Genetics Revision Lecture Flashcards
What is the central dogma?
DNA to RNA through Transcription + Splicing
RNA to protein through translation
What structural element of DNA prevents transcription?
It’s association with histone proteins
What are the main differences between RNA & DNA?
RNA is single stranded. Ribose is present rather than deoxyribose in its nucleotides. Finally, it has Uracil instead of adenine
What is splicing?
The removal of introns from pre mRNA to form mRNA.
What are the stages of the cell cycle?
G0 - cell doing celly things G1 - growth S- DNA synthesis G2- growth & prep for mitosis M- mitosis
What is the function of DNA helicase?
DNA helicase breaks the hydrogen bonds between the DNA strands, it “unzips the DNA”
What is the role of DNA polymerase in DNA synthesis.
DNA polymerase copies the DNA strands.
What are Okazaki fragments?
These are small fragments of connected nucleotides created by DNA polymerase from the 3’-5’ DNA strand.
What is the function of DNA ligase?
To join the Okazaki fragments into a full DNA strand.
What are the differences between Mitosis and Meiosis?
Mitosis - 2 genetically identical diploid daughter cells.
Meiosis- 4 genetically variable haploid cells.
What is a polymorphism?
A DNA variant that has a population frequency of greater than 1%.
Doesn’t have to cause disease.
What is a mutation?
DNA variant which causes or predisposes to a specific disease
What is a premature stop mutation?
The codon sequence ends early due to a new stop codon
What is a missense mutation?
A base changes so the codon is sequence is now incorrect
What is an insertion mutation?
Base inserted in the sequence
What is ab Out of frame deletion mutation?
Base or 2 deleted so all the triplets in the sequence change
What is an In frame deletion mutation?
Multiple of 3 bases or triplet or 2 are deleted so remaining triplets don’t change.
What is a triplet expansion mutation?
A triplet of bases are duplicated
What is the base excision pathway of DNA repair?
Damaged bases are removed
What is the nucleotide excision pathway of DNA repair?
Dimerised bases are removed (thymine bases, occurs due to UV light)
What is the mismatch pathway of DNA repair?
Mismatched bases are removed.
What is homologous recombination? (DNA repair pathway)
A DNA sequence from the sister chromatid is used to fill a double strand break
What is non-homologous end joining? (DNA repair pathway)
The 2 ends of a double strand break are joined together (lots of mistakes happen here)
What are the advantages of karyotyping?
Karyotyping allows you to identify large deletiosn (>5mbp), can see location of centromeres, acrocentric chromosomes, aneuploidy, sex chromosomes & translocations
What is a balanced translocation?
An even exchange of genetic material between chromosomes, no missing or extra material. Normally fully functioning.
What is an unbalanced translocation?
Exchange of genetic material is unequal resulting in extra or missing information
What is an Acrocentric chromosome?
A chromosome where the centromere is located very near the end of the chromosome
Why can an Acrocentric chromosome predispose to cancer?
2 acrocentric chromosomes can stick together, these are common in cancer.
What does FISH involve?
FISH involves using a flouresent probe to attach to a gene
What is FISH good for identifying?
It is good for identifying specific changes such aneuploidy or translocations with a gene. (Need to know what you’re targeting)
What is ACGH?
Array comparative genomic hybridisation. Fluorescent markers with wells of patient & control DNA. Differences in colour mean changes in gene expression.
What does Next generation sequencing allow for?
It allow for massive, parallel sequencing of genomes or exomes (exons only).
What is the problem with Next generation sequencing?
You gain a huge number of results that you have to filter through. Unknown if mutations, polymorphous, variants of uncertain significance
Autosomal dominant pattern of inheritance?
Affected individuals in every generation. M + F affected. All forms of transmission are present.
Autosomal recessive pattern of inheritance?
Affected individuals are usually in one sibship in one generation. M+F affected. Disease often skips generations. Increases risk with consanguinity.
X-linked recessive pattern of inheritance?
Males affected almost exclusively. Transmitted from female carriers to sons. Affected males cannot transmit the condition to their sons.
Risk of autosomal dominant pattern of inheritance?
If there is an affected mother, risk of an affected child is 50%
Risk of autosomal recessive pattern of inheritance?
Normal Risk of affected child 25%
Risk of X-linked recessive pattern of inheritance?
Risk of affected child 25% Risk of carrier child 25%
What is Expression?
The process by which information from a gene is used in the synthesis of a functional gene product.
What is Penetrance?
The extent to which a particular gene is expressed in the phenotype of an individual carrying it.
What is X-inactivation?
A cell only requires one working copy of the X chromosome. In females, each cell has a random X chromosome inactivated.
What is meant by Multi-Factorial disease?
Mutations in multiple genes combined with environmental factors to cause disease. These genes display low penetrance.
Common disease- common variant hypothesis
States mendelian diseases are due to rare variants which have a huge effect on the body. Common diseases are due to common variants (and environment factors) which each have a small effect on the body.
How does DNA methylation and acetylation impact transcription?
These both impact how tightly DNA is wrapped around its associated histone proteins. This means they impact the rate of transcription.
What is Imprinting?
Maternal or paternal inheritance will cause differences in gene expression
What is Mitochondrial DNA inheritance?
Almost exclusively maternal inheritance of genes for mitochondrial metabolic pathways and ribosomal RNAs.
What are oncogenes?
These genes when activated are associated with cancer.
What are tumoursupressor genes?
These genes regulate expression, inactivation is associated with cancer.
What is the 2 hit hypothesis?
2 hits are needed to inactivate a gene due to the 2 alleles. These can be inherited or an acquires, somatic mutation.
What is mosaicism?
Present of 2 or more population of genotypical different cells in one individual.
What is somatic mosacisim?
Post-zygotic mutation derived. Not inherited.
What is gonadal mosacisim?
2 populations of cells in the gonads. Will be inherited.
6 hallmarks of cancer?
Sustaining proliferative signalling Evading growth suppressors Resisting cells each Inducing angiogenesis Enabling replicative immortality Activating invasion and metastasis
What is the CTFR protein?
This is a channel protein that regulates chloride ions and thus movement of water ions.
What is the population carrier frequency of CF?
1 in 24/25
2 most common CF mutations?
F508del
G551D
How do you calculate risk of inheritance?
Maternal risk x Paternal risk x chance of passing on 2 copies of genes = risk
