Ch. 4 Principles of Clinical Cytogenetics and Genome Analysis

Flashcards on human genetic diversity, mutations, and polymorphisms.

What is a reference genome?

The sequence of DNA that is expected for a species, constantly updated.

The “standard”

Define locus (or loci).

A position on a chromosome, ranging from a large span of nucleotides to a single nucleotide.

What is an allele?

Forms of a gene (dominant or recessive).

Define mutation in genetics.

Change in nucleotide(s) within DNA.

What is polymorphism?

Having 2 or more common alleles at a locus (occur in >1% of population).

Mutations are classified by size and functional outcome. What are the three ?

Chromosomal - affect the entire chromosome

Regional or subchromosomal - affect a portion of the chromosome

Gene mutations - only affects the individual gene (deletion, insertion, substitution, frameshift)

What are indels?

Insertions or deletions of base pairs in DNA.

What are microsatellites?

Repeats of specific DNA sequences, also called short tandem repeat polymorphisms (STRs), used in DNA fingerprinting.

What are retrotransposons?

Mobile element insertion polymorphisms, also known as "jumping genes", with common examples being Alu elements and LINEs (long interspersed nuclear elements).

Define copy number variants.

Variations in the number of copies of large segments of the genome.

Define inversion polymorphisms.

Sequences that are inverted; if balanced, no DNA is gained or lost, but if unbalanced, may result in duplications or deletions.

Define the different types of mutations.

1. Germline

2. Somatic

3. Gene Mutations

1. Germline mutations occur in gametes and can be passed to offspring

2. Somatic mutations occur in body cells and are not passed on

3. Gene mutations can be…

   1. spontaneous (not common because of repair mechanisms) - Mutations that occur naturally such as depurination, deamination, demethylation

   2. Induced - caused by mutations (UV light, chemicals)

What is the result of gene mutations causing frame shifts?

They alter the reading frame of the gene, potentially leading to missense or nonsense mutations and truncated proteins.

Missense vs nonsense

A missense mutation changes a codon so that it codes for a different amino acid, while a nonsense mutation changes a codon so that it becomes a stop codon, prematurely terminating protein synthesis

What are dynamic mutations?

Amplification (copying) of a sequence that sometimes expands during gametogenesis, with effects varying depending on their location and the genes affected (e.g., Huntington’s disease).