Concepts of Genetics: Unit 4

DNA methyltransferase

Methylation occurs via enzyme DNA methyltransferase, which attaches to 5 position of cytosine base.

Factors promoting Epigentic Changes

- Genomic imprinting - X-chromosome inactivation - Cell Differentiation * Temperature * Diet * Toxins

Transversion mutation

- Mutation changing a purine into a pyrimidine or a pyrimidine into a purine (A->C; T->G)

Intragenic supressor

A mutation at a second site that relieves the effect of the first mutation and restores the original phenotype (psuedo reverant) on the same gene

Silent mutation

A mutation that changes a single nucleotide, but does not change the amino acid created.

Using coat color in mice and the development if female honeybees as examples, how can dietary factors cause epigenetic modifications and thereby lead to phenotypic effects?

Happens mostly in the early stages of development. Dietary may affect level of DNA methylation. Effects S-adenisylmethionine or function of DNA methyltransferase and thereby influence particular genes are methylated or not.

Localization of histone variants effect on Epigenetic Gene Regulation

Histone variants may become localized to specific location (near promoter) and affect transcription

Depurination

Loss of a purine base (A or G)

Let's suppose that a vertebrae organism carries a mutation that causes cells that normally differentiate into nerve cells to differentiate into muscle cells. A molecular analysis of this mutation revelaed that it was a gene that encodes a methyltransferase. Explain how an alteration in methylationtranferase could produce this phenotype.

Methylation may be responsible for methylating and inhibiting a gene that causes cell to become a muscle cell. Methyltransferase is inactivated by the mutation.

Supressor mutation

Mutation at a locus that returns the allele to the original phenotype with a different mutation

Germline mutation

Mutation that occurs directly in sperm or egg cell or precursor cell that produces gametes

Chromatin Remodeling effect on Epigenetic Gene Regulation

Nucleosomes moved or evicted. When near promoter, level of transcription is altered

Deamination

The removal of an amino group from an amino acid. (C to U or T)

Deleterious mutation

describes mutations that are harmful to an organism

Histone Variant

histone genes that have accumulate mutations that change the amino acid sequence

Up promoter mutation

increases affinity for regulatory factors, increases rate of transcription

Frameshift mutation

mutation that shifts the "reading" frame of the genetic message by inserting or deleting a nucleotide Addition/deletion in DNA

Transition mutation

- Mutation changing one purine into another purine or one pyrimidine into another pyrimidine (A->G;T->C)

Molecular mechanisms that underlie epigenetic gene regulation

1) DNA Methylation 2) Chromatin remodeling 3) Covalent histone modification 4) Localization of histone variants 5) Feedback loop

Two effects of insulator

1. Barrier to changes in chromatin structure (gene within insulator is unaffected) 2. Blocking effect of enhancers (Gene A effected, but insulator keeps it from effecting Gene B)

Nonsense mutation

A mutation that changes an amino acid codon to one of the three stop codons, resulting in a shorter and usually nonfunctional protein.

Neutral mutation

A mutation that has no effect on the organism

Missense mutation

A point mutation in which a codon that specifies an amino acid is mutated into a codon that specifies a different amino acid.

Base substitution mutation

A type of mutation involving replacement or substitution of a single nucleotide base with another in DNA or RNA molecule.

Briefly describe 3 ways that ATP-dependent chromatin remodeling complexes may change chromatin structure.

ATP-dependent chromatin remodeling may effect position of nucleosomes, evict histones, and may replace histones with histone variants.

Feedback loop

Activation of gene that encodes transcription factor may result in feedback loop in which transcription factor continue to stimulate own expression

Wild type

An individual with the normal phenotype.

Mutant allele

Caused by a mutation in the DNA of the wild type allele

Histone acetyltransferases effect on chromatin compaction

DNA is - charged while histones are + charged. The covalent attachment of acetyl group decreases the amount of + charge of histone proteins and therefore decrease the binding of DNA and histone. Acetylation may attract other proteins to region that loosen chromatin compaction.

Explain how DNA methylation and formation of DNA loop control the expression of the Igf2 gene in mammals. how is this gene imprinted so that only the parental copy is expressed in offspring?

ICR and DMR in oogenesis is not methylated, so CTCF cab bind to these site to form a loop. Loop prevents nearby enhancer from activating the Igf2 gene. During sperm production, methylation of there site prevents CTCF binding and thereby prevents loop formation. Nearby enchancer activated Igf2 gene. Therefore copy of Igaf2 gene is inherited from father via sperm is active

DNA Methylation effect on Epigenetic Gene Regulation

Methyl groups attachment near promoters will inhibit transcription

Insulator

Segment of DNA that functions as boundary of two genes. Protects and insulates gene from regulatory effects of neighboring gene.

Point mutations

Silent Missense Nonsense Frameshift chemical changes in just one base pair of a gene

Covalent histone modification effect on Epigenetic Gene Regulation

Specific amino acid side chains found at amino terminal tails of histones may covalently modified (acetylated or phosphorylated) and could inhibit/enhance transcription

Define epigenetics. Are all epigenetic changes passed from parent to offspring? Explain.

Study of mechanisms that lead to changes in gene expression that can be inheritable and are reversible, but do not change DNA sequence. Not all epigenetic changes are passed, esp. if it is in a somatic cell.

Intergenic supressor

Supressor mutation that occurs in a gene that is different from the gene containing the original mutation

Somatic mutation

Takes place in a body cell, can affect the organism, not passed on to the offspring.

DNA Methylation

The addition of methyl groups to bases of DNA after DNA synthesis. Inhibits initiation of transcription when occurs near promoter.

Random mutation theory

The fluctuation test performed by Luria and Delbrück and the replica plating experiments performed by Lederberg and Lederberg were consistent with the

What is a nuclosome-free region? Where are they typically found in a genome? How are nucleosome-free regions thought to be functionally important?

They are a region of the gene that has no nucleosomes and are normally found at the core promoter or at the beginning or end of a gene. The beginning NFR is important so gene can be activated. End NFR important for proper termination.

Lethal mutation

a gene or chromosomal mutation that influences the development of an organism in such a way that the organism cannot survive

Induced mutation

a mutation caused by external agents such as mutagenic chemicals or radiation

Reversion mutation

a mutation that can be mutated a second time to revert DNA to it's original sequence

Spontaneous mutation

a random change in the DNA arising from errors in replication that occur randomly

Down promoter mutation

reduces affinity for regulatory factors, decreases rate of transcription