Lecture 16 Flashcards
Types of mutagens
Teratogens- Congenital malformations
Carcinogens- Tumor formation, cancer causing agents
Clastogens- chromosomal abnormalities
Non-specific- DNA damage
What is a codon
A codon is a DNA or RNA sequence of three nucleotides (a trinucleotide) that forms a unit of genomic information encoding a particular amino acid or signaling the termination of protein synthesis (stop signals).
DNA
- A nucleotide is the basic building block of nucleic acids.
- RNA and DNA are polymers made of long chains of nucleotides.
- A codon is a trinucleotide sequence of DNA or RNA that corresponds to a specific amino acid.
- Mutagenesis is the process by which an organism’s DNA changes, resulting in a gene mutation, which can result in altered protein function and phenotypic changes.
What is translocation
A translocation, as related to genetics, occurs when a chromosome breaks and the (typically two) fragmented pieces re-attach to different chromosomes. The detection of chromosomal translocations can be important for the diagnosis of certain genetic diseases and disorders.
Single Nucleotide Polymorphism (SNP)
DNA sequence variation that occurs when a single nucleotide (adenine,
thymine, cytosine, or guanine) in the genome sequence is altered.
For example, a G nucleotide present at a specific location in a reference genome may be replaced by an A in a minority of individuals. The two possible nucleotide variations of this SNP – G or A – are called alleles.
Single Nucleotide Polymorphism (SNP)- three categories…
- SYNONYMOUS – Silent
- MISSENSE – Amino acid change
- NONSENSE – Stops transcription
Amorphic / Genetic null effect on genes
Complete loss of function
Hypomorphic effect on genes
A reduction in expression and/or function
Hypermorphic effect on gene
An increase in expression and/or function
Antimorphic effect on gene
Active, but opposite effect of normal gene
Neomorphic effect on gene
New function
Gene components
- The information contained within genes can be divided into several parts.
- The promoter region is located upstream from the coding region of the gene. Within the coding region of a gene are nucleotide sequences referred to as exons and introns. It initiates a particular gene expression.
- Exons contain the code that directs the assembly of amino acids that produce the protein product(s) of the gene.
- The introns, which are interspersed among the exons, do not code for amino acids and are spliced out of the final messenger RNA (mRNA) transcript.
- Research suggests that alternative splicing patterns within the gene give rise to sequences of DNA that may behave as exons or introns, depending on the circumstances.
- The end of the coding region of the gene is signified by a special nucleotide sequence called the terminator sequence.
SNP Location
- SNPs are single-nucleotide substitutions of one base for another that occur in more than one percent of the general population.
- SNP identification could serve as predictive
markers that inform us about effects of toxins on genes including causing specific diseases,
effectiveness of various medicines/toxins and
adverse reactions to specific drugs. This can save time, money, and discomfort for patients through accurate diagnoses and matching patients with appropriate medicines.
What do exonic SNP’s alter
Protein functions
What do Intronic / promoter SNP’s alter
Gene expression
Ethyl methanesulfonate (EMS)
Ethyl methanesulfonate (EMS) is a chemical mutagen believed to mainly induce G/C to A/T transitions randomly in genomes.
Ethyl methanesulfonate (EMS) mutagenesis of plants is a well-tested approach, which can induce point mutation in DNA of plants altering gene expression and help screen out favorable phenotypic
expression.
What is DNA alkylation
DNA alkylation refers to the addition of alkyl groups to specific bases, resulting in
alkylation products.
It causes DNA mutations.
What is DNA Oxidation
Oxidative DNA damage provides direct routes to mutations. While guanine usually pairs with cytosine, 8-oxo-7,8-dihydroguanine (8-oxoG), the most frequent type of oxidative base damage, may cause mispairing with adenine through a conformational change. This is one route to oxidative DNA damage induced mutations.
Crosslinking of DNA
INTRASTRAND
Adjacent pyrimidines on the same DNA strand form dimers
*Deletion
*SNPs
INTERSTRAND
*Replication blocked
*Transcription blocked
What are Intercalating agents
Insertion into DNA
*deletions
*insertions
*duplications
Insertion of these agents distorts the DNA
double helix, thereby interfering with DNA
replication, transcription, and repair. Such DNA distortions often result in mutations,
so intercalating agents are also mutagens.
Mutagenicity Test - Ames Test
It is used to detect the mutagenicity of environmental samples such as drugs, dyes, reagents, cosmetics, waste water, pesticides and other substances which are easily solubilized in a liquid suspension.
Mutagenicity Test - Ames Test- Principles
- Ames test uses several strains of bacteria
(Salmonella, E.coli) that carry a particular
mutation. - Point mutations are made in the histidine
(Salmonella typhimurium) or the tryptophan (Escherichia coli) operon, rendering the bacteria incapable of producing the corresponding amino acid. - These mutations result in his- or trp-
organisms that cannot grow unless histidine or tryptophan is supplied. - But culturing His- Salmonella is in a media
containing certain chemicals, causes
mutation in histidine encoding gene, such
that they regain the ability to synthesize
histidine (His+). This is to say that when a
mutagenic event occurs, base
substitutions or frameshifts within the
gene can cause a reversion to amino acid
prototrophy. This is the reverse mutation. - These reverted bacteria will then grow in
histidine- or tryptophan-deficient media,
respectively.
