Lecture 2

Chromosome mutation

Alters the number of an entire chromosome, not its sequence.

Subchromosomal mutations

Alters the structure of part of one or more chromosomes, including large duplications, deletions, inversions, and translocations.

DNA mutations

Comprises 'small' changes in DNA sequence, including substitutions, deletions, and insertions of 1-100 kb.

Errors in chromosome segregation

Common occurrences of errors during meiotic divisions, with over 1 error occurring in every 25-50 divisions.

Non-homologous end joining (NHEJ)

A process that joins spontaneous double stranded DNA breaks, which can lead to translocations and inversions.

Non-allelic homologous recombination

Recombinations between related sequences that can cause duplications, deletions, and inversions.

DNA replication mutations

Mutations are rare due to proofreading, occurring at a rate of less than 1 mutation per genome per cell division.

Somatic mutations

Mutations that occur in somatic cells (do not produce gametes) and are found in the descendants of the cells in which the mutation occurred.

Germline mutations

Mutations that occur in germ cells (produce gametes) and are transmitted to offspring, responsible for most inherited genetic diseases.

DNA damage

Approximately 10^4 to 10^6 nucleotides are damaged per cell per day due to mutagens and spontaneous chemical processes.

Spontaneous deamination

The most common type of DNA damage where 5-methylcytosine is converted to thymine at CpG doublets.

Inversions and translocation

Types of alterations that can happen within subchromosomal mutations.

Reference sequence

The most common sequence in a population.

Locus

A segment of DNA occupying a particular location on a chromosome.

Allele

Alternative versions of a locus.

Wild type allele

The most common allele, usually present in > 50% of the population.

Variant (mutant) allele

Less common alleles in a population.

Private allele

Very rare alleles found in a population.

Polymorphism

Alleles with frequency > 1% in a population.

Single-nucleotide Polymorphism (SNP)

Single base pair substitutions that usually have 2 alleles.

Indel

Insertions and deletions, the most common polymorphisms typically ranging from ~1-1000 bp in length.

Copy number variant

Changes in number of copies of DNA segments (~100 to 1 Mb), often spanning multiple genes.

Amorphic alleles

Completely eliminates gene activity (Example: premature stop codon)

Hypomorphic alleles

Reduced gene activity, but not eliminated.

Hypermorphic alleles

Increased gene activity (Example: gene duplication, or deletion in repression sequence)

Antimorphic alleles (dominant-negative)

Produces a "poisoned" product that makes other wild type alleles less effective.

Neomorphic alleles

New function; gene product does something it shouldn't.

Synonymous Mutation

Functionally silent mutations that do not change the amino acid sequence of a protein.

Nonsynonymous Mutation

Mutations that result in a change in the amino acid sequence of a protein.

Frameshift Mutation

Mutations that change the entire reading frame of the genetic code due to insertions or deletions.