Genes and Disease Flashcards
How common are rare genetic diseases?
There are around 6,000 rare genetic diseases
Each has a prevalence of 5/10,000 people
Combined they effect 260 to 450 million people
What is the most common type of genetic disorder mutation?
45% of disorders are autosomal recessive
32% are autosomal dominant
10% are sex linked.
How many and in what ways to genetic disorders tend to affect children?
83% of rare genetic disorders affect the child
Almost 90% of which affect the nervous system
What is the progress with the human genome project?
Cost £2 billion and 13 years to complete, sequences the whole genome in 2003.
By 2018, sequenced 100,000 genomes.
What is a gene?
A functional unit of DNA, that composes of transcribed regions and regulatory sequences.
Directs the production of polypeptides or RNA (not always mRNA).
What is the idea of the central dogma refering to the transfer of information?
Information flows from DNA to RNA to proteins in humans.
Give an overview of the functional elements of genes.
1-2% of the human genome is protein coding
The encylopedia of DNA elements is looking into the remaining 99-98%.
Most of our DNA is transcribed into non-protein forming RNAs which perform useful functions.
What type of RNA might non-protein coding gene produce?
Regulatory RNA
Long non-coding RNA (LncRNA)
miRNA
siRNA
Describe the structure of a human gene.
5’
promotor region
5’ UTR or untranslated region
Transcription state site indicated by a start codon
Then a sequence of introns (removed during splicing) and exons.
Poly A signal
Termination codon
3’ UTR region
Where might eukaryotic gene expression be controlled?
Transcriptional control
(premRNA stage)
RNA processing control
(mRNA stage)
RNA transport and localisation control
mRNA degregation
Translation control
Protein activity control
What is alternative splicing and why is it important in protein production?
When exons from the same gene are joined together in different combinations, often caused by differences in the splicing process.
Creates different tertiary structure proteins,
Creates a wide range of protein functions from the same gene.
What is the RNAi pathway?
THe process by which RNAi is produced.
In the nucleus double stranded RNA is proced by DROSHA (RNAase enzyme) resulting is shorter dsRNA.
In the cytoplasms the shorter dsRNA is cleaved into smaller fragments by a second RNAase enzyme.
dsRNA associated with a protein complex, stands unwind and one strand in neglected.
The remaining strand in the portein-RNA complex binds to complementary mRNA.
The attaches protein complex inhibits the translation of the associated mRNA sequence through mRNA cleavage.
Why is RNAi important?
Found in all eukoryotes except fungi –. ancient evolutionary origin
Defends against pathogens mainly viruses by stopping protein production
Protects against transposins and other insertional elements
Indicates that gene expression rather than encoding genes themselves is important to evolving complex organisms.
What is the key difference between miRNA and siRNA?
siRNA has a more specif target mRNA molecule
miRNA has a wider target options
What is meant by the degenerative nature in DNA?
Why is this important when considering the location of substitution mutations in a triplet codon?
Degenerate - two different triplet codon may code for the same amino acid
A susbtitution eralier (base 1) in the triplet codon is more likley to change the resulting amino acid
A substituion laater in the triplet codon (base 2 or 3) is less likley to change the resulting amino acid.
Changing the resulting amino acid is more likely to have a phenotypic effect.
What are the different types of point mutations?
Substitution
Deletion
inversion
What are the different types of block mutations?
Duplication
Inversion (reversed order)
Deletion
Insertion (moved from one to the other - no exchange)
Translocation (exchange)
What is a missense mutation?
Why is it important in genetic disease?
A change in the triplet codon due to a single base substitution that results in a different amino acid.
May create a functional or non-functional protein.
Depends of the biochemical similarity between the original and the new AA
What is a conservative substitution mutation?
When the resulting changed amino acid is similar biochemically to the original, so the function of the protein is less impacted, this has a smaller effect phenotypically.
What is a silent mutation and why is it important clinically?
Is a genetic alteration in which a single base pair substitution in the protein coding portion of a gene does not change the resulting amino acid.
Most likley to occur in the third base of the triplet codon
However, it may affect mRNA splicing or stability to still change protein function
What is a nonsense mutation and why is it important in genetic disease?
A single base pair substitution in a protein coding gene results in a premature stop codon, this results in a truncated protein.
This is often non or less functional
What is a nonstop mutation?
When the stop codon is removed and transcription occurs past the normal range resulting in an elongated protein that may be non or less functional.
What is meant by a frameshift mutation?
Often an addition or a deletion mutation in which multiple triplet codons are changed.
What is Hurler syndrome?
An autosomal recessive disease
A type of lysosomal storage disease.
Is also known as severe MPS1
Causes by a deficient IDUA enzyme, a lysosomal enzyme
Dermatan and heparan sulfate (GAGs) accumulate within the cell (including within the lysosome) within tissues or organs
Causes developmental delay, corneal clouding, skeletal, respiratory and cardiac abnormalities.
Often have thickend lips, flat bridge in nose and prominent foreheads.
