Genetics Exam 4

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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


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