Genetics and Genetic Disorders Flashcards
What process produces diploid cells from diploid cells?
Mitosis
What process produces haploid cells from diploid cells?
Meiosis
What processes produce diploid cells from haploid cells?
Fertilisation
What offspring receive an X chromosome from their father?
Daughters only
Describe a nucleotide monomer.
Deoxy or ribose sugar + base + phosphate
What charge is the phosphate group?
Negative
How many carbons exist in the sugar rings?
4 carbons (5th is side chain)
What direction is the chain of nucleotide monomers?
5’ to 3’
How are complimentary base pairs bound?
Via Hydrogen bonds.
Name the purine bases.
Adenine and Guanine
Name the pyrimidine bases.
Cytosine, Thymine and Uracil
How many hydrogen bonds are formed between Cytosine and Guanine?
3
How many hydrogen bonds are formed between Adenine and Thymine?
2
How many DNA bases exist?
5
What replaces thymine in RNA?
Uracil
What linkage forms covalent backbone if DNA?
Phosphodiester linkage
In what direction does the sense/leading strand of DNA run?
5’ to 3’
In what direction does the anti-sense/lagging strand run?
3’ to 5’
How is DNA described?
Semi-conservative and bi-directional
During replication, what enzyme ‘unzips’ the DNA?
Helicases
What enzyme controls elongation during DNA replication?
DNA Polymerases
In what direction does DNA polymerase work?
5’ to 3’
In lagging strand, what enzyme seals Okazaki fragments?
DNA ligase
What enzyme proof reads new double helix?
Nucleases
How is a base sequence of DNA transcribed into a base sequence in RNA.
- Initiation
- Elongation
- Termination
Where does transcription occur?
In nucleus
What regions of DNA are known as coding regions?
Exons
What regions of DNA are known as non-coding regions?
Introns
What determines the reading frame?
Initiation codon
Describe the post-transcriptional processing of RNA.
Exon splicing
What is required for the translation of mRNA?
- rRNA for assembly plant
- tRNA for translation of mRNA to AA sequence
- AUG start codon
- ribosome
- stop codons (to disassemble ribosome and release polypeptide.
Where does translation occur?
In the cytoplasm
What does DNA package with histones form?
Chromatin
What are nucleosomes?
DNA wrapped around core of histone protein. ‘Beads on a string’.
What is chromatin?
Packed nucleosomes (supercoiled).
Further wrapping of chromatin fibre loops and nucleosomes form what?
Chromosome
What charge is histone proteins?
Positive (neutralises negatively charged DNA)
What is used in the laboratory to diagnose a genetic disease?
Karyotype
What is FISH?
Fluorescent In-Situ Hybridisation (visualise and map genetic material)
In FISH, what probes can be used?
- Centromeric probes (determine chromosome structure)
2. Whole chromosome probes (detect translocations and rearrangements)
Describe the types of structural chromosomal abnormalities.
Balanced or un-balanced rearrangements:
- Translocations
a) Reciprocal (breaks in two chromosomes)
b) Robertsonian (fusion of two acrocentric chromosomes) - Deletions
- Insertions
- Inversions (paracecntric or pericentric)
Give an example of a Robertsonian Translocation.
Down syndrome
What is the first law of mendelian inheritance?
Law of segregation (during gamete formation, each member of the allele pair separates)
What is the second law of mendelian inheritance.
Law of independent assortment (genes for different traits assort independently of another in the formation of gametes)
Describe the characteristics of autosomal dominant traits.
- each child has 50% chance of inheriting mutation
- no skipped generations
- equally transmitted by men and women
- male to male transmission can occur
Describe the characteristics of autosomal recessive traits.
- unaffected parents have affected children
- males and females equally affected
- horizontal inheritance pattern
- conditions usually have early onset
- reduced penetrance than autosomal dominant
What trait can be more common in ethnic groups?
Autosomal recessive trait.
What is the risk for a sibling of an unaffected individual to be affected?
25% (1 in 4)
Describe x-linked traits.
- Males more commonly affected
- If mother not carrier then affected males have unaffected children
- All daughters are carriers from affected carriers and no sons inherit conditions.
Describe the types of chromosomal mutations.
- Numerical
- Structural
- Mutations
Give examples of numerical chromosome mutations.
Down syndrome = trisomy 21 Patau's syndrome = trisomy 13 Edward's syndrome = trisomy 18 Kleinfelter's = 47XXY Turner's = 45X
Give examples of structural mutations.
Translocations (reciprocal and robertsonian)
Deletions
Insertions
Inversions (paracecntric and precentric)
Give examples coding mutations.
- Silent (ARG to ARG)
- Misense (ARG to GLY)
- Nonsense (ARG to STOP)
- Frameshift (deletion/insertion)
What are the main types of chromosomal mutations?
- Non-coding
- Coding
- Point (transitions and transversions)
Give 5 examples of molecular genetic technology.
- PCR
- Gel electrophoresis
- Amplification refractory mutation system (ARMS)
- RFLP
- DNA Sequencing
What is the role of PCR?
Amplify single or a few copies of a segment of DNA
What is required for PCR?
Sequence info, oligonucleotideprimers, DNA nucleotides and DNA polymerases.
What is the role of gel electrophoresis?
Separates DNA fragments by size by applying an electrical current through an agarose gel matrix.
What are the advantages of gel electrophoresis?
Speed, ease of use, sensitive, robust.
Give an example of when RFLP is used?
Test for sickle cell anaemia. Uses restriction endonucleases to cut out genes.
Give an example of a gold standard DNA sequencing method.
Sanger sequencing
What is DNA sequencing used for?
Detecting mutations
Define population genetics.
The frequency of alleles in whole population affects health of population.
What is often associated with genetic variation?
Selective pressure changes.
According to the Herdy-Weinberg equilibrium, genotype and allele frequencies remain constant. Is this true or false?
True
What does non-random mating lead to?
Increase mutant alleles thereby increasing proportion of affected homozygotes.
Describe two types of non-random mating.
- Assortive mating (choosing partners due to shared characteristics e.g deafness)
- Consanguinity (marriage between close blood relatives)
Describe the effects of negative natural selection.
- Decrease reproductive fitness
2. Decrease prevalence of traits
Describe the effects of positive natural selection.
- Increase reproductive fitness
2. Increase prevalence of adaptive traits.
Define genetic drift.
Random fluctuation of one allele transmitted to high proportion of offspring by chance.
Define founder effect/bottleneck effect.
Reduction in genetic variation that results when a small subset of a large population is used to establish a new colony.
Cultural and geographic founder mutations can be subdivided into what?
Dominant (e.g BRCA1/2) & recessive (e.g CF)
What are the basic mechanisms of inherited predisposition to cancer?
- Oncogenes (accelerate cell division)
- Tumour suppressor genes (inhibit cell cycle or promote apoptosis)
“two-hit hypothesis”
What is the result of failure of mismatch repair genes?
- micro satellite instability (MSI).
- cells with abnormally function MMR genes accumulate errors.
- inherited cancer likely at young age.
Describe most cancer susceptibility genes.
Dominant with incomplete penetrance. Need second mutation to develop cancer.
Give two examples of predictive gene tests in cancer.
- BRCA 1/2 associations with breast cancer and lifetime risk
- Colorectal cancer (non-polyposis or polyposis)
In the genetics clinic, what is the most important tool to investigate indirect linkages?
Drawing a pedigree.
What needs to be considered when looking at genetics?
‘Founder effect’
What is the steps in the clinical assessment in a genetics clinic?
History Pedigree Clinical examination (individual and family) Genetic test Synthesis
Who provides genetic counselling?
Clinical geneticist, counsellor, hospital doctor, GP, nurse
What has caused wet lab costs to fall less that 50% and decreased the time taken to interpret data?
Next generation sequencing
Describe two ethical issues related to genetic testing.
- Limitations - i.e some tests may not provide all the info families want and may require difficult decisions.
- Should info be obtained if no treatment or intervention exists?
Describe non-mendelian inheritance.
Doesn’t fit in with Medel’s laws of segregation and independent assortment e.g gene conversion or intermediate phenotype.
What are the mechanisms of complex inheritance?
- Incomplete penetrance
- Genomic imprinting
- Extracellular inheritance
- Anticipation
Define penetrance.
Frequency at which a trait is manifested by individuals carrying the gene.
Define epigenetic modifications.
Changes in gene function not explained by changes in DNA sequences.
Define uniparental disomy.
Inheritance of a chromosome pair from one parental origin.
Describe mitochondrial inheritance and give examples of mitochondria disease.
Mitochondrial disease affect tissues with high metabolic demand e.g Leigh’s syndrome, Leiber’s hereditary optic neuropathy, DM and deafness.
What is recombination?
The process of forming new allelic combination in offspring by exchanges between genetic materials (as exchange of DNA sequences between DNA molecules). This process is a natural process, such as the crossing over between homologous chromosomes during meiosis.
Does meiosis involve recombination?
Yes.
Does fertilisation cause recombination?
Yes
Describe FAP (familial adenomatous pulpous)
A hereditary colorectal cancer syndrome with severe colonic polyposis. Untreated polyposis leads to 100% risk of cancer.
What are the assumptions underlying the Hardy-Weinberg equilibrium?
- mating is random
- population size is large
- migration is negligible
- All of this helps explain the difference between expected population (as per HWE) and observed population (what is actually seen in real life)
What is the phenotype of a person with Kleinfelter’s (XXY)?
Male. The presence of a single Y chromosome, regardless of the number of X chromosomes, is what causes development as a male.
Does mRNA have a distinct lifetime within the cytoplasm of the cell and its degradation helps control protein production?
Yes.
What is the chance of and unaffected child whose parents are both carriers of cystic fibrosis to be homozygous for the normal allele?
In a family like this, each child has a ¼ chance of being affected (homozygous for the CF allele), a ½ chance of being a carrier (heterozygous and unaffected), and a ¼ chance of being homozygous for the normal allele and unaffected. So, of the unaffected children, 1/3 of them are homozygous normal.
