Dr Rosato Flashcards
Define a eukaryote.
An organism with a true nucleus.
Define diploid.
When two copies of each gene are present.
Define Haploid.
When one copy of each gene is present.
Define Alleles.
Alternative forms of the same gene (Normal = wildtype)
Define Homologues
Copies related by descent (same gene different species)
Define Orthologs
Genes in different species which have evolved from a common ancestral gene via speciation. Usually retain the function and are vital for prediction of gene function in newly sequenced genomes.
Define speciation
Origin of a new species capable of making a living in a new way from the species before. Some genetic barriers faced between exchange of information between new and parent species.
Define Paralogs
Genes related by duplication within a genome. They tend to evolve new functions.
Why do high levels of sequence similarities occur?
Chance or convergent evolution (genes which respond in similar ways). Sequences are analogs rather than homologs.
Define genotype
Specific allele composition (genetic composition).
Define phenotype
Set of observable features resulting from the interactions between genotype and the environment.
Why is the sickle cell anaemia allele maintained in the population?
Those who have sickle cell anaemia die at a young age without producing offspring whereas those individuals who have homozygote normal Hb die from malaria. Malaria is caused by the protozoa Plasmodium, which is unable to develop in the heterozygotes so the sickle cell allele can be passed on to the next generation.
What is balanced polymorphism?
Heterozygotes have a greater fitness than the homozygotes. This is the process by which selection maintains multiple alleles in the gene pool at frequencies higher than the predicted values.
What is co-dominance?
Both alleles contribute to the phenotype of the individual.
In blood groups which gene determines the antigen produced?
Gene I which codes for an enzyme which adds a sugar to the end of the chain (glycosyltransferase) A = N-acetylgalactosamine B = galactose. (O blood group has no antigen).
Give an example of a dominant mutation which causes a disease.
Huntington’s disease
Gene has 40-121 repeat CAG units (may correlate to age at onset).
Achondroplasia - Mutation in the Fibroplast growth factor receptor 3 causing an abnormality in cartilage formation.
What mechanisms occur causing mutations?
Mispairing at replication - occur due to mutations in polymerase; mispairing due to development of tautomers producing imino form of the nucleotide (introduction of N=C bond and an enol group is added) and deoxycytidine deamination.
Backward slippage - addition of a codon (loop in the strand being produced).
Forward slippage - deletion of a codon (loop in the coding strand).
Chemicals:
Alkylating agents - Addition of an alkyl groups to DNA bases inducing mispairing. EMS transfers an ethyl group while MNNG transfers a methyl group (If G becomes alkylated then it will pair with T).
Intercalating agents - chemicals which fit between base pairs of dsDNA causing the addition or deletion of single nucleotide (induced frameshift mutations) Agents include Ethidium Bromide (used to dye gels during electrophoresis)
What mechanisms can be used to repair damage to DNA (pyrimidine dimers)?
Dimers produce kinks in DNA blocking replication (Caused by UV exposure).
Photoreactivation -Photolyase enzyme binds to damaged DNA, light energy is absorbed splitting the dimer and polymerase then fixes the issue.
Excision repair - removal of the damaged section and then repair by DNA polyermase.
Post-replication recombinational repair - Use of homologous chromosome to copy the sequence from the undamaged area and inserting this into the gap produced on the opposite strand to the damaged strand.
Transdimer synthesis.
Give an example of a disease caused by damage to the repair systems.
Xeroderma pigmentosum - Mutation in excision repair so S0S-repair systems required however these are prone to errors so further mutations occur leading to the development of tumours (Melanomas).
What is high energy ionising radiation?
Electromagnetic radiation and particles that carry enough energy to liberate and electron from an atom or molecule ionising it. Examples: X-rays and gamma-rays; alpha particles (He2+ nuclei) and beta particles (electrons).
How does radiation affect DNA?
Causes nucleotide damage (mispairing); Single-strand breaks and double-strand breaks. Double-strand breaks cause large scale mutations including translocation.
If inversion occurs then chromosomes are unable to pair up during meiosis so balancer chromosomes are required to prevent crossing over if damage has occurred.
How does radiation effect somatic cells?
Cause cancers. The proto-oncogenes responsible for cellular growth, differentiation and apoptosis may become damaged becoming oncogenes encoding proteins which lead to the development of proteins which promote cancer. Mutation may also occur in the tumour supressor gene (TP53) which codes for P53 preventing control of proliferation of cells.
How does radiation effect the germline cells?
Induce mutations causing structural changes which lead to abortion (miscarriage) or still born progeny with the ability to kill sperm or eggs.
How can radiation effects be studied in germlines?
No direct experimental approach on humans as unethical so can only be studied when opportunity arises. Sir Alec Jefferys discovered mini-satellites which are hyper-variable regions with very high mutation rates (10^-3 to 10^-4 per locus per generation) so high levels of polymorphism within the population (low rate of unrelated individuals having the same varient). Used to study mutations in Chernobyl disaster (high mutation rate in offspring whose parents involved in disaster (loci different to both parents)). Now use micro-satellites instead as they have a lower mutation rates so mutation more likely to have occurred due to environmental factors such as ionising radiation.
How are transposable elements used by bacteria to cause mutations?
Used to transfer genes into host genome and act by chance as a mutagen. The TE is replicated and the nascent form is then inserted into the DNA at another point. Technique has now been exploited and is a used to insert GFP into a target sequence.
What is transgenesis?
Genes can be expressed using a known promoter between IR.
What is the ames test?
Used in bacteria to test the type of mutations which can occur and whether they can be repaired or not.
How do you calculate mutation rate?
Mutation frequency x size of genome
What is chromatin made up of?
DNA - one unreplicated chromosome containing a dsDNA molecule.
Protein - DNA metabolising enzymes and structural proteins (histone complex).
What is a genome?
Complete set of genetic material
How is DNA packaged into eukaryote chromosomes?
Packaged into nucleosome made up of an octamer of core histones. 147bp wrap around the histone in 1.67 left-handed helical turns.
