human genetics exam 4

What causes cancer?

Cancer is caused by the accumulation of mutations that collectively contribute to uncontrolled cell proliferation

Describe the characteristics of cancer cells

Cancer cells are characterized by uncontrolled proliferation, the ability to invade new tissues outside the tissue of origin, immortality, and a high metabolic rate.

Benign tumor

A mass of abnormal cells that are not cancerous. Do not spread to and proliferate in other tissues

Hyperplasia

Cells divide faster than normal and build up. Cells look normal under microscope. The cells are benign.

Dysplasia

Cells divide faster than normal and build up. The cells do not look normal under the microscope. The cells are benign. Can be low grade or high grade.

Carcinoma in situ

Cells that have high grade dysplasia. Cells are benign but have high risk of becoming malignant (cancerous)

Malignant tumor

Mass of abnormal cells that are cancerous. Can spread to and proliferate in other tissue.

Metastasis

Malignant cells enter the blood or lymph fluids and seed in other tissues to develop new tumors.

Mutagen

An agent that causes mutation. Most mutagens are carcinogens due to potential to cause mutation in oncogenes and tumor suppressor genes.

Carcinogen

An agent that can promote that development of cancer. Not all carcinogens are mutagens.

Proto-oncogene

Normal genes that cause normal cells to become cancerous when they develop a gain of function. Mutation are typically dominant.

Oncogene

The mutated version of Proto-oncogenes

Name two groups of proteins, discussed in class, that proto-oncogenes commonly encode

Proteins that promote cell division and proteins that inhibit/prevent cell death

are cancer promoting in photo-oncogenes gain of function or loss of function

gain of function, meaning that the gene product is over-active

are cancer promoting mutation in proton-oncogenes typically dominant or recessive

dominant

tumor suppressor gene

cause normal cells ro become cancerous when they develop a loss of function mutation

name 3 groups of proteins, discussed in class, that tumor suppressor genes commonly encode

proteins that prevent/inhibit cell division, proteins that promote cell death, and proteins that are involves in DNA repair

are cancer promoting mutation in tumor suppressor genes gain of function or loss of function

loss of function

are cancer promoting mutation in tumor suppressor genes typically dominates or recessive

recessive

a mutation causes loss of function that normally promotes cell division

proton-oncogenes, not cancer promoting, and recessive

a mutation causes loss of function of protein involved in DNA repair

tumor suppressor gene, cancer promoting, and recessive

a mutation causes gain of function of a signaling protein that normally promotes cell division

proton-oncogenes, promotes cancer, and dominant

a mutation causes loss of activity of a protein that normally promotes apoptosis

tumor suppressor gene, cancer promoting, and recessive

A mutation causes over-activity of a protein that normally prevents apoptosis

proton-oncogenes, cancer promoting, and dominant

A mutation causes loss of activity of a protein that normally inhibits cell division

tumor suppressor gene, cancer promoting, and recessive

A mutation activates telomerase, the enzyme that adds telomers, thereby preventing a cell reaching senescence

proton-oncogenes, cancer promoting, dominant

A mutation causes gain-of-function of a protein that normally promotes apoptosis

tumor suppressor gene, not cancer promoting, and dominant

Why is an inherited predisposition to develop a cancer usually due to inheriting a mutation in a tumor suppressor gene rather than in a proto-oncogene (the RET proto-oncogene being an exception because it is expressed in only certain tissue types)?

If an individual has an inherited predisposition to developing a cancer, it means the individual inherited a mutation that gives them a higher risk of developing cancer than an individual who did not inherit the mutation.

population

all interbreeding individual of same species in the sea location at the same time

gene pool

all alleles of every gene in a population or all alleles in a population

what are the 5 assumption of the hardy-weinberg equilibrium

no natural selection, no genetic drift, random mating, no migration, no mutation

microevolution

changes in the allele and genotype frequencies that occur in a population from one generation to the next.

changes in the gene pool from generation to generation

fitness

the likelihood that a particular genotype will contribute genes to the next generation relative to other genotypes. the fitness genotype will transmit the most DNA to the next generation.

reproductive success

natural selection

Natural selection means a genotype that enhances survival and/or reproductive success will contribute more alleles to the next generation relative to other genotypes and will therefore increase in frequency
over time.

which traits do natural selection select for and why

individuals who survive longer are more likely to produce more offspring and contribute more genes to the next generation. Individuals with a reproductive advantage are more likely to reproduce more and contribute more genes to the next generation

which phenotype has the highest fitness in directional natural selection

Individuals with a phenotype on one side of the mean have the greatest fitness and are naturally selected

which genotype has the highest fitness in balancing natural selection during to the heterozygous genotype

The heterozygous genotype has the highest fitness, which results in the recessive allele becoming prevalent at a higher frequency in the population than would otherwise be expected

which phenotype has the highest fitness in stabilizing natural selection

the mean phenotype has the highest fitness

which phenotype had the highest fitness in disruptive/diversifying natural selection

two or more phenotype are naturally selected in a population that occupies a diverse environment

genetic drift

changes in alleles/genotype frequency in a population due to random chance

is genetic drift more likely to change allele frequencies in ambler populations or larger populations

Genetic drift is more likely to affect small populations versus large populations because smaller populations are more susceptible to random fluctuations in allele frequencies

describe in a few sentences how the bottleneck effect changes allele/genotype frequencies in a population.

A natural event randomly eliminates individuals irrespective of genotype. By chance, allele/genotype frequencies may be altered. After the event, population size may eventually recover, but allele/genotype frequencies can be forever changed.

population decreases dramatically in size due to a natural event.

describe in a few sentences how the founder effect changes allele/genotype frequencies in a population

A small, founder population migrates out of a large population to a new location to start a new population. the founder population may, by chance, have a gene pool that is not representative of the larger, original population from which they came, so the founder population has different allele/genotype frequencies than the original population

what is the difference between founder effect and migration

In the founder effect, a small group of individuals migrate to a new location to establish a new, founding population. In migration, individuals migrate into an existing population and interbreed with the existing population

If individuals migrate from population A into population B, what effect does migration have on genetic diversity within population B? What effect does migration have on the genetic diversity between populations A and B?

When individuals migrate from population A into population B, it will increase the genetic diversity within population B because new genetic material has been introduced into population B.

It will reduce the genetic diversity between populations A and B

polygenic trait

more than one gene is involved in producing the phenotype

complex trait

trait that is determined by more than one gene as well as environmental factors

quantitative trait

trait that can be described quantitatively. numerically

what are the categories of complex trait

continuous trait, meristic trait, threshold trait

continuous trait

trait shows continuous phenotype distribution in the population, so phenotype do not fall into discrete categories. height and weight

meristic trait

trait can be counted and described in whole numbers, so ,multiple whole number discrete categories. litter size in cats, hair follicles on the head.

threshold trait

traits take discrete values, but multiple gene and environmental factors contribute to the likelihood of developing the condition. diabetes, heart disease

continuous traits usually show normal distribution in a population. what shape is a normal frequency distribution curve

In a normally distributed population, most individuals have the mean phenotype and there is symmetrical phenotype variation on either side of the mean. When plotted on a graph the curve shows a bell-shaped curve with symmetrical variation about the mean.

Continuous traits show phenotypic variation in a population. What are variance and standard deviation measures of? What is the relationship between variance and standard deviation?

They are both a measure of how spread-out values are from the mean.

Variance is the average squared deviation of values from the mean, and standard deviation is the square root of variance

What is covariance a measure of? What is correlation coefficient a measure of?

Covariance and correlation coefficient measure the relationship and dependency of two variables.

Covariance is an absolute number, so the value depends on the values in the dataset. It indicates the direction of the relationship (positive or negative), but the strength of association is difficult to determine.

Correlation coefficient is a standardized number ranging from -1 to +1, so it enables determination of the direction and strength of association between 2 variables

Define broad sense heritability (represented by either H² or h_B²).

For a trait, the phenotype variance in a population may be due to genetic factors or environmental factors or a combination of both. Broad-sense heritability of a trait is an estimate of how much phenotype variation about the mean is due to genetic factors.

Define narrow-sense heritability (represented by either h² or h_N²).

Narrow-sense heritability is an estimate of how much phenotype variance is predictably inherited, i.e., predictably transmitted from parents to offspring.

Genetic variance is composed of additive genetic variance, dominance genetic variance and interactive geneticvariance. Variance due to additive genetic factors is the only component of genetic variance that can be predictably inherited, so narrow-sense heritability is the ratio of variance due to additive genetic factors over total variance.

Narrow-sense heritability for heart rate in a particular study was calculated to be 0.17. Is variance in heart rate predictably inherited (i.e., predictably transmitted from parents to offspring)? 

A value of 0.17 tells us that only 17% of variance can be predictable inherited, so most of the phenotypic variance in heart rate is not predictably inherited.

What is polymerase chain reaction (PCR) used for?

It is used to amplify a target DNA sequence to produce many copies.

What four core components are required as starting material for any PCR reaction?

Template DNA, DNA nucleotides, primers, and Taq polymerase.

What are the three basic steps that are repeated each PCR cycle?

Denaturation: template DNA strands are separated by heating the DNA to 95c

Primer annealing: temperature lowered to 55-62c to allow the primers to anneal to the template strand.

Primer extension: temperature is raised to 72c, and Taq polymerase synthesize new DNA strands.

What is quantitative PCR (qPCR) used for

It is a quantitative version of traditional PCR, which enables determination of the starting number of DNA copies in a sample. Standards of known concentration are included and used to produce a standard curve. The samples are then plotted on the standard curve to determine starting copy number.

What additional component is needed for qPCR that is not needed for standard PCR?

A reporter molecule that produces a signal for each DNA copy present. There are several different reported molecules that can be used. The example I gave in class is SYBR Green, which fluoresces when it is incorporated in double stranded DNA. Therefore, the level of fluorescence after each cycle is proportional to the number of DNA copies present.

What is the threshold cycle (Ct)?

The cycle number when fluorescence from a sample passes background.

How does the threshold cycle number correlate with the number of target DNA copies in the starting sample?

The lower the threshold cycle number, the greater the number of DNA copies in the starting sample and vice versa.

What is cDNA?

A DNA copy of mRNA. Therefore, it is the coding sequence of a gene without the introns.

Which enzyme makes cDNA from mRNA?

Reverse transcriptase

Give an example of a situation where cDNA is needed rather than DNA.

i)For gene cloning, it is often desirable to use only the coding sequences of the gene so the sequence is shorter and so it can be expressed in a prokaryotic organism

ii) If analyzing mRNA expression in a sample, the mRNA would have to be converted to DNA prior to performing PCR.

On what basis are DNA sequences separated during gel electrophoresis

DNA sequences are linear and have a uniform negative charge. When a voltage is applied to the gel, DNA sequences therefore migrate at different rates based on size.

In the gels below, which DNA sequences are the smallest in size- the DNA sequences at the top of the gels or the DNA sequences at the bottom of the gels?

Larger sequences migrate slower (and are therefore at the top) and smaller sequences migrate faster (and are therefore at the bottom).

How do dideoxy nucleotides (ddNTPs) differ from deoxy nucleotides (dNTPs)?

ddNTPs have a hydrogen (H) at the 3’ position instead of a hydroxyl (OH). When incorporated into a DNA strand being synthesized, ddNTPs terminate replication because there is no 3’-OH to add more nucleotides.

Opposite which base in the DNA template could dideoxy cytosine (ddCTP) be added to terminate replication?

ddCTP will terminate replication opposite G in the template strand.

Which molecule is detected in a Southern blot? What acts as a probe to locate the target molecule? Give an example of when a Southern blot would be used?

A DNA probe is used to locate a target DNA molecule; the DNA probe will hybridize to a complimentary DNA sequence. Some applications of Southern blotting include:

- Finding homologous genes (genes that are derived from the same ancestral gene) including orthologs (homologous genes in different species) and paralogs (homologous genes within an organism that arose through gene duplications).

- Detecting genome deletion or duplication events

Southern blot (which can be a laborious procedure) is often replaced now by PCR based technologies, DNAsequencing, and computer software that can analyze and compare sequenced genomes.

Which molecule is detected in a Northern blot? What acts as a probe to locate the target molecule? Give an example of when a Northern blot would be used?

A DNA probe is used to locate a target RNA molecule; the probe will hybridize to a complimentary RNA sequence. Some applications of Northern blotting include:

- Determining if a particular gene is expressed in a particular cell type or during a particular time during development.

- To determine if a gene is alternatively spliced (different sized mRNAs produced by alternative splicing will migrate differently on a gel).

Which molecule is detected in a Western blot? What acts as a probe to locate the target molecule? Give an example of when a Western blot would be used?

To determine if a particular protein is present in a sample. Proteins are extracted from a sample and run on a gel. Commonly an antibody specific for the target protein of interest is used as probe.

What is a vector?

DNA molecule used as a vehicle to carry foreign DNA into a host cell.

Name two examples of vectors that were discussed in class.

Two examples of a vector are plasmids and viruses.

What does a restriction endonuclease enzyme do? How is it utilized to create a recombinant plasmid containing a target DNA sequence?

An enzyme that cuts DNA at a specific sequence (most cut at a specific palindromic sequence). The plasmid and target DNA sequence are both cut with a restriction enzyme that produces sticky ends. The plasmid and target DNA have complementary sticky ends that can hybridize together through complementary base pairing.

transgenic organism

A transgenic organism is an organism that has been genetically modified by incorporating foreign DNA into its genome.

Name three uses of transgenic organisms discussed in class.

- Transgenic organisms (e.g., microorganisms or livestock) are used to produce useful proteins that they do not naturally produce.

- Transgenic crops are modified to produce a desirable quality, such as pest resistance, increased yield, larger fruits, etc.

- Transgenic mice can be produced to investigate the function of a gene product or to create an animal model of a human condition.

- Gene therapy to deliver a therapeutic gene to a patient’s cells.

What is the aim of gene therapy? Which type of vector is mostly used to deliver a therapeutic gene to cells?

The aim is to deliver a therapeutic gene to a patient’s cells. A genetically modified virus is typically used to deliver the therapeutic gene. The viral genome is genetically modified to contain the therapeutic gene as well as the viral sequences needed to infect cells and deliver the gene.

Briefly explain (a short paragraph) how the CRISPR/cas9 gene editing system is used to make precise edits to a genome. Give a couple of examples of some practical uses for the CRISPR/cas9 system.

The system modifies a natural immune mechanism that is present in some bacteria and archaea. Guide RNA molecules are modified to guide the cas9 enzyme to a highly specific DNA sequence (the guide RNAs can be modified to recognize any sequence). The cas9 enzyme then cuts DNA at the desired location. Following the cut, the cell can be manipulated to delete, add, or edit the DNA during the repair process. The CRISPR/cas 9 can potentially be used for many of the same uses that we discussed for cloned genes, including creation of genetically modified organisms, to correct a gene defect, and creation of genetically modified crops.

What characteristics define stem cells?

1) self-renew and 2) differentiate into one or more specialized cell types.

What is the difference between totipotent, pluripotent, and multipotent stem cells regarding their differentiation potential?

Totipotent stem cells are at the earliest developmental stage and can give rise to any cell type in the body as well as extraembryonic tissues, so they have the potential to produce an entire organism.

Pluripotent stem cells can give rise to any cell type in the body, but not extraembryonic tissues, so they do not have the potential to produce an entire organism.

Multipotent stem (also known as adult stem cells) can differentiate into more than one cell type, but their differentiation potential is much more limited than totipotent and pluripotent stem cells. They are undifferentiated cells that are committed to produce only cell types of a certain lineage. For example, hematopoietic stem cells in the bone marrow give rise to all blood cells, but not other cell types

Other than embryonic stem cells, what are two other sources of pluripotent stem cells that can differentiate to cells of all three germ layers in the laboratory?

Embryonic-like stem cells from umbilical cord blood and induced pluripotent stem cells (iPSCs) that have been reprogrammed from adult differentiated cells back to a pluripotent state.