Exam III Review Flashcards
Overdominance
Heterozygote advantage- heterozygotes are favored over homozygotes and have reproductive advantage
-Equilibrium will be reached
Underdominance
Heterozygotes selected against- heterozygote has a lower fitness than both homozygotes. This leads to unstable equilibrium
The frequency of a recessive allele at equilibrium is equal to what
The square root of the mutation rate divided by the selection coefficient
The frequency of a dominant allele at equilibrium is equal to what
The mutation rate divided by the selection coefficient
Four forces that (in the short term) cause changes in allelic frequencies
Mutation
Migration
Genetic drift
Natural selection
Genetic drift will eventually lead to
Fixation of one allele
What populations are good for studying rare variants in allelic frequencies for certain diseases
Small populations
Evolution occurs through
Genetic change within populations
Biological species concept
A group of organisms whose members are capable of interbreeding with one another but are reproductively isolated from members of other species
What must be present for evolution to take place
Genetic variation
Anagenesis vs Cladogenesis
Anagenesis is evolution within a lineage with the passage of time
Cladogenesis is the splitting of one lineage into two
3 Types of variation talked about
Molecular variation
Protein variation
DNA sequence variation
Molecular variation methods
Can be used with all organisms
Can be applied to huge amount of genetic variation
All organisms can be compared
Quantifiable
Provide information about the process of evolution
Prezygotic reproductive isolating mechanisms
Ecological- Differences in habitat- individuals do not meet
Behavioral-Difference in mating behavior
Temporal- reproduction at different times
Mechanical- anatomic differences
Gametic- gametes are incompatible
Postzygotic reproductive isolating mechanisms
Hybrid inviability- hybrid zygote does not survive
Hybrid sterility- hybrid is sterile
Hybrid breakdown- F1 hybrids viable/fertile but F2 are not
Phylogeny is
The evolutionary relationships among a group of organisms
The variability selection hypothesis
Key events in human evolution were not shaped by any single type of habitat, but rather by environmental instability
Allopatric vs sympatric speciation
Allopatric has geological barrier to gene flow b/w two species, sympatric does not
Parsimony phylo tree approach
Favors tree that has the fewest necessary changes to explain evolution
Rates of evolution include
Rates of nucleotide substitution
Nonsynonymous and synonymous rates of substitution
Substitution rates for different parts of a gene
The molecular clock
The rate at which a protein evolves is roughly constant over time
Therefore, the amount of molecular change that a protein has undergone can be used as a clock
Exon shuffling
Type of genome evolution
- Function domains encoded by exons can be shuffled to create new genes of different but related function
- can be caused by crossover or transposons
Continuous/quantitative characteristics
Phenotypes vary continuously
Discontinuous characteristics
Traits posses only a few phenotypes
GWAS
An examination of many common genetic variants in different individuals to see if any variant is associated with a trait
Polygenic inheritance
Occurs when one characteristic is controlled by two or more genes
i.e. height, skin color, weight
Did mendel study continuous or discontinuous traits
Discontinuous
If he studied continuous- there would be a range of phenotypes instead a few, easily distinguishable ones
Quantitative characteristics
Exhibit complex relationship b/w genotype and phenotype Likely polygenic Important environmental influences Overlapping phenotypes Cannot use standard methods to analyze
Meristic characteristics
Quantitative- determined by multiple genetic/environmental factors, can be measured in whole numbers
-i.e. animal litter size
Threshold characteristics
Quantitative- measured by presence or absence, so only two phenotypes possible. They are quantitative because the underlying susceptibility to the characteristic varies continuously. When the susceptibility exceeds a threshold value, the characteristic is expressed
Population vs sample
Population is whole group, sample is a representative group from the population
Variance vs standard deviation
Variance- the variability within a group of measurements
SD- Square root of the variance
The mean provides info about
The center of a distribution
When regression coefficient is 0.2, a 1 unit increase in x is associated with
A 0.2 increase in y
Heritability
The proportion of the total phenotypic variation that is due to genetic difference
-An individual does not have heritability, a population does
Broad sense heritability
Ratio of total genetic variance to total phenotypic variance
Narrow sense heritability
Variation in a phenotypic trait in a population that is due to genetic variation between individuals in a population)
Components of phenotypic variance
Genetic variance
Environmental variance
Genetic x environmental variance
Components of genetic variance
Additive genetic variance
Dominance genetic variance
Genic interaction variance
Narrow sense- when h2 equals 0, 1, or .5
0- no relationship between parent/kid phenotype
1- perfect correlation b/w parent/kid phenotype
.5- genes and environment interact to determine phenotype
Does heritability indicate the degree to which a trait is genetic, and why/why not?
No, it measure the proportion of phenotypic variance that is the result of genetic factors in a given environment
Heritability indicates ______ about the nature of population differences in a characteristics
Nothing
Natural selection arises through
The differential reproduction of individuals with different phenotypes- will increase freq of certain alleles
Artificial selection is
Selection by promoting the reproduction of organisms with traits perceived as desirable- also will increase freq of certain alleles
Segregation analysis
Multiple genes analyzed together
Association analysis
Small areas of genome examine
Larger areas- false positives more common
GWAS uses what to help with mapping
SNPs
Higher MZ concordance compared to DZ concordance suggests what
The disease is familial or that there is a genetic influence
Epigenetics
Heritable change in phenotype that does not involve changes in DNA sequences
Behavioral epigenetics
Life experiences, especially early in life, have long lasting effects on behavior
The thrifty phenotype theory
When environmental conditions are poor for parent, internal biological processes know that the environment will be poor for offspring. With food shortage for parents- biochemical modifications allow pre-adaptation to produce offspring that will be better suited for that environment
-Reproductive advantage in severe environments
Methylated DNA vs methylated/acetylated histones
Methylated DNA causes silencing- usually M-cytosine
Methylated histones can have variable gene activity depending on which lysine is methylated
-Acetylated histones are activating
Critical concept of histone code hypothesis
Histone modifications serve to recruit other proteins by specific recognition of modified histone - these proteins then repress or promote transcription
Methyl transferase classes
I- DNA methyltransferase
II- Histone methyltransferase
III- membrane associated
Genomic imprinting
The expression of an allele depends on whether it is inherited from the male or female parent
Uniparental disomy and Prader Willis syndrome
Due to nondisjunction, a fertilized egg receives an extra chromosome, if it is not eliminated quickly, the result is miscarriage.
The extra chromosome could have come from the mom, meaning 2x mom chromosome and 1x dad chromosome
If dad chromosome is deleted, you are left with 2x mom chromosome and this can cause Prader Willis syndrome
During what time in life is epigenetics most important
First 1000 days of life
Epigenome
Overall pattern of chromatin modifications possessed by each individual organism
What is used to detect histone modifications
ChIP
What are used to detect DNA methylation
Restriction endonucleases
Bisulfate sequencing
Lead exposure and epigenetics
Lead exposure can alter DNA methylation
Benign vs malignant vs metastatic tumors
Benign- tumor remains localized
Malignant- tumor cells invade other tissues
Metastasis- tumor cells induce secondary tumors elsewhere in body
Knudsons multistep theory for cancer
Proposed that retinoblastoma results from two separate genetic defects, both of which are necessary for the cancer to develop
What is the singular key event in cancer
Genomic instability
- it leads to multiple mutations that activate all of the secondary hallmark events
Main cause of hereditary cancers
Establishment of genomic instability is the initiating event
Main cause of sporadic cancers
Deregulation of growth-regulating genes may be the initiating event, leading to DNA damage
Loss of heterozygosity
Person could be heterozygous for tumor-suppressor gene.
Loss of wild type allele through chromosomal deletion will leave only mutant allele and tumor suppressor activity is lost
Mutations is Ras pathway contribute to
Cancer
Lynch syndrome
Inherited disorder that increases risk of many types of cancer
-Mutated genes in this syndrome prevent proper repair of DNA replication mistakes
t(14;18)(q32;q21)
Chromosomal translocation that lead to hyper-upregulation of BCL2 (blocks mitochondrial apoptotic pathway) expression in cancer cells
-Hallmark of follicular lymphoma
Epigenetics and cancer
Mutations in the three classes of epigenetic modifiers (DNA methylation, nucleosome remodeling, and histone modification) are frequently observed in cancers
-These mutations probably cause genome wide epigenetic alterations in cancer
MicroRNA and cancers
Deregulation of miRNA can lead to cancer because some mRNAs are able to escape regulation by miRNAs
Retroviruses cause cancer by
- Mutating and rearranging proto-oncogenes
- Inserting strong promoters near proto-oncogenes
- Inactivating tumor suppressors
Rituximab function
MAB against protein CD20 on B cells. It selectively targets and destroys B cells in cancers with overactive/dysfunction B cells like lymphomas
CRISPR and CAR-T
CRISPR can be used to genetically alter the patients T cells so they are better equipped to fight the cancer
The cancer genome atlas
TCGA researchers will identify the genomic changes in more than 20 different types of human cancers to help us understand what turns a normal cell into a cancer cell.
What have we learned from The cancer genome atlas project
There are certain areas of the genome commonly affected in several types of cancers
Specific changes allow us to tell one type of cancer from another
Elephants and cancer
P53 is a tumor suppressor gene and elephants have 20 copies of it
What created the FDA animal rule
Anthrax
CHAMP
Cardiac high acuity monitoring program
Helps doctors monitor their HLHS patients more closely to reduce mortality rates
Is it possible to sequence a single molecule of DNA
yes
Restriction enzymes
Cut DNA at specific nucleotide sequences
Prokaryotes have restriction enzymes to ward off viral parasites. They methylate their own recognition strands to avoid destroying their own DNA
Gel electrophoresis
DNA fragments of different sized placed in gel
Electrical current is passed through gel
DNA fragments move toward positive pole, small fragments migrate faster than large
Dye is added, DNA fragments appear as bands
Southern vs northern vs western blot
Southern- DNA
Northern- RNA
Western- Protein
Cloning vector
A replicating DNA molecule attached with a foreign DNA fragment to be introduced into a cell
Making plasmid vectors
Circular DNA plasmid molecule from bacteria
Insert foreign DNA into plasmid using restriction enzyme
Linkers- synthetic DNA fragments containing restriction sites
LacZ use in cloning
LacZ gene is a selectable marker in the pUC19 cloning vector
It encodes a protein which breaks down x-gal to form a blue precipitate.
When the lacZ gene is interrupted with an inserted piece of DNA it produces a white colony and shows that the bacteria is carrying a recombinant plasmid
5 things required for PCR
DNA template DNA polymerase Primers Nucleotides Reaction buffer
PCR technique
DNA is heated to 90-100c to separate strands
DNA is quickly cooled to 30-65c to allow primers to anneal to complementary strands
Heated to 60-70c, DNA polymerase synthesizes new strands, doubling DNA amount
Cycle is repeated
Uses of PCR
Identify genetic variation
Isolate DNA from mammoths
Detect virus in blood sample
Amplify small amounts of DNA from crime
Limits of PCR
Requires knowledge of at least part of sequence of target DNA for construction of primers
Contamination can be a problem
Taq polymerase is used and cannot proofread
cDNA library
Consists only of DNA sequences that are transcribed into mRNA
Chromosome walking
Sequencing fragments from a point near to a gene of interest
Chromosome jumping
Large fragment is circularized and the junction is sequenced
Identifying CF gene
Linkage studies identified the CF locus
Clones from region were isolated by DNA walking/jumping
Analysis of genes in clones revealed 4 possible genes
DNA sequencing revealed 3bp deletion in the gene of the CF patient
Sanger sequencing
Single strand target DNA added
-Primer and all four dNTPs are added with polymerase
One type of ddNTP is added to each tube
Sequences terminate at different positions because ddNTP lacks 3’ OH
Fragments are separted by gel electrophoresis and can be read
Metagenomics
Involves identification of organisms present in the intestine, sewage, water, dirt etc…
What caused the skeleton to be so small
Mutations in certain genes previously linked with diseases of small stature, rib anomalies, cranial malformations and osteochondrodysplasia
Humanized mice
Limitations of development and function of certain lineages of human cells in mice can be overcome by transgenic expression of human HLA molecules, cytokines and other factors by targeting mouse genes to eliminate host MHC antigens and reduce host immunity
shRNA
Form hairpains back on themselves and can be used to silence genes. Must be introduced via vector
Crispr/Cas9
Prokaryotic immune system that confers resistance to foreign genetic elements such as plasmids and phages. Combination of Crispr, Cas9, guide RNA and template DNA can induce precise gene editing and the correction of genetic diseases in adult mammals
Bioinformatics
Develops methods for understanding of complex biological data
CMH genome center algorithms do what
Dramatically improve the speed and reliability of genetic testing
OMIM (online mendelian inheritance in man)
Catalog of human genes and genetic disorders and traits. Focuses on gene-phenotype relationship
ClinGen
Shares genomic and phenotypic data provided by health care providers through centralized database
EncODE (Encyclopedia of DNA elements
Goal is to identify/map all functional/regulatory elements in the human genome sequence
eMERGE (electronic medical records and genomics network)
Develops methods for the utilization of electronic medical record as a tool for genomic research
Gene expression omnibus (GEO)
A public functional genomics database of array and sequence based expression profiles
