Human Genetic Diversity: Mutation and Polymorphism

Flashcards covering key concepts in human genetic diversity, mutations, and polymorphisms.

Mutation

A rare permanent heritable change in the sequence of genomic DNA.

Polymorphism

The occurrence of two or more alleles at a locus with gene frequency greater than 1% in a population.

Gain-of-function mutation

Mutations that result in overexpression or inappropriate expression of a protein product, often resulting in dominant diseases.

Loss-of-function mutation

Mutations resulting in the loss of the protein product, commonly associated with recessive diseases.

Dominant negative mutation

Defective protein production that inhibits the normal protein produced by the wild-type allele in heterozygotes.

Base-pair substitution (point mutation)

A type of mutation involving the replacement of a single base pair by another.

Insertion mutation

A mutation involving the addition of one or more nucleotide base pairs into a DNA sequence.

Deletion mutation

A mutation that involves the loss of one or more nucleotide base pairs from a DNA sequence.

Splicing mutation

Mutations that affect the ability of pre-mRNA to be properly spliced at intron-exon junctions.

Transposons

Mobile genetic elements that can insert into various locations within the genome.

Mutation hot spots

Regions of the genome that are more susceptible to mutations.

Induced mutation

Mutations caused by environmental agents or mutagens.

Spontaneous mutation

Mutations that occur naturally without the influence of external agents.

Xeroderma Pigmentosum

An autosomal recessive disorder caused by a defective NER system, leading to extreme photosensitivity and skin cancer.

Huntington Disease

A genetic disorder caused by expanded CAG tandem repeats, leading to neuron degeneration and motor control loss.

Familial Hypercholesterolemia

An autosomal dominant disorder caused by mutations in the LDLR gene, leading to high levels of circulating cholesterol.

Non-ionizing radiation

Electromagnetic radiation that doesn’t form charged ions but can move electrons from inner to outer orbits

Mutagens

Environmental agents that significantly increase the rate of mutations above the spontaneous

Base analogs

Chemicals with structures similar to DNA bases that can be incorporated into DNA during replication, potentially causing mutations.

Osteogenesis Imperfecta (OI)

Skeletal deformity and easy fracturing of bones

Caused by heterozygous mutations in COL1A1 or COL1A2 that encode the chains of type one collagen → disruption of the triple helical domain

Allele

Alternative forms of a single gene

Locus

A designated location of a chromosome

Monomorphic

Locus of the genomic DNA where the sequence is the same in a population ie. when the polymorphism criteria isn’t fulfilled

Silent substitution

Base pair substitution that doesnt result in an amino acid change to due codon redundancy

Missense mutation

Base pair substitution that produces a change in a single amino acidcausing potential functional alterations to the resulting protein.

Nonsense mutation

Base pair substitution that produces a premature stop codonresulting in truncated protein translation.

Promotor mutations

Reduces the binding affinity of a RNA polymerase to its promotor site, may increase or decrease the rate of transcription

Cryptic splice sites

Intronic DNA sequences that are similar to the ordinary splicing sites, but are normally unused during pre-mRNA splicing

Xanthomas

An irregular yellow patch or nodule on the skin, caused by cholesterol deposition