Genes & Disease Flashcards
What is a gene, what are they made up of & what do they do?
-Functional unit of DNA
-Made up of transcribed regions & regulatory sequences
-Directs the production of/encodes polypeptides or RNAs
How much of the human genome is protein coding?
1-2%
What is the rest of the human genome (that that isn’t protein coding)?
RNAs
What is the structure of a human gene?
-Transcribe in 5’->3’ direction
-Promotor region - where TF & RNA polymerase bind - to transcribe the gene
-UTR = will be transcribed but not translated
-Have micro-RNA binding sites - regulate gene expression
UTRs = x2 sections either side of a mRNA strand - are non-coding parts of mRNA
-Make pre-mRNA = has exons & introns - splice out introns = mRNA
-DNA/gene also has exons & introns!
What steps can eukaryotic gene expression be controlled?
From numbers 1-6
–> going from DNA to protein (i.e., where gene expression can be controlled during protein synthesis)
What is alternative splicing?
= creates many proteins from same strand of DNA
-Exons from same gene are joined in different combinations - leads to different but related mRNA transcripts
–> can translate these mRNAs = different proteins - have distinct structures & functions — all from 1 single gene
-So proteins produced will have different exon combinations - as image shows = introduces variation protein function - all from same gene = variation
–> ‘increases diversity of mRNA expressed from genome’
What is meant by the degenerate nature of the genetic code?
-Number of sense codons exceeds the number of amino acids
–> so many codons encode the same amino acid
–> so mutations - substitutions may be silent - as the base changed may mean the same amino acid is still coded for = no change to protein function
What are point mutations?
= Changes to one base in the DNA code and may involve either
Give the 4 different types of point mutation.
-Substitution
-Insertion
-Deletion
-Inversion
What are the 3 types of substitution mutations?
-Silent
-Nonsense
-Missense
Where is a silent mutation more likely to occur?
When the base pair substitution occurs in the 3rd nucleotide in a codon
What impact can silent mutations have?
-No effect on protein production
BUT
-Can affect mRNA splicing
&/or
-Stability - i.e., binding sites for micro-RNA
–> so this can impact protein function
What is a missense mutation?
Single base pair is changed = alters a single amino acid in polypeptide chain
Effect of missense mutation?
-Functional protein - but may have some altered properties -> similar function as AA changed to may have similar biochemical properties to the one it replaced = conservative mutation/substitution
or
-Non-functional protein
What is a conservative mutation/substitution?
Replace AA with one that has similar biochemical properties - so function of protein is similar to how it would be without the mutation - small effect on protein function
= due to missense mutation
What are the 5 types of block mutations?
-Duplication = part of chromosome is copied
-Inversion = segment of a chromosome is removed then replaced in chromosome in reverse order
-Deletion = portion of the chromosome is removed (along with any genes contained within this segment)
-Insertion = portion of chromosome is added to another
-Translocation = segments of 2 chromosomes are exchanged (may interrupt gene sequences)
What is Hurler syndrome?
-AKA mucopolysaccharidosis I (MPS I)
-Lysosomal storage disease
Cause of Duchenne muscular dystrophy?
-Mutations in dystrophin gene
-Dystrophin = rod-shaped protein - gives strong mechanical link between muscle cytoskeleton & ECM
–> dystrophin’s N-terminus domain binds to cytoskeletal F-actin & dystrophin’s C-terminus binds to the dystrophin-associated complex
= affects plasma memb integrity & intracellular Ca2+ concs
–> this affects mitochondria - leading to cell death
–> dystrophin = links from actin-based cytoskeleton of muscle cell through plasma memb (sarcolemma) to ECM = NORMALLY!!! - not in DMD/Becker’s MD
Dystrophin-glycoprotein complex - contains: dystrophin, sarcoglycans (x4) & dystroglycans (x2)
*Sarcoglycans - anchor to sarcolemma
*Dystroglycans - attach to laminin on outside of cell & to endomysium (surrounding muscle fibre)
–> so get intracellular contraction of sarcomere putting traction on overlying CT - this pulls on endomysium - which then pulls perimysium - which then passes to epimysium
Cause of Hunter syndrome?
-Deficient/absent iduronate-2-sulfatase (IDS) = lysosomal enzyme!!!
-Substrates to this enzyme accumulate - which includes: herpan sulfate & dermatan sulfate
-One of the lysosomal enzymes degrades GAGs
-Undegraded /partially undegraded GAGs = will accumulate in tissues & organs
