Study Guide for Exam 1

Study Guide- Exam 1

(covers Classes 1.1 through 1.7)
Class 1.1--The Language of Genetics
Know the following terms:
Genetics, gene, genome, chromosomes, traits, single-gene traits, multifactorial traits, pleiotiropic
genes, genotype, phenotype, autosomes, sex chromosomes, homologous chromosomes,
homozygous, heterozygous, hemizygous, dominant allele, recessive allele, Mendelian genetics,
elementon, law of segregation, 3:1 phenotypic ratios, law of independent assortment, 9:3:3:1
phenotypic ratios, chromosome linkage, penetrance, expressivity, epigenetics, forward genetics,
reverse genetics.
Understand the Following Concepts:
1. Understand how the genome is packaged in prokaryotes versus eukaryotes.
2. Realize that some viruses use a single-stranded DNA or RNA genome.
3. Understand the difference between traits controlled by a single gene or by multiple genes.
4. Be aware that most complex traits are controlled by allele interactions, gene interactions,
and the environment.
5. Know the difference between genotype and phenotype.
6. Know that diploid organisms (like humans) have two copies of the genome. Understand
how those copies of the genomes are packaged (autosomes, sex chromosomes,
mitochondrial genomes).
7. Know what homologous chromosomes are and how they are related to the concept of the
allele.
8. Know the difference between alleles in a homozygous condition and alleles in a
heterozygous condition.
9. Know the conditions needed to classify an allele as either dominant or recessive. Have a
general idea of how these terms are related to wildtype, gain-of-function, and loss-offunction.
10. Know Mendels two laws, how they are related to separation of homologous
chromosomes at meiosis, and why these rules still apply today.
11. Be familiar with Mendels biography.
12. Know that Mendels first law explains how two alleles of one gene segregate at meiosis,
resulting in a 3:1 phenotypic ratio in the F2.
13. Know that Mendels second law explains how two alleles of two genes independently
assort during meiosis producing a 9:3:3:1 phenotypic ratio in the F2.
14. Know the five basic genetic concepts that Mendel could not explain.
15. Understand that unlike the genes that Mendel worked with, most genes contain wildtype,
complete loss, partial loss, and gain of function alleles.
16. Understand how and why a gene residing on a sex chromosome would not conform to
Mendels laws.
17. Know why if two genes were linked to the same chromosome, there would be a
deviation in the law of segregation as proposed by Mendel.
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18. Understand how expressivity and penetrance of an alleles phenotype affected by the
environment would complicate the analysis of traits even if controlled by one gene.
19. Understand that the packaging of the genome can lead to a change in the expression of a
gene even though the gene sequence is not changed and this is referred to as an epigenetic
effect.
20. Know how the study of genetics has shifted from an analysis of phenotypes in order to
identify a gene to the study of phenotypes in the 21st century in which the genotype is
known because of DNA sequence, but the function of many genes is not yet elucidated.

Class 1.2: Genes and DNA

Know the following terms:
Nucleosides, nucleotide, ribose, deoxyribose, purine, prymidine, guanine, cytosine, thymine,
adenine, uracil, minor groove, major groove, negative supercoiling, positive supercoiling, DNA
polymerase, RNA polymerase, reverse transcriptase, central dogma, replication, transcription,
translation, hybridization, transition, transversion, induced mutation, spontaneous mutation,
insertion, deletion, back mutation, true reversion, second-site reversion, suppressor mutation.
Understand the Following Concepts:
1. Know the structures and names of nitrogenous bases, nucleosides, and nucleotides for DNA
and RNA
2. Know the structure of the nucleotide (sugar, phosphate group, nitrogenous base) and how a
ribonucleotide is different from a deoxy-ribonucleotide.
3. Know how the positions of the Carbons on the pentose sugar define the orientation of the
DNA strands.
4. Know the difference between purine and prymidine nitrogenous bases.
5. Know how nucleotides are assembled into nucleic acid molecules.
6. Be familiar with the overall structure of double-stranded DNA: Know the concepts of
antiparllel strands, 5' and 3' polarity, and major and minor grooves.
7. Understand the concept of supercoiling and how cells use it to help package and access
DNA.
8. Know the three major types of polymerases and the types of molecules they produce.
9. Know the rules of complementary base pairing in DNA/DNA and DNA/RNA molecules.
10. Understand how nucleotide triphosphates build DNA and RNA from the 3' end.
11. Know what semiconservative replication means.
12. Understand how the concept of the central dogma has changed from its original inception.
13. Understand the concept of Tm and how it changes with AT content in DNA.
14. Understand how denaturation/renaturation (hybridization) of DNA or RNA can be used to
quantify the amount of nucleic acid.
15. Know the difference between spontaneous and background levels of mutations.
16. Know the difference between transitions and transversion, and be able to recognize the
difference from a DNA change.
17. Know the difference between a back mutation and a true reversion.
18. Know the difference between a true reversion and a second-site reversion.

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19. Know the difference between a second-site reversion and a suppressor mutation.
20. Understand the concept of a hot spot and how it might relate to the concentration of Cs and
DNA methylation.

Class 1.3-: Gene Structure and Alleles

Terms:
Complementation, complementation group, loss-of-function, gain-of-function, null,
hypomorphic, leaky, hypermorph, neomorph, wildtype, haploinsufficiency, polymorphism,
meiosis, gametes, homologous chromosomes, DNA recombination, codon, open reading frame,
message strand, template strand, genomic DNA, cDNA, hybridization, introns, exons, preRNA,
mRNA, alternative promoter use, differential splicing, transcription unit, gene family,
pseudogenes.
Concepts:
1. Know how the concept of the gene has changed over the last 100 years.
2. Know the difference between a protein and a polypeptide.
3. Know the relationship between the terms dominant and recessive and gain-of-function
(GOF) and loss-of-function (LOF).
4. Understand how the complementation test is used to classify types of mutations as
representing alleles of one gene or as defining two different genes.
5. Understand the difference between null and hypomorphic (leaky) LOF mutations.
6. Understand the difference between hypermorphic, antimorphic, and neomorphic gain-offunction alleles.
7. Know how genetic tests are used to classify mutations.
8. Understand the concept of an allele and the potential for 1000s of alleles at any one gene
locus.
9. Be familiar with the types of nomenclatures to represent alleles of a gene.
10. Understand the importance of context when classifying alleles as dominant or recessive.
11. Understand the molecular basis for how a gene that displays haploinsufficiency can behave
as a dominant loss of function allele in a genetic test.
12. Understand the concept of a wildtype and why it might be difficult to define.
13. Understand the molecular basis for the co-dominant and recessive alleles of the ABO gene.
14. Know that homologous chromosomes can physically recombine by crossing over.
15. Understand the concept of mapping linked genes based on recombination frequencies.
16. Be aware that mutations can occur in many different parts of a gene (not just the coding
information).
17. Know the difference between a message and template strand of DNA. Be able predict the
RNA produced from a template strand.
18. Know at least one difference between eukaryotic and prokaryotic genes.
19. Know the difference between preRNA and mRNA.
20. Be aware of the splicing mechanisms that generate mRNAs.
21. Know that intron lengths and positions can be indicators of evolutionary relationships.
22. Know the 3 different ways of producing different polypeptides from the same gene.

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23. Understand the concept of a transcription unit and how it relates to a modern definition of
the gene.
24. Understand how genes and proteins can be grouped into family and superfamilies.
25. Understand some of the current theories to explain the presence of pseudogenes
Class 1.4-: Personalized Genomes
Terms:
Personalized medicine, Thousand dollar genome, whole-genome sequencing, exome sequencing,
genome scan (genotyping), 23andMe, odds calculator, probabilistic information, deterministic
information, ApoE4 allele, Alzheimers disease, Huntingtons disease, burden of knowing,
BRCA1 mutant allele, actionable gene/allele, early prediction early detection, genome-specific
drug metabolism (pharmacogenetics), XIAP gene, cystic fibrosis, CFTR gene, kalydeco, magic
bullet, metastatic melanoma, cancer genomics, BRAF overexpression, PET scan, mammoprint
(gene expression test for breast cancer treatment), preimplantation genetic diagnosis (PGD),
eugenics, genetic elite, dopamine, stigmatization, anonymized information, genetic debris,
genome hacking.
Be able to answer the following questions from the video:
1. How is the ancient Greek motto of know thyself being manifested today in the era of
personalized medicine?
2. What is the relationship between whole-genome sequencing and personalized medicine?
2. Be aware of the limitations of personalized medicine. For example, will knowing your risk
factors alone lead to better health or wellness?
3. What is the difference between whole-genome sequencing and the economy-class genome
scans (genome genotyping) provided by companies such as 23AndMe?
4. If you were to have your DNA genotyped today, what is the source of DNA that you would
send to the company?
5. Know that as of today, you can send DNA and receive genetic information without
consulting with a physician. This may change in the future if regulatory agencies become
involved.
6. Be able to offer an explanation for why Francis Collins received contradictory information
about his risk for prostate cancer when he sent DNA to three different companies for
economy-class genotyping. Would this uncertainty go away if his compete DNA sequence
were analyzed instead?
7. Does having a variant allele associated with a disease always guarantee that you will get the
disease? What other factors can influence the disease state?
8. When James Watson had his DNA sequenced, there was one piece of information that he did
not want released to him. What was that allele and what disease is it associated with?
9. What is the difference between genetic associations being deterministic or being
probabilistic?
10. Is the most common form of Huntingtons disease caused by a gain-of-function or loss-offunction allele? Explain mechanistically how the mutant allele causes the disease?
11. Explain what is meant by the phrase, the burden of knowing.

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12. Having a mutant form of BRCA1 is a strong risk factor for what diseases? If you knew you
had the mutant allele are there any interventions that might minimize your risks of
contracting the diseases? If so, what are they?
13. What is an actionable gene? Note that this should really be what is an actionable allele?
Why is the term allele a better descriptor than gene in this case?
14. The science of pharmacogenetics is based on the observation that many people respond to
life saving drugs in different ways. How might pharmacogenetics be enhanced by wholegenome characterization?
15. The little boy in the video (Andrew Schmitz) with the rare medical condition characterized
by strokes had his whole genome sequenced. What are the physicians looking for and what
is their strategy for finding it?
16. Cystic Fibrosis is caused by a loss-of-function mutation in a single gene. What happens at
the molecular level to individuals who are homozygous for the mutant allele that causes the
symptoms of the disease? Be sure to describe the problems with the salt transporter, beating
cilia, mucus, and chronic infections.
17. What is the mechanism of action for the drug, Kalydeco, that should help SOME patients
with CF deal with the disease?
18. What is the connection between sequencing the genome of melanoma cancer cells and
looking for an effective treatment for the disease? What is the BRAF connection?
19. In the video, the BRAF inhibitor was a very effective treatment for some types of melanoma
cancers. Unfortunately, many times the cancer returns. How might whole-genome
sequencing solve this problem?
20. How does Preimplantation Genetic Diagnosis (PGD) work and how could it be used to
reduce the incidence of a specific disease in the population?
21. Explain the concern over PGD and its possible relationship to eugenics.
22. Many scientists believe that the ethical concerns about engineering a population of genetic
elite are far in our future. What is it about the traits of intelligence and physical ability that
are responsible for this belief?
23. In the video, the twins Alexis and Noah Beery were mis-diagnosed with cerebral palsy.
What did whole-genome DNA sequencing reveal to be the real cause of their disorders?
24. One concern of whole-genome sequencing/genotyping is privacy and who may have access
to this information. Are the concerns about discrimination in terms of insurance coverage
legitimate? What laws are currently on the books to support this concern?
25. Describe genomic hacking.

Class 1.5: Genomes and Gene Distributions

Terms:
Transcriptome, proteome, interactome, linkage maps, restriction maps, restriction enzymes,
single nucleotide polymorphisms, restriction-fragment length polymorphisms, haplotype, C
value, morphological complexity, non-repetitive DNA, moderately repetitive DNA, highly
repetitive DNA, transposon, zoo blot, cDNA, non-mendelian inheritance, organelles,
mitochondrial genome, chloroplast genome, endosymbiosis, genome sequencing, proteinencoding genes, archaea, synthetic life.

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Concepts:
1. Know the relationship between genome, transcriptome, proteome, and interactome.
2. Understand how linkage maps are derived using classical transmission genetics.
3. Know how restriction and sequence maps are different from linkage maps in terms of
resolutionthe precise relationship between the map and physical distance on the
chromosome.
4. Understand that most polymorphisms are found in DNA sequence outside of coding
information.
5. Understand how gel electrophoresis is used to display DNA polymorphisms.
6. Understand how polymorphisms can be mapped and followed through a pedigree.
7. Understand how polymorphisms are used to map disease genes.
8. Understand the relationship between C value and morphological complexity.
9. Know the three types of repetitive sequences found in the eukaryotes.
10. Understand how the movement of transposable elements within an organism can be a
driving force for evolution and the creation of new species.
11. Understand the concept of the ORF and how it is used to evaluate genome organization and
the number of protein-encoding genes.
12. Understand how a zoo blot may be an important analysis for identifying conserved exons
and important genes within a genome.
13. Understand the relationship between non-Mendelian inheritance and genes localized to the
DNA found in organelles.
14. Have a basic understanding of the mitochondrial and chloroplast genomes and how they
relate to bacterial genomes.
15. Know that not all proteins found in mitochondria and chloroplasts come from the DNA
found in the organelles. Where do the other proteins found there come from, and how do
they get into the organelles.
16. Understand the concept of endosymbiosis and how it relates to the possible origin of
mitochondria and chloroplasts.
17. Have a basic understanding of the information that can currently be obtained from genomic
sequencing and what some of the limitations are.
18. Have a basic idea of the number of genes it takes to make a obligate parasite, free living
bacteria, unicellular eukaryote, multicellular eukaryote, and an animal or plant with complex
tissue/organ systems.
19. Know that in eukaryotic genomes there may not be a direct correlation between genome size
and morphological complexity.
20. Know that most genomes are represented in mega bases of DNA.
21. Appreciate the importance of obligate parasite genomes and the generation of synthetic life.

Class 1.6: Genome Organization: Clusters and Repeats

Terms:
Model organisms, yeasts, C. elegans, Drosophila, Arabadopsis, desert regions in the genome,
proteome, core proteome, gene families, interactome, ortholog, homolog, essential genes,

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housekeeping genes, luxury genes, genetic redundancy, synthetic lethal, RNA abundance and
complexity, SAGE, HDA oligonucleotide arrays, deep sequencing, tandem duplications, unequal
crossing over, globin genes, thalassemias, rDNA transcription units, translocations, satellite
DNA, constitutive heterochromatin, centromeres, cconsensus sequence.
Concepts:
1. Have an idea of the comparative sizes of representative and model organisms' genomes
(bacteria, yeast, C. elegans, D. melanogaster, mammals, A. thaliana).
2. Know the size of the human genome in Mb and in number of genes.
3. Understand how the human genome breaks down in terms of repetitive DNA, introns,
exons, etc.
4. Understand the general trend relating genome size, number of gene families, and organism
complexity.
5. Know the difference between ortholog and homolog.
6. Understand why it would be important to understand the interactomedefining how
proteins interact during different circumstances.
7. Understand the concept of essential genes and redundancy.
8. Know how one can test for redundancy in an essential function.
9. Understand the concept of expressed genes and the transcriptome.
10. Understand the relationship between abundance and RNA complexity.
11. Know the difference of housekeeping genes and luxury genes and their relationship to RNA
complexity
12. Understand how a DNA microarray is performed to examine profiles of expressed genes
under a defined set of circumstances.
13. Know how deep sequencing technologies are being used to directly sequence cDNA pools.
14. Understand the relationship between tandem duplications and the generation of gene
clusters.
15. Know two mechanisms in which tandemly duplicated genes can be moved to different
chromosomes.
16. Understand how unequal crossing over can expand or shrink the number of genes in a
cluster. Know how this relates to the globin genes and Thalassemia diseases.
17. Understand the general organization of highly repetitive DNA.
18. Know how gene duplications can lead to the evolution of novel protein functions in an
organism.
19. Know how globin genes are differentially expressed during development.
20. Know that not all tandem repeats will diverge: Understand the role of selection in the
process.
21. Understand the types of satellite DNA in mammals and the concept of how it evolved from a
short nucleotide sequence.
22. Understand how some satellite sequences are used as polymorphic markers in a DNA
fingerprint.

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Class 1.7: Genome Evolution and Packaging
Terms:
Molecular clocks, synonymous mutation, non-synonymous mutation, introns early hypothsis,
introns late hypothesis, exon shuffling, green fluorescent protein (GFP) exon trapping, C-value
paradox, extracellular domain, transmembrane domain, polyploidization, autopolyploidy,
allopolyploidy, transposable elements, retrotransposons, capsids, nucleoid, nucleoid loop
domains, metaphase chromosome, chromatin, euchromatin, constitutive heterochromatin,
facultative heterochromatin, G-banding, karyotype, centromere, cohesion proteins, spindle
microtubules, kinetochore, chromatids, CEN fragments, CDE-I, CDE-II, CDE-III, Cse4 protein,
Cbf1 protein, CDE complex, telomere, t-loop, TRF2 protein, telomerase complex, TLC1 RNA,
EST2 protein.
Concepts:
1. Understand how the amino acid sequences of orthologs are used to establish a molecular
clock for species divergence; know the difference between synonymous and nonsynonymous mutations.
2. Know the difference between the introns early and introns late hypotheses for the origin
of interrupted genes. Which hypothesis is favored at this time/
3. Understand the relationship between exon shuffling and exon trapping with GFP.
4. Understand the relationship between the evolution of larger eukaryotic genomes and the Cvalue paradox.
5. Know that as organisms trend toward complexity there is a dramatic increase in proteins
with transmembrane and extracellular domains.
6. Understand the relationship between protein domains, protein subfunctions, and the added
complexity of the human proteome. Be familiar with the ways that new exons can be added
to the genetic information of existing proteins.
7. Understand the contribution that whole genome duplications have made to the evolution and
C-vale of some species like flowering plants or ray fishes. Know the difference between
autopolyploidy and allopolyploidy.
8. Be familiar with the role of transposable elements (DNA elements and retrotransposons) in
the evolution of complex genomes. Know about the mechanisms (RNA interference and
DNA methylations) that are used by cells to silence transposable elements.
9. Be familiar with the ways that the genomes of some types of viruses are packaged into
capsids.
10. Know how bacterial chromosomes are packaged.
11. Know the difference between euchromatin and heterochromatin.
12. Know the difference between constitutive and facultative heterochromatin.
13. Know the relationship between chromosome banding and karyotypes.
14. Understand how cohesions and microtubules are involved in separating chromosomes during
mitosis or meiosis.
15. Know the general structure of a yeast centromere and how it acts to recruit the spindle
microtubules.
16. Understand the structure of CEN fragments in yeast and how the CDE sequences associate
with specific proteins to make the centromere and kinetchore.
17. Know the general characteristics of telomeres.

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18. Be familiar with the structure of telomeres in terms of DNA sequence and formation of tloops.
19. Know how telomeres shorten during subsequent rounds of DNA replication and cell division
and why this causes normal cells to have a limited lifespan.
20. Be familiar with the composition of the telomerase system and how it works to prevent
telomere shortening.
21. Know what types of cells have a telomerase system and why it is an active area of current
research.

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