Molecular basis of inherited disease Flashcards
What percentage of the human genome is non-coding?
90%
Approximately how many protein coding genes are found within the human genome?
20,000
What is satellite DNA?
Heterochromatin
How are genes structured?
Exons
- coding DNA
Introns
- non-coding, spliced out of mature RNA
Regulatory sequences
- enhancers, promotors, locus control regions
Where does RNA splicing take place?
Nucleus.
Aside from splicing, what other modifications are made to RNA?
Capping
Polyadenylation.
What is alternative splicing?
Exons may be skipped (spliced out with introns) to produce a variety of mRNA products.
What is mutually exclusive exon choice?
A form of alternative splicing where if a particular exon is chosen for inclusion a different exon will be excluded, and vice versa.
What are gene families?
Evolution of genes progresses by duplication and divergence
Most genes belong to a family of structurally related genes
Members of a gene family may be clustered or widely dispersed
What are pseudogenes?
DNA sequences that resemble protein-coding genes but are not transcribed a messenger RNA (mRNA) in a way that could then be translated into functional protein.
What are interspersed repeats?
Short stretches of repetitive, non-coding DNA scattered around the genome.
What are processed genes?
Intronless copies of other genes - Usually remote from parent gene
Reverse transcription and reintegration - cf. retroviruses
Occasionally remain functional - e.g. PGK2 (testis-specific)
Most are non-functional
Where would you find large blocks of heterochromatic DNA?
Centromeres
What is alphoid DNA?
A type of satellite DNA found at centromeres
171-bp repeat unit
Repeat unit sequence shows chromosome-specific sequence variation - Probes for individual chromosome identification
Alphoid DNA is required for assembly of the centromere
What is the use of alphoid DNA?
Used for identifying specific chromosomes.
Why might there be many copies of the Alu repeat scattered across the genome?
Retrotransposition.
How might unequal crossing over cause molecular pathology?
Unequal crossing over may result in one long arm with DNA duplications and one truncated arm with loss of DNA.
What are the different types of mutation possible?
Large deletions or insertions
–Effects may be variable
–May be missed by PCR-based screening methods if heterozygous
–Duchenne muscular dystrophy (deletions)
–Charcot-Marie-Tooth disease (duplication)
Gross rearrangements
–Haemophilia A
Point mutations
Trinucleotide repeat expansions
What is the mechanism behind the haemophilia A mutation?
End of chromosome loops up and a recombination event occurs, resulting in an inverted segment.
What is the result of a missense point mutation?
Insertion of the incorrect amino acid.
Why is cystine particularly prone to mutation?
Because it is very easily methylated. This results in a CG -> TA mutation. Happens in roughly a 3rd of mutations.
What is the result of a nonsense point mutation?
The mutation results in the premature insertion of s stop codon and a truncated protein.
What is the most common feature of dominatly inherited mutations?
Usually result in a gain/altered function rather than a loss.
Give two diseases that are caused by polyglutamine (CAG) repeats.
Huntington’s disease
Spinocerebellar ataxia
Give examples of diseases that are caused by large non-coding repeat expansions.
Fragile X (CCG)
Myotonic dystrophy
