Exam 2- Genetics Flashcards
Nucelosides
- contain a nitrogenous base and 5-carbon carbohydrate group (a sugar either ribose or deoxyribose)
- linked together through glycosidic linkage
Nucleotide
- nucleoside with a phosphate group
- phosphodiester bond makes strands
- Ex: Guanylic acid (GMP), Cytidylic acid (CMP), Adenylic acid which means Adenosine monophosphate(AMP)
Which bonds are stronger?
GC bonds are stronger than AT because there are three hydrogen bonds holding them together
Histones are also called
nucleosomes
Chromatin
Nucleosomes organized in a coiled and supercoiled structure
DNA is wrapped around
core histones (nucleosomes)
What happens at the M phase of cell cycle
- chromatin is segregated as thread-like structures (chromosomes)
DNA -> RNA
Transcriptions
RNA -> Proteins
Translation
Gene
functional genetic unit that is transcribed
Characteristics of genes
- 30,000 genes can code for 20,000 proteins
- one gene can code for multiple proteins
- Introns are spliced out
- DNA is read in the 5’ to 3’
Mutations
- alteration in DNA sequence
- they occur during DNA replication which is rare and upon DNA damage
Types of mutation
- Synonymous (neutral)
- Non-synonymous (causative)
- Point mutation
- Insertion
- Deletion
Point mutation
- change of a single nucleotide
Ex: ATGTTT to ATGTAT
Insertion mutation
Insertion of a nucleotide
Ex: ATGTTT to ATGTTAT
Deletion mutation
- Deleting a nucleotide or base pair
Ex: ATGTTT to ATTTT
Synonymous mutation
- Leads to no change
- Ex: The base codes for the same amino acid
- If nucleotide is changed and the amino acid is the same so there is no overall change
Types of Non-synonymous mutation
- Missense
- Nonsense
- Frameshift
Missense
- Amino acid change
- Nucleotide changes and it codes for a different amino acid
Nonsense
- early truncation of protein
- Protein normally 200 amino acids will give you 50 amino acids
- Early stop codon
Frameshift
out of frame mutation
- this can happen by deletion or insertion
SNPs
single nucleotide polymorphisms
Indels
insertions or deletions of one or few nucleotides
CNVs
copy number variations
De novo mutation
- a mutation that is not in either of the patients parents
- a spontaneous or new change at a specific genetic locus (point)
- caused by: replication erros, misalignments, exposure to mutagens (chemicals, UV)
Homozygous
two copies (mom vs. dad) are the same at any point in the sequence
Heterozygous
- two copies (mom vs. dad) are different at any point in the sequence
Inherited mutation
- a germline mutation do novo mutation that has been passed to offspring through 1 or more generations
- less severe than de novo
- late onset severe mutations
- individual must be fertile and survive to reproductive years to pass on mutation
Wild type
common and functional gene version
- aka reference allele
Genetic polymorphism
deviations = polymorphic or mutant variants
Loss/ Gain or function
decreased or increased activity of the affected protein
Genetic diversity
1 SNP per 1,000 base pairs, or >3 million per genome
AGGTCAGT. (first allele)
AGGTCGGT ( second allele)
SNP is A>G
CYP2D6 Polymorphism
- metabolizes codeine (weak analgesic) to morphine (strong analgesic)
- we have more than 20 different CYP2D6 alleles
- can be either a poor, normal or ultra-rapid metabolizer
Germline mutation
- mutation from parent that is passed to offspring
Somatic mutations
- only affects cell of mutation and all downstream lineage ( important in cancer)
- occurs on somatic cells like muscle, skin and neuron cells
Genetic diseases
- A disease cause by a deleterious single change or some combination of multiple changes in an organisms genetic makeup
Monogenic disorder
- single gene
- mutation in one gene causes diseases
- mutations affect on single gene is large
Polygenic disorders
- multifactorial or complex
- 2 or more genes (+ environment) causes diseases
- each gene effect is small
Genotype
Genetic makeup of an organism
- set of genes it carries
Phenotype
Observable characteristics of the organism
- influenced by genotype and the environment
Ex: hair color, eye color
Autosomal Dominant
Only one copy of mutant allele required for phenotype/disease
- usually gain of function mutant
Autosomal Recessive
Both alleles must be mutated for phenotype/disease
- typically loss of function mutant
X-Linked Recessive
- Non-dominant mutation on X-chromosome, disease predominantly in males because they only have 1 X
- Males have maternal copy. Females are carriers of mutation
X-Linked Dominant
- Mutation on Y chromosome, parental inheritance only
- Very few genes on Y, most genes on Y affect fertility (poor inheritance)
What is BRCA 1/2?
They are tumor suppressor genes
- mutations cause tendency to suffer from breast/ovarian cancer
Pharmacogenomics
study of how a persons unique genetic makeup (genome) influences his or her response to medications
- Multiple genetic variants across populations
F508del
the deletion of a phenylalanine at residue 508 which leads to the gene, CFTR, misfolding resulting in disease Cystic fibrosis
Recessive Genetic diseases
Loss of function (LOF)
-Therapeutic- Put back what is missing
Dominant Genetic diseases
Gain of Function (GOF)
Therapeutic- mitigate toxic protein problem
Recessive Treatment approaches
- Activate alternative pathways ex: sickle cell anemia
- Replace protein therapy ex: Hunter syndrome iduronase 2-sulfatase (IDS)
- Gene therapy ex: inherited retinal disease
Dominant Treatment approaches
- Get rid of toxic effect ex: Familial hypercholesterolemia ( gets rid of excess cholesterol)
- Antagonize it’s function ex: Familial hypercholesterolemia
- Gene silencing ex: ATR amloidosis (Patisiran RNAi therapy)
Pharmacogenetics
single gene mutation affecting drug responsiveness in a single patient
Phase 1 polymorphisms
Both GOF and LOF
- Many CYP enxymes
- can be poor metabolizers (PM)
- can be ultrarapid metabolizers (URM)
- can be extensive metabolizers (EM) -middle
Phase 2 polymorphisms
- Mostly LOF
- can be slower enzyme reactions
- can be deficient in enzyme
- the role of testing in drug efficacy and safety
- may be important in determining extreme cases of toxicity, activation, or drug efficacy
TPMT is
an enzyme that breaks down a class of drugs called thiopurines. They suppress the immune system and are used to treat various immune related conditions or blood disorders
Activate alternative pathways is when
you use another pathway to make whats missing
- part of recessive gene. treatment
- Ex: sickle cell anemia (HBB mut)
Replace protein therapy is when
you use complex drugs then you infuse the patient with the protein that they’re missing
- part of recessive gene treatment
Ex: Hunter syndrome iduronase-2-sulfatase (IDS)
Gene therapy is when
using a vector, go into the DNA and place the gene in there
- cant be done for every gene because some genes are too large and it’s hard to place them into DNA
- part of recessive gene treatment
- Inherited retinal diseases (RPE65 mut)
Get rid of toxic effect is
getting rid of whatever excess of the gene is being made
- part of dominant gene treatment
- Familial hypercholesterolemia (cholestyramine get rid of excess cholesterol)
Antagonize its function
-a certain product is causing an issue. An antibody can be designed to neutralize the protein (attach to protein and make it stop working)
-part of dominant gene treatment
Ex: Familial hypercholesterolemia (monoclonal antibodies anti-PCSK9)
Gene silencing is
- when you can silence the gene so it stops making the bad protein
- part of dominant gene treatment
Ex: ATTR amyloidoses (Patisiran RNAi therapy)
What is 6-MP
a gene that is a very effective anti-leukemia agent in many combination protocols
- extensively metabolized by TPMT
- can lead to severe bone marrow suppression
Ethical issues
- genetic information is sensitive
OMIM:
how many genes does a disease affect
Blast
match sequence across genomes, compare species
CPIC:
FDA recommended gene tests
Web.Expasy
nucleotide sequence to protein sequence
