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Genetics and Genomics Notes
Genetics and Genomics Notes
Forward genetics
o Phenotype to genotype
Reverse genetics
o Genotype to phenotype
Cell is the basic component of organisms
o Nucleus contains the genes
o Mitochondria have their own genome
o Prokaryotic cells differ
Genetic material in a nucleoid region
Cell is organized but has no organelles
Almost everything is encoded in the DNA
o DNA karyotype-lay out chromosomes
Centromere
o Helps the chromosomes migrate from the middle of cell to poles
o Metacentric=middle
o Submetacentric=below the middle
o Telocentic=at the end
Cell division is essential to life
o Mitosis-division (exact copy)
o Meiosis-gametes (not an exact copy due to crossing over)
Spermato/oogenesis
2 separations to get haploid cells
o Cell must condense into chromatin
o Spindle attaches to kinetochore via the centromere
DNA replication can induce errors
o Mutations or other changes
o If it was perfect there would be no variation
Source for variation
o DNA replication and repair
o Crossing over and chromosome segregation
Cell cycle is monitored by checkpoints
o G, S, and M
o G0= nondividing cell
o Interphase is G and S
o The checkpoints can let mistakes through
They check for DNA damage or a failure to replicate
Something is wrong=apoptosis
Phenotype
o Appearance
o What is expressed
o Could be complex
Genotype
o What do the genes say
o Homo/heterozygous
o Dominant vs recessive
WT vs Mutant
o Wildtype is the normal that is defined
o Mutant is any changes
o Only 1 WT, but many mutants
Mendel
o Found that in the F1 generation only one gene/phenotype dominated
o But if F2 it was a 3:1 phenotypic ratio
o Chose phenotypes coded for by 1 gene
Monohybrid cross
o Only one gene being crossed
o Start with homozygous parental strains
Recessive alleles
o Only expressed when two copies of the gene are present
o In most cases the WT is dominant, but WT can also be recessive
Homozygous
o Two alleles the same
o Can be dominant or recessive
Heterozygous
o Two alleles are different
o Dominant will be expressed in most cases
Hemizygous
o Only one allele present
Dihybrid cross
o Two genes cross to see effect
o 9:3:3:1 outcome in the F2 generation
o Independent assortment
Independent assortment
o Combine the probability of one trait w/ probability of getting another
o Multiply
Test cross
o Can determine genotype if unknown but have a known phenotype
o Difference between homo and heterozygous
o Cross unknown with homo recessive
If homo- get all dominant expression
If hetero-get some recessive expression (1/2)
Human crosses
o Multiple different disorders
o Dominant diseases
o Recessive diseases
Pedigrees
o Can follow a disease in a family
o Can determine its genotype
o Recessive-skips generations
o Dominant- in all generations
o X-linked=expressed in more males then females
Females carry
Expressivity-the overall expression of the disease (how bad it is)
Penetrance-not everyone gets the disease (have the gene but dont express
it)
o Out of the people who have the disease what % express it
Probability and statistics of Mendelian genetics
o P(A,B)=P(A) X P(B)
o P(A or B)= Pa +Pb
o P(a/b)=Pa/Pb
Binomial theorem
o Used to calculate the probability of any specific set of pairs of
outcomes among a large # of potential events
o P=n!/s!t! X asbt
o S=# of a outcomes
o T=# of b outcomes
Chi-square analysis
o Variation between the observed and expected
o See if there is enough variation to reject the null hypothesis which
states that nothing is happening (random chance)
o P must be less than 0.05 to reject the null
o Use a graph of degrees of freedom (# of phenotypes-1) and x squared
to determine P
Classes of mutations
o Null mutation
Destroys the gene
Removes the allele completely
o Loss of function mutation
Could be null
Diminishes expression or function, or destroys a gene
Usually recessive, need two mutations to alleles
o Gain of function mutation
Some mutation causes a new function
Can change the phenotype
Ex: flies with legs in their head
Dominant mutations
o Why is simple genetic dominance most often observes for
geno/phenotype?
Only need one allele present to function completely
Mutations
o Missense
Point mutation where the codon and changes the AA and protein
o Neutral
Changes the codon and AA but not the protein
o Silent
Changes the codon but not the AA or protein
o Nonsense
Premature stop codon
Complete dominance
DNA
Functions
o Replication
o Information storage
o Info expression
Variation through mutation
o Allows new characteristics to evolve
Central Dogma
o DNA
Transcription
RNA
Translation
o Protein
Has to flow in this direction unless a virus goes from RNA to DNA with reverse
transcriptase
Ribosome is formed by rRNA
mRNA is loaded into the ribosome
tRNA brings AA to the ribosomes
DNA and genome size
o More genes doesnt mean more complexity
o Such thing as alternative splicing
DNA as the genetic material
o Griffiths transformation
Found that transformation occurred by some molecule
o Avery, Macleod, McCarthy
Only when using DNAse did transformation not occur
o Hershey-Chase
Used bacteriophages and labeled molecules
DNA with phosphate
Protein with Sulfer
Found labeled DNA in the cell
RNA can be the genetic material
o Viruses can have ss/ds DNA or RNA
o Reverse transcriptase
o Integration
Discovery of DNA
o X ray crystallography gave the idea of double helix
DNA facts
o DNA is right-handed (right hand rule and thumb up)
o Every strand has a 5 and 3 end
o A is always bound to T
o G is always bound to C
o A+T+C+G=1
o G3C
o A2T
o Phosphate connected to sugar, then the sugar is connected to a base
Purines (Double Ring)
o G, A
Pyrimidines (Single Ring)
o C, U, T
Sugar backbone
o RNA has an additional hydroxyl at the 2 carbon
o DNA lacks the 2 hydroxyl
When a sugar and base are bonded with phosphate=nucleotide
Without phosphate=nucleoside
o Up to 3 phosphate groups
o
Transcription
Transcriptome-all transcripts
Proteome-all proteins
Metabolism-all metabolic compounds
Transcription
o Help get an RNA message
o Need a template strand of DNA to get to RNA
o RNA is identical to the coding strand, but is matched up with the
template strand
Prokaryotic cell
o Replication, transcription, translation occur in the nucleus (nucleoid
region)
o Need an RNA polymerase
o Scans for an RNA binding site
o Need the sigma subunit to recognize the specific initiation sequence
Nascent RNA
o Transcript
Sigma factor dissociates after a few nucleotides of the RNA strand is built up
o Only necessary for binding and recognizing the promotor
o Recognize TATA box upstream
Operons
o Genes often found in a segment together
o Get a polycistronic mRNA
o Only found in prokaryotes
Ribosomes translate as mRNA is being transcribed
o No posttranslation modification
o Occurs faster than in Euk
o Quickly ramp up protein production
Eukaryotes
o Many more regulation of the mRNA
o Separated into compartments
RNA types
o mRNA
o tRNA
o rRNA
o miRNA
o catalytic RNA
Chromatin in Euk
o Densely packed DNA and organized by histones
o Before transcription may need to modify the chromatin
Hetero/Euchromatin
o 3 types of RNA polymerase
I=rRNA
II= mRNA and snRNA (nucleoplasm)
III=ssrRNA, tRNA (nucleoplasm)
o RNA Polym II promotors have a core promotor, and enhancer elements
TATA box
o Not a lot have it, but if a gene has it, it is essential to transcription
o Binds the RNA polymerase after binding TATA Binding Protein
o Allows for a transcription regulation
o Brings other RNA poly to site to increase regulation
CAAT box
o Another example of a TATA like binding element
Enhancers
o Specific sequence that can be located in front of, in, or after the gene
o If located in the gene it keeps the gene from being translated
o Can activate or depress depending on location
TF
o Generalized proteins that bind specific sequences to regulate genes
and expression level
Transcript
o Eukaryotes need to mature it
o Add a methyl G cap and poly A tail to stabilize
o Alternative splicing
Exons vs introns
Introns spliced out
Immature RNA s always longer than mature RNA (remove
introns)
Complexity
o Think about number of proteins, not the number of genes
o Genes also interact with each other in different ways (regulate)
Splicing
o Group 1
Make rRNA
Need a guanine to bind to an active site within the intron
Expressed hydroxyl, this attacks the donor site at the other end
of the intron and splices it out
o Group 2
mRNA
needs snRNPs
get a complex that forms lariat loops that splice out introns
exons ligated
modify the transcript
o RNA editing
o Substitution editing
Get a change of a nucleotide in a transcript
o Two forms of a protein depending on editing
o Insertion/deletion editing
Can alter the function and shape of protein
Or bring proteins into the proper reading frame to establish
function
Translation
o Elongation
o Termination
Ribosome is not formed until the mRNA binds the small subunit
o Then the large subunit binds
3 ribosomal sites
o Aminoacyl site=AA sits in the tRNA
o Peptide=growing peptide chain
o Exit
Stop codon causes the complex to fall apart
o Releases the peptide
Multiple translational complexes form on a single mRNA
Amino Acids
o R Group only thing that changes
o Hydrophilic/hydrophobic
o Polar (charged)
The r group differs in forl/function
o Change the folding by mutations
Protein sequence
o Primary=AA sequence
o Secondary=alpha helix or beta sheet (H-Bond stabilized)
o Tertiary=whole protein folding
o Quaternary=multiple proteins folding
Domain-functional part of protein that has a certain structure
Post protein modifications (post-translational)
o N terminal AA is often modified
o Add carbs to the protein
o Golgi editing
Functions of proteins
o Structural
o Contractile
o Signaling
o Storage
o Transport
o Enzymatic
Roles
o Enzymatic
Lower activation barrier
o Signal sequence-domain that attracts substrate
o Membrane anchoring
Mutations
Germline vs soma
o Much more dangerous in germline, passed onto future generations
Classes= LOF, GOF, null
Transition
o Purine changed into a different purine
Transversion
o Purine changed for pyrimidine
Repeat expansion
o Continue to get repeated sequences
Genetic analysis
o Use mutations to ID mutations and their resultant phenotyoes
o Induce many mutations to get a specific mutation
Origin
o Proofreading errors
DNA replication
But you do get a lot of repair of these mutations
o Tautomeric shift
One H switches position within nucleotide
Leads to mispairing and replication errors
T to G and C to A
When replicated back to their normal binding partner, causes
mutation
o Deamination
Amino group in C or A converted to a keto group, which changes
the basepairing
o Depurination
Lose a nucleotide within the DNA
o Oxidative damage
Oxygen damages the DNA
o Transposons
Pieces of DNA that can insert or move within the genome
o Replication slippage
Multiple repeats
Get an increased # of copy number variants
o Base Analogs
Incorporates a different nucleic acid
5 bromouracil (binds to A)
o Alkylation
Donate methyl or ethyl groups to amino or keto groups
Guanine to 6-ethylguanine
o UV radiation
Thymine dimers
Repaired by nucleotide excision repair
Accessing genotoxicity
o Before anything is released used the Ames Test
o Have a control side and get the number of random background
mutations
o Add the mutagen, see if any difference than the background rate
Repair
o DNA polymerase can proofread
o Mismatch repair
Mut S/L/and H scan the DNA for the incorrect base pairs
Evolutionary Genetics
Darwinian evolution
o Species have a common ancestor
Neodarwinism
o Discovery of genetics
Evolution requires:
o Variation between organisms
o Competition between individuals
o Selection
Descent from common ancestors
o Can use genetics to find these relationships
Two forms
o Micro/macroevolution
o Large and small scale
Phylogenetic tree-shows relationship between species
o Stasic-doesnt change
o Anagenesis-one species evolved into a different one
o Cladogenesis-species diverged into 2 separate ones
Morphology
o Species based on the way they look?
o Not a great model due to different looking organisms being of the
same species
Biological species concept
Inbreeding
o Inbreeding depression (lose heterozygotes)
o No new influx of genetic material
o F value
F=1 all homozygous
F=0 no inbreeding
Distance apart in years=# of mutations X mutation rate
DNA organization
Simple chromosomes
o Viral and bacterial chromosomes often consist of single DNA molecules
o Bacteriophage=lambda (lollipop head)
Circular replication
o Cut bu a nuclease
o Copied discontinuously and continuously
Bacterial DNA packaging
o Ecoli supercoils the DNA
o DNA has no tension due to turns
Eukaryotes
o Organize using histone proteins
o Condensed state get G-bands (dark and light)
o Can alter the packaging to get to genes
DNA loops out of chromosomes when needed
Nucleosome
o Histone octamer
Solenoid
o Group of 6 nucleosomes
Looped domains
Chromatin fiber
Chromatid
Net packing ratio of 500:1
Repetitive DNA
o 98% is repetitive DNA
o Centromeres
Sister chromatid cohesion
Assembly site for kinetochore
o CEN
The minimal DNA required for centromere function
o Satellite DNA
Repetitive pieces of 2 or 3 nucleotides that are constantly
repeated
o DNA isolation
Satellite DNA has a lower density
Less dense with more A-T bonds
o VNTR
Variable number of tandem repeats
STR
Short tandem repeats
Very short 5 or less bases
o LINE
Long interspersed nuclear elements (transposon)
o SINE
Short
o Ribosomal genes
Repeated in the DNA
Epigenetics
o Histone modification
o Can be passed on
o Reversible
Epigenators
o Environmental signals (internal or external)
o Signal is transduced to the cell
Histone modification
o Histones have a tail that can be modified
Acetylation
o Opens up
o Deacetylation closes
Methylation
o Opens or closes depending on location
HDAC
o Histone deacetylation complex
o Closes the DNA up
HAT
o Histone acetylation complex
o Opens dna up
CPG islands
o Sites where the DNA is methylated
Imprinting
o IGF2 not turned off
o Hypo/hyper methylation
o Epigenetic inheritance can lead to cancer
o
Karyotype
o Group chromosomes and banding patterns
Aneuploidy
o 2nx chromosomes
Euploidy
o Multiples of n chromosomes
Polyploidy
o Multiples of the same gene
o Auto/allopolyploidy
Microbial genetics
Extranuclear inheritance
IS elements (bacteria)
o Insertion sequence
o Defined by inverted terminal repeats
o Flanked on both sides of the gene
o Transposons
Recognizes inverted terminal sequences specific for an IS
Inserts the sequence somewhere else in the genome
o DNA bases transposon elements (tn)
Can be larger
Heteroduplex
o The complementary sequence that helps it bud off
In the presence of Ac, Ds is not transposable
o But Ac alone can transpose
o Ac must still have its transposase gene
o Ds lost its transposase function
But still have the inverted sequences
Nonreplicative/replicative transposons
Rearrangements are mediated by pairs of tns
o Deletion between two transposons
o Get crossovers between repeats
o Get circular deletion
o Separate from chromosome
RNA based TEs
o Retrovirus
LTR=attracts RNA polymerase to make its products
o LINE
o SINE
Replication (copy elements)
o Transcribed into RNA and protein
o Can silence the transposon DNA
o Target for destruction
Retrovirus
o Integrase
Mediates integration of DNA into genome
o Retroviral integration
ssRNA to dsDNA
reverse transcriptase cant proofread
o retroviral budding
products packaged and moved to the PM
DNA viruses
o Have a lytic/lysogenic life cycle
RNA virus
o Remain RNA always
o Can be + or stranded
+=no rdrp (translated directly)
Recombinant DNA
Genomics
Sanger sequencing
o Able to do short segments of the genome (about 1000)
Next gen sequencing
o Sequences the entire genome
Clone by clone sequencing
o Cut up the genome into pieces using REs
o Smaller and smaller pieces
o Then insert into a large plamid
YAC/BAC
o Fit together with overlapping clones
Shotgun based sequencing
o Use different REs to cut
o Sequence contigs (next gen sequencing)
o Overlap contigs using a computer system
Repetitive DNA is hard to overlap
Gene models
o ID the UtR, initiation site, promoter, regulator elements, introns, and
exons
Sequence the cDNA or RNA so that you know what is expressed in a mature
cell
Can also get different mRNA based on alternative splicing
Determine the expressed pieces of a genome
o Computer reads all three frames
o Best when there are no introns
Databases
o BLAST
Uses an algorithm to see how close a protein overlaps with the
alignment of known proteins
Determine % overlap
Also can determine functional domains
Human Genome Project (HGP)
o 20,000 genes
o 3 billion base pairs
o 98% noncoding
o The noncoding DNA may have a regulatory function
o Made partial chromosomal maps
Genes cluster
o Deserts in between genes
Disease maps
o Map the genes that cause diseases and where it is located on the
chromosome
ENCODE
o Look at hetero/euchromatin and changes from cell/cell
o Shows where the genes are going to be expressed
CHIP
o Chromatin immunoprecipitate
o tag the protein with antibodies to find the protein of interest
Omics
Human Genetics
Females XX (homogametic)
Males XY (heterogametic)
Theory-the embryo can develop into male/female
o At one point important changes due to the presence of the Y
chromosome set the male into action
Y chromosome
o PAR region (pseudo autosomal region)-allows the Y chromosome to pair
with the X for mitosis and meiosis
o MSY region (male specific)-genes that make a male a male
o SRY region (sex determining region)-induces the development of testes
Expressed 6-8 weeks into development
o TDF=testes determining factor
X inactivation
o Due to dosage compensation
o Creates a barr body
Utilizes the Xic region and the T-six gene
Single Nucleotide polymorphisms (SNPs)
o Differences in genomes between organisms, or genetic variation
Genomic variation (types of SNPs)
o RFLP
Restriction fragment length polymorphisms
One of the first ways to distinguish between genomes
Appearance/disappearance of specific restriction sites
o VNTR
Variable # of tandem repeats
Operons
o The idea of an operon is that in prokaryotes, many genes that are
expressed together are under the control of the same promoter
elements
Inducible operons (also known as adaptive, facultative)
o Only expressed when necessary
o System can be turned on/off depending on environmental stimuli
o Positive control
Inducer in the system that turns on gene expression
o Negative control
Genes that are normally on get shut off by the presence of the
molecule
Constitutively active
o Always on
Lac operon (inducible)
o Cis acting regulatory sites are present upstream of gene clusters
3 genes
LacZ=B-galactosidase
Lactose to glucose and galactose
LacY=lactose permease
Facilitates entry of lactose into the cell
LacA=lactose transacetylase
Detoxifying enzyme
o Repression
Lac I
Expressed and binds to the operator site to stop transcription
o Polycistronic RNA is created after transcription
o Repression of the Lac operon
LacI repressed when present
Binds the operator regon
Only leaves when lac is present and binds to the repressor (and
glucose is absent)
Mutations
o LacI mutants
Cant bind to the promotor
Stays on constantly
o LacI mutants
Can bind to the promoter but not lac, so always off
o Operator region
Wont bind the repressor-always on
Known as the Oc mutation because it is constitutively active
Make diploids to see mutation effects (Merodiploids)
o The operator needs to be in front of the genes
So if a mutated operator is in the plasmid, will not have an effect
o Repressor can be made anywhere and travel to bind the promoter
o IPTG can induce the lac operon expreeion
Glucose is the preferred carbon source
o Less energy cost to the cell
o Glucose levels high, cAMP levels low
cAMP levels are high when no glucose
o cAMP binds to CAP (catobolite activating protein)
CAP induces expression of the lac operon (assuming lac is
present)
Lac repressor
o Homotetramer
o Inserts 4 O sequences that then are pulled together to form a
repression loop and stop transcription
Trp operon
o Repressible system
o Opposite of lac
o The presence of trp shuts off the operon
o The lack of trp turns it on
o The repressor is bound to the operon when it is bound to trp
o
Trp mutants
o trpR mutants
always on
o trpO mutants
always on because it cant be blocked
o trpP mutants
always off
attenuation
o an interaction between transcription and translation that regulates
expression
o leader region is in front of the trp operon
transcribed onto the mRNA and has a regulatory function
trp present=terminator hairpin and no transcription
trp absent=anti-terminator hairpin and transcription
charged tRNAs determine if trp is present or not
if charged tRNA present-there is trp present
o mediated by trp RNA binding attenuating protein (TRAP)
TRAP enables formation of the transcription terminator hairpin if
it binds to enough trp
ANTI-TRAP
No binding of trp, forms the antiterminator hairpin loop
Arabinose operon
o Under both inducible and repressible control
o 3 genes and a CAP binding site in the E.coli
o Both types of control are mediated by Ara C
Dont invest in the synthesis of any other sugar if glucose is present
Focused
Always initiates transcription from the same site
o Dispersed
Initiates transcription from multiple sites
Get multiple transcripts
o Focused promoter elements
BRE
B recognition elements-affect complex binding
TATA
INR
MTE
Motive 10 elements-help RNA polym bind
DPE
Downstream promoter elements-help RNA polym bind
CAAT box
Required for initiation
GC box
Binds TFs
o Effect of mutations
Mutate promoter elements-reduce the transcription level
Cis acting elements bind TFs
o TFs often expressed in time and tissue specific patterns and can
recruit or interact with RNA polymerase, and other Tfs, and respressor
proteins
Basal transcription level vs induced transcription level
Functional domains of TFs
o Can screen the genome and ID the TFs based on their properties
o DNA binding domains
Helix turn helix
Trans-activated domains (repressors)
Zinc finger DNA binding domain
Basic leucine zipper
Assembly of TFs
o Ex: RNA polymerase
o TBP (Tata Binding Protein)
Binds to the sequence and brings in TAF (TATA associated
factors)
o Polymerase comes in and forms the complex
o TBP and TAF stays in place to recruit additional transcription complexes
Enhancers
o More upstream
o Help attract TFs
o Can affect how fast a complex is made
o Increase the rate of DNA unwinding and RNA polymerase release from
the promoter to initiate transcription
o Ex: UASg
o
Constitutively active
post translational regulation
o alternative splicing
o ex: sex determination in Drosophila
SLX gene is only active in females
Get female only splicing that leads to the production of the DSXF protein
DSX-M protein present in males
o mRNA stability control
control the half life of the mRNA
depends on the transcription rate, processing, and degredation
Protein level
o Autoregulation
Ex: tubulin subunits bind to the growing polypeptide chain
Can stall the translation
Get RNAse to degrade the mRNA
o Iron regulation
Regulates the ferrin gene
No translation if an Iron regulatory protein is bound (which
means no iron is in the cell since iron binds to release it)
Too much iron?
Binds to IRP, which down-regulates the mRNA (which is
only stable when IRP is bound to it)
o miRNA and siRNA
both bind to the RICS and RITS complexes
created from dsRNA via the dicer protein
o RISC
Degradation of mRNA complementary to the sequence of the
small RNA
Downregulates the mRNA that is not exactly complementary but
close
o RITS
Goes directly into the cell nucleus and downregulates the
production of the gene directly
Gene Function
Forward genetics
o Genome wide genetic screens for mutants with specific phenotypes
o Id the genotype that creates the phenotype
Reverse genetics
o Define every gene in the genome based on sequence analyses
o Reduce/eliminate functions of specific genes and assess the
phenotypic impacts
Model organisms
o Easy to grow
o Short generation
o Abundant progeny
o Can cross in large numbers
Yeast
o Simplest eukaryote
o Haploid and diploid alternating generations
o Phenotypes are evident in haploid
o Diploid allows for recessive lethal mutations to be studied
Drosophila
o No meiotic crossing over in males
o Diploid
o Recessive lethal mutations are maintained in strains heterozygous for
balancer chromosomes
P-Elements
o DNA transposons that insert into the genome
o Can enable transformation
Wild type or altered copy of the gene to assess transgene
function
Reporter gene in which enhancer/promoter drives expression of
beta-gal or other detectible genes
o Need a positive selective marker
o Can use this to destroy genes
Randomly inserts itself into the open reading frame
o P elements either insert or destroy gene
Mice
o Genomic synteny with humans
o Large scale genomic screens difficult
o Creating transgenics and gene knockouts/replacements is more
feasible
Mutagenization
o Mutagenize parental strain, then perform crosses to generate progeny
that can be assessed for phenotypes of interest
Types of mutations
o Chemical
EMS, ENU
o Radiation
X-Rays, gamma radiation
Screen mutations
o Genetic screen helps select out the ones which were mutated
o Can look at yeast and determine the stages of cell cycle
See any arrested development
Will not grow if mutated
o Replica plating
Get the same colony and grow under different stressors to see if
mutations are sensitive or if new mutations appear under stress
o Screening mutants (Balancer Chromosomes)
Bioengineering
Body Plan
Developmental genetics
o Genetic and molecular mechanisms underlying cellular and organismal
development, homeostasis, aging and senescence
Development
o Develop tissues
o Death of specific tissues
o Balance between growth and death
Specification
o When genetic and positional cues confer a spatially discrete ID on
cells
Determination
o Cells time when a specific developmental state becomes fixed
Differentiation
o Process by which a cell achieves its final form and function
Hypothesis
o Development-attainment of a different state by all somatic cells in an
organism
Variable gene activity hypothesis
o Differential expression and action of genes
Controls development
o When and where are genes expressed and active
o How is gene expression regulated
Preformation
o Sperm had little human inside that became bigger
Fertilization occurs when an egg and sperm fuse
o Maternal cytoplasmic components
o mRNA and proteins
first components to trigger development
without these nothing would happen
body plan
o very similar in organisms within the same species
o Pattern of organization-characteristics and recognizable traits
Pattern formation
o Aspects of development of the body plan
o Leads to genesis of patterns or structures that make up the body plan
Number of axes (primary)
o Anterior
o Posterior
o Dorsal
o Ventral
Animal body plans are segmented
o The body plan has 11 segments
o Often has appendages
Drosophila
o Homologies among embryonic, larval, and adult body plans
o Governed by a set of genes
Cancer genomics
o SNPs
o Amplification
Clonality
o Tumors are comprised of clonal cell populations that all originate from
a single founder cell
o Disregulated growth and then disregulated movement
o Are all cells dividing?
Think that cancer stem cells are the only ones dividing
Proto-onco genes
o Genes that promote/ stimulate normal cell division and growth
o Gain of function: by overexcitation or loss of regulation, proto-onco
genes become onco genes, which stimulate hyperproliferation
Tumor suppressor genes
o Genes required for negative control
o Shut down cell division if activated
o So if you lose control via a Loss of function mutation, it leads to cancer
1-2% of cancer is hereditary
Ex: FAP (Familial adenomatous polyposis)
o Heritable cancer based on mutated copy (single) of APC gene on
chromosome 5
o Keep growing-dont stop division
o APC=tumor suppressor gene
o Role in contact mediated growth inhibition
o Get polyps in the SI
Driver mutations
o Confer growth advantage to cancer cells
o Cancer becomes worse with these mutations
Passenger mutations
o Other mutations that happen in the course of cell division that do not
confer growth
Epigenetic variation
o Demethylation or acetylation of chromatin encompassing genes that
stimulate cell division/migration
o Hypermethylation or histone deacetylation accompany genes that
arrest cell division or mediate cell death
Cell cycle control
o Altered function of genes regulating the cell cycle can lead to
dysregulation of cell division and excessive cell proliferation
o Abundance of different cyclins during the cell cycle that regulate
transitions from one part to the next
o Mutate cyclins
Get cell division when cell shouldnt be dividing
Apoptosis
o Programmed cell death
o BCL 2 level important (low for cell death)
o Cell death triggered by caspases