Genetics Exam 4
If all the variation is due to environment, heritability equals
0
p^2 equals (0.4)^2
0.16
q^2 (0.6)^2
0.36
2pq 2(0.4)(0.6)
0.48
Rexp for siblings and parent to offspring
0.5
Typical difference between individuals estimated at 20 Mbp
0.6% of the total of 3.2 billion base pairs
If all variation is due to genetics, heritability equals
1
Rexp for twins
1
Retinoblastoma requires two mutations to occur
1. People with the inherited form already have one hit, or mutation. Only need one more mutation for cancer to occur. 2. People with non inherited form must have two hits, or mutations. Non inherited form occurs much later in life, and only rarely
Probability of fixation is the same as the initial allele frequency in the population. If N=20, probability of fixation
1/(2X20) or 2.5%
Genome size varies from
10Mb in fungi to >100,000 Mb in some flowering plants (humans are about 3,000 Mb)
What is the chance of an offspring being GG
16% because allele frequency was 40% (0.4)^2 = 0.16
Humans have lost 80% of genes from the last common ancestor between chimps
170 genes duplicated in humans (90 different ones in chimps)
Most microbes cannot be cultured in the lab
1980s and 1990s Pace showed that environmental samples have a huge variety of microbial genes that could be PCRd from unculturable microbes
CRISPR-Cas sytems naturally require
2 RNA molecules: crNRA and tracrRNA. Pair and combine with Cas protein to from an effector complex
Genotype frequency of heterozygous (Gg)
2 times the allele frequency of G times the allele frequency of g
Draft of neanderthal genome has provided
2/3s of the genome of modern humans
Horizontal gene transfer may account for
20-30% of variation in the genetic composition of modern prokaryotic species
Number of proteins identical between humans and chimps
29%. Most differ by only 1-2 amino acids
Using a genetically modified retrovirus as a vector
3 essential virus genes removed and human DNA inserted. Unable to replicate in cells, but can integrate into human chromosomes and hopefully express the inserted gene
Complete sequences of various organisms show that number of genes humans share with other species is very high, ranging from
30% with yeast, 80% with mice, 98% with chimpanzees
2A, 5A, 11A, and 19A are strongly associated with large fruit size. This suggests that
4 QTLs like close to these markers
Genomic studies suggest that interbreeding took place between neanderthals and modern humans between
45-80,000 years ago
Each SNP is represented by
5 oligonucleotides that differ by one base or a deletion. Many sets exist for mutations in genes including p53 and BRCA1
IF G allele frequency is 40% then g frequency has to be
60%
Comparative genomic analysis will help identify genomic areas where humans have undergone rapid evolution since diverging from neandertahsl
99% identical, 78 new protein encoding sequences since divergence
An environmental agent that causes cancer is called
A carcinogen
If no functional Rb protein is present
A cell can always progress through the cell cycle
The most common class of human genetic abnormality is
A change in chromosome number
Metagenome
A collection of genes from a particular environmental sample. Can be analyzed similarly to the study of a single genome
Homology implies
A common ancestry
The new population from migration (the recipient population) is called
A conglomerate
Most quantitative traits are polygenic and exhibit
A continuum of phenotypic variation
Large numbers of computer data files are collected and stored in a single location
A database
Homologous recombination can be used to add
A desired sequence of DNA
Seven observations have been identified that suggest
A disease has a genetic basis
At the level of a human pedigree, a predisposition for cancer in inherited in
A dominant fashion
Homologous recombination
A donor DNA template can be added (with homologous ends to the break) which will be switched into the chromosome
About 4% of cases of cystic fibrosis are caused by a mutation known as G551D
A drug called ivacaftor has ben developed that is a very effective treatment for individuals with this particular mutations
Most cancer causing viruses are not very potent at inducing cancer, but
A few types of viruses can rapidly induce tumors in animals and efficiently transform cells in culture. Called acutely transforming viruses
Physical mapping
A form of genetic mapping based on direct analysis of DNA, in which the physical distance between DNA fragments are measured. This is used to assign DNA fragments to specific chromosomes. Relies on DNA cloning, distance measured in base pairs
Transgene
A gene that has been extracted from the DNA of one organism and transferred into the DNA of an organism of another species
Monomorphic
A gene that predominately has only one allele (fixed allele)
Monomorphin
A gene that predominately has only one allele (not a very common situation)
Proto-oncogene
A gene that regulates normal cell division but that can become a cancer-causing oncogene as a result of mutation or recombination
Polymorphic
A gene with two or more alleles or a noncoding piece of DNA that shows variation in sequence
Population
A group of individuals of the same species that occupy the same region and are able to interbreed
Epidermal growth factor (EGF)
A growth hormone that causes a cascade of gene expression when recognized by receptor. Regulated by RB1 (tumor suppressor)
Epidermal growth factor (EGF)
A growth hormone. Stimulates cells to reproduce and heal
Most cancers originate from a single cell
A growth is clonal in origin. Cancer itself is a population of cells
Genomics
A holistic study of genomes
Chromosomal abnormalities can be detected with
A karyotype
two-dimensional gel electrophoresis
A laboratory method that separates proteins according to their isoelectric points and molecular weights
A new mutation is more likely to occur in
A large population than in a small one
A cell must be homozygous for
A loss of function allele
In familial retinoblastoma
A mutated RB1 allele is inherited causing an 85% chance of developing retinoblastomas and increased change of developing other cancers
The function of tumor suppressor genes can be lost in 3 main ways
A mutation in the tumor suppressor gene itself, inhibition by DNA methylation, aneuploidy
Huntingtons disease is a result of
A mutations in a gene that encodes a protein termed huntington. Mutation adds a polyglutamine tract to the protein (TNRE). Causes an aggregation of the protin in neurons
Different phenomena may initiate directional selection
A new allele may arise in a population by mutation or a population may have a change in environment
Stabilizing selection tends to have greater genetic diversity for
A particular gene. Eliminates alleles that cause variation
Protoplasts
A plant or bacterial cell without its cell wall. Plant cells with wall removed
The x^2 test can be used to see if
A population really exhibits HW equilibrium for a particular gene
Homology between genetic sequences can be identified by computer programs and databases
A powerful tool for predicting the function of sequences
Ras GTPase
A proto-oncogene. 30% of all human cancers involved ras. Missense mutations in ras genes are found in a large number of different cancers
Contigs are a set of overlapping DNA clones that represent
A region of a chromosome
Heterozygous individual acquires
A second somatic mutation. Called loss of heterozygosity (LOH). Loss of function of the one normal allele
T DNA
A segment of plasmid transferred to plant cells. Used in nature to manipulate hormone levels
A CRISPR array consists of
A series of palindromic sequences separated by spacers derived by foreign DNA molecules (from viruses or plasmids
Local populations
A set of individuals that live in the same habitat patch and interact with each other
In one study viruses used as vector caused
A significant number of cancers. Halted clinical trials
Sometimes there is no obvious phenotype
A single gene may make only small contribution to phenotype. Another gene with similar function may compensate (gene redundancy)
Directional selection may act on phenotypes determined by
A single gene or phenotypes determined by multiple genes
CRISPR-Cas systems have been engineered into
A single guide RNA (sgRNA). A 20 nt region pairs with target DNA. By altering the 20 nts the effector complex can be targeted to different sequences
Point mutation destroys an MstII site, resulting in
A single large frament on a southern blot. Family has an unaffected homozygous daughter, an affected son, and an unaffected carrier fetus
Restriction fragment length polymorphism (RFLP)
A single nucleotide polymorphism (SNP) that exists in the restriction site for a particular enzyme, thus making the site unrecognizable by that enzyme and changing the lengths of the restriction fragments formed by digestion with that enzyme. A RFLP can be in coding or noncoding DNA
Quantitative traits do not naturally fall into
A small number of discrete categories
Linked alleles or molecular markers are identified along
A small region of chromosome
Hardy weinberg equilibrium
A state where allele and genotype frequencies do not change over the course of many generations (usually not the case)
Correlation coefficient
A statistical index of the relationship between two things (from -1 to +1)
Electroporation
A technique to introduce recombinant DNA into cells by applying a brief electrical pulse to a solution containing the cells. The pulse creates temporary holes in the cells' plasma membrane, through which DNA can enter
The introduced gene
A transgene
Over 80% of all processed food contains
A transgenic food product. Usually corn or soybean (there is no GMO wheat in the USA)
An organisms that has integrated recombinant DNA into its genome is called
A transgenic organism. Often called genetically modified organisms (GMOs)
Human fingerprints can be categorized as having an arch, loop, or whorl. The difference among these is the number of triple junctions, each known as
A triradius
An r value that is statistically significant suggests
A true association but does not necessarily mean a cause and effect relationship exists
Most inherited cancers involve a defect in
A tumor suppressor gene. Individual is heterozygous with one normal and one inactive allele
Daily, the human body suffers
About 10,000 lesions due to the actions of oxygen free radicals
Our manipulation of the genetics of other species began
About 12,000 years ago when humans began to domesticate animal and plants
Last common ancestor between humans and chimps was
About 6.3 million years ago. Mutations have accumulated in both
Broad sense heritability Hb2
Accounts for all genetic variation that may affect the phenotype
Age related cancer is an indication that cancer develops from
Accumulation of multiple mutations (or epigenetic changes)
3 stages of action of CRISPR-Cas system
Acquisition, expression, interference
Ras-GTPase normal role
Activates RAS via converting GDP to GTP, this initiates the pathway that results in cell division
Cyclins bind to a specific CDK
Active as a complex
p53 normal role
Acts as TF that detects DNA damage and regulates pathways in response cell death, maintains genome integrity; negative regulator of cell division. Prevents formation of cyclin; CDK complex
For polymorphic genes, frequencies of all alleles should
Add up to 1
The first inherited diseases treated with gene therapy
Adenosine deaminase deficiency (aka severe combined immunodeficiency disease or bubbly boy disease)
Metastasis suppressor genes are known
Affect only metastatic tumors, often affected (reduced) by epigenetic factors
Five common features of autosomal dominant inheritance
Affected offspring usually have one or both affected parents. An affected individual with only one affected parent is expected to produce 50% affected spring. Two affected heterozygotes will have 25% unaffected offspring. Trait occurs with the same frequency in both sexes. For most dominant disease casing alleles, the homozygote is more severely affected with the disorder
Vitamin A deficieny
Affects 200 M woman and children. 500,000 children go blind per year. 2 million children die per year
Bacterial species can also be used as biological control
Agents
Genome
All of the DNA in a single cell of an organism. Really focusing on the nuclear DNA. Structural, functional, comparative, and metagenomics
The gene pool
All the alleles of every gene in a population
Sequencing and analysis of an entire genome can identify
All the genes that given species contains but not all of the proteins and their variants
HW equilibrium predicts if
Allele and genotype frequencies will change in following generations or if the population has reached equilibrium (frequencies won't change)
Migration between populations can alter
Allele frequencies
HW equilibrium relates
Allele frequencies with genotype frequencies within a population
Genotype frequency of homozygous dominant (GG)
Allele frequency of G squared
Genotype frequency of homozygous recessive (gg)
Allele frequency of g squared
Hardy-Weinberg equation provides a quantitative relationship between
Allele of genotype frequencies
In the long run random fluctuations result in
Alleles being lost or fixed
Genome bases may provide information concerning
Alleles, researchers and bibliographic information (direct links to research articles and organisms "knock out" resources
Research efforts in gene therapy seeks to
Alleviate inherited diseases, treat diseases such as cancer and heart disease, combat infectious diseases such as AIDS
Dominant negative mutations
Altered gene product acts antagonistically to normal product
Many genes encode multiple proteins through
Alternative splicing
The proteome is larger due to
Alternative splicing, RNA editing, postranslational modifications
The ethical, legal, and social implications (ELSI) program was established as
An adjunct to the human genome project to address these issues
Synthetic genome
An artificially constructed genome to generate artificial cells or designer organisms
Two ways to see contigs
An assembled piece of DNA sequence built from short sequencing reads (most common use today). A set of overlapping DNA clones that represent a region of chromosome
Inbreeding increases the likelihood that
An individual will be homozygrous and therefore afflicted with the disease
5-10% of cancers are due to
An inherited predisposition
Functional genomics
Analysis of gene interactions. Includes proteomics
DNA fingerprinting (DNA profiling)
Analyzes DNA from individuals based on sizes of repeats at specific sites in their genome
When a human disorder is caused by a mutation in a single gene, the pattern of inheritance can be deduced by
Analyzing human pedigrees
Quantitative traits can be categorized as
Anatomical, physiological, behavioral, as well as human diseases
In two dimension electrophoresis a track or tube turned 90 degrees
And subjected to SDS-PAGE (all proteins coated with SDS and hence vely charged, and heated to denature. Separates based on molecular weight
Edible vaccine haven't been adopted due to
Animosity towards GMOs. Not accepted by the W.H.O.
Two common approaches to protein microarray analysis
Antibody microarray and functional protein microarray
Bioinformatics
Application of mathematics and computer science to store, retrieve, and analyze biological data
If r is less than zero
As one factor increases, the other factor will decrease
If r is greater than zero
As one factor increases, the other factor will increase too
In population genetics it is most useful to consider new mutations in this context
As they affect the survival and reproductive potential of the individual that inherits them, a new mutation may be beneficial, neutral, deleterious
Contigs
Assembled piece of a DNA sequence created from shorted sequenced pieces
Non random mating
Assortative mating
Dolly was gentically older than her actual age
At 3 years old, her telomere length were similar to a 9-10 year old sheep
Quantitative genetics
Attempt to mathematically describe/understand/predict patterns of inheritance in traits with continuous variation
Huntingtons disease is inherited in an
Autosomal dominant manner
Disorders that involve defective enzymes typically have an
Autosomal recessive mode of inheritance. Heterozygote carrier has 50% of the normal enzyme. Usually this is sufficient for a normal phenotype
Four common patterns of inheritance
Autosomal recessive, autosomal dominant, X linked recessive, X linked dominant
Mean fitness of the population
Average reproductive success of members of a population
Gene density in eukaryotes is very low compared to
Bacteria and varies even between chromosome in a species
Yeast is useful because it can do things to proteins that bacteria cannot
Bacteria don't do post translational modification because it's a prokaryote
CRISPR RNAs are encoded by DNA sequences found in
Bacterial and archaeal genomes (found in 50% of bacteria and 90% of archaea)
Negative frequency dependent selection is another mechanism of
Balancing selection
BLAST stands for
Basic local alignment search tool
Motivation behind genome sequencing projects come from a variety of sources
Basic research, medicine, agriculture, evolution
Oncogenes
Before mutation, then they become proto-oncogene. Mutations in these genes cause the cell growth signaling pathway to always be one
Cancer is a multistep process
Begins as a benign growth (not invasive). Additional genetic changes occur over many years
DNA microarrays (aka genotyping microarrays)
Being used to detect mutations in genomic DNA and gene expression patterns in diseased tissue
RB1 normal role
Binds E2F-prevents transcription because holding onto TF negative regulator of cell division
Nextgen sequencing presents 2 challenges
Bioinformatics: software to analyze the huge amounts of data generated. Bottleneck in research will move from gene discovery to functional analysis
DNA can be transferred into plants by
Biolistic gene transfer, microinjection, electroporation, introduction into protoplasts
Some alleles encode proteins that enhance an individual's
Biological fitness
Some alleles may encode proteins that enhance an individuals
Biological fitness
Locus heterogeneity in Hemophilia
Blood clotting uses several different proteins. A defect in any of these proteins can cause the disease
How nextgen sequencing has transformed how we do genetic research
Both in model organisms and opening up molecular study of non model organisms, as well as microbes we have not been able to study before
Members of different local populations are less likely to
Breed with each other
Biotechnology
Broadly defined as technologies that involve the use of living organisms, or their products, to benefit humans
Bacillus thuringiensis protein toxin
Bt kills insects. Not harmful to humans, plants, or animals. Produced and sold as powder
The transgenic crops carrying Cry1A are marketed as
Bt. Bt corn and cotton are extremely successful
In 2008 scientists chemically synthesized the complete genome of the bacteria Mycoplasma genitalium
But could not transplant it into another bacterium
Genes play a role in the development of all traits
But the variation of a trait in a population could be due entirely to environmental factors
MstII restriction site
CCTNAGG
After the discovery of small RNAs in eukaryotes, a similar small RNAs called
CRISPR RNAs were discovered in prokaryotes
Most widely used system
CRISPR-Cas 9 from streptococcus pyrogenes
In natural populations, inbreeding will lower overall fitness
Called inbreeding depression. Inbreeding can result from habitat destruction by humans
Agrocin 84 genes lie on a plasmid
Can be transferred by conjugation to A. tumefaciens
DNA fingerprinting use
Can be used to identify individuals and their relationship, used in forensics, can identify bacterial types in infections
Continous
Can have any value between numbers ie 1-3 spectrum
Meristic
Can only have defined values. ie 1, 2, 3 whole numbers
DNA microarrays (gene chips)
Can show the mRNA expression of thousands of genes simultaneously
The leading cause of death in western countries
Cancer
A mutation in RB1 may result in
Cancer because of the cell cycle losses regulation/becomes unregulated
Oncogene
Cancer causing gene
Metastatic
Cancer cells that can move throughout the body
1 in 3 people are diagnosed with
Cancer in their lifetime
The cumulative nature of mutations leading to cancer is what leads to
Cancer rates increasing dramatically with age
Gene therapy is being used for treatment of acquired diseases such as
Cancer, neurodegenerative diseases, cardiovascular disease, and infectious diseases such as HIV
RB1 result of mutation
Cannot bind E2F, thus uncontrolled division because no regulation of E2F (hormone positively regulating cell division)
p53 result of mutation
Cannot detect DNA damage or cannot stop cell cycle
Ras-GTPase result of mutation
Cannot hydrolyze GTP as effectively and this spend more time bound to RAS (in its active form) increasing stimulation of cell division
Some natural substances and natural processes are potentially
Carcinogenic
Ti plasmid (tumor inducing)
Carried by agrobacterium tumefaciens
Apoptosis is facilitated by proteases known as
Caspases
HapMap
Catalog of common genetic variants. What the variants, where they are located, distribution among human populations
Hemophila A (classical hemophilia)
Caused by a defect in an X linked gene that encodes clotting factor VIII
CRISPR-Cas9 uses relatively long recognition sequence (but not 100% specific)
Causes edits elsewhere in a genome. Still needs some screening
Agrobacterium tumefaciens is a bacterium that naturally infects and transforms plants
Causing crown gall tumor
Many cancer causingn genes disrupt
Cell cycle control
Cancer is a disease characterized by uncontrollable
Cell division
Spots present only given circumstances
Cell exposed to hormone versus those that are not
G1
Cell prepares to divide. Restriction point-cell will commit to cell division
Apoptosis involves
Cell shrinkage, chromatin condensation and DNA degradation resulting ultimately in programmed cell death
The proteins a cell produces depends on
Cell type, stage development, environmental conditions
Once DNA has been cleaved by CRISPR-Cas9
Cells immediately activate DNA repair mechanisms to fix the break by two main pathways
Chorionic villus sampling
Cells obtained from chorion (fetal part of placenta). Cane be performed earlier than amniocentesis, but poses a slightly greater risk of miscarriage
Gels can be compared between extracts made from
Cells under different conditions
Cells that are killed are one of two types
Cells with no recombinant DNA. Cells with non homologous recombination
Microevolution
Change in allele frequencies in a population over generations
Microevolution
Change in one population's gene pool from generation to generation
Microevolution describes
Changes in a population's gene pool from generation to generation
A mutation in rasH
Changes the twelfth amino acid in the protein from a glycine to a valine makes it an oncogene. Chemical carcinogens have been shown to make these changes
Complex traits
Characteristics determined by several genes and/or influenced by environmental factors. Ex: height, nose shape, metabolic rate
Motivation behind genome sequencing for basic research
Characterization of genes and genomes
Complex does not form if DNA damage is detected
Checkpoint proteins (i.e. G1 and G2) prevents formation
G2 checkpoint
Checks for cell size and DNA replication
G1 checkpoint
Checks for cell size, nutrients, growth factors and DNA damage
Organisms produce chemical products more efficiently than we can through
Chemistry. They have catalytic enzymes that make them more efficient
The primary difference between artificial and natural selection is the
Choosing of parents
Aneuploidy
Chromosome loss may contribute to the progression of cancer if the lost chromosome carries one or more tumor suppressor genes
S phase
Chromsomes are replicated (chromatids). Sister chromatids are joined at the centromere (dyad)
Chromosomal translocation
Chronic myelogenous leukemia- abi fused to bcr and its promoter
Restriction enzymes recognize specific (usually 6 base) sequences and
Cleave the DNA at those sequences
A glyphosphate resistance EPSP gene was identified in E. coli
Cloned and transformed, put into plants
Gene addition
Cloned gene is added at a second site in the genome. Independent of whether or not a copy is in the host, recombinant copy can undergo non homologous recombination
Gene replacement
Cloned gene replaces normal gene in its site on the chromosome (doesn't work in plants). If a copy of the gene already exists in the host, the recombinant copy can undergo homologous recombination which can lead to gene knockout of recombinant copy is defective
Ti plasmid has been modified to create T-DNA vectors to introduce
Cloned genes into pairs
Homologs
Closely related genes (high DNA sequences similarity)
CRISPR
Clustered regularly interspaced short palindromic repeats
Antibody microarray
Collection of antibodies that recognize short peptides. Used to assess the level of protein expression
Clones are identified that represents a contiguous region of a chromosome (as overlapping regions)
Collection of clones forms a contig
Gene knockout collections
Collection of knockout strains for every gene
NIH knockout mouse project
Collection of mouse ES cells with loss of function mutations in every gene in the genome
Transcriptomes
Collection of transcribed mRNA molecules in a cell
Negative freqeuncy dependent selection common vs rare individuals
Common individuals lose fitness because of being common. Rare individuals gain fitness because of being rare. No genotype becomes too rare or too common
Motivation behind genome sequencing for evolution
Comparative genomics
BLAST is a software application used to
Compare a segment of genomic DNA to sequences in the major databases and identify portions that align with or are the same as existing sequences
Comparative genomics
Compares genomes of different organisms to answer questions about genetics and other aspects of biology
Comparative genomics
Compares genomes of different organisms to answer questions about genetics and other aspects of biology. Genome evaluation and how differences in genome contributes to phenotype
Many of the traits that allow species to adapt to their environment are
Complex traits thus important for evolution (ie running speed of cheetahs, behavioral patterns)
Quantitative genetics examines
Complex traits where a phenotype is determined by many genes (polygenic) and is influenced by the environment i.e. height, fruit size, disease resistance
Bioinformatics
Conceptualizing biology in terms of macromolecules and then applying informatics techniques to understand and organize that information associated with these molecules, on a large scale
Functional protein microarray
Consists of many different cellular proteins. Used to probe the function of proteins
Mutations provide the raw material for evolution but does not
Constitute evolution itself
Concerns about GM foods center on
Consumer safety and environmental consequnces
Databases are typically annotated
Contain information such as gene sequence, description of gene, and other important information
Files are typically annotated
Contain the genetic sequence, a concise description of it and other useful information
The overlapping fragments collectively form one continuous DNA molecule within a chromosome and are called
Contigs
In threshold traits, different genes will
Contribute to the likelihood of an individual developing this disease
Tricky technique
Controls are critical, DNA sequencing often used to confirm positive diagnosis
Transformation
Converting a normal cell to a malignant cell
Transformation
Converting a normal cell to malignant cell
Haploid association studies
Correlate presence of haploid marker with disease. Two assumptions
To gain insight into comparing two different variables, a statistic known as
Correlation coefficient is often applied
Decreasing fertilizer application in agriculture
Could considerably reduce pollution of aquatic ecosystems. Enable non legume species to form symbiotic associations with rhizobium species. Reduce fertilizer applications and hence nitrate/nitrite run off
Tumor suppressor genes inhibit cell proliferation
Counteract growth factors and prevent cells with mutations from dividing. Help maintain genome integrity-genome maintenance
Other mammals that have been cloned
Cows, mice, goats, cats, and pigs
Providing sustainable sources of energy example
Crops for ethanol production and biofuel
Linked alleles or molecular markers change through
Crossing over, depending on distance between markers- useful for mapping
Agrobacterium tumefaciens
Crown gall disease
Extensive testing is needed before they are released for
Cultivation or consumption
Qualitatively and quantitatively expression of genes both can be done by RNAseq
Current standard for demonstrating reproducibility=sequence a minimum of 3 biological replicates libraries made from 3 identical RNA extractions
Shotgun sequencing
Cut o DNA randomly (partially digest with restriction enzyme), sequence resulting fragments, match overlapping sequences using computers to generate contigs
The cell cycle is regulated via both sets of genes
Cyclin proteins (result of a proto-oncogene) and cycling dependent kinase (CDK) control the cell cycle
Cell cycle progress is regulated by
Cyclin proteins and cyclin dependent protein kinases. Synthesized and degraded in a precise pattern
Cyclin dependent kinases (CDKs) are regulated byb
Cyclin synthesis and destruction
Three common ways to study the organization of DNA regions
Cytogenetic mapping, linkage mapping, physical mapping
Apoptosis
DNA becomes fragmented, internal structures are broken down and the cells dissolve into small spherical structures (apoptotic bodies)
If a mutation occurs (loss of function) the p53 cannot identify
DNA damage or cannot prevent formation of the cyclin-CDK complex
Acquisition stage of CRISPR-Cas
DNA entering cell is identified, processed and inserted into CRISPR array as a new spacer
Natural radiation (UV light, X rays), natural dietary substances, and substances in the external environment can cause
DNA lesions, producing mutations that lead to cancer
Protein microarrays are similar to
DNA microarrays
Genomic data can provide important information about the proteome
DNA microarrays/transcriptomes identify genes that are transcribed under a given set of conditions. Genomic studies have to be followed up with protein studies
Cells usually halt progress through the cell cycle if
DNA replication, repair, or chromosome assembly are abnormal
Algorithm based software programs were developed for creating
DNA sequence alignments where similar sequences of bases (contigs) are lined up for comparison
Repetitive sequences
DNA sequences that are present in many copies in the genome
A pair of California twins were misdiagnosed with cerebral palsy
DNA sequencing pointed to a new diagnosis, and treatment to which both children are responding well
Pyrosequencing
DNA sequencing technology that is based on the generation and detection of a pyrophosphate group liberated from a nucleotide triphosphate
Natural metabolism creates oxidative end products that can damage
DNA, proteins, and lipids
To use a human pedigree, a geneticists must obtain
Data from large pedigrees with many affected individuals
Edible vaccines can and have been produced in plants
Decreases cost of production. Avoid needles, need for registration, and need for sterile equipment to administer
Why whole genome shotgun sequencing as become the favored
Decreasing sequencing costs and increased computing power
A computer program is a
Defined series of operations that can analyze data in a desired way
Huntingtons disease major symtpom
Degeneration of certain types of neurons in the brain, leading to personality changes, dementia, and early death
Concordance
Degree to which a disease is inherited. Should be higher in identical twins
Polymorphism is caused by changes such as
Deletion, duplication, single nucleotide polymorphisms (SNPs)
During sporulation, Bt strains produce crystal proteins called
Delta-endotoxins that have insecticidal action. Led to their use as insecticides (as bacteria in organic agriculture and more recently genetically modified crops using Cry1A)
ADA homozygous affected individuals accumulate deoxyadenosine
Deoxyadenosine is toxic to B and T cells. Causes dysfunctional immune system and is severe combined with (SCID)
Gene pool
Describes all the alleles of every gene in a population
Covariance
Describes the degree of variation between two variable within a group
Checkpoint proteins
Detect genetic abnormalities and prevent cell division. DNA repair enzymes. If inactivated by mutation cancer is more likely to occur
Primary role for the p53 protein is to
Determine if a cell has incurred DNA damage
Chromatin immunoprecipitation (ChIP) assays are used to
Determine if proteins can bind to a particular region of DNA
Goal to find the DNA sequence from the protein sequence
Determine the possible codon sequences. Used as a query sequence in a DNA database search. Gene sequence is used to predict the amino acid sequence of the entire protein
Hybridize to specific ASO probes under high stringency conditions
Determined by salt concentration and temperature
Motivation behind genome sequencing for agriculture
Development of improved traits
Normally, insulin is made by the pancreas, and regulates uptake of glucose into fat and muscle cells
Diabetes patients can't synthesize insulin
Example of threshold traits
Diabetes/cancer. You either have it or you don't
Knowledge of how normal and dysfunctional genes work and interact with the environment is important for understanding of disease for
Diagnosis, treatment, and prevention
Sequences of different people are usually very similar
Differ at about 1 in every 1200 bases. Single nucleotide polymorphisms (SNPs) - differences in individual bases
Within populations allelic variation arises in various ways such as mutation
Different alleles of genes may encode proteins of differing function
Different alleles of genes may encode proteins with
Different functions
Cancers involve multiple genetic changes in
Different oncogenes and tumor suppressor genes
In eukaryotic genomes, the basic features are similar in
Different species, genome size in eukaryotes is highly variable, but the # of actual genes is fairly consistent
RNAseq can study relative expression of all genes in
Different tissues, different developmental stages, disease vs non disease, drug treatments
To metastasize from the primary tumor, cancer cells must
Digest components of the extracellular matrix and basal lamina that normally inhibit migration of cells
A new allele may promote a greater fitness in individuals
Directional selection may cause this favored allele to eventually become predominant in the population
Four ways natural selection can operate
Directional selection, balancing selection, disruptive selection, stabilizing selection
Genetic drift
Disappearance of alleles due to random chance in small populations
Haploid association studies have two assumptions
Disease causing allele originated in single a individual or founder. When disease-causing allele originated in the founder, it occurred in a region with a particular haplotype
Comparative genomics has great implications for medicine, particularly with
Disease causing prokaryotes
Closely related individuals have more similar fingerprints than
Distantly related ones
Discontinuous traits have discrete categories
Distinct and few different possible qualities
Naturally occurring pesticides and antibiotics in plants can be carcinogenic but
Do not diminish the serious cancer risk upon exposure to synthetic pesticides or asbestos
Linked alleles or molecular markers
Do not dramatically change from one generation to the next (few new mutations)
Unlike most insecticides, Bt insecticides do not have a broad spectrum of activity
Do not kill beneficial insects (which lack the receptor needed)
Genetic testing and screening are medical practices with many social and ethical dimensions
Do people have the right to know their genetic makeup, does it do more harm than good, privacy issues
Pattern recognition
Does not rely on specialized sequence information. Program identifies a pattern of symbols that can occur within any group of symbol arrangements
The easier and faster method of shotgun sequencing
Doesn't require an extensive physical map, faster and easier, clones from a genomic or chromosomal library isolated randomly and sequenced, overlapping sequences matched together using computers
Continuous traits
Don't have clear categories, show wide variation with lots of intermediate phenotypes (a continous spectra)
Bottleneck effect
Dramatic reduction in population size, population re-established by only a few individuals
Functional protein microarray is most used by
Drug companies for drug discovery. Hugh through out screens of compounds that disrupt interations
Natural selection for choosing parents
Due to natural variation in reproductive success, their genotypes will influence their fitness
Only two transgenes account for almost all GMO acreage
EPSP synthase (enzyme which confers resistance to glyposhphate) and roundup herbicide which does the same
Eukaryotic cells must use a complex process
Each daughter cell must receive the right number of each chromosome. Series of phases called the cell cycle
Different kinds of tumors tend to have the same changes, but
Each individual tumor has its own individual profile of mutated genes
Cyclins form complexes with CDKs that are important regulators of
Each phase of the cell cycle
If the values follow a normal distribution, then the amount of variation is
Easier to evaluate by standard deviation
DNA sequencing is being used to investigate infectious disease outbreaks, including
Eboda, drug resistant strains, and food poisoning following contamination from E. coli
Protospacer adjacent motif (PAM)
Effector complex binding site. After associating with PAM, Cas9 unwinds adjacent DNA allowing sgRNA to pair with the DNA. Once paired, Cas9 cuts the DNA
Interference stage of CRISPR-Cas
Effector complex binds homologous foreign DNA by base pairing. Cas protein cleaves the foreign DNA (making it non functional)
Metastasize is though to be controlled by many genes, including those that
Encode cell adhesion molecules and proteolytic enzymes
M phase or mitosis which is also broken into phases
Ends with cytokinesis-division of cell into t2
Proteome
Entire collection of a species proteins
If Vg is very low and Ve is very hgih
Environment causes much of the phenotypic variation (not worth breeding for)
Metagenomics
Environmental genomics; by sequencing DNA from the environment to look at microbial populations
Identification of viruses in metagenomics
Environmental samples are analyzed to identify human viruses
3. The disease does not spread to individuals sharing similar
Environmental situations
For monomorphic genes, allele frequency for the single will be
Equal or be close to 1
Potential creation of superweeds
Escape of transgenes into crop plant relatives giving them a competitive advantage in the wild. Crop to wild species gene flow happens
Major advantage of Bt insecticides
Essentially nontoxic to people, pets and wildlife
Repetitive sequences are also widespread in
Eukaryotic genomes. Largest factor in the difference in genome size
To increase the efficacy and yields, many biopharmaceuticals are now produced in
Eukaryotic hosts. Ideally plats (cost/efficiency wise)
DNA oligonucleotides specific to
Every gene in genome
Allele and genotype frequencies do not change over the course of many generations unless
Evolution is occuring
P value less than 0.05
Evolution is occuring
Biological control can also use microorganisms in the field
Ex: Agrobacterium radiobacter produces agrocin 84, an antibiotic that kills A. tumefaciens
Directional selection may act on phenotypes determined by multiple genes
Ex: Body weight in mammals. If directional selection favored higher body weight, it would affect the allele frequencies of many different genes
6. The human disorder may resemble a disorder that is already known to have a genetic basis in an animal
Ex: albinism
Some tumors have specific chromosomal translocations
Ex: chronic myelogenous leukemia (CML) is correlated with the Philadelphia chromosome
In the US genetic screening for certain disorders has become common
Ex: pregnant women >35 years old are screened to see if they are carriers of chromosomal abnormalities. Widespread screening for phenylketonuria
Directional selection may act on phenotypes determined by a single gene
Ex: resistance to insecticide in a mosquito population
Horizontal gene transfer
Exchange of genetic materials between different species
To determine if the genotypes of a population are not changing from one generation to the next
Expected frequencies of the genotypes can be calculated and compared to those observed
At least 80% of cancers are related to
Exposure to mutagens. Alters the structure and expression of genes
Transcriptome analysis or global analysis of gene expression studies
Expression of genes qualitatively and quantitatively
Conversion to oncogenes can increase
Expression of the protein, can change structure and this increase activity, express protein in a cell it originally was not expressed in
The goal of bioinformatics is to
Extract information from genetic sequences with a mathematical/computational approach
Somatic gene therapy
Extremely dangerous from a population genetics viewpoint. Increase in prevalence of mutant alleles in our population. Committed to ever increasing number of people needing treatment
If the P value is 0.2 (larger than 0.5)
Fail to reject null hypothesis (no evolution)
Discontinuous traits
Fall into discrete categories, the alleles that govern these traits affect the phenotype in a qualitative way
Balancing selection
Favors maintenance of 2+ alleles. Heterozygote advantage. Negative frequency dependent selection - rare individuals are more fit than common
Balancing selection
Favors maintenance of two or more alleles
Disruptive selection
Favors survival of 2+ different phenotypes. Fitness varies in different environments
Stabilizing selection
Favors survival of individuals with intermediate phenotypes
Stabilizing selection
Favors survival of individuals with intermediate phenotypes. Extreme phenotypes selected against and intermediate phenotypes have highest fitness
Stabilizing selection
Favors survival of individuals with intermediate phenotypes. Removes variation
Directional selection
Favors survival of one extreme phenotype that is better adapted to an environmental condition
Disruptive selection
Favors survival of two or more different phenotypes
Two common features of X linked dominant inheritance
Females are much more likely to exhibit trait if its lethal in males. Affected mothers have a 50% chance of passing the trait to daughters (also have 50% chance of passing the allele onto sons but often lethal in sons, so they aren't observed in the pedigree)
Amniocentesis
Fetal cells are obtained from the amniotic fluid
DNA microarrays/transcriptome can be used for
Finding genetic variations, cell specific gene expression, gene regulation, tumor profiling, microbial stain identification
Disruptive selection is caused by
Fitness values for a given genotype that vary in different environments
Examples of meristic traits
Flower petal number or vertebra or rib bones. You cant have part of one of those
Structural genomics
Focuses on sequencing genomes and analyzing them to identify genes and other important sequences such as regulatory elements
Proteomics use 2D gel electrophoresis
Followed by mass spectrometry. Can use protein microarrays
High margin of safety recommends the use of Bt insecticides on
Food crops and other sensitive sites where pesticide use can cause adverse effects
Most genes fall between 0 and 1
For being due to genetics and environment
Genome sequencing is trying to move towards everyone having their genome sequence as part of their medical records
For genetic diseases, genetic pre-disposition to disease, life recommendations, preventative medicine. Main issue is cost
Preimplanation genetic diagnosis
For in vitro fertilization, testing of embryo before implantation
Transport proteins
For uptake of drugs into the bloodstream. Uptake into specific cell types. Uptake into liver cells
Chromosomal DNA is partially digested smaller pieces with restriction enzymes
Fragments are cloned to create a genomic DNA library
4. Different populations tend to have different
Frequencies of the disease
If a polymorphic gene exists in two alleles A and a
Frequency of allele A can be denoted by p and frequency of allele a can be denoted by 1
Four common features of autosomal recessive inheritance
Frequently affected offspring have two unaffected parents. When unaffected heterozygotes have children, the percentage of affected children is on average 25%. Two affected individuals will have 100% affected children. Trait occurs with the same frequency in both sexes
Neomycin-resistant gene (NeoR)
From bacterial transposon cloned into the middle of the DNA to be recombined-confers resistance to neomycin
Thymidine-kinase gene (TK)
From herpes simplex virus cloned adjacent to the DNA that is to undergo recombination- confers sensitivity to gangcyclovir
A preliminary list of functional categories to which human genes have been assigned based on
Functions determined previously, comparison to known genes from other species, predictions based analysis of protein functional domains and motifs
Interphase is broken into three phases
G1 phase or Gap 1, S phase or synthesis, G2 or Gap 2
Eukaryotic cell cycle
G1 phase, S phase, G2 phase, M phase
Interphase
G1, S, G2. Period of the cell cycle between cell divisions
Gg has 15, GG has 10, gg has 5
GG is 10:15 so 2:3 2/3=0.66. gg is 5:15 1/3=0.33
Gene for Bt has been cloned and expressed in
GMO plants to make them insect resistant
G1 phase
Gap 1. The first gap, or growth phase, of the cell cycle, consisting of the portion of interphase before DNA synthesis begins.
G2 phase
Gap 2. The second growth phase of the cell cycle, consisting of the portion of interphase after DNA synthesis occurs.
Missense mutations
Gas GTPase
One of the most important databases
GenBank. Maintained by the national center for biotechnology information (NCBI)
QTLs may contain more than one
Gene
Comparative genomics incorporates the study of
Gene and genomic evolution
Knowing all gene sequences has allowed the synthesis of
Gene chips. Enables analysis of all genes simultaneously
Genetically modified eukaryotes involves two types of cloning
Gene cloning and reproductive cloning
DNA microarrays reveal profiles of
Gene expression
Delete a gene
Gene knockout
Once you have identified a gene of interest
Gene knockout
Two types of recombination
Gene replacement and gene addition
Computer analysis can generate insight into
Gene structure, gene function, relationships between genes and organisms, protein function and protein interactions, predicting drug structure and function
Computer analyses generate insights into
Gene structure, gene function, relationships between genes and organisms, protein function, protein interactions, predicting drug structure and function
Enhancement gene therapy
Gene transfer to enhance traits such as intelligence and athletic ability rather than to treat a genetic disorder. Controversial and unapproved
Orthologs
Genes at the same locus in different species inherited from a common ancestory
Whole genome transcriptome analysis of pathogens is used to inform researchers about
Genes that are important for pathogen infection and replication
Genome sequence is annotated to identify
Genes, their regulatory sequences, their functions
In the GenBank, genome sequence is annotated to identify
Genes, their regulatory sequences, their functions
Changes in population size may affect
Genetic drift
The process by which genes are lost by random fluctuations is known as
Genetic drift
The period of the bottleneck, when the population size is very small, may be influenced by
Genetic drift.
Quantitative trait locus is related to
Genetic linkage mapping
Gene knockout
Genetic manipulation in which one or more of an organism's genes are prevented from being expressed
Five stage of domestication all involve
Genetic modification of wild species. What varies is the method used
1. When an individual exhibits a disease, the disorder is more likely to occur in
Genetic relative than in the general population
About 12,000 genetic disease are known (likely an underestimate)
Genetic tests are available for many of these
Heritability is the proportion of the phenotypic variance that is attributable to
Genetic variation
The phenomenon that underlies selective breeding is
Genetic variation
To study quantitative trait variation, we divide it into components
Genetic variation (Vg), environmental variation (Ve), variation due to interactions between genetic and environmental factors, variation due to associations between genetic and environmental factors
Population genetics focuses on
Genetic variation withing the gene pool and how it changes from one generation to the next
Vg and Ve can be determined by comparing the variation in traits between
Genetically identical and disparate groups
Ridge count correlation in fingerprints were relatively high in
Genetically related individuals
All traits of biological organisms are influenced by
Genetics and the environment. Especially true for quantitative traits
If Vg is very high and Ve is very low
Genetics is more important in promoting variation (worth breeding for)
CRISPR-Cas systems have been modified for
Genome editing
Genomincs is the study of
Genomes
Large variation in introns size and number between and within
Genomes
Systems biology is trying to interpret
Genomic information in the context of the structure, function, and regulation of biological pathways
Cancer cells contain genetic defects affecting
Genomic stability, DNA repair, and chromatin modifications
Functional genomics combines
Genomics, transcriptomics, proteomics
To calculate darwinian fitness
Genotype with the highest reproductive ability is set to 1, all genotypes are then ratios with the genotype of highest ability. Calculating relative fitness, denoted with w
Gene environment association
Genotypes may not be randomly distributed in all possible environments
Local populations are often separated from each other by
Geographic barriers
CRISPR/CAS systems might help address some of the technical problems with
Germ line genomic engineering
Source of genetic variation: rare DNA mutations
Give rise to new variants (mutations is the only way to get completely novel sequences)
Each step requires a mutation which is why cancer is
Gradual
Heterozygote advantage
Greater reproductive success of heterozygous individuals compared to homozygotes; tends to preserve variation in gene pools
Population
Group of individuals of the same species that occupy the same region and can interbreed with each other
More recent studies have revealed how Rb regulates cell division
Growth factors and other mechanisms control synthesis of a protein that phosphorylates Rb protein. Rb phosphorylation causes it to release a transcription factor, E2F
Microevolution is driven by the opposite of
HW conditions for equilibrium
Haplotype
Haploid genotype
Three common explanations for dominant disorders
Haploinsufficiency, gain of function mutations, dominant negative mutations
In reality, no population satisfies the
Hardy-Weinberg equilibrium completely
A functional synthetic genome of Mycoplasma mycoides was created in 2010 and successfully transplanted into an existing cell of M. caprocolum
Has led to the speculation of a future world in which new bacteria, and perhaps new plant and animals cells, can be designed and programmed as desired
A patient misdiagnosed (for 30 years) with cerebral palsy was also found to
Have a treatable dopa-responsive dystonia thanks to whole exome sequencing
Examples of continuous traits
Height and weight
Whole genome sequencing or whole exome sequencing has been used to
Help doctors diagnose, and in some cases to identify, available treatments in rare disease cases
Growth factors
Help regulate cell division by binding to cell and initiating a cascade of cellular events
A defect in any of these proteins causes blood clotting
Hemophilia A and B are X linked, Hemophilia C is caused by a defect in a gene found on chr 4
Pedigrees for hemophilia A and B will different than that of
Hemophilia C, even though they all have abnormal blood clotting defects
Example of subunit vaccines: hepatitis B
Hepatitis B virus surface protein has been cloned into a yeast expression vector and purified from yeast
In 2003, 6 year old Dolly was euthanized after an examination showed progressive lung disease
Her death raised concerns that the techniques used to produce Dolly could have caused premature aging
Two main transgene plants
Herbicide and naturally pest resistant plants
Realized heritability
Heritability determined by a response-to-selection experiment
Balancing selection can occur because of
Heterozygote advantage or negative frequency dependent selection
2pq
Heterozygous
Ex of relative fitness values to the highest
Highest has 5 offspring, second highest has 4, lowest has 1. 5 is given fitness of 1 or 100%, second highest is given 4/5 or 0.8, lowest is given 1/5 or 0.2
Homozygous for normal hexA allele
Highest levels of fluorescence
A young boy in Wisconsin was cured of an extreme form of inflammatory bowel disease after
His genome sequence revealed that a bone marrow transplant would likely be life saving
Polymorphism
Historically variation in inherited traits (phenotypes)
Mammalian knockouts created using
Homologous recombination
In complex eukaryotes, gene addition or non homologous is much more frequent
Homologous recombination is rare. Only about 0.1% of the time
BLASTS starts with a sequence and then locates
Homologous sequences in a large database. Will search the entire database selected and determine which sequence are the closest matches
In most cases, similarity is due to
Homology
P^2
Homozygous dominant
Monomorphic
Homozygous for the same allele of a given gene
q^2
Homozygous recessive
Correlation coefficient ranges between +1 and -1 and indicates
How two factors can vary in relation to each other
Despite claims to the contrary, there is not substantiated evidence of any transgene product released for
Human consumption harming human health
Sequencing the human genome is advancing our understanding of
Human genetics and biochemical research and health care, but applications of this knowledge raise ethical, social, and legal issues
Genetech made the first genetically engineered drug
Human insulin (FDA approved in 1982)
Uses of metagenomics
Human medicine, agriculture, bioremediation, biotechnology, global change, identification of viruses, aquatic biology
Proteins can be stained and spots can be cut for
Identification by mass spectrometry
Motivation behind genome sequencing for medicine
Identification of genetic bases of disease
Gene annotation aims to
Identify and label important structural features of genes (known or unknown)
Microarrays can be used to
Identify genes transcribed in a particular sample
Researchers can compare cancer cells to normal cells
Identify groups of genes that are turned on in the cancer cells and off in the normal cells. Other groups of genes that are turned off in the cancer cells and on in the normal cells. Can compare different tumor types
Physical mapping involves
Identifying overlapping clones across whole chromosome to create contigs
Qualitatively
Identifying which genes are expressed and which are not in a given sample
The HW equation can be used to detect evolutionary change
If allele frequencies do not maintain the HW equilibrium, they are evolving
Checkpoints in cell cycle prevent damaged cells from completing cell division
If checkpoints are damaged (mutations) genome integrity is not maintained
Dog size variation is due to alleles in the
Igf1 gene (insulin like growth factor 1)
Sever combined immunodeficienct disease (SCID)
Immunodeficiency disease typically fatal at an early age (1-2 years old). Caused by mutation in adenosine deaminase (ADA)
Reasons for generating transgenic crops include
Improving growth characteristics and yield of crops. Increasing/improving nutritional value of crops. Providing crop resistance against insect and viral pests, drought, and herbicides. Providing sustainable sources of energy
Gene replacement in mice
In bacteria and yeast, gene replacement is the common outcome. Relatively small genomes allow homologous recombination to occur at a high rate
Amplification of erbB-2
In breast cancer
Genetic variation is generated in many ways
In eukaryotes, sexual reproduction produces new combination of alleles. Prokaryotes also possess mechanisms for gene transfer
Amplification of c-myc
In leukemia
Amplification of N-myc
In neuroblastoma
In the absence of other evolutionary forces, allele frequencies are not affected by
In or out breeding
In some large natural populations, there is little migrations and negligible natural selection
In these cases the HW equilibrium is nearly approximated for certain genes
Biotransformation without biodegradation can occur
In these cases, the pollutant is rendered less toxic by oxidation or reduction reactions and polymerization reactions
Some individuals have extra sites or lack a site due to sequence variations
In these individuals, a restriction enzyme will produce different sized fragments
Systems biology
Incorporates data from genomics, transcriptomics, proteomics, and other areas of biology as well as engineering applications to attempt to elucidate components of interacting pathways and the inter relationship of molecules
Mutations in proto-oncogenes that can convert them to oncogenes are mutations that
Increase expression of the protein, change structure to increase activity of the protein, express protein in a new cell type
Amplification of particular oncogenes leads to
Increased copies of the gene result in more protein
Patterns of mating do disrupt the balance of genotypes predicted by the HW equation
Increased number of homozygotes
Gene amplification
Increases copies of the genes resulting in more protein- c-myc and N-myc
Phytase is produced in the salivary glands and secreted in the saliva
Increases digestion of phosphorus contained in feed grains
Positive assortative mating occurs when
Individuals are more likely to mate due to similar phenotypic characteristics to themselves
Gene flow
Individuals migrate between populations with different allele frequencies
Negative assortative mating occurs when
Individuals with dissimilar phenotypes mater preferentially
Gene expression microarrays can be used to study
Inherited mutations and somatic mutation causing diseases
Two types of retinoblastoma
Inherited, which occurs in the first few years of life. Non inherited, occurs later in life
The genetic information nondiscrimination act was designed to
Inhibit improper use of genetic information in health insurance and employment
Growth factors bind to cell surface receptors
Initiate a cascade of cellular events leading ultimately to cell division. Many of these cellular events are changed in cancers
A series of proteases called caspases are responsible for
Initiating apoptosis and digesting the intracellular components
Directional selection graph
Instead of a bell graph, the hump will be really far to one end
A network map shows
Interacting proteins, genes, and other molecules (interactome)
Heterozygous
Intermediate levels of fluorescence
International HapMap project
International effort to identify haplotypes in human populations
Cancer cells metastasize
Invade other tissues
Malignant
Invasive. Invades surrounding tissue
Tumor suppressor genes
Involved in checkpoint proteins to detect genetic abnormalities and prevent cell division
Postranslation covalent modification
Irreversible changes may be necessary to produce a functional protein. Reversible changes that transiently affect protein function
Microinjection
Is a technique for introducing a solution of DNA into a cell using a fine microcapillary pipette
The two dimensions
Isoelectric point horizontally and size vertically
Why enhancement gene therapy is an issue
Issue of whether genetic technology should be used to enhance human potential either of individuals or their offspring
GenBank is massive
It contain more than 300 billion base of sequence and doubles every 14 months. Each sequence deposited receives an accession number
Cancer is hard to target because
It has extremely similar genetics as our own, since these are our cells just with a few mutations
When the cell is not undergoing division
It is in the G0 phase
If a disease correlates with several of these 7 obervations
It is likely that the disease has a genetic basis
What a value of 0.6 heritability means
It means that 60% of the variation is due to genetic factors in a particular environment
Although a cell only produces some of the proteins that it is capable of
It still has thousands of proteins
If a new mutation is fixed
It will be 100% and out compete the others
Mutations that convert the proto-oncogene to an oncogene lock ras into
Its active conformation, constantly stimulating the cell to divide
Net result of natural selection is a population better adapted to
Its environment and/or more successful at reproduction
Population genetics focuses on genetic variation
Its extent within populations, why it exists, how it changes over generation
Nonhomologous end joining
Joins without template. Tends to produce small insertions or deletions. Knocks out genes by disrupting reading frame
Importance of quantitative genetics
Key characteristics for plant and animal breeders are complex traits, many human diseases are complex traits, many of the traits that allow species to adapt to their environment are complex traits
Concerns about the use of Bt
Killing native species and causing proliferation of resistant insects
Example of disruptive selection
Land snail that lives in woods and open fields. Different colors are favored in different habitats
Databases
Large amounts of biological data are stored in online databases
Allele fixation takes much longer in
Large populations
Bottle neck effect steps
Large, genetically diverse population to start, a bottleneck effects that leads to fewer individuals with less diversity, then there is a large population with low allele diversity
Whole genome shotgun sequencing relative to other methods
Less labor, more sequencing, but harder to assemble
For a given trait, allele and genotype frequencies are always
Less than or equal to one
Nonviral approach
Liposome technique most common. Uses lipid vesicles
Homozygous for affected hexA allele
Little or no fluorescence
Bioreactors or biofactories
Living factories that continuously make milk containing therapeutic protein (herd of goats or cows)
Population can be broken down into
Local populations
A large population is usually composed of smaller groups called
Local populations (demes)
Programs used in bioinformatics have three ways of analyzing a sequence
Locate specialized sequences within a long sequence, locate predefined sequences and then identify specific types of sequence organization or sequence elements, locate a pattern of symbols
Quantitative trait locus (QTL)
Locations on chromosomes where the genes that influence quantitative traits reside (affect trait's outcome)
QTLs are identified by QTL mapping
Look more a molecular marker (genetic polymorphism- already known, will do limited sequence) that is inherited with your trait of interest)
Chromatin immunopreceipitation assay (ChIP)
Looking at the interaction of proteins with DNA (think transcription factors)
DNA microarrays
Looking at the mRNA expression of thousands of genes simultaneously. Can do comparative studies-look for differently expressed genes
Example of predisposition for cancer inherited in a dominant fashion
Loss of function mutation BRCA-1. Predisposes to breast cancer. Dominant pattern of inheritance (with incomplete penetrance)
Retinoblastoma 1 tumor suppressor gene
Loss or mutation of both allele of RB1 contributes to the development of many cancers due to unregulated progression through cell cycle. (Breast, bone, lung, and bladder cancers)
Transgenic cows have been generated incorporating a lysostaphin gene (from staphylococcus simulana)
Lysostaphin cleaves S. aureus cell walls
Staphylococcus aureus
Main cause of mastitis in cows. Causes losses of over $2 billion/year. Antibiotics not very effective
Example of X linked recessive inheritance: hemophilia
Major symptom is blood clotting problems. Minor accidental injuries may be life threatening
Nutritional quality
Making amino acid composition of seeds more appropriate for human/mammalian nutrition (grains and legumes)
Physical mapping is historically involved in
Making libraries of chromosomal DNA
Three common features of x linked recessive traits
Males are much more likely to exhibit the trait. Mothers of affected males often have brothers or fathers who are affected. Daughters of affected males produce on average 505 affected sons
Cancers can be staged
Malignant or metastatic
Metalloproteinases (proteolytic enzyme) are present at higher than normal levels in
Malignant tumors and are not susceptible to normal controls conferred by regulatory molecules such as tissue inhibitors of metalloproteinases (TIMPs)
Strategy for cloning Dolly
Mammary gland cells were collected and grown in the lab. Using electrical pulses, mammary cell was fused with nucleus free egg from a second sheep. Zygote began to develop. Embryo was implanted into a surrogate mother sheep. 148 days later, Dolly was born
Other desirable but less implemented use of GMO plants
Manipulating vitamin content
The development of cancer is the result of
Many different mutations, because cells have many levels of regulation and thus, defense against cancer
Negative side of inbreeding
Many genetic diseases are inherited in a recessive manner
5. The disease tends to develop at a characteristic age
Many genetic disorders exhibit a specific age of onset
Polymorphism refers to the observation that
Many traits display variation within a population
Physical mapping
Mapping via sequencing. Clones from a physical map can be used for sequencing
Three main phases of genomic analysis
Mapping, sequencing, functional genomics
Once you find a protein spot of interest you need to figure out what it is
Mass spectrometry. Determining the amino acid sequence of a protein from a two dimensional gel
Inbreeding
Mating between genetically related individuals
Outbreeding
Mating between genetically unrelated individuals
Positive association between factors may not be due to genetics
May be due to environmental factors
Proteins which are very abundant in a cell type
May be important for that cells structure or function
Microarrays can be used to identify the genes in a tumor whose expression correlates with each other
May lead to treatments targeting those genes
Tumors are classified by appearance under a microscope
May not reveal underlying genetic changes. May lead to misdiagnoses and incorrect treatmen
Ways to analyze a normal distribution
Mean
Darwinian fitness
Measurement of reproductive success
Selection coefficient
Measures the degree to which a genotype is selected against
Narrow sense heritability is estimated by
Measuring a quantitative trait among groups of genetically related individuals and using data to compute a correlation between the individuals
Quantitatively
Measuring varying levels of expression of genes
Many aspects of protein structure can give insight into function
Membrane spanning domains, targeting signals, functional motifs: helix turn helix, leucine zipper, or zinc finger motifs
Agriculture in metagenomics
Metagenomic analysis of soil samples reveals astonishing complexity of soil microorganisms, which may improve yields. Some microbes are beneficial, some disease causing. Most crops are not grown where they evolved
Human medicine in metagenomics
Metagenomics is used to characterize populations of microorganisms in/on every surface of the human body and find differences associated with disease
Whole genome shotgun sequencing
Method of sequencing a genome in which sequenced fragments are assembled into the correct sequence in contigs by using only the overlaps in sequence
Inhibition by DNA methylation
Methylation of CpG islands near the promoters of tumor suppressor genes, inhibits transcription
Biotechnology in metagenomics
Microorganism can synthesize a vast array of useful chemicals. Ex: new antibiotics for bacterial infections
Biotransformation
Microorganism's metabolic pathways change the toxic pollutant
Global change in metagenomics
Microorganisms carry out half the photosynthesis on earth and cycle elements such as carbon, phosphorus and nitrogen
Bioremediation in metagenomics
Microorgansims in soil and water can be used to help decompose pollutants in the environment. Identification of useful microorganisms
Repetitve sequences can be classified as
Microsatellites or minisatellites
Founder effect
Migration of only a few individuals to establish a new local population that remains reproductively isolated
Founders effect
Migration of only a few individuals to establish a new local reproductively isolated population. Less genetic variation
Golden rice provides a possible solution to vitamin A deficiency
Milled rice has no beta carotene. Daffodil genes used produce B-carotene, a pro-vitamine
There are four types of mutation frequently found that change a phot-oncogene into an oncogene
Missense mutation, gene amplification, chromosomal translocation, viral integration
Conversion to oncogenes can be a result of
Missense mutations, gene amplifications, chromosomal translocations, or viral integration
Chromosomal abnormalities are associated with cancer
Missing chromosomes-carried tumor suppressor. Duplicated chromosome- overexpress proto-oncogenes
Many mutated genes involved in human diseases are also present in
Model organisms
Detailed genomic maps have been obtained from
Model organisms and organisms of agricultural importance
Molecular genetics and recombinant DNA technology have allowed a direct approach to
Modifying organisms
DNA sequences that do not encode genes can also be mapped, such sequences are known as
Molecular markers
Several types of DNA sequence are commonly used as
Molecular markers
A family pedigree can be used to help identify
Molecular markers and eventually the gene involved in a disease
Researchers map eukaryotic genes by identifying
Molecular markers that are close to them
Gene cloning
Molecular methods that produce many copies of a gene using a vector
Researchers developed the drug imatinib mesylate (Gleevec)
Molecule fits into the active site of the ABL protein, preventing ATP from binding, so ABL cannot phosphorylate targets
Gene therapy usually uses a genetically modified retrovirus as a vector
Moloney murine leukemia virus (MLV, a modified mouse virus)
A gene that has one allele that is found in 99% of all cases within a population is termed
Monomorphic
After many generations, the population will eventually become
Monomorphic for all or most of the desirable alleles in question and additional selective breeding will have no effect
2. Identical twins share the disease more often than non identical twins
Monozygotic (MZ) twins are formed from the same sperm and egg. Dizygotic (DZ) twins are formed from separate pairs of sperm and eggs
A lot of genes are still annotated as "unknown function"
More difficult to study, but potential for novel finding is greater
Genetically modified animals are more of grey area ethically than plants
Most animals do not naturally clone themselves. The techniques are directly applicable to humans
Viral approach
Most common are retroviruses, adenoviruses and parvoviruses
Over the course of domestication of dogs we have created a spectacular variety of breeds
Most have a small genetic base, based on selection for phenotype, tend to be homozygous (exposes recessive mutations), often genetic diseases are associated with particular breeds
Gene therapy has problems and risks
Most have been traced to the vectors. Many viral vectors eventually cause an immune response (has killed patients). Development of leukemia has also been a big problem. Cloning capacity too low to deliver many genes
Metastatic
Moves to a different site in body
RNA editing
Much less common than alternative splicing, leads to changes in the coding sequence of mRNA
Tumorigenesis results from
Multiple genetic alterations that release the cell from the normal cell cycle control
Geneticists cannot conduct human crosses to discover the genetic basis for diseases
Must rely on pre-existing families
Mutations are random events that occur spontaneously at low rates
Mutagens increase the mutation rate
7. A correlation is observed between a disease and a
Mutant gene or a chromosomal alteration
A missense mutation in Ras produces
Mutated protein that cannot hydrolyze GTP as effectively and thus spend more time bound to GTP (active form) resulting in increased stimulation of cell division
Gain of function mutations
Mutation changes a protein so it gains a new function
Tumor suppressor gene function can be lost via
Mutation in gene, inhibition by DNA methylation, aneuploidy
Cancer cells show higher than normal rates of
Mutation, chromosomal abnormalities, genomic instability
Microevolution is driven by
Mutation, natural selection, genetic drift, migration, nonrandom mating
Microevolution occur due to
Mutation, natural selection, genetic drift, migration, nonrandom mating
Oncogenes
Mutations in these genes promote cancer by keeping the cell growth signaling pathway permanently on
Over many generations, allele frequencies of many different genes may change through
Natural selection
Factors that promote widespread changes in allele or genotype frequencies
Natural selection, genetic drift, migration, nonrandom mating
Over many generations, allele frequencies of many different genes may change through
Natural selection. Can significantly alter the characteristics of a species
Clustered regularly interspaced short palindromic repeats
Naturally found in 40% of bacterial genomes. Viral/plasmid defense mechanisms in prokaryotes
Number of HIV gene therapy trials actively underway in the US
Nearly 1000
Cloned genes need to integrate into a host chromosome to be inherited
Need to be in the germ line to be inherited in offspring
Recombinant microorganisms are an area of great research interest and potential but
Negative public perception, safety, and environmental concerns have slowed commercial use of recombinant microbes. Associated risks vary depending in application
RB1 tumor suppressor gene
Negative regulation of cell cycle
Positive regulator of DNA damage repair and apoptosis
Negative regulator of cell division
Two selectable markers
Neomycin resistant gene (NeoR) and thymidine kinase gene (TK)
Directional selection is potentially caused by
New alleles or change in environment
The value of N (number of individuals) has opposing effects with regard to
New mutations and their eventual fixation
When N is very small
New mutations are less likely to occur, but each new mutation has a greater chance of being fixed from the population due to genetic drift
When N is very large
New mutations are much more likely to occur
Innovations in DNA sequencing
No need to clone the DNA, highly automated, high throughput sequencing, pyrosequencing, sequencing by synthesis
HW conditions for equilibrium (no future frequency change)
No new mutation, no genetic drift (no random change, requires large population), no migration, no natural selection, random mating
The Hardy-Weinberg equation predicts an equilibrium in allele frequencies based on certain conditions existing for a population
No new mutations, no genetic drift, no migration, no natural selection, random mating
If the r values differ from zero only as a matter of chance
No real correlation
2 main pathways to fix the break
Non homologous end joining and homologous end joining
Biological control agents can prevent disease in two ways
Non-pathogens are used to compete against pathogens for nutrients or space. Microorganisms may produce toxins that inhibit other microorganisms or insects, but not the plant
Benign
Noncancerous tumor that is not invasive and cannot metastasize (migrate)
Introduction of cloned genes into human cells. Two transfer methods are used
Nonviral approach and viral approach
A network map helps model potential interaction of molecules involved in
Normal and disease processes
Genes influence human health whether alleles are
Normal or dysfunctional
Tumor suppressor genes
Normally prevent proliferation of cancer cells. Mutations that inactivate these genes make it more likely that cancer will occur
BLASTn
Nucleotide to nucleotide
BLASTx
Nucleotide to protein
blastn
Nucleotides vs nucleotide databases
Accession number
Number generated by laboratory information system (LIS) when specimen request is entered into the computer
Allele frequency
Number of copies of a specific allele in a population/total number of alleles in the population
Allele frequency is calculated by
Number of copies of an allele in a population/total number of all alleles for that gene in a population
Gene density
Number of genes in a given length of DNA
Genotype frequency
Number of individuals with a particular genotype in a population/total number of all individuals in a population
Genotype frequency
Number of individuals with a specific genotype in a population/total genotypes (individuals) in a population
Ultimate goal of physical mapping is to
Obtain a complete contig for each type of chromosome
Goals of the human genome project
Obtain a genetic linkage map of the human genome, obtain a physical map of the human genome, obtain the DNA sequence of the entire human genome, develop technology for the management of human genome information, analyze the genomes of other model organisms, develop programs for ethical and legal, develop technological advances in genetic methodologies
Neutral and deleterious mutations are more likely to
Occur
Assortative mating
Occurs when individuals do not mate randomly
The geneotype with the highest reproductive ability is given fitness value
Of 1
Chromosomal translocation can form
Oncogenes
Mutations in proto oncogenes can convert them to
Oncogenes
Mutations in proto-oncogenes can convert them to
Oncogenes
Genes that are involved in cancers are classified as
Oncogenes and tumor suppressor genes
Some viruses cause cancer by carrying
Oncogenes into cells
RSV research led to the discovery of
Oncogenes. Discovered the viral oncogene, src
For monomorphic traits allele frequency for a single allele will be equal or close to
One
For polymorphic genes, frequencies of alleles should add up to
One
Homologous recombinants are identified using two drug resistance genes
One drug selects for cells that have recombinant DNA. The other drug kills cells that have undergone non homologous recombination
Confounds pedigree analysis
One gene may be X linked, another may give the same trait but be autosomal
Mold on bread and corn, aflatoxin
One of the most carcinogenic chemicals known
Cystic firbrosis
One of the most common genetic diseases, caused by mutations in a gene called CTFR
Each step in tumorigenesis (development of a malignant growth) appears to result from
One or more genetic alterations that progressively release the cell from the normal controls on cell proliferation (the cell cycle) and malignancy
Subunit vaccines
One or more surface proteins from a virus or bacterium
Fitness values of other genotypes besides the highest reproductive value is assigned relative to
One, which is given to the highest reproductive ability
RNA interference (RNAi) trials are underway and promising but
Only good for diseases caused by
Whole exome sequencing
Only the exons are sequenced
Gene knockout
Organism that has a specific gene that has been inactivated
Comparative genomics studies differences and similarities between
Organisms and how differences contribute to phenotype, life cycles, etc
Major current focus of the NIH
Organisms that live in or on our bodies, many are beneficial and critical to health (microbiomes, increasing evidence for importance to human health)
To calculate allele frequencies in the conglomerate we must know
Original allele frequencies in the donor and recipient populations, and proportion of the conglomerate population that is due to migrants
The study of human genetic diseases provides insights regarding
Our traits. Knowledge can be used to develop drugs/therapies. Determining what kind of inheritance pattern a disease has is usually a first step
FDA has cleared or approved 45 human genetic tests and
Over 100 nucleic acid based tests for microbial pathogens
Alignment identifies
Overlapping sequences, allowing reconstruction of their order in a chromosome
Missense mutants in the four ras genes are associated with
Particular forms of cancer
5-10% of all cancers involve germ line mutations
People who have inherited such mutations have a predisposition to develop cancer
When DNA repair enzymes miss these damages, they become
Permanent mutations
Over 100 FDA approved drugs have
Pharmocogenomics information in their labels, in diverse fields such as analgesics, antivirals, cardiovascular durgs, and anti-cancer therapeutics
Locus heterogeneity
Phenomenon of a disease being caused by mutations in two or more different genes. The genes may encode multiple subunits of a protein or multiple proteins in a cascade
Natural selection acts on
Phenotypes (which are derived in part from an individual's genotype)
Negative frequency dependent selection
Phenotypes favored only when rare. Example is left-handed fighting ability
Natural selection
Phenotypes vary with regards to reproductive success
Quantitative traits exhibit a continuum of
Phenotypic variation
Reversible changes that transiently affect protein function
Phosphorylation, methylation, acetylation
First method used to DNA sequence entire genomes
Physical mapping
Genome sequencing is used to make
Physical maps
Production of transgenic plants is easier than transgenic animals
Plant cells are totipotent. Entire plant can be regenerated from a somatic cell
What are the most efficient way to make bioproducts?
Plants
Ethically plants pose less issues than animals
Plants often naturally clone themselves (asexual reproduction). Techniques are not directly applicable to us
Example or negative frequency dependent selection
Pollinators learn to avoid the common flower color, don't learn to avoid rare flower color, visit it more frequently than the common type
Biotransformation often results in biodegradation
Pollutant is degraded into nontoxic metabolites
Genotypes and phenotypes may overlap for
Polygenic traits
If an inherited trait displays variation in a population, then the trait is considered
Polymorphic
Commitment to cell division is regulated in part by
Polypeptide hormones known as growth factors
Determining alleles and genotype frequencies is central to
Population genetics
A polymorphism may reach an equilibrium where opposing selective forces balance each other
Population is not evolving toward allele fixation or elimination, such a situation is known as balancing selection
Evolution occurs at the
Population level
Genetic drift rate depends on
Population size
Genetic screening
Population wide genetic testing. Tests can be biochemical, immunological, DNA or chromosomal
In nature, it is common for individuals to migrate between
Populations in both directions
Germ line therapy not currently an option
Possible with CRISPR technology, but not authorized
Bt insecticides do not kill natural enemies on insects
Predators and parasite, as well as beneficial pollinators, such as honeybees
An important aspect of narrow sense heritabilities is their ability to
Predict the outcome of selective breeding
Biotechnology isn't really new and has been around for
Preparing food/beverages, fermentation
CRISPR-Cas targets genetic changes
Previous methods usually involve: randomly changes and lots of screening (to knock out genes) and insertion of new genes in random places (can create problems)
Study of the abl gene led to an effective treatment for CML
Previously, treatment was to destroy the patient's bone marrow and then infuse donor bone marrow
In 1990, gene therapy was approved for a girl with ADA deficiency
Prior to clinical trial, the normal ADA gene had been cloned into a retroviruses that can infect lymphocytes
A new allele may be lost from the population
Probability of elimination= 1-1/2N
How likely it is that a new mutation will be fixed or eliminated due to random genetic drift
Probability of fixation=1/2N
The mutation rate
Probability that a gene will be altered by a new mutation
Microorganisms are used to benefit humans in various ways
Production of medicine food fermentation, biological control, bioremediation
Reproductive cloning
Production of two or more genetically identical individuals. Whole plants can be regenerated from somatic cells. Animals need an egg cell to create a zygote and go through embryogenesis
How can we determine which mutations are causing an individual cancer?
Profile deferentially expressed genes (of known proto-oncogenes and tumor suppressor genes) in an individual. Can do this with techniques such as microarrays or RNAseq
Transcriptional analysis of gene expression reveal
Profiles of gene expression in cells and tissue
Horizontal gene transfer occurs by
Prokaryotic cell may be engulfed by a eukaryotic cell, and bacterial conjugation, transduction, and transformation
If a cell has incurred DNA damage, p52 promotes cellular pathways that activate genes that
Promote DNA repair, arrest cell division (and repress genes required for cell division), promote apoptosis (programmed cell death)
A mutation in the tumor suppressor gene itself
Promoter could be inactivated. Early stop codon could be introduced in the coding sequence
Narrow sense heritability
Proportion of the phenotypic variance that can be attributed to additive genetic variance
Broad sense heritability
Proportion of the phenotypic variance that can be attributed to genetic variance. Genetic variance/total variance
Mass spectrometry can aslo be used to identify
Protein covalent modifications. Ex: mass of a phosphorylated protein increases by the mass of a phosphate group
Protein microarrays are used to study
Protein expression, protein function, and pharmacology
BLASTp
Protein to protein
blastp
Protein vs protein databases
tblastn
Protein vs translated nucleotide
The previous five factors are affected by genetics because
Proteins (encoded by genes) are directly involved
Protein microarrays are more challenging
Proteins are more easily damaged during microarray fabrication. Synthesis and purification of proteins more difficult
Chromatin immunoprecipitation works by
Proteins cross linked to DNA, DNA isolated from cells and broken into small pieces, anitbody used to precipitate the protein DNA complexes, DNA is purified and amplified with PCR. Sequence of the amplified DNA can be identified by using it as a probe on a microarray, or directly sequence all PCR products
Using two dimensional gel electrophoresis
Proteins extracted under native conditions. Separated by their isoelectric point (pI)-pH at which they have no net charge. Called isoelectric focusing
Before running proteins on a gel
Proteins have to be denatured by SDS to filter by size through gel
Spots present only in abnormal cells
Proteins in cancer cells
Cyclins
Proteins that regulate the timing of the cell cycle in eukaryotic cells
Specific spots that differ between samples may be of special interest
Proteins which are very abundant in a cell type, spots present only given circumstances, spots present only in abnormal cells
Irreversible changes may be necessary to produce a functional protein
Proteolytic processing, disulfide bonds, attachment of prosthetic groups, sugars or lipids
Proteomics
Proteome is more complex than the genome. More proteins that genes and its harder to determine sequence of amino acids. Harder to predict function
Before they are mutated, the "normal" version of the gene is called a
Proto-oncogene
Is Ras-GTPase proto-oncogene or tumor suppressor
Proto-oncogene
Cyclin D1 and cyclin E are
Proto-oncogenes
CRISPR RNAs can combine with Cas (CRISPR associated) proteins to
Provide defense against invasion of specific DNA molecules (with homology to the spacer DNA sequences). Have been compared to the vertebrate immune system
Adenosine deaminase (ADA) is an enzyme involved in
Purine metabolism
Often using BLAST searches can help assign
Putative function to a sequence you are interested in
Systems biology
Putting everything together to understand how organisms function from the gene to the final structure and all of the interactions along the way
Fingerprints are inherited as a
Quantitative trait
When a complex trait can be described numerically it's a
Quantitative trait
Locations on chromosomes that affect the outcome of quantitative traits are called
Quantitative trait loci (QTLs)
Realized heritabilty is
R/S
Only 5-10% of all mutations can be detected by
RFLP analysis
More typically used now to generate transcriptomes
RNAseq
DNA microarrays are often used as a tool in the molecular profiling of tumors, but
RNAseq is now replacing microarrays
Transcriptomics
RNAseq to analyze gene expression in diseased tissue (cancers). Characteristic expression patterns for different forms of cancer. More accurate diagnosis. Better designed treatments
Genetic drift
Random changes in allele frequencies due to chance. Allele frequencies may drift from generation to generation by chance alone
BLAST results
Ranked alignments with similar sequences. Similarity score (identity value) sum of identical matches/total # of bases or amino acids alligned. E value
High throughput sequencing
Rapid DNA sequencing on a micro scale in which many fragments of DNA are sequenced in parallel
Sequencing has also recently been used to diagnose bacterial meningoencephalitis
Rapidly identifying the correct therapeutic agent for patients
Acutely transforming viruses
Rapidly induce tumors in animals
Ras normally gets activated by
Ras GTPase causing a biochemical cascade resulting in the promotion of cell division
Proper drug dosage depends on a variety of factors including
Rate of transport of the drug from the digestive tract into the bloodstream, rate of transport into the body cells where the drug acts, ability of the drug to affect the function of the target protein, ability of the drug to be metabolized by the liver, rate of excretion of the drug from the body
Ras pathway
Receptor senses growth factor, receptor autophosphorylates, recruits GEF, GEF stimulates ras to exchange GDP for GTP, Ras GTP activates a kinase phosphorylation cascade, ends with transcription factors that cause cell to enter cell cycle
At the cellular level, the development of cancer is
Recessive
Along a long chromosome, a particular restriction enzyme will
Recognize many sites
Before 1982, insulin was isolated from cattle/pig stomachs
Recombinant insulin (made in E. coli) is safer, cheaper and without side effects
Biopharming
Recombinant microorganisms to produce medicines
Angiogenesis
Recruitment of blood vessels by a tumor
Cancer is angiogenesis
Recruitment of blood vessels by a tumor
EPSP and roundup allows spraying of fields with herbicide to
Reduce competition with weeds (weeds account for 10% of crop loss world wide)
Bidirectional migration
Reduces differences in allele frequencies between populations. Can enhance genetic diversity within a population if a new mutation is introduced
Bottleneck effect
Reduction in population size causing reestablishment by only a few individuals
Contigs
Regions of contiguous (uninterrupted) DNA sequence without gaps. Can be clone or DNA sequence
What gene annotation aims to identify and label
Regulatory elements in promoter and enhancers, exons and introns (splice sites), translation start and stop sites, polyadenylation site
P value of 0.001
Reject null. Potential for evolution
The Hardy-Weinberg equation is used to
Relate allele frequencies and genotype frequencies within a population and assess whether these frequencies change from one generation to the next
Paralogs
Related genes within or between species (come from duplication events in one of the genomes)
Normally the phosphorylation of RB1 causes it to
Release a transcription (E2F), this then can go off and influence genes required for cell division
Linkage mapping
Relies on genetic crosses. Genes are mapped relative to each other. Distances measured in map units
SCID was the first disease to be treated with gene therapy
Replacement ADA cloned into MLV. Used to transform isolated T cells. 1bn cells cultured and injected into blood stream. Some migrate to bone marrow
An E-value (exprect value) is calculated
Represents the number of times that a match or a better one would be expected to occur simply by random change
Darwinian fitness is a measure of
Reproductive success
Relative fitness
Reproductive success
Prenatal diagnosis of sickle cell anemia is a genetic test based on
Restriction enzyme analysis
Example of a molecular marker
Restriction fragment length polymorphism (RFLP)
Some mutations decrease the ability of the ras protein to hydrolyze GTP
Results in more of the GTP bound active form of the protein, keeping the signaling pathway turned on and stimulating the cell to divide
The first human tumor suppressor gene identified
Retinoblastoma gene. Causes a tumor of the retina in the eye
Knudson proposed a two hit model for retinoblastoma
Retinoblastoma requires two mutations to occur
Viral integration can form oncogenes
Retro-viruses integrate into host DNA as part of their life cycle. Can cause activation of a cellular proto-oncogene by the viral promoter or enhancer
Calculating narrow sense heritability as
Robs/Rexp
Need for rotation of transgenes
Roundup and Bt resistance are becoming common place. One of the main reasons for animosity vs GMO crops, organic farmer will lose Bt bacteria as an effective pesticide (and they don't have many options)
S phase
S phase. The synthesis phase of the cell cycle; the portion of interphase during which DNA is replicated.
Many attempts have been made to speed growth using growth hormone genes, but has been largely unsuccessful. Except for
Salmon expressing growth hormones. Grow 400-600% faster than wild type without adverse health effects
The significance of the correlation coefficient is directly related to
Sample size and degrees of freedom (one less than the degrees of freedom of variance)
Aquatic biology in metagenomics
Samples from rivers, lakes and oceans reveal great complexity of microbial communities
BLAST searches can be used to
Search databases to find alignment between newly sequences genome and genes that have already been identified in the same or different species
Positive side of inbreeding
Seen in agriculture. Inbreeding results in a higher proportion of homozygotes, which may exhibit a desirable trait
Some organisms used in biotechnology are naturally found or the result of
Selection of mutants that have occurred randomly
Prior to genetic engineering, modifying plants and animals to enhance production was restricted to
Selective breeding of naturally occurring or mutagen induced variants (mutants)
Dog breeds have been obtained by
Selective breeding stategies
Cyclins bind CDK, activate a complex
Selectively phosphorylate other proteins that are regulating the cycle
Mass spectrometry
Separates peptides based on size and charge, peptide mass correlates with amino acid composition, amino acid composition can be searched against a database to determine gene identity
Programs designed to identify features of interest generally fall into two categories
Sequence recognition and pattern recognition
Similarity means
Sequence similarity
RNAseq
Sequences cDNA to see what is being expressed in a given tissue. Can do comparative studies-look for differently expressed genes
Clones from a physical map can be used for
Sequencing
The cell cycle is a
Series of stages that cells progress through leading up to and including division
Revolutionary changes are happening in medicine
Several hundred genetic tests are in clinical use
QTLs may contain 1 gene or more
Several tightly linked genes
Since the early 1900s, microorganisms have been used in
Sewage treatment
Sources of genetic variation
Sexual reproduction, crossing over, gene transfer (horizontal gene transfer), DNA mutations, changes to chromosome structure
Repetitive sequences
Short sequences repeated many times in a genome. Can originate with transposable elements
Repetitive sequences
Short sequences repeated throughout the genome (tandomly repeated-prone to changes)
Allele specific oligonucleotides (ASOs)
Short single stranded DNA fragments (about 20 bases) that can be used to identify any single nucleotide polymorphism (SNP)
Repetitive sequences can be microsatellites
Short tandem repeats (STR)
Chronic myelogenous leukemia (CML) is correlated with the Philadelphia chromosome
Shortened chr 22 due to a translocation between chromosomes 9 and 22. Results in the proto-oncogene abl being fused to the promoter and coding sequences for the bcr gene
Quantitative traits
Show a continuum of variation within a group of individuals. Do not fall into discrete categories
Molecular markers need to be polymorphic
Show variation between individuals in a population. Similar to different alleles of a gene
PCR based methods using ASOs are available to screen for many disorders including
Sickle cell anemia and cystic fibrosis (hence very small amounts of starting DNA). Can be used in early stage human embryos created for in vitro fertilization=pre implantation genetic diagnosis (PGD)
In 2000, gene therapy used on patients that had another form of SCID
Similar protocol as ADA trial, first clear demonstration that gene therapy can be clinically useful
It is important not to confuse the terms homology and
Similarity
ASOS can be used in genotyping (DNA) microarrays to
Simultaneously examine SNPs in thousands of genes
About 90% of the CML patients treated with the drugs showed no progression of their disease
Since 2001 Gleevec has been used to treat CML and some other cancers
Many genes have variations in single nucleotides which are known as
Single nucleotide polymorphisms
Human genome is 99.4% identical (regardless of racial or ethnic origins) with most differences resulting from
Single nucleotide polymorphisms (SNPs. Many associated with disease conditions). Copy number variations (CNVs. Segments of DNA that are duplicated or deleted)
SNPs
Single nucleotide polymorphisms. 90% of variation of DNA sequences
The most common type of genetic variation
Single nucleotide polymorphisms. About 10 million SNPs are found in the human genome
Certain mini satellites tend to vary in length in human populations and can be amplified from sample using PCR
Sizes of repeats compared by gel electrophoresis. The automated detector produces a series of peaks, characteristics for each individual
DNA microarray
Slide spotted with different DNA sequences (oligos). Sequences can be from clones, PCR products, synthetic sequences. Each spot corresponds to a known gene. Up to 10k spots on one slide. Labelled cDNA binding to a spot is detected by fluorescence
The probability of losing alleles from a population increases in
Smaller populations
Transgenic livestock includes production of medicines in milk
Sometimes called molecular pharming. Examples: lactoferrin, tissue plasminogen activator, antibodies
Prenatal diagnosis of sickle cell amenia
Southern blot analysis to detect a restriction fragment length polymorphism (RFLP) in the beta globin gene
Various approaches can be used to identify and align members of a contig
Southern blotting (using radioactive markers), molecular markers (such as STSs, usually PCR), analysis of restriction enzyme digests
Contigs can assemble using
Southern blotting, molecular markers (PCR), analysis of restriction enzyme digests, or computationally (modern approaches)
Alternative splicing
Splicing of introns in a pre-mRNA that occurs in different ways, leading to different mRNAs that code for different proteins or protein isoforms. Increases the diversity of proteins
Most change in chromosome results in
Spontaneous abortions (miscarriages). About 1 in 200 live births are aneuploid or have unbalanced chromosomal alterations
90-95% of cancers are due
Spontaneous mutations and viruses, exposure to mutagens
Amplifying gene by PCR
Spot onto a DNA binding membrane
Variance
Statistic to evaluate variation in a population
Totipotent
Stem cells with the potential to differentiate into any type of cell
Some plasmids that have lost the ability to be transferred
Strains with conjugation-deficient plasmids are used commercially to prevent crown gall disease
Open reading frames (ORF)
Stretches of nucleotides that when translated to protein generate a series of AA prior to a stop codon
Open reading frames (ORFs)
Stretches of nucleotides that when translated to protein generate a series of amino acid prior to a stop codon, suggestive of a protein encoding gene
Predicting function from structural analysis of protein domains and motifs
Structural analysis at the amino acid
Genomics encompasses
Structural genomics (genomic DNA), functional genomics (transcriptomics), comparative genomics (>1 genome), metagenomics (multiple genomes of a population of different organisms)
Genetic variation can be generated from changes in chromosome
Structure
Blastocyst
Structure formed in the early development of mammals. Possesses an inner cell mass (ICM) which subsequently forms the embryo
Natural selection
Struggle for existence, individuals best adapted to the particular environment will survive and reproduce, environmental factors select those individuals that carry the best genes survive in that environment
Telomeres in cloned mice and cattle appear to be correct length, however
Studies have shown other genetic flaws: aberrant gene expression and shorter lifespan
Functional genomics
Study of gene function based on the RNAs or possible proteins they encode as well as regulatory elements
Proteomics
Study of the proteome (all of the proteins produced) and how they interact with each other
Proteomics
Study of the structure and function of proteins in the human body. How proteins interact
Quantitative genetics
Study of traits that can be described numerically
Genomics
Study of whole genomes, including genes and their functions. The complete set of DNA in a single cell of an organism
Pharmocogenetics
Study or clinical testing of genetic variation that causes differing responses to drugs
Mutation can provide new alleles, but does not
Substantially alter allele frequencies in a population
Livestock cloning may be advantageous with regard to agricultural yield, but
Such a heard may be more susceptible to rare diseases
Finding variance
Sum of all the differences between each value and the mean divided by the number of observations minus one
Differences in fitness may be due to
Survival, likelihood of mating, fertility
Differences in reproductive achievement could be due to
Survival, likelihood of mating, fertility
Individuals with beneficial allele combinations are more likely to
Survive and reproduce
Many biological characteristics follow a normal distribution
Symmetrical bell curve
A. radiobacter has genes for
Synthesis and resistance to agrocin 84
Steps of QTL
Take individuals who you know are going to be homozygous for several markers and differ in phenotype for your trait. Cross individuals (all F1 offspring are hetero), backcross F1 with parents, identify those markers that are closely linked with your trait
Physical mapping is very labor and time intensive
Takes a collaborative effort
CRISPR is also being modified to provide a tool for investigating epigenetics by
Targeting enzyme complexes involved in histone/DNA modification to specific sites
Glyphosphate
Targets chloroplast EPSP synthase which kills plants
Single gene mutation that affect proteins example
Tay Sachs disease (TSD). The artificial substrate 4 methylumbelliferone (MU) is covalently linked to N-acetylglucosamine (GlcNAc)
Genetic testing has also been conducted on specific populations in which a genetic disease is prevalent
Tay-Sachs diease in Ashkenazi jews
Example of a disorder that involves defective enzymes that has an autosomal recessive mode of inheritance
Tay-Sachs disease
Cytogenetic mapping (cytological mapping)
Technique that uses a microscope to create a map from stained chromosomes. Relies on microscopy. Genes are mapped relative to visible band locations
Commercial adoption of GM crops has been on of the most rapid cases of
Technology transfer in the history of agriculture. 4000% increase since 1996
We can divide our proportions of genotypes by these relative fitness values
Tells us what we expect in the next generation
Bidirectional migration has two important consequences
Tends to reduce differences in allele frequencies between the populations and can enhance genetic diversity within a population if a migrant introduces a new mutation
First acutely transforming virus
The Rous sarcoma virus (RSV), was isolated from chicken by Peyton Rous
The number of a specific allele divided by the total number of alleles in the population is known as
The allele frequency
Heritability describes
The amount of phenotypic variation due to genetic variation for a particular population raised in a particular environment
Haploinsufficiency
The appearance of a mutant phenotype in an individual cell or organism that is heterozygous for a normally recessive trait. Heterozygote has 50% of the normal protein-not sufficient for a normal phenotype
The basis of QTL mapping is
The association between genetically derived phenotypes (quantitative traits) and molecular markers
t=
The average number of generation to achieve fixation
Artificial selection for choosing parents
The breeder chooses individuals with traits that are desirable from a human perspective
If enough E2F is released
The cell becomes committed to division
Complexes selectively phosphorylate (and activate) other proteins to regulate
The cell cycle
Incorrect timing or levels of cyclins disrupt the process of
The cell cycle
When DNA damage is so severe that repair is impossible
The cell may initiate apoptosis, or programmed cell death. Cell commits suicide. Prevents cancer also eliminates cells not contributing the final adult organism
Normally when a cell's DNA is damaged cell replication is halted
The cell will undergo apoptosis (programmed cell death). When check points in the cell cycle are mutated, cancer can arise
G2 phase
The cells accumulate the material for nuclear and cellular division
Cancer is a genetic disease at
The cellular level
The strength of association between two variables can be evaluated by
The correlation coefficient
To calculate the correlation coefficient you have to first determine
The covariance
For many model organisms you can order specific gene knockouts and study
The effects of losing those genes on phenotype
Greater risk when releasing GMO bacteria into
The environment
Rexp
The expected correlation based on the known genetic relationship
If an individual has two copies of the gene of interest then
The expected number of new mutations is 2 time the number of individuals in a population time the mutation rate
Linkage mapping relies on
The frequency of recombinant offspring
Metagenomics (environmental genomics)
The functional and sequence based analysis of the collective microbial genomes that are contained in an environmental sample
Proteomics examines
The functional roles of the proteins that a species can make
Genome transplantation is a true test of
The functionality of a synthetic genome
Only individuals that reproduce contribute to
The future gene pool
Gene knockouts may reveal
The gene function by the mutant phenotype that results when the gene is gone
A first step in the computer analysis of genetic data is
The generation of a computer data file
Rather than considering transmission of genes at the level of individuals, population genetics considers
The genes and their alleles within a population
Molecular profiling involves identifying
The genes causing the development of cancer
Although no laws preventing genetic discrimination exist, the US house of representative passed
The genetic information nondiscrimination act in 2007
The proteome is much larger than
The genome
The number of a specific genotype divided by the total number of individuals within the population is known as
The genotype frequency
Balanced polymorphsisms can sometimes explain
The high frequency of alleles that are deleterious when homozygous. Ex: sickle cell amenia (heterozygotes have a better chance of survival if infected by the parasite)
One of the conditions required to establish HW equilibrium is random mating
The individuals choose their mates regardless of their genotypes and phenotypes
Long term genetic drift favors either
The loss or fixation of an allele. Rate depends on population size
Heterozygote advantage: higher fitness of heterozygote is balanced by
The lower fitness of both corresponding homozygotes
Artificial selection can increase or decrease
The magnitude of the trait because they're at an intermediate value in unselected populations
Selective breeding (artificial selection)
The modification of phenotypes in plants and animal species of economic importance
The lower the E value
The more significant the match. 0 means identical
Alternative splicing
The most important attention that occurs in eukaryotes, a single pre-mRNA is spliced into more than one version, splicing is often cell specific or related to environmental conditions
The high level of genomic instability in cancer cells is known as
The mutator phenotype
The heritability of a trait due to the additive effects of alleles is called
The narrow sense of heritability
Bt GMOs express genes from
The naturally occurring bacterium Bacillus thuringiensis (Bt)
Studying hemophilia led to a greater understanding of
The normal process of blood clotting
Many polygenic traits are difficult or impossible to categorize into discrete genotypic categories especially when
The number of genes controlling the trait increases and the influence of the environment increases
If fixation occurs, the number of generations it's likely to take depends on
The number of individuals in the population
N=
The number of individuals in the population, assuming males and females contribute equally to the next generation
The mutation is expressed as
The number of new mutations in a given gene per generation
Repeats can undergo mutation which changes
The number of repeat units. May involve replication errors or recombination
Robs
The observed phenotypic correlation between related individuals
M phase
The phase of the cell cycle that includes mitosis and cytokinesis
Null hypothesis
The population is at equilibrium
When genes change through natural selection, the result is that
The population is more successful at reproducing and potentially better adapted to its environment
Tumorigenesis
The process by which normal cells become cancerous
Sequence recognition
The program has the information that a specific sequence of symbols has a specialized meaning
In many cases, single gene mutations that affect proteins can be examined at
The protein level
Comparative genomics explores
The relationship between organisms and the environment
For both traits and disease, geneticists want to know
The relative contributions from genetics and the environment
Fitness
The relative likelihood that a phenotype will survive and contribute to the gene pool of the next generation
R in realized heritability
The response in the offspring to selection
S in realized heritability
The selection differential in the parents
Breeders choose parents with desirable characteristics
The selective breeder will often choose genetically related individuals as the parental stock. Known as inbreeding
All the clones that are sequenced can be used to regenerate
The sequence of a chromosome as their relationship is known
Interactome
The set of protein-to-protein interactions that occurs in a cell
Standard deviation
The square root of the variance
Missense mutations in ras can change
The structure of the protein to make it permanently activated. Cannot hydrolyze GTP (lose enzyme activity, but retains biological activity)
Metagenomics
The study of complex mixtures of genetic material obtained from environmental samples
Functional genomics
The study of the relationship between genes and their function
Transcriptomics
The study of transcriptomes and their functions
Variance of genetic and environmental factors that contribute to a quantitative trait can be added to predict
The total variance for the trait
Human cancers are classified according to
The type of cell that has become cancerous
Biological control refers to
The use of microorganisms or their products to alleviate plant diseases and pests
Biolistic gene transfer
The use of microprojectiles to introduce DNA into plant cells. DNA shot into cells with gene gun
The significance level table is only valid if
The values of X and Y are obtained by an unbiased sampling of the entire population, the scores of X and Y follow a normal distribution, the relationship between X and Y is linear
Va
The variance due to the additive effects of alleles
Vi
The variance due to the effects of alleles that interact in an epistatic manner
In cancer cells, one or more proto-oncogenes are altered in such a way that
Their activities cannot be controlled normally
A mutation can occur that prevents the production of RB1
Then nothing prevents E2F from promoting transcription of genes stimulating cell division
Mice used in labs are usually genetically homogeneous through inbreeding and are monomorphic
Therefore all phenotypic variation is due to Ve
Tumor suppressor genes inhibit cell proliferation
These genes prevent cells from dividing
Molecular markers can be used as reference points along chromosomes to make QTLs
These markers have been used to construct detailed genomic maps. (Maps make it easier to determine the number of genes that affect a quantitative trait)
Many forms of cancer show distinctive patterns of gene expression
These patterns can be detected by microarrays, and mRNAs expressed only in cancer cells represent targets for therapy and drug development
Variances are very important in the analysis of quantitative traits because
They are additive under certain conditions
Proteins have to be isolectric focused first because
They have to be in their native confirmation. Separated without denaturing the proteins such that they keep moving through the gel until they reach a point where the pH gives it a zero charge
Mice knockouts and knockins help us understand human diseases
This research is called using a mouse model
GloFish, a transgenic strain of zebrafish. Contain a fluorescent proteins from sea anemones
Though marketed as pests, these animals may be useful for assaying heavy metal contamination in water
DNA microarrays are good for studying
Tissue/cell type differences, developmental progressions, virulent vs avirulent progressions, + or - pathogen attack, diseased vs non diseased tissue, responses to environmental stress
Alternative way to describe quantitative traits is a frequency distribution
To construct a frequency distribution, the trait is divided arbitrarily into a number of discrete phenotypic categories
The goal of functional genomics
To elucidate the roles of genetic sequences in a given species
Goal of international HapMap project
To generate and disseminate the HapMap so researchers can find links between genetic variants and specific diseases
Genome bases primary aim
To organize the sequencing and mapping information from a single species
Proteins are too complex a mixture to be adequately separated by 1D gel electrophoresis
To separate all these proteins, two dimensional gel electrophoresis is used. Can resolve two proteins that differ by a single charged amino acid
Stabilizing selection ex laying eggs
Too many eggs drains resources to care for young, and too few eggs reduces contribution to next generation
Genes from Bt express
Toxins that are lethal to many insects that feed in trees, shrub and fruit, toxins geneidentified - Cry1A
Threshold traits
Traits inherited quantitatively but are expressed qualitatively in terms of phenotype. Ex: diabetes-either have it or don't
Meristic traits
Traits that can be counted and expressed in whole numbers
Threshold traits
Traits with complex inheritance but phenotypically are simply expressed
Expression stage of CRISPR-Cas
Transcribed into a long CRISPR precursor RNA. Cleaved by CAS proteins and processed into crRNAs, each having one spacer sequence, crRNA combined with Cas protein to form an effector complex
p53
Transcription factor that detects DNA damage; prevents cycling CDK complex; initiates cascade of gene expression. This stops the cell cycle, repairs DNA damage, if not possible, starts apoptosis
Chromatin immunoprecipitation is useful for what kind of protein
Transcription factors and chromatin modifying agents. What promoter regions and genes are regulated
Proto-oncogenes include
Transcription factors that stimulate expression of other genes, signal transduction molecules that stimulate cell division, cell-cycle regulators that move through the cell cycle
Genome sequences have opened new possibilities for analyzing
Transcriptomes and proteomes
Gene therapy
Transferring specific genes into human cells to treat genetic disorders. Normal allele of a gene is transferred into a patient's cell that has one or more mutant alleles
Enviropigs
Transformed with a gene for phytase. Breaks down dietary phosphorus. Reduces phosphate pollution caused by pig farming
Introducing recombinant DNA that contains and expresses specific genes or alleles
Transgenes
One famous use of transgenic crops with no obvious downside
Transgenic papaya express a ringspot virus coat protein making it resistant to the virus, was introduced to Hawaii, and has saved the papaya industry
Agrobacterium tumefaciens can be manipulated to make
Transgenic plants
Bt GMOs
Transgenic plants that produce their own insecticide
blastx
Translated nucleotide vs protein database
tblastx
Translated nucleotide vs translated nucleotide
Identification of open reading frames requires
Translation of all six reading frames
Polygenic inheritance
Transmission of traits that are governed by two or more genes
Bacterial knockouts created using
Transposons
>900 different mutations that cause cystic fibrosis have been identified
Treatments vary depending on the mutation
Retinoblastoma
Tumor arising from a developing retinal cell (a congenital, malignant tumor)
Malignant
Tumor composed of cancer cells
RB1 proto-oncogene or tumor suppressor
Tumor suppressor gene
p53 proto-oncogene or tumor suppressor
Tumor suppressor gene
In many biological problems, it is useful to compare
Two different variables. We may wish to compare the occurrence of two phenotypic traits, compare traits and environmental factors, compare traits and genetic relationships
Disruptive selection graph
Two humps that show maximums in the population for more than one phenotype
Sporadic retinoblastoma requires
Two independent mutational events of RB1 within the same cell
Disruptive selection favors the survival of
Two more more different genotypes with different phenotypes
If r=0
Two two factors are not related
Use of GMOs comes with complex issues dependent on
Type of organism involved, where and how that organism is grown, implications to human biology
Most types of cancer are not directly heritable
Typically cancers involve 6-12 mutations, some of these may be heritable whilst the actual disease is not. Hence the likelihood of contracting cancer often is heritable
Five stages of domestication
Unconscious selection for desirable traits, conscious cultivation, deliberate breeding to improve traits, scientific breeding, direct genetic manipulation
Cancers are identified by
Uncontrolled cell division
A population may have a change in environment
Under the new conditions, the relative fitness values may change
Due to the low frequency of homologous recombination it is difficult to find cells that have
Undergone gene replacement
KanR is commonly used
Unique restriction sites inserted to aid in cloning
All cancer cells share two fundamental properties
Unregulated cell proliferation and metastatic spread
Quantitative traits are often at an intermediate value in
Unselected populations
Personalized medicine
Use of information about a patient's genotype and other clinical data in order to select a medication of therapy specifically suited to that patient. Likely to become an increasingly important aspect of health care
Bioremediation
Use of microorganisms to reduce environmental pollutants
Genetic testing
Use of tests to discover if an individual has a genetic abnormaility
Naturally occurring nitrosamines
Used as meat preservatives are known to cause cancer
Importance of quantitative genetics
Used by breeders when characterizing plants and animals (taste, yield, inputs, tolerance to conditions, etc)
Breeders equation
Used to calculate the mean phenotypes of offspring based on the mean weights of the parents, the starting population, and the heritability
BLAST searches
Used to screen databases and compare a sequence to a known sequence
Molecular genetic tools allow for directed changes to create
Useful strains
KEY
Uses an RNA strand to target and edit specific sequences in genomes. Enginerred for genome engineering (editing) in many organisms
Genome/transcriptome annotation
Using BLAST searches and motif databases to assign putative functions to all expressed genes (using software such as BLAST2GO
Pharmocogenomics
Using an individual's genome to determine whether or not a particular therapy, or dosage, will be effective
Transcriptomes in theory show all transcribed genes
Usually illumina methodology used, extract mRNA, make into cDNA and sequence all of it
Gene knockout in plants
Usually t-DNA insertions (transformed with a piece of DNA that inserts randomly into the genome)
Genetic variation (Vg) is subdivided into three different genetic categories
Va, Vd, Vi
Narrow sense heritability
Va/Vt
Vd
Variance due to the effects of alleles that follow a dominant/recessive pattern of inheritance
Heritability is a population value that pertains to
Variation
Quantitative traits have continuous
Variation across individuals
Releasing transgenic plants has the potential of escape genes which make pharmaceuticals or industrial precursors into
Varieties of the same crop used for food. Using non food species as bioreactors would make a lot of sense, but politics and money mean corn is the main focus
Continuous traits
Vary continuously, do not fall into clear categories. Ex: height and weight
QTLs
Varying genes that each make a small contribution to variation of a quantitative phenotype in a population
Equilibrium is never reached in real life
Very large populations can get close
Modern day variation between people
Very little variation. Most variation in the alleles of a given gene (2+)
Baculovirus
Virus used to infect insect cells
Up to 15% of human cancers are associated with
Viruses
Viral integration
Viruses may cause cancer by carrying oncogenes into cell
70% of children under 5 in South East Asia are deficient in
Vitamin A
Human use beta carotene to make
Vitamin A
Encyclopedia of DNA elements (ENCODE)
Was created with the aim of using experimental approaches and bioinformatics to identify and analyze functional elements that regulate expression of human genes
Bioremediation has expanded into the treatment of hazardous and refractory wastes
Wastes from chemical and industrial activity. Include petroleum hydrocarbons, pesticides, herbicides, organic solvents, plastics, etc
GMO is a very misleading term to use for agricultural biotechnology
We have been altering plant and animal genomes for about 10,000 years: all crops and domesticated animals have been immensely genetically modified relative to their wild ancestors
Previously it was impossible to do in depth investigations into microbial populations
We have no idea how to culture most of them
The dog has been a particularly useful model organism for humans
We share 75% of the same genes, similar genome size, suffer from many of the same genetic disorders
Linkage disequilibrium
When disease causing allele and nearby marker are associated more frequently than expected
Inbreeding depression
When individuals with similar genotypes - typically relatives - breed with each other and produce offspring that have an impaired ability to survive and reproduce
Polygenic inheritance
When one phenotype that is affected by many genes
Apoptotic bodies are engulfed by
White blood cells (phagocytes)
Most widely used method for physical mapping
Whole genome shotgun sequencing
With one million breeding members in a population, it will take a 4 million generations to reach fixation
With 100 individuals, fixation will take only 400 generations
Members of a local population are far likelier to breed with each other than
With members of the general population
Germ line therapy
Would stop increase in mutant alleles, but brings other ethical issues: affects genomes of future generatons
Mean is computed with the formula
X=SigmaX/N. X is the mean, Sigma X is the sum of all values in the group, N is the number of individuals in the group
Threshold
Yes or no. Quantitative in inheritance patterns
Allele frequency can't be more than one because
You can't have more occurrence of an allele than total alleles in a given population
RNAseq uses nextgen sequencing to sequence
cDNA made from specific tissue samples
KEY uses CAS9 intrinsic nuclease to introduce
ds break or ss nick. Repair using recombinant DNA template-custom modification
50% pf all human cancers are associated with defects in
p53
The second tumor suppressor gene discovered
p53
DNA microarrays have been designed to scan for mutations in many disease related diseases including
p53 (mutated in a majority of human cancers), and BRCA1 gene, which when mutated predisposes women to breast cancer
The Hardy-Weinberg equation states that
p^2+2pq+q^2=1
The human genome has four ras genes
rasH, rasN, rasK-4a, rasK-4b
Selection coefficient equation
s = 1 - w. One minus the fitness
Fixation depending on the number of individuals in the population
t=4N
Relative fitness values are denoted by the variable
w
