Chromosomal Mutations, DNA Damage, and Repair Mechanisms

Comprehensive vocabulary flashcards covering chromosomal alterations, copy-number variations, human genetic disorders, environmental mutagens, and cellular DNA repair pathways.

Duplication

A chromosomal mutation occurring when a region of a chromosome containing one or more genes is presented twice.

Charcot-Marie-Tooth disease

A genetic condition caused by the duplication of the PMP22 gene on chromosome 17, which leads to excess PMP22 protein that breaks down the protective myelin sheath around nerves, causing nerve damage and muscle weakness.

Deletion

A chromosomal mutation in which a region of the chromosome is missing, arising from an error in replication or the joining of breaks that occur on either side of the deleted region.

Cystic fibrosis

A disease associated with a mutation in the CFTR gene (specifically Delta F508, a deletion of the amino acid at position 508) that impacts the chloride channel moving water in and out of cells, causing abnormally thick and sticky mucus.

Cri du Chat syndrome

A genetic disorder resulting from a deletion of variable size on the short arm of chromosome 5 ($5\text{p}-$), characterized by a high-pitched monochromatic cry, epicanthal folds, hearing loss, heart defects, low motor skills, and partial webbing of digits.

Duplication and divergence

The evolutionary process of forming new genes from duplicate copies of old ones, where the resulting genes usually retain similar functions.

Gene family

A group of related genes that arise from an ancestral gene through multiple successive rounds of duplication and divergence.

Copy-number variation (CNV)

A form of genetic variation involving differences in the number of copies of a large genomic region (average length $200\,\text{kb}$ to $300\,\text{kb}$) due to duplication and deletion events, affecting approximately $10\%$ to $15\%$ of the genome.

Tandem repeat

A special type of copy-number variation consisting of short sequences ($2\text{--}50$ base pairs) repeated in multiple adjacent copies across tens of thousands of locations in the human genome.

DNA typing

A method of identifying individuals by analyzing differences in tandem repeat alleles separated by gel electrophoresis, providing identification as reliable as fingerprints from minute biological samples.

Inversion

A chromosomal mutation produced when a chromosome breaks and the segment flips in orientation before repairing itself, altering the gene order without changing gene copy number.

Reciprocal translocation

A chromosomal rearrangement in which two nonhomologous chromosomes break and exchange terminal segments, altering gene arrangement without changing gene number.

Gene dosage

The number of copies of a particular gene present in an individual, which requires proper chromosome balancing and can be disrupted in gametes following reciprocal translocation.

Mutagen

Any physical, chemical, or biological agent that increases the probability of a mutation occurring in DNA.

Ethidium bromide

A chemical reagent used to view DNA during gel electrophoresis that can cause frameshift mutations upon overexposure.

Mustard gas

A warfare chemical that acts as a mutagen by adding alkyl groups to DNA bases, resulting in base mispairing.

Pyrimidine dimers

Molecular lesions in DNA caused by UV radiation in which adjacent pyrimidine bases (such as thymine) become cross-linked, distorting the DNA helix.

Mismatch repair

A post-replication DNA repair mechanism that catches remaining errors missed by proofreading (leaving about $10^{-6}$ mismatches), utilizing MutS, MutL, MutH, an exonuclease, DNA polymerase, and DNA ligase.

Base excision repair

A repair mechanism that removes single abnormal or damaged bases (such as uracil in DNA) via DNA uracil glycosylase and AP endonuclease before gap filling by DNA synthesis.

Nucleotide excision repair

A repair pathway that removes short single-stranded segments of DNA containing damaged or distorted bases by cleaving the backbone at flanking sites and using the unblemished strand as a template.

Xeroderma pigmentosum (XP)

A human disease caused by defective nucleotide excision repair, leading to extreme sensitivity to UV exposure and a heightened risk of skin cancer.