factor 8. Makes patients more susceptible to severe haemorrhage from trauma as there is a defect in coagulation.
Causes by deletion or inversion in the F8 gene.
Cystic fibrosis
Autosomal recessive disorder
Mutation of the cystic fibrosis transmembrane conductance regulator protein (CFTR), causes a loss in function.
Sickle cell disease
Autosomal ‘incomplete’ recessive disorder.
Caused by mutation in the HBB gene on chromosome 11:
Glutamic acid is replaced with valine at the 6th position.
‘incomplete’: Carriers of this mutation still have the recessive advantage of protection against malaria.
Trisomy and monosomy
Caused by errors in meiosis, either disjunction or translocation.
Trisomy: An extra chromosome. 3 instead of 2. Only mainly seen in chromosome 21, 13 and 18.
Monosomy: Only 1 chromosome, baby will only survive if it is the X chromosome
Turner’s syndrome
Caused by monosomy of the X chromosome.
Causes problems with reproductive systems and hormoen regulation with them
