Advanced Pathophysiology Module 2
Transcription
(1st step in creating a protein) when a gene is read and copied on an individual mRNA
Translation
(2nd step) when ribosomes assemble proteins from amino acids
How is DNA structured?
- DNA bases pair up to form units called base pairs - Each base pair is attached to a sugar and phosphate molecule creating a nucleotide. - nucleotides are arranged in two long strands forming a spiral (double helix)
Types of epigenetic modifications
- DNA methylation - X- inactivation - Histone modification - Microribonucleic acids (miRNAs) - environmental factors (ex. diet or chemicals)
What are the 3 main types of epigenetic modifications?
- DNA methylation - histone modifications - micro ribonuecleic acids
What are some examples of diseases that are associated with anticipation?
- Huntington's Disease - Fragile X Syndrome - Myotonic Dystrophy (neuro-degenerative diseases)
Describe the process or transcription and translation to assemble proteins.
- Transcription is the process through which RNA is synthesized from DNA ( for protein synthesis) - translation is the process where protein assembly occurs from theinteraction of mRNA and tRNA!
examples of trisomy disorders
- down syndrome (trisomy 21) - trisomy x (females have 3 X chromosomes instead of 2)
What are the 4 types of regulatory elements of non-coding DNA
- promoters - enhancers - silencers - insulators
What are the different types of cell mutations?
- random or spontaneous - translation/transcription errors - base substitutions - translocation - insertion or deletions - mispairing of nitrogenous bases
Describe the relationship between epigenetics and cancer
-Too much or too little DNA methylation can promote cancer -aberrant methylation is the silencing of tumor suppressor genes in cancer development, which can promote the development of cancer
What percentage of DNA is made up of protein-coding genes?
1%; all the rest is non-coding
Nucleotide
A building block of DNA, consisting of a base sugar and a phosphate
What role does a codon play in protein synthesis?
A codon is a triplet of base pairs of RNA that are necessary to code for a specific amino acid. Each codon will code for a specific protein. Amino acids are the building blocks of protein.
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.
carrier
A person whose genotype includes a gene that is not expressed in the phenotype.
A person has an autosomal dominant disease. Both his mother and his wife are unaffected. What is the probability that his first child will have the disease?
A person with an autosomal dominant disease has a 50% chance of passing the disease to each child
RNA
A single-stranded nucleic acid that passes along genetic messages
allele
An alternative form of a gene; small differences in DNA bases contribute to each person's unique features
What is precision medicine?
An emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person.
Provide an example of an epigenome
An important example is DNA methylation, which can lead to gene silencing (not expressed, the protein is not produced). Implications of epigenetic error are development of cancers, metabolic disorders, and degenerative diseases
haploid
An organism or cell having only one complete set of chromosomes. (23)
Homozygous
An organism that has two identical alleles for a trait
autosomes
Any chromosome that is not a sex chromosome
DNA methylation
The addition of methyl groups to bases of DNA after DNA synthesis; may serve as a long-term control of gene expression.
What is the epigenome?
The epigenome comprises all of the chemical compounds that have been added to the entirety of one's DNA (genome) as a way to regulate the activity (expression) of all genes within the genome. The chemical compounds of the epigenome are not part of the DNA sequence. but are on or attached to DNA. Epigenomic modifications remain as cells divide and in some cases can be inherited through the generations.
gene regulation
the process of turning genes on and off. Gene regulation can occur at any point during the gene expression, but most commonly occurs at the level of transcription (when the gene's DNA is transfered to mRNA). Signals from the environment or from other cells activate proteins called transcription factors. These proteins bind to regulatory regions of the gene and increase or decrease the level of transcription. By controlling the level of transcription, this process can determine the amount of protein product that is made by a gene at any given time. Gene regulation is an important part of normal development.
Define epigenetics
the study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself.
What are the two ways gene mutations can occur?
they can be inherited from a parent or acquired during a person's lifetime.
What is the purpose of non-coding DNA?
they contain sequences that act as regulatory elements, determining where genes are turned on and off
What is the purpose of transfer RNA and ribosomal RNA?
they help assemble amino acids (protein building blocks) into chains that form proteins
How many copies of a gene does each person have?
two; one inherited from each parent
How might precision medicine impact patient care?
will allow doctors and researchers to predict more accurately which treatment and prevention strategies for a particular disease will work in which groups of people. For example blood donor match accuracy prior to infusing blood to decrease chance of reactions.
penetrance
The percentage of individuals with a particular genotype that actually displays the phenotype associated with the genotype.
histone modification
changes in the structure of histones (proteins) that make it more or less likely that a segment of DNA will be transcribed
Polyploidy
condition in which an organism has extra sets of chromosomes
What is DNA?
deoxyribonucleic acid; hereditary material in humans and almost all organisms
genotyope
genetic makeup
codon
groups of 3 letter bases that give a certain signal; ex. start or stop
Heterozygous
having two different alleles for a trait
examples of multifactorial disorders
heart disease, Type 2 DM, schizophrenia, and some types of cancer
What makes DNA unique?
it can make copies of itself; each strand of the double helix can serve as a pattern for duplicating the sequence of bases - this is critical for cell division because the new cell needs an exact copy of the DNA
Maternal genomic imprinting
maternal allele silent
X-linked recessive
mutations in genes on the X chromosome. in males, one altered copy of the gene in each cell is sufficient. in females a mutation would have to occur on both copies of the gene to cause the disorder. much more common in males ex. hemophilia, fabry disease
acquired mutations (somatic)
mutations that occur at some time in a persons life and are only present in certain cells, cannot be passed to the next generation
Where is DNA located?
nucleus; small amount can be found in the mitochondria (mtDNA)
monosomy
only 1 copy of a chromosome
Phenotype
outward manifestation of a trait; what's observed
Paternal genomic imprinting
paternal allele silent
insulators
provide binding sites for proteins that control transcription in multiple ways: prevent enhancers in aiding transcription, prevent structural changes in the DNA that repress gene activity and can act as a barrier
enhancers
provide binding sites for the proteins that help activate transcription (can be found before or after the DNA they control on the strand)
silencers
provide binding sites for the proteins that repress transcriptions (can be before or after the gene they control, or even far away)
promoters
provides binding sites for the proteins carry out transcription (typically found just ahead on the DNA strand)
miRNA (microRNA)
short lengths of RNA that block the process of protein production
Provide an example of reduced penetrance
the BRAC1 and BRAC2 gene-not everyone with develop breast or ovarian cancer that has the gene and there is no way to predict who will develop cancer
How do epigenetic changes occur?
Chemical modifications of DNA sequences that alter the expression of genes, resulting in disease and phenotypic variations.
How can pharmacogenetics impact patient care?
Combines the science of drugs with the study of genes and their functions to develop, safe medications, and doses tailored to a person's genetic makeup.
How does DNA work?
DNA is made up of 4 different bases; the order or sequence of these bases determines the information available for building and maintaining an organism
noncoding DNA
DNA that does not code for any kind of functional RNA; doesnt provide instructions for making proteins
A couple has 2 children and 1 child has an autosomal recessive disease and the other child is normal. What conclusions can you make about the parent's genetic make-up?
Each parent is a carrier of the autosomal recessive disorder.
How does lifestyle produce differences in epigenetic modifications?
Environmental factors such as diet and exposure to certain chemicals may cause epigentic changes. - Additionally, differences in methylation patterns are seen depending on things like environmental exposures to chemicals and pollution as well as dietary patterns; which can affect the aging process quite radically. And it is not just the individual's lifestyle; but environmental exposures from parents and grandparents can modify epigenetics of offspring. So in short, you can have identical twins that age very differently depending upon lifestyle.
Nondisjunction
Error in meiosis in which homologous chromosomes fail to separate.
IncRNA (long non-coding)
Long non coding RNA, diverse gene regulating activity
Why are x-linked recessive disorders seen more often in males than in females?
Males only have one X so more likely for them to be affected verses females since they have 2 X's and both would need be affected
hereditary mutations
Mutations passed from parents to the offspring via gametes
What is the role of a genetic counselor?
Provides info and support to people who have or at risk for genetic disorders. Discuss risks or diagnosis and can help to confirm or rule out genetic conditions.
What makes males and females different?
22 pairs of chromosomes are the same in all genders; the 23rd chromosome will have two copies of X in females and an X and a Y copy in males
trisomy
3 copies of a chromosome
Triploidy
3 sets of chromosomes (69)
tetraploidy
4 complete sets of chromosomes (92)
How many chromosomes do humans have?
46 (23 pairs)
What was the major goal of the human genome project?
Goal was to provide a complete and accurate sequence of the 3 billion DNA base pairs that make up the human genome
What are the different types of genetic testing?
Newborn Screening- Done on newborns just after birth to identify genetic disorders to be treated early in life Diagnostic- Identify or rule out genetic or chromosomal conditions if suspected (possibly to confirm a dx or showing s/s) Carrier- Identify people who carry one copy of a gene mutation (history of family with the disorder) Prenatal- Detect changes in fetus' genes or chromosomes before birth (done during early pregnancy) Preimplantation- Detects changes in embryos used in IVF to prevent babies from being created with disorders (since IVF is creating a baby with sperm and egg outside the body) Predictive- Determine if you will develop a disease in your life usually for people with history of family disease but not currently showing s/s
reduced penetrance
Penetrance refers to the proportion of people with a particular genetic change (such as a mutation in a specific gene) who exhibit signs and symptoms of a genetic disorder. If some people with the mutation do not develop features of the disorder, the condition is said to have reduced (or incomplete) penetrance.
What is pharmacogenetics?
Pharmacogenetics is the study of how genes affects a person's response to drugs.
genomic imprinting
Process of gene silencing in which genes are silenced depending on which parent transmits them and transcriptionally silenced genes are said to be imprinted. -
What are the causes of gene mutation?
Spontaneous mutations, errors introduced during DNA repair, errors during DNA replication and induced mutations.
Silent mutation
a mutation that changes a nucleotide, but does not change the function of the protein
X-linked dominant
a mutation that occurs one of the two sex chromosomes. a mutation in one of the the two copies of the gene in each cell is sufficient. Ex. fragile x syndrome
anticipation
a phenomenon where the s/sx of genetic conditions tend to become more severe or expressed at an earlier age from one generation to the next
chromosome
a threadlike structure of nucleic acids and protein found in the nucleus of most living cells, carrying genetic information in the form of genes.
mutagen
agent that can induce or increase the frequency of mutation in organisms ex. radiation
What are gene mutations?
alterations in normal DNA sequence and can result in abnormal DNA, RNA, and proteins.a gene mutation is a permanent change in the DNA sequence that makes up a gene. Mutations range in size from a single DNA building block (DNA base) to a large segment of a chromosome
What is gene therapy?
an experimental technique that uses genes to treat or prevent disease. In the future, it may allow doctors to treat a disorder by inserting a gene into a person's cell verses drugs or surgery. It is risky and still under study
autosomal dominant
at least one parent is affected by the trait, the affected parent has a 50% chance to pass on the trait to their child
genes
basic units of inheritance; code for a trait
autosomal recessive
both parents of the affected child carry one copy of the mutated gene, but both do not typically show s/sx of the disease themselves
