Genetics Exam 5

Anticipation

a phenomenon where genetic disorders become more severe or have an earlier onset in successive generations due to expanding nucleotide repeats

Base Excision Repair (BER)

A DNA repair mechanism where glycosylases remove damaged bases; the site is then cut and filled in with correct nucleotides.

Base Substitution (point mutation)

A mutation that replaces one nucleotide with another; includes transitions and transversions.

Conservative mutation

A type of missense mutation where the substituted amino acid has similar chemical properties to the original.

Coding region mutation

A mutation that occurs in a gene’s coding sequence and may alter the protein's amino acid sequence.

depurination

Loss of a purine base from DNA, creating an apurinic site that may result in substitution mutations during replication.

deamination

The removal of an amino group from a base, such as 5-methylcytosine, often resulting in C→T transitions.

endogenous mutation (spontaneous)

Mutations that occur naturally without external influence, e.g., errors in replication or spontaneous chemical changes.

Enhancer mutation

A change in regulatory DNA that can affect gene transcription levels.

forward mutation

A change from the wild-type allele to a mutant form (e.g., A⁺ → A⁻)

frameshift mutation

Insertion or deletion not in multiples of three, altering the reading frame of translation.

Gain of Function mutation

Mutation that results in a new or enhanced gene function, often with dominant inheritance.

Hypermorphic mutation

A GOF mutation that causes overexpression or a more efficient gene product.

hypomorphic mutation

A LOF mutation that results in reduced gene function.

in-frame mutation

An insertion/deletion in multiples of three, preserving the reading frame.

indel

Short insertion or deletion of nucleotides in the DNA sequence.

intragenic suppressor mutation

A second mutation within the same gene that compensates for the effect of a prior mutation.

intergenic suppressor mutation

A second mutation in a different gene that restores function lost by the first mutation.

Loos of Function mutation

A mutation causing reduced or abolished activity of a gene product, often recessive.

mismatch repair

A system for correcting base mispairings that arise during DNA replication.

missense mutation

A base substitution that changes one amino acid in the protein sequence.

mutation

A heritable change in the nucleotide sequence of DNA

Neomorphic mutation

A GOF mutation causing a gene to be expressed at the wrong time or in the wrong place.

nonsense mutation

A base substitution that changes a codon to a stop codon, truncating the protein.This results in a prematurely shortened protein that may lose its function.

nonconservative mutation

A missense mutation where the new amino acid has different chemical properties, often affecting protein function.

noncoding region mutation

A mutation outside the coding sequence that may impact regulation, splicing, or mRNA stability.

Nonhomologous end joining (NHEJ)

An error-prone DNA repair mechanism that joins broken DNA ends without a template.

promoter mutation

A change in the promoter region that can alter transcription levels.

reverse mutation (revertant)

A mutation that restores the original wild-type sequence or phenotype.

silent mutation

A base substitution that does not alter the amino acid due to codon degeneracy.

somatic mutation

A mutation in body cells that is not passed to offspring.

spontaneous mutation

A naturally occurring mutation, such as replication errors or chemical changes.

strand slippage

A replication error where DNA polymerase slips, causing indels or repeat expansions.

suppressor mutation

A secondary mutation that compensates for the effect of a primary mutation.

transition

A base substitution between purines (A↔G) or between pyrimidines (C↔T).

transversion

A base substitution between a purine and a pyrimidine (A/G ↔ C/T)

triplet repeat disorder

A disorder caused by expansions of three-nucleotide sequences (e.g., CAG in Huntington's).

trinucleotide repeat expansion

An increase in the number of three-nucleotide repeats, often causing genetic disorders.

epigenetics

inherited changes in gene expression or phenotype without changes to the DNA sequence; often due to chromatin modifications

epigenome

the complete set of chromatin modifications in an individual

chromatin

DNA-protein complex that organizes and compacts DNA in the nucleus; its structure affect gene accessibility

Histones

proteins (H2A, H2B, H3, and H4) around which DNA wraps to form nucleosomes

Nucleosome

basic unit of chromatin made of DNA wrapped around histone proteins

Histone tail

N-terminal region of histones that can be chemically modified to regulate gene expression- positively charged

histone code

the combination of histone modifications that collectively influence chromatin structure and gene expression

acetylation

addition of acetyl groups by HATs; usually activates transcription by loosening chromatin

methylation (of histones)

addition of methyl groups by HMTs; can activate or repress transcription depending on the site

Histone Acetyltransferases (HATs)

enzyme that adds acetyl groups to histones

Histone Deacetylase (HDAC)

enzyme that removes acetylene groups, often leading to gene repression

Histone Methyltransferase (HMT)

enzyme that adds methyl groups to histones

Histone demethylase (HDMT)

enzyme that removes methyl groups from histones

DNA methylation

addition of methyl groups to cytosine bases (usually in CpG dinucleotides); often represses gene expression

5-methylcytosine (5meC)

methylated cytosine in DNA; often associated with silenced genes

DNA Methyltransferase (DNMT)

enzymes that catalyze methylation of DNA

Maintenance DNMT

i.e. DNMT1; copies methylation patterns to new DNA strands during replication

De novo DNMT

i.e. DNMT3; establishes new methylation patterns without a methylated template

Chromatin Immunoprecipitation (ChIP)

technique used to determine DNA regions associated with specific proteins or histone modifications

Bisulfite Sequencing

method to detect methylated cytosines by chemically converting unmethylated cytosines to uracil

Flowering Locus C (FLC)

a gene that represses flowering; must be silenced for flowering to occur

Flowering Locus D (FLD)

represses FLC via histone demethylation (and possibly deacetylation), promoting flowering

vernalization

requirement of prolonged cold to trigger flowering in some plants

Xist

a long noncoding RNA that coats the inactive X chromosome (Xi) and intimates silencing

PRC2 complex

protein complex recruited by Xist that methylates histone H3 on lysine 27 (H3K27me3), leading to heterochromatin formation

monozygotic twins

identical twins from the same fertilized egg; share 100% of their DNA

dizygotic twins

fraternal twins from two separate eggs; share ~50% of their DNA

concordance

the percentage of twin pairs that share a trait

adoption studies

used to separate genetic and environmental influences by comparing adoptees to biological vs. adoptive parents

Dmrt1

gene required for male development in turtles; high expression at 26°C leads to males

Kdm6b

histone demethylase that activates Dmrt1 expression; higher at male-producing temperatures

H3K27me3

repressive histone modification linked to female development

heterochromatin

tightly packed form of DNA that is transcriptionally inactive

model organism

a non-human species used to study biological processes due to traits like short generation time, well-characterized genome, and similarity to humans

forward genetics

starts with a phenotype and works to identify the responsible gene (phenotype → genotype)

reverse genetics

begins with a known gene and manipulates it to study resulting phenotypes (genotype → phenotype)

transgenic organism

an organism that carries foreign DNA (trans gene) inserted into its genome

knockout

gene is entirely inactivated (loss of function)

knock-in

a specific mutation is introduced into a gene (altered function)

RNAi

technique used to reduce gene expression (knockdown) using small RNA molecules

CRISPR

a bacterial immune system adapted for precise genome editing

Cas9

a DNA cutting enzyme guided by RNA to create double-strand breaks

single guide RNA (sgRNA)

a synthetic RNA that directs Cas9 to a target DNA sequence

Photospacer Adjacent Motif (PAM)

a short DNA sequence required for Cas9 to bind and cut