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Basic Genetics Flashcards (PGMM)
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- 1The Central Dogma of Molecular Biology1) DNA replicates intself using DNA polymerase.
2) During transcription, RNA polymerase uses DNA as a template to make RNA. mRNA: contains DNA's genetic info.
rRNA: complexes with proteins to make the ribosome.
tRNA: carries amino acids and works with rRNA within the ribosome to enable translation.
3) During translation, mRNA is read as a template by rRNA and the proteins in the ribosome, which use tRNA to make proteins out of amino acids.
4) Proteins then go on to fulfil cellular functions.
5) Reverse transcription can also occur, which is when RNA's genetic info is transcribed into DNA.
An example is in retroviruses like HIV.
Reverse transcriptase is the enzyme used. - 2A-DNARight-handed,
10.9 bases/turn,
shorter, broader. - 3B-DNARight-handed,
10 bases/turn. - 4Z-DNALeft-handed,
12 bases/turn,
elongated, thin. - 5The Human Genome46 chromosomes (diploid),
44 autosomes + 2 sex chromosome;
198cm DNA;
3.2 x 10^9 base pairs;
~20,000 genes;
Must be packaged into the nucleus. - 6DNA Replication IssuesNuclear DNA replication is performed by DNA polymerases alpha and delta;
Copies must be (almost) completely perfect, DNA must be unwound, DNA synthesis must be initiated, Polymerases only work in the 5’ to 3’ direction. - 7DNA ReplicationDNA replication is semiconservative,
High fidelity through proofreading
~10 errors/genome/generation (1 in 10^9), Multiple origins of replication per
chromosome - even on leading strand, Replication rate of approx. 2kb/minute. - 8Junk DNANon-coding DNA:
>95% of human genome has unknown function.
Reduced risk of mutation occurring in important area of genome?;
Repetitive sequences:
Structural importance?;
Introns... - 9Gene TranscriptionThe copying of part of one DNA strand into a complementary single-stranded messenger RNA molecule;
One gene to one polypeptide;
RNA polymerase II transcribes protein-coding genes to produce messenger RNA (mRNA);
RNA polymerase II cannot recognise the
transcription start site by itself;
Transcription factors bind at the gene promoter and recruit RNA polymerase II. - 10Gene RegulationThe transcription complex must assemble
when and where it is required;
~20,000 genes require regulation:
If there is 1 regulatory factor/gene, we require 20,000 regulatory factors,
And another 20,000 genes!,
What regulates them?!;
Instead, we use combinations of transcription factors. - 11Steroid Hormone Receptors: A Gene Regulator1) The steroid hormone binds to the steroid receptor.
2) Translocation of steroid-receptor complex to the nucleus.
3) Binding of complex to DNA regulatory site.
4) Transcription
5) Translation - 12mRNA Processing1) Splicing
2) 5' Capping (essential for ribosomal binding to mRNA)
3) 3' poly-adenylation (the poly(A)tail) (addition of 50-200 adenines), (Important to RNA stability), (RNA half-life)
4) Transport to the cytoplasm. - 13tRNAForms a clover leaf with an attached amino acid at the top (phe) on the 3' end. It also has an anticodon at the bottom at the anticodon loop. The right side holds a T-loop and the left side holds a D-loop.
- 14Genetic MutationSequence determines structure and structure determines function. therefore when the DNA sequence is altered, this can alter the resulting protein's structure, and therefore its ability to function
(Genotype -->phenotype) - 15Types of Genetic Mutation1) Point Mutations/Single Nucleotide Polymorphisms (SNP's).
-Silent
-Missense
-Nonsense
2) Frame-shift mutations
-Deletion/Insertion
N.B.-Mutation: Frequency <1% of population.
-Polymorphism: Frequency >1% of population. - 16Silent MutationE.g. Mutation at position 12 in DNA (A instead of C), which causes the position in mRNA to have a U instead of a G. This does not result in a change in the amino acid sequence.
- 17Missense MutationE.g. Mutation at position 14 in DNA (A instead of T), which causes the position in mRNA to have a U instead of an A. This causes an amino acid change at position 5 causing Val instead of Asp.
- 18Nonsense MutationE.g. Mutation at position 5 in DNA (T instead of C), Which causes the position in mRNA to have an A instead of a G. This causes only one amino acid to be translated and no protein is made.
- 19Frame-shift MutationE.g. Mutation by insertion of T between bases 6 and 7 in DNA. This adds an extra A before the rest of the other bases in the mRNA. This results in all amino acids being changed beyond this insertion.
- 20Chromosomal Mutations-Deletion: in a pattern of ABCDEFG, removing C and D resulting in ABEFG.
-Duplication: In two patterns of ABCDEFG, taking a copy of CDEFG from one, and a copy of EFG from the other, and swapping them and inserting the copies into the opposing patterns.
-Inversion: Taking a pattern of ABCDEFG and swapping CDE to EDC, making it ABEDCFG.
-Translocation: In two patterns, one of ABCDEFG and one of HIJKLMNO, breaking CDEFG off from the first (ABC) one, and LMNO from the second (HIJK) one, and swapping them to reattach them in the opposite patterns (ABLMNO, and HIJKCDEFG) - 21PolymorphismImplies genetic variation at a designated locus, A locus that is
polymorphic has at least two alternate alleles. - 22Genetic MarkerVariable DNA sequence that has a non‐variable component
specific enough to localise it to a single genomic locus/location.
This variable component is sufficiently heterogeneous to identify
differences between individuals and between homologous
chromosomes in an individual. - 23MicrosatellitesConsist of multiple repeats of a short sequence. (e.g. CACACACA,
n=4, or ATGATGATGATGATG n=5). The alleles of a microsatellite
are differentiated by the number of repeats. - 24Single Nucleotide Polymorphism (SNP)DNA variant that represents variation in a single base,
A common SNP can be defined as a locus at which two SNP alleles are
present both at a frequency of 1% or more. (10million, 1 every 300
bases) - 25HomozygousIndividual is homozygous at a locus if they have two
identical alleles at a locus. - 26HeterozygousIndividual is heterozygous at a locus if they have
two different alleles. - 27Megabases (mB)A measure of physical distance, e.g. Chr1 =250 Mb. Human Genome 3.1 Gb.
- 28CentiMorgan (cM)Unit of genetic distance equivalent to a 1% probability of recombination during meiosis e.g 1cM is the 1 recombination event in 100 meiosis.
- 29Autosomal Dominant InheritanceOccur in the heterozygous state. Only one mutant version of the gene (allele) of a gene necessary to express the trait.
Affected person usually has at least one affected parent. Dominant disorders tend to crop up in every generation.
Affects either sex, transmitted by either sex.
Child of an affected/unaffected pairing has a 50% chance of being affected. (this
assumed that affected parent is heterozygous). - 30Autosomal Recessive InheritanceBoth alleles of a gene must be identical to express the trait.
Affected people are usually born to unaffected parents.
Parents of affected people are usually asymptomatic carriers.
Affects either sex.
After the birth of an affected child, each subsequent child has a 25% chance of being affected. - 31X-Linked Recessive Inheritance• Affects mainly males, who are usually born to unaffected parents; mother is normally an asymptomatic carrier and may have affected male relatives.
• Females may be affected if the father is affected and mother is carrier, or could be due to non‐random X‐activation. - 32X-Linked Dominant InheritanceAffects either sex, but more females than males.
Females are often more mildly and more variably affected than males.
Child of an affected, has a 50% chance of being affected.
For an affected male, all his daughters but none of his sons are affected.
Can have affected males and females in same generation if mother is affected. - 33Y‐linked inheritanceAffects only males.
Affected males always have an affected father.
All sons of an affected man are affected.
No major health disorders apart from male sexual function have been found. - 34What is Gene Therapy?Gene therapy is the direct use of
genetic material to treat a disease.
Limited to the treatment of somatic
cells, i.e. no genetic material can be
introduced into the germline. - 35Why Gene Therapy?Diseases with no pharmacological therapy.
Diseases with sub-optimal drug therapies.
Identification of genetic deficiencies.
Increased understanding of molecular mechanisms of diseases.
Increased identification of candidate therapeutic genes.
Procedures that allow gene delivery at the time of surgery.
Gene transcription cassettes can easily be engineered.
Many diverse vectors for gene delivery to cardiovascular tissues.
Clear opportunity to beneficially treat diverse diseases. - 36Gene delivery - RequirementsTranscription cassette - promoter, gene (cDNA), polyA.
Package the cassette into a delivery ‘ vector’ .
Produce large amounts of the vector - scale up.
Deliver the vector to the target tissue:
local vs systemic gene delivery.
Vector delivers the cassette to the nucleus - variable.
Must result in high level production of the gene. - 37Haemophilia - TypesHaemophilia A: Factor VIII is lacking.
Haemophilia B: Factor IX is lacking. - 38Due to individual variation...20-40% of patients benefit from an approved drug.
70-80% of drug candidates fail in clinical trials.
Many approved drugs removed from the
market due to adverse drug effects. - 39Percentage of the patient population for which a particular drug in a class is ineffective.Anti-Depressants (SSRIs): 38%
Asthma Drugs: 40%
Diabetes Drugs: 43%
Arthritis Drugs: 50%
Alzheimer's Drugs: 70%
Cancer Drugs: 75% - 40Imprecision MedicineFor every person they do help, the ten highest-grossing drugs in the United States fail to improve the conditions of between 3 and 24 people.
- 41Percentage of patients whose tumors were driven by certain genetic mutations that could be targets for specific drugs.Melanoma: 73%
Thyroid: 56%
Colorectal: 51%
Endometrial: 43%
Lung: 41%
Pancreatic: 41%
Breast: 32%
Other Gynecological: 31%
Genitourinary: 29%
Other Gastrointestinal: 25%
Ovarian: 21%
Head and Neck: 21% - 42Requirements for stratified medicine to become the standard in disease management1. Continued research to understand the genetic and molecular basis of disease.
2. Development and use of increasingly sophisticated and powerful informatics technology.
3. Improvement and standardization of clinical data collection and linkage
with genomic and other databases.
4. Increased collection of tissues for biomarker research and evaluation, and
their organization in national and international biobanks.
5. Greater efficiency and productivity in the development of therapeutics and
diagnostics.
6. Flexible and novel approaches to regulatory assessments of innovative
stratified medicine products.
7. Improved flexibility in pricing for stratified medicine products—for both
diagnostic and associated therapy—to ensure cost-effectiveness for payers
and encouragement of innovation
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- Clinical Trials and Stratified Medicine Karteikarten am Basic Genetics Flashcards (PGMM) , erstellt von Justice Mundy am 24/02/2017.
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- Justice Mundy · Feb 2017
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