Genetics Midterm 3
Transformation studies show able to go from non-disease causing > disease-causing, Taking up something to transform
Enzyme that degrades DNA: DNase, Enzyme that degrades protein: protease, Enzyme that degrades RNA: RNase
Somatic Cells = Non-reproductive, Gametes (haploid) have half as much DNA as somatic cells (diploid)
DNA made of 4 nucleotides: A C G T
Chargaff Rules: A/T= 1.0 G/C=1.0. G+C content vary in different organisms
% of A and T are the same, % of G and C are the same, HOWEVER the G-C content in relation to A-T content varies among organisms ( not equal )
Bases DNA Cytosine Thymine = Pyrimidines Guanine Adenine = Purines Base + Deoxyribose + Phosphate = Nucleotide, GC bond is 3 Hydrogen Bonds stronger than AT which is 2 Hydrogen Bonds
Two anti-parallel strands:
5′ – AAACCTGTAGT – 3′
3′ -TTTGGACATCA – 5′ . (The bottom strand is complementary to the top strand ( vice versa) )
4^n = possibilities of sequence. n= base pairs. example: n=1000, 4^1000 possible arrangments
RNA = A C G U. RNA serves as the genetic material in some organisms like retroviruses, like HIV, DNA – > RNA, A and U pair
Mutations ( DNA changes) are the fuel for evolution, most deleterious.. In humans change of more than 1% = Polymorphism
Mutations in Somatic Cells are not passed to the next generation, greater effect if dominant / x-linked in males (recessive) , masked by WT cells with same tissue. Mutations in Germline Cells ( gametes) WIll be passed to the next generation
Substitution ( Point mutation): One nucleotide is changing. Missense: Change one amino acid to another . Nonsense: Change one amino acid to a stop codon (premature stop codon) , nonsense usually causes loss of function, (when a tumor suppressor loses function most likely to get cancer ). Silent: nucleotide changes but amino acid does not, due to code redundancy, should have no effect on protein. If 3 letters inserted / deleted ( will not lose frame). If 1 OR 2 letters insertions bases will cause frameshift
Insertion: Can cause a frameshift. Deletion: Can cause “frameshift” ( affects the protein-coding frame) , can ruin entire protein, especially if it occurs early in the sequence
Loss-Of-function: changes in the DNA that changes protein, loses function: due to insertion, deletion, pre-mature stop (nonsense), or missense that changes an important amino acid , Most loss of function are recessive
Null mutation: Complete loss of function in protein :due to complete deletion of gene, early pre-mature stop, point mutation on critical amino acid . Partial loss of function: mutant protein has some function but not as much as WT
Gain of Function: Too much functional protein is made, new function of protein is acquired, due to deletion of a regulatory domain, missense mutation that changes amino acid that normally as “off switch” to the protein, (ALWAYS ON) , Mostly Dominant, UNREGULATED Oncogeene
Dominant Negative Mutation: Causes a loss of protein function but is not Recessive, Heterozygous one copy is mutant loss function impairing WT ability to function so it would be dominant, See the effect in heterozygous even though the loss of function. Example: Someone in class falls asleep not effective, Someone talking to you in class effective DN (DISTRACTION)
Haplo-insufficient mutations : Loss of function of a gene that is very sensitive to dosage, one copy of the gene is not enough: dominant (heterozygote has one WT copy but looks mutant)
Spontaneous Mutations ( internal): Changes in nucleotide sequence without external cause, accidental, very low rate but varies among organisms
DNA replication Errors: DNA polymerase is very accurate occasional mistakes are made. DNA replication slippage: A portion of the template strand may loop out during replication, can lead to deletion in the new strand, most common in repeat regions .Tautomeric Shifts + Depurination/ Deamination (change in the structure of nucleotide) = CHANGE in Base Pairing , for Example UA instead of CG , AC instead of TA
Induced Mutations ( external): Due to external factors, natural/artificial
Heritability: Is not a fixed trait / and is context specific. It is a portion of phenotypic variation that can be attributed to a genetic variation within a certain population in a particular environment. Example: .65 heritability estimate means that 65% of variation in height could be explained by genotypic differences among individuals in a particular population in a particular environment
Inducible System: If certain sugars are present in the environment, bacteria express enzymes to utilize those sugars. Only makes enzymes when the substrate is present. An inducibleenzyme (induced by substrate) Double Negative ( Repressing the repressor / blocks repressor Example Lac-Operon). Repressible System: a repressible operon is an operon that blocks transcription of a gene at the presence of a substrate produces no enzyme (Activates repressor proteins)
Allosteric Regulation: Lactose causes a conformational change in lacl repressor so that it can no longer bind to the operator
Cis-Acting Element : DNA sequence that regulates expression of a gene located nearby. Example promoter, operator (enhancer)
Trans-Acting Element: Factors (usually proteins) that control gene expression through a cis element. Example: Transcription Factor Activator, Repressor (Protein move around) (more regulated than promoter)
Repression System: Only makes enzymes when end-product is absent. ‘Repressible” Enyzmes (repressed by end product) 8
Cancer: A large number of complex diseases, uncontrolled growth, and spread of cells. Most cancer is caused by mutations in somatic cells, Germ-line mutations small % of cancers high lifetime risk of cancer . Translocations, deletions, aneuploidy ( abnormal # chromosomes)
Clonal Origin of Cancer: Originated from a single common cell, all cells have same pattern of X-Inactivation, Pts w/chromsomal abnormalities that cause cancer – all cells have the same translocation.
Age-related Cancer: Takes time to accumulate multiple mutations, occurs 1 in 10^6. 10^16 cell division in the human body, Delay in exposure to carcinogens, and development of cancer. Example cancer appeared in Hiroshima/Nagasaki
DNA repair defects can lead to cancer
Cancer cells lose control over cell proliferation, only a few cell types continue to grow and divide in adult animals
Many cancer-causing viruses are RNA viruses: retrovirus
Apoptosis: If cells are really messed up they are programmed to die ( Limit Cancer Cells), normal in development example : gaps between toes and fingers
Loss of function of both alleles is usually a signature of tumor suppressors . If if PROTO-ONCOGENE —> ONCOGENE it is a GAIN OF FUNCTION ( example: c-myc is moved next to enhancer)
dNTP = GO ddNTP = Stop (termination)
Qualitative Traits: monogenic, specified by single genes, mostly no environmental factors ( Discontinuous) ( discrete categories like Tall/Dwarf) . Sometimes monogenic can be continuous ( Incomplete dominance)
Quantitative Traits: Polygenic, effected by the environment ( nutriton), can have different WT genes. (Example humans) (Continous) (Distribution Curve) ( can be discontinious)
1/4^n = ratio f F2 individuals expressing one of the extreme phenotypes , number of distinct phenotypes ( 2n+1) . N = # of genes involved
Heritability: Is not a fixed trait / and is context specific. It is a portion of phenotypic variation that can be attributed to a genetic variation within a certain population in a particular environment. Example: .65 heritability estimate means that 65% of variation in height could be explained by genotypic differences among individuals in a particular population in a particular environment
V(G) is greater in DZ than in MZ , V(E) is similar for DZ AND MZ
Twins: If concordance is much higher in MZ twins than DZ twins suspect a STRONG GENETIC omponent. If concordance is the same in MZ and DZ twins suspect a strong ENVIRONMENT componet
V(P)henotype = V(G)enotypic + (V(E)nvironmental + V(GXE)
Small RNAs inhibit Gene expression. by degrading mRNA siRNAs: outside source like a virus, could come from within cell. microRNAs: from cell of interest.
Monozygotic Twins: Share 100% genetic info, due to division of splitting of a SINGLE Egg. Dizygotic: share 50% of genetic material, due to separate fertilization events. (in the uterus together but different sperm and egg)
Variance: The average of the squarded differences of the mean. (sometimes n-1) 206^2 + 76^2 + (-224)^2 +36^2 + (-94)^2 / 5 = 21704 = Standard Deviation root of variance
# of Distinct Phenotypes = 2n + 1 (n = # of genes). Additive Alleles: count the capital letters.
Mismatch repair: Nucleotide is removed: Old strand is marked , new strand the one more likely to be wrong is not marked