IMMS: Genetics Flashcards
DNA; Autosomal inheritance; X-linked inheritance; Multifactorial & non-Mendelian inheritance; DNA mutations; Genetic testing & society
What is a macromolecule?
A large complex molecule, often polymers of smaller molecules (monomers). Examples of macromolecules include DNA, proteins, carbohydrates, and lipids.
What is a heterogenous structure?
Made up of different components e.g. DNA, haemoglobin.
Why is water polar but uncharged?
Water molecules are polar because they have an uneven distribution of charge: oxygen end = negative, hydrogen end = positive. Overall they have no net charge.
What is the chemical structure of a carbohydrate?
Chain of carbon with attached water molecule.
Cn(H2O)n
What is a disaccharide?
Two monosaccharides (carbohydrates) linked together.
What is the difference between an oligosaccharide and a polysaccharide?
Oligosaccharide = 3-10 monosaccharides.
Polysaccharide = more than 10 monosaccharides.
What is an isomer?
Molecules made up of the same atoms but have a different structure.
What is a hexose?
A monosaccharide with 6 carbon atoms. E.g. Glucose.
Name two ways to classify a monosaccharide.
- Number of carbon atoms. E.g. Triose = 3 carbon atoms.
- Type of carbonyl group (if carbonyl group is a ketone, monosaccharide is a ketose, if an aldehyde, it’s an aldose).
What is a carbonyl group?
A carbon atom double bonded to an oxygen atom.
What differs in molecular structure between a ketone and an aldehyde?
The position of the carbonyl group (aldehyde has carbonyl group at the end of the carbon backbone, ketone has carbonyl group in the middle of the carbon backbone).
What sort of bond between a carbohydrate and another functional group forms a glycoside?
A glycosidic bond.
What sort of bond joins monosaccharides to make di/oligo/polysaccharides?
O-gylcosidic bond (bond via oxygen atom)
What bond joins the nitrogenous base and pentose sugar in nucleotides?
N-glycosidic bond (bond via nitrogen atom)
What are the three components of a nucleotide?
Nitrogenous base (e.g. adenine), pentose sugar (deoxyribose in DNA, ribose in RNA), phosphate group.
Name the purines.
Adenine and guanine.
Name the pyrimidines.
Cytosine and thymine (uracil in RNA).
Which nitrogenous bases are joined by 2 hydrogen bonds?
Adenine and thymine (uracil in RNA).
Which nitrogenous bases are joined by 3 hydrogen bonds?
Cytosine and guanine.
How are nucleotides joined together to form DNA?
Polymerised by covalent bonds into long chains.
What does antiparallel mean in relation to DNA?
DNA alpha helix is made up of two antiparallel strands. One running 5’ to 3’ and the other in the opposite direction 3’ to 5’ (which way up the pentose sugar is) this causes the twisting of the two strands.
How is DNA supercoiled to fit into the nucleus?
Antiparallel double helix wrapped around histone proteins to form a nucleosome. Nucleosomes fold together to make a chromatin fibre. Chromatin is tightly coiled together to form a chromosome.
How long does DNA replication take?
8-12 hours.
What is the function of DNA helicase?
Enzyme which separates double-stranded nucleic acids into single strands in DNA replication, repair, and transcription.
Which enzyme reads the DNA strand for replication? Which direction does it read and print in when replicating, and what are its other functions?
DNA polymerase alpha. Reads 3’ to 5’, prints 5’ to 3’. Proof-reads and edits - repeats replication if wrong.
What are Okazaki fragments?
The sections of the lagging DNA strand which has to be replicated in these Okazaki fragment sections, because DNA polymerase alpha only reads in one direction and DNA is antiparallel.
Primase synthesises short RNA sequences called RNA primers. What is the main function of RNA primers?
Act as starting point for the synthesis of Okazaki fragments. DNA polymerase later removes them and fills in the gaps with DNA.
What enzyme joins the Okazaki fragments?
Ligase
What is the difference between mitosis and meiosis?
In mitosis the cell divides to produce 2 genetically identical daughter cells each containing 46 chromosomes. Mitosis occurs for growth in tissues and to replace dead cells.
Meiosis only occurs in gametes. Cell divides twice and produces 4 genetically diverse haploid daughter cells, each only contain 23 chromosomes. Meiosis is NOT a cycle.
What does mitotically active mean?
Tissue where there is high cell turnover e.g. in bone marrow, epithelial lining of gut, skin.
What are labile cells?
Cells that constantly in the cell cycle, repeatedly undergo mitosis throughout their life e.g. epidermis.
What are stable cells?
Cells that spend most of their existence outside the cell cycle in G0 but can be induced to enter the cell cycle and undergo mitosis. E.g. hepatocytes.
Is interphase part of mitosis?
No, it is part of the cell cycle which occurs before mitosis. The majority of the cell cycle is interphase.
What are the 3 stages of interphase?
G1 = cell growth.
S = DNA synthesis.
G2 = further cell growth.
Name the stages of mitosis in order.
- PROPHASE
- PRO-METAPHASE
- METAPHASE
- ANAPHASE
- TELOPHASE
What 3 steps occur in prophase?
Chromatin condenses into chromosomes.
Centrosomes move to opposite sides of the cell.
Microtubules assemble between them - this is the mitotic spindle forming.
What 3 steps occur in pro-metaphase?
Nuclear membrane breaks down.
Microtubules of mitotic spindle invade nuclear space.
Microtubules attach to chromatids at centromeres.
What happens in anaphase?
Sister chromatids separate and are pulled to opposite poles of the cell as microtubules depolymerise and shorten.
In which phase of mitosis do the chromatids line up on equatorial plane?
Metaphase.
In which phase of mitosis do the nuclear membranes reform, and what else happens in this phase?
Telophase.
In telophase the nuclear membranes reform and chromosomes unfold into chromatin.
What is cytokinesis?
Cytokinesis is the process where the cell membrane develops a cleavage furrow, which increases to the point at which the cell and cytoplasm is divided into two.
When does the process of cytokinesis start and finish?
Cytokinesis might start to occur in anaphase or telophase and completes shortly after telophase.
Relating these different terms to each other, what are chromatin, chromosomes, chromatids, and centromeres?
Chromatin condenses during DNA replication to form a chromosome which is two chromatids (identical strands) joined at a centromere.
What is a karyotype?
The number, size, and shape of the chromosomes of an individual.
Taxol is a drug which stops the mitotic spindle from developing. Why would this be helpful in treating cancer?
If the mitotic spindle doesn’t develop then mitosis won’t be completed, the cell can’t divide, so the cancer cannot continue growing.
In what phase of meiosis does crossover occur and how does it happen?
Prophase 1, when homologous pairs form. Non-sister chromatids of homologous pairs break and reconnect to each other, causing exchange of genetic material.
What are primordial germ cells?
Embryonic stem cells which differentiate into spermatogonia or oogonia.
How many sperm cells are in one ejaculate?
100-200 million cells!
During spermatogenesis, spermatogonia undergo meiosis to become spermatozoa. How long does this process take?
60-65 days (millions of sperm cells are continuously produced!)
What are the 2 key differences between spermatogenesis and oogenesis?
Spermatogenesis begins at puberty and the cytoplasm divides equally to create 4 haploid daughter cells.
Oogenesis begins in the foetus, and the cytoplasm divides unequally to create 1 haploid daughter cell and 3 polar bodies.
What is required for oogenesis to complete meiosis-II?
Fertilisation.
What is a homologous pair of chromosomes?
A set of one maternal and one paternal chromosomes.
Why is are tRNA anticodons important for protein synthesis?
The tRNA anticodon corresponds to the mRNA codon for the specific amino acid the tRNA caries, which is required to synthesise the protein the mRNA codes for.
A polypeptide is the primary structure of a protein, made of a chain of molecules. What molecules form this chain, and what type of covalent bond joins them together?
A chain of amino acids joined by peptide bonds between their carboxyl and amino groups.
What is splicing and where does it occur?
Removal of introns (non-coding sections) from mRNA so only exons (coding sections) remain.
Occurs inside the nucleus.
What is the codon for methionine and why is it important?
Adenine, Uracil, Guanine (AUG). The START codon for all proteins.
Why is the genetic code redundant and non-ambiguous?
Redundant: there are multiple codons for the same amino acid.
Non-ambiguous: each codon only codes for one amino acid.
How many amino acids are in a protein?
Can be anywhere between 10 and 1000s!
Why is the 3D shape of a protein important?
The shape/structure affects the protein’s function.
What bonds form the secondary structure of a protein?
Hydrogen bonds.
Name the two types of secondary protein structure.
Alpha helix spiral, where side chains face outwards. Beta sheet, can be folded or straight.
What four types of bonds can be involved in the 3D tertiary structure of a protein?
Electrostatic, hydrophobic, hydrogen, covalent.
What are Van der Waals forces?
Weak electrostatic forces which attract neutral molecules to one another.
Do all proteins have a quaternary structure?
No, only proteins made up of multiple subunits have a quaternary structure.
What does it mean if a fatty acid is unsaturated?
There’s at least one double bond between carbon atoms.
Ring mitosis is visible on light microscopy. In which phase does ring mitosis occur?
Anaphase, when chromosomes are being pulled to opposite sides of the cell.
What is the relationship between melting point and degrees of unsaturation in a fatty acid?
The melting point decreases with increasing degrees of unsaturation. For example, at room temperature butter is solid, oil is liquid.
What is the 3’ tail (poly-A tail) on mRNA made of?
Adenine, repeating 50-250 times.
When and why is the poly-A (3’ tail of repeating adenine) added to mRNA?
Added during splicing to increase stability of mRNA.
What causes anticipation in Huntington’s disease?
Trinucleotide repeat expansion.
The number of repeats can increase in successive generations, causing increased severity and earlier onset.
What is “regression towards the mean” in genetics? Give an example.
Statistical phenomenon where offspring tend to be close to the average population than their parents.
E.g. two parents with high IQ are more likely to have a child of average IQ.
What affects a person’s phenotype?
A combination of their genotype and environmental factors.
Name the Robertsonian (acrocentric) chromosomes.
13,14,15,21,22.
In Robertsonian translocation, the whole of one acrocentric chromosome is joined end-to-end with another.
What characteristic do the Robertsonian/acrocentric chromosomes (13, 14, 15, 21, 22) have in common that pre-disposes them to this translocation?
All have very short p arm with similar repetitive DNA sequences that predispose their fusion.
Which chromosome abnormality is more likely to cause disease; deletion or duplication?
Deletion.
Why might chromosomal abnormalities causing unbalanced translocation (deletion or duplication) cause disease?
Deletion/duplication causes loss/gain of genetic material, so the cell produces a different amount of that protein. Many genes are “dosage sensitive” - they need 100% of the signal (made by proteins) to be healthy.
How many genomes does the human body have and what are they?
- Germline (sperm/eggs, heritable).
- Somatic (in other tissue, not heritable).
- Mitochondrial (heritable).
What is mutagenesis ?
Alteration to genomic code by exposure to a mutagen, either pre or postnatally. e.g. smoking -> damage DNA in lining of lungs -> lung cancer. Mutagens can cause damage to DNA and then act in a teratogenic manner.
What is teratogenesis?
Damaging effect on embryonic/foetal development by exposure to teratogen. Not necessarily causing damage to DNA. Teratogen can also be a mutagen e.g. ionising radiation might cause developmental issues in foetus but also cause damage to DNA in mother causing mutations -> cancer.
What is the difference between a malformation and a deformation? Which usually has a genetic cause?
A malformation is an intrinsic issue with the development of organ/tissue, commonly genetic.
A deformation is where extrinsic factors impinge upon development of organ, less commonly genetic.
Minor malformations are common. When might a malformation indicate an underlying genetic condition?
Multiple minor malformations (e.g. skin change) or a major malformation (e.g. cleft palate).
How might you identify an autosomal dominant disorder from a pedigree? What is the recurrent risk?
Males & females are affected equally.
Multiple generations are affected.
Affected males can have affected sons.
50% recurrent risk.
The same gene variant can have a wide range of symptoms of physical features. This most often occurs in autosomal dominant conditions. What term is used to describe this variation?
Variable expressivity.
Why might someone with an autosomal dominant disorder variant not develop the disease? Give an example.
The variant might have incomplete penetrance, or could be sex-limiting. For example, a variant causing ovarian cancer would still be present in a male but the variant would not be expressed.
Why are sperm cells more likely to be the cause of de novo mutations, particularly in older males?
Sperm cells are being made continuously. DNA is copied less accurately as males age, which increases the likelihood of a sperm cell having a de novo mutation.
How might you identify an autosomal recessive disorder from a pedigree? What is the recurrent risk, and what can increase this risk?
Males & females are affected equally.
Often only see disease in single generation.
Affected males can have affected sons.
25% recurrent risk.
Increased risk in consanguineous mating.
What is the carrier frequency of cystic fibrosis in Northern European population?
1 in 25.
Why is somatic mosaicism not detected in normal genetic testing (blood/saliva sample or cheek swab)?
Because, by definition of mosaicism, not all cells have the variant. The variant is only present in the particular tissue e.g. cancer, need to biopsy the tumour.
Mitochondrial heteroplasmy is common in healthy human populations. What is heteroplasmy, and why can it help prevent disease?
Not all mitochondria in a cell have the same genome. Only some mitochondria in a cell might have a disease-causing mutation, so other mitochondria can compensate to prevent disease expression.
A synonymous change might change the nucleotide, but still code for the same amino acid. A non-synonymous change (missense) codes for a different amino acid.
Why can a non-synonymous change cause disease?
Can cause loss of function by changing protein structure, or change from amino acid to a premature STOP codon can cause nonsense mediated decay where mRNA is destroyed.
What is the difference between in-frame and out-of-frame insertion/deletion? Which is more likely to cause disease?
In-frame insertion/deletion will always be a multiple of 3 nucleotides, lose/gain single amino acid.
Out-of-frame insertion/deletion will not be divisible by 3 and leads to frameshift mutation. This is more likely to cause disease.
Copy number variation (CNV) is a source of genetic diversity in humans. What are CNVs?
Sections of the genome are repeated and the number of repeats in the genome varies between individuals. Can involve deletion or duplication.
Lyonisation occurs in all females during embryological development. What is lyonisation?
Random x-inactivation where female cells randomly inactivate one of their X-chromosomes. Normally 50-50 which x-chromosome is inactivated.
What is the difference between locus heterogeneity and allelic heterogeneity?
Locus heterogeneity is where variants in different genes can cause the same disease.
Allelic heterogeneity is where different variants in the same gene can cause the same disease.
Proteins can form a variety of different structures. Alpha helixes and beta sheets are examples of which type of protein structure?
Secondary structure
DNA replication involves several stages. Which enzyme causes the double helix to unzip?
Helicase
What is the basic structure of a ribosome?
One large and one small subunit.
Where are ribosomes assembled?
In the nucleolus, inside the nucleus.
DNA replication is dependent on the action of various enzymes. Which enzyme unwinds supercoiled DNA?
Topoisomerase
How does deoxygenated sickle cell haemoglobin cause sickling of RBCs?
Deoxygenated HbS polymerises and binds to the cell cytoskeleton which distorts the normal biconcave disc shape into a sickle shape.
Sickle cell disease can be treated with hydroxyurea. Describe the action of hydroxyurea.
Increases the synthesis of HbF (foetal Hb)
mRNA plays a key role in protein formation. Which process describes how mRNA specifies the amino acids required for protein formation?
Translation
