Genetic Disease Mechanisms

Vocabulary needed for this class that is fair game for me to know

Polymorphism

Refers to the occurrence of two or more alleles at a particular locus within a population, each have a frequency greater than 1% regardless of mutation type, size, or effect on health. Commonly seen in DNA sequences. A locus is arbitrarily considered to be polymorphic if the rarer allele has a frequency of at least 0.001 so the heterozygote frequency is at least 0.02.

Mutation

any permanent heritable change in the Sequence or Arrangement of DNA

Variant

an allele that differs from wild type

Missense Mutation

A single-nucleotide substitution that swaps in a different amino acid creating a non-synonymous change and makes up 50% of disease causing mutations.

Effects range from silent to a misfolded/ non-functional protein.

Non-sense Mutation

A single base substitution in DNA resulting in a premature Stop codon. Makes up 10% of disease causing mutations.

Usually triggers nonsense- mediated mRNA decay or produces an unstable truncated protein.

Deletion

The loss of a sequence of DNA from a chromosome. The deleted DNA may be of any length, from a single base pair to a large part of a chromosome.

Duplication

The addition of a repeated sequence of DNA from a chromosome. The additional DNA may be of any length from a single base pair to a large part of a chromosome.

Insertion

A chromosome abnormality in which a DNA segment from one chromosome, or from exogenous source such as a retrovirus, is inserted into another chromosome.

Frameshift Mutation

A mutation involving a deletion or insertion that is not an exact multiple of 3 base pairs and thus changes the reading frame of the gene downstream of the mutation.

Promoter

A region with specific sequence of DNA located upstream of a gene that binds proteins to start the transcription of that gene into RNA

Intron

Non-coding segments of a gene that sit between the exons (INtervening). They do not code for proteins. A cellular machine called a spliceosome (a mix of proteins and RNA) cuts out introns and glues the remaining exons together in a process called splicing. Transcribed into the initial pre-mRNA in the nucleus, but removed before the RNA goes on to make proteins

exon

Coding segments of a gene that remain in the final mature messenger RNA (mRNA). They contain the actual instructions (EXpressed) used to build proteins during translation. Found in both the initial RNA transcript and the final mature RNA that travels to the cytoplasm.

Splice Site Mutation (RNA processing)

Disruption in the slice donor/ acceptor sequences (or creates new, competing splice sites), causing mis-spliced mRNA; Often lead to frame-shifts and premature stop codons (10% combined)

Small insertions/deletions (indels)

If the number of bases added/removed is Not a multiple of 3, it causes a frameshift— every downstream codon is misread, usually hitting a premature stop.

If it is a multiple of 3, amino acids are simply removed or added in frame so no frameshift.

Make up 25% of disease causing mutations.

Locus

Is a DNA segment postion on a chromosome

Allele

The different versions of the sequence at the locus