AK

Which statement regarding sequencing technologies is correct?

A) The cost for sequencing has dropped much faster than the cost for computer chips in the last 20 years

B) Illumina machine sequence single DNA molecules via nanopores

C) The recently published Cancer Genome Atlas contains genomes of ~ 100 million cancer patients

D) The Human Genome Project was finished earlier due to the development of Illumina sequencing

E) The current cost for sequencing one million basepairs is ~0.05 $

Which statement regarding genomes is NOT correct?

A) Over 50% of the human genome is annotated as repeat and most of these are transposable

elements

B) The number of protein-coding genes varies approximately by an of magnitude among vertebrates

C) ~30 Mbp code for proteins in the human genome

D) Humans have ~20000 protein-coding genes

E) The onion has a genome that is ~5-times larger than the human genome

Which statements regarding alleles, their frequencies and their fixation is NOT correct?

A) B) An allele at 100% frequency is called “fixed” in the population

Mutation, Selection, Drift, Recombination and Geneflow are regarded as the five big evolutionary

forces changing allele frequencies.

C) If a new neutral allele emerges by a mutation in diploid population with an effective size of 2

individuals, the chance that this new allele will eventually get fixed is 25%

D) An allele with a selection coefficient of s = 0 is said to evolve neutrally

E) If a diploid population doubles in size, new neutral alleles are expected to fox twice as often

What is NOT true for alleles that evolve under negative selection?

A) They decrease the fitness of its carrier

B) Compared to neutral alleles, they are less likely to get fixed in a population

C) When the (effective) population size gets smaller they are more likely to get fixed in a population

D) They are less often polymorphic than neutral allele neutral alleles

E) By definition they mutate less often

Which statements regarding the comparison of DNA sequences among species is NOT correct?

A) When comparing sequence conservation across mammals, introns are more conserved per

basepair than exons since they encode more enhancers

B) Using more species increases the power/resolution to detect sequences conserved in these

species

C) The largest fraction of functional sequence in the human genome does not encode proteins

D) Zoonomia is a comparative genomic project that recently analyzed sequence conservation using over 200 mammals

E) The phyloP score is a measure of sequence conservation

Which statements regarding the Ka/Ks ratio are correct?

1) Since Ks is assumed to approximate the neutral mutation rate, a Ka/Ks higher than one indicates positive selection on the protein sequence

2) Ka/Ks is also known as dN/dS or omega

3) There are more non-synonymous sites in a coding region than synonymous sites

4) Ka is higher than Ks since there are more non-synonymous sites than synonymous sites

5)All third codon positions are four-fold degenerate sites

A) Only 3 and 4 are correct

B) Only 1, 2 and 3 are correct

C) Only 2, 3 and 4 are correct

D) Only 2, 3 and 5 are correct

E) Only 1, 2, 3 and 4 are correct

7.Which statements regarding the allele frequency spectrum shown below are correct?

1) The derived allele frequency must be smaller than 1 and larger than zero

2) For all four classes of sites more than 60% of the alleles have an allele frequency less than 10%

3) The “Zerofold degenerate sites” class is skewed more towards rare alleles than the other three classes of sites

4) The “Zerofold degenerate sites” class is skewed more towards common alleles than the other three classes of sites

5) As the four classes of sites are spread throughout the genome, they are affected similarly by demographic factors like population bottlenecks or population splits

A) None is correct

B) Only 1 is correct

C) Only 2 and 4 are correct

D) Only 3 and 5 are correct

E) Only 1, 2 and 3 and 5 are correct

8.Which statements regarding gene regulation is true?

A) A transcription factor is a cis-regulatory element

B) Euakryotic transcription actors have on average longer DNA binding motifs than prokaryotic transcription factors

C) Reducing the diameter of a sphere by a factor of 10, reduces the volume of the sphere by a factor of 100

D) The concentration of human transcription factors in the nucleus are so high that ~99% of their (accessible) consensus binding sites are expected to be found given their dissociation constants

E)The motif GTATATGCAA has an information content of 20 bit (assuming 50% GC content)

9.Which statement regarding transcription factors encoded in the human genome is NOT true?

A) There are ~1600 manually curated transcription factors in the human genome

B) A position weight matrix of a transcription factor is always at least as long as its binding motif

C) By definition a transcription factor activates transcription

D) JASPAR and TRANSFAC are databases of transcription factor binding motifs

E) Almost 50% of transcription factors are C2H2 Zinkfingers that are involved in repressing transposable elements

10.Which statements regarding human promoters are true?

1)CAGE is a method that crosslinks DNA to detect chromosome loops by sequencing

2)The promoter is a cis-element of gene regulation

3)Many genes have alternative protomers and there is good evidence that most of them are not functionally relevant (i.e. adaptive)

4) Sigma Factors are important transcription factors for eukaryotic transcription initiation

5)The FANTOM consortium used CAGE to annotate human and mouse promoters

A) None is true

B) Only 2 is true

C) Only 1 and 2 are true

D) Only 2, 3 and 5 are true

E) All are true

11.Which statement regarding mammalian enhancers is NOT true?

A) An enhancer usually binds only one transcription factor

B) Enhancer assays in mice are often done in E11.5 embryos since at this stage the whole embryo can be imaged

C) Deletion of one enhancer often does not lead to a phenotype in mice

D) Many conserved non-coding elements show enhancer activity in a mouse assay

E) To detect enhancer activity in cells, one can measure the activity of a reporter gene under a minimal promoter in the presence and absence of the putative enhancer

12.Which statement regarding methods to identify regulatory region regulatory regions in human cells is NOT correct?

A) ChIP-seq requires the isolation of chromatin

B) Massively parallel reporter assays (MPRAs) use combinations of different luciferases to read out enhancer activity in parallel

C) Many enhancers produce short lived RNA (eRNA) that can be used to identify enhancers

D) Chromatin accessibility as assessed by ATAC-seq is associated with active enhancers

E) A problem of annotating human enhancers is that there is no gold standard assay that has enough throughput to characterize the hundreds of thousands of enhancers in the hundreds of different cell

types

13.Which statement regarding methods to identify regulatory regions in human cells is NOT correct?

A) Hi-C is a method that can identify topologically associated domains (TADs)

B) With a Hi-C experiment one can determine whether two DNA regions in the nucleus are closer to each other than expected

C) Hi-C identifies transcription factors bound to chromatin

D) ATAC-seq uses a transposase o cut and add oligonucleotides in regions of open chromatin

E) Bisulfite is a chemical that converts non-methylated Cytosine to Uracil

14 Which statement regarding the ENCODE project is correct?

A) It is the major project to determine driver mutations in cancer

B)It proved that >80% of the human genome is junk

C) It’s a consortium effort generating data e.g. on genetic variation, gene expression and chromatin modifications in different human cell lines

D) It determined essentially all functional element in the human genome

E) It determined histone modifications in all ~200 cell types of the human body

15 Consider the hidden Markov model sketched below. It models the transition from an exon (E) to a 5’ splice site (5) to an intron (I) for a given DNA. Which statement regarding this model is NOT

correct?

A) The model has three hidden states: exon, 5’ splice site and intron

B) The transition probability from a 5’ splice site to an intron is 100%

C) The probability that the 5’ splice is a G is 95%

D) The 5’ splice site is one base long as the transition probability to the intron is 100%

E) The model has four hidden states: the bases A, G, C and T

16. Which statement regarding human mutation is correct?

A) Most mutation in the human genome have negative effects, i.e. lead to a reduction in offspring number

B) The mutation rate is larger than zero probably because organisms need to adapt during evolution

C) Oxidation converts Cytosine to Uracil

D) A mutation from A to G is a transition

E) CpGs have a higher mutation rate since there are three hydrogen bonds in a CG basepair

17 Which statement regarding mutations rates in humans is NOT correct?

A) New insertions of Alu and L1 elements do not occur in genomes of currently living humans

B) Transitions have a higher mutation rate than transversions

C) CpG dinucleotides have a higher mutation rate than GpC dinucleotides

D) The mutation rate (per generation and locus) for CpG dinucleotides is expected to be higher than for non-CpG dinucleotides only if the CpG dinucleotide is methylated in the germ line

E) Microsatellites are loci with a high rate of insertions and deletions

18 Which statement regarding (human) mutations rates (point mutations per bp and generation) is NOT

correct?

A) Females have higher mutation rates than males

B) Estimating mutation rates from species comparisons requires fossil calibration points

C) When estimating the mutation rates phylogenetically from regions that evolve under purifying selection,

the mutation rate gets underestimated

D) Approximately 20-100 point mutations are found in a child that are not found in the parents

E) Mutation rates differ among species and are lower in species with a higher effective population size

19. What the approximate average mutation rate for point mutations per basepair and generation in the human genome?

A) 1-2x10^-2

B) 1-2x10^-4

C) 1-2x10^-6

D) 1-2x10^-8

E) 1-2x10^-10

20. A SNP with an A and a T allele is found homozygous for A in 81%, homozygous for T in 1% and heterozygous in 18% of 1000 human DNA samples. The minor allele frequency is then …

A) 1%

B) 9%

C) 10%

D) 18%

E) 81%

21. Which statement regarding DNA polymorphisms in the human genome are correct?

1) Neutral polymorphisms do not change their allele frequencies

2) Before an allele can fix in a population it must be polymorphic

3) SNPs are the most abundant type of DNA polymorphism in humans

4) The higher the mutation rate, the larger the amount of polymorphisms

5) Most SNPs in humans are evolving under positive selection since it is unlikely for a SNP to reach highfrequencies just by chance

A) Only 2 and 3 are correct

B) Only 1, 2 and 3 are correct

C) Only 2, 3 and 4 are correct

D) Only 2, 4 and 5 are correct

E) All are correct

22 Which statement is NOT correct for the shown genealogies of DNA sequences?

A) Compared to the genealogy a, the genealogy b will result in a stronger skew of rare allele in the allele frequency spectrum

B) Genealogy a is more congruent with a constant population size while genealogy b is more congruent with a population expansion after a bottleneck

C) In genealogy b almost all SNPs would be unique to one DNA sample, i.e. all SNPs would have an allele frequency of 1/5

D) The two genealogies are expected to have the same allele frequency spectrum

E) In both genealogies 5 DNA sequences have been sampled

23. Which statement regarding the effect of recombination on genetic diversity is FALSE?

A) Recombination increases the number of haplotypes present in the population

B) More recombination leads to more linkage disequilibrium

C) Recombination that affects genetic diversity in a population just happens in the germline

D) The recombination rate is measured in centimorgan per basepair

E) The average recombination rate in the human genome is ~1cM/Mbp

24. How many different haplotypes are theoretically possible for five bi-allelic SNPs?

A) 5

B) 10

C) 16

D) 24

E) 32

25 This figure displays linkage disequilibrium (LD) for a part of the human genome collected by the HapMap consortium for two datasets. Which statements are correct?

1) There is more LD in the left dataset than in the right dataset

2) CEU and YRI refer to populations of European and African ancestry, respectively

3) Dark colour indicates low LD, white colour indicates high LD

4) Between the start and the end of the shown DNA sequence is substantial LD in both data sets

5) There are over 100 SNPs typed in this DNA stretch

A) Only 1, 2 and 3 are correct

B) Only 1, 2 and 5 are correct

C) Only 1, 3 and 4 are correct

D) Only 2, 3 and 4 are correct

E) Only 2, 4 and 5 are correct

26. Which statement regarding mapping of human diseases variants is NOT true?

A)Heritability is a fraction of the total phenotypical variation

B) If a genetic variant is completely positively correlated with a monogenic disease, this can be considered as proof that this is the causative variant

C) If the penetrance if a monogenic allele decreases, the (statistical) power to find it also decreases

D) Linkage analysis requires pedigree data

E) If a phenotype is measured with more technical noise, the heritability of the phenotype decreases

27. Which statement regarding Linkage analysis are correct?

1) Y-linked Mendelian diseases do not exist as Mendelian diseases affect by definition always males and females

2) In an X-linked recessive Mendelian disease more males than females are affected

3) In an X-linked dominant Mendelian disease more males than females are affected

4) A gene causing a sporadic disorder (i.e. is due to de novo mutations) cannot be mapped by linkage

analysis

5) Linkage analysis was more important for the identification of Mendelian diseases genes before next generation sequencing became available

A) None are correct

B) Only 2 is correct

C) Only 3 and 4 are correct

D) Only 2, 4 and 5 are correct

E) All are correct

28. An autosomal recessive disease occurs at frequency of 1:40000 in a population. Which conclusion can be drawn?

A) Since two diseases allele are required for a recessive Mendelian disorder to manifest, the frequency of

all disease alleles is (1:40000)2

B) There is only one disease allele segregating in the population

C) The frequency of the disease will likely be different in males and females

D) The expected frequency of all causative alleles in this population is 0.5%

E) Before the disease gene is not known, it is not possible to draw any conclusion

29. In the context of linkage analysis, the “LOD score” is an important term. Which statement is NOT correct?

A) A LOD score of three means that it is three times more likely that two markers are linked than that they are not linked

B) A LOD score of three is considered as a genome-wide significance threshold for linkage

C) The LOD score is calculated for a given recombination rate

D) The higher the LOD score the higher the likelihood that two loci are linked

E) LOD is short for logarithm of the odds

30. Which statement regarding the identification of causative mutations/disease genes in human monogenic diseases is correct?

A) Causative mutations in regulatory regions are more difficult to identify than causative mutations in coding regions

B) Silent mutations are as likely to be causative as missense mutations

C) Causative mutations in regulatory regions are well-identifiable by whole exome sequencing

D) Non-sense mediated decay is an experimental method to determine whether a variant might be causative

E) A mutation with a frequency of 5% in the population can NOT be causative for an autosomal recessive disease that has a frequency of 0.1% in this population

31 Which statement regarding the identification of causative mutations/disease genes in human monogenic diseases are correct?

1) A non-sense mutation is a mutation generating a STOP codon

2) Causative mutations in regulatory regions are well-identifiable by whole exome sequencing

3) ClinVar is a database that stores information about clinically relevant genetic variants

4) SIFT and PolyPhen-2 are two databases that store information on known disease variants

5) OMIM is a central resource for clinicians to look up “actionable” clinical variants for precision medicine

A) None is correct

B) Only 1 and 3 are correct

C) Only 1 and 5 are correct

D) Only 2 and 4 are correct

E) Only 1, 2, 3 and 4 are correct

32 Which statement regarding the identification of Mendelian disease genes are correct?

1) For ~20% of all human genes a Mendelian disease phenotype is known

2) The Human Genome Sequencing boosted the identification of causative mutations for linkage Analyses as it allowed to identify the genes that are located in a mapped interval

3) For most of the human genes a Mendelian disease phenotype is known

4) gnomAD is a consortium to sequence patients with a Mendelian disease

5) gnomAD useful for identifying causative mutations for mutagenesis diseases as it allows to estimate he frequency of a particular mutation in different populations

A) Only 1 is correct

B) Only 3 is correct

C) Only 2 and 4 are correct

D) Only 1, 2 and 5 are correct

E) Only 2, 3, 4 and 5 are correct

33. Which statement regarding quantitative and complex traits in humans is NOT correct?

A) The heritability for a Mendelian inherited trait is usually close to 100%

B) Monogenic inheritance is the exception and polygenic inheritance is the rule for the most traits in most human and non-human populations

C) Inheritance of quantitative traits can be explained by Mendelian inheritance of many loci that contributeto the trait

D) A locus that doesn’t contain genetic variation within a population cannot be a QTL in this population

E) Quantitative traits need to be explained by Lamarckian, not Mendelian genetics

34. Which statement regarding the “heritability” of a trait is NOT correct?

A) Heritability is a ratio of two variances

B) Narrow Sense heritability is always equal or smaller than broad sense heritability

C) In a population of genetically identical individuals, heritability is zero

D) Heritability can be measured in a single individual

E) If you change the environment, heritability can also change

35. One genotypes 10 people with a particular disease that have a particular mutation (homozygous or heterozygous), 20 people without the disease that have the mutation (homozygous or heterozygous),100 people with the disease that do not have this mutation and 200 people without the disease that do

not have this mutation. The odds ratio for this mutation for getting the disease is:

A) -10

B) Zero

C) 1

D) 2

E) 10

36. Which statement regarding genome wide association studies (GWAS) is NOT correct?

A) Most SNPs that show a significant association with a trait in a GWAS study are not causative alleles for

this trait

B) The higher the frequency of a causative allele, the more likely it is detected in a GWAS

C) More tag SNPs are needed in regions of low linkage disequilibrium

D) GWAS studies become technically possible only due to next generation sequencing

E) If cases and controls have different proportions from two populations (e.g. European and African),many SNPs will show a significant association just because they differ in frequency among the two populations

37. Which statement regarding Genome Wide Association studies (GWAS) is NOT correct?

A) Correction for multiple testing is needed because so many individuals are tested

B) Correction for multiple testing is needed because so many loci are tested

C) Manhattan plots have the chromosomal positions of SNPs on the X-axis and their log-p value on the Y-

axis

D) Alleles that increase the odds ratio significantly for a disease, are usually also found in control

individuals

E) Imputation of SNPs refer to the statistical inference of SNPs that were not genotyped

38. 500 disease patients and 1000 controls have been genotyped for one SNP with two alleles A and C. Allele A occurs in a total of 250 chromosomes from the patients and 500 chromosomes from the

controls. Allele C occurs in a total of 750 chromosomes from the patients and 1500 chromosomes from the controls. Which statement is correct?

A) Since the C allele is three times more frequent in the patients than in the controls it has an odds ratio of

three

B) The odds ratio for this SNP is one

C) It is likely that the allele A is a risk variant for this disease

D) Since both the A and the C allele are two times more frequent in patients, the SNP has an odds ratio of 2

E) An odds ratio cannot be calculated from only one SNP

39. Which of these statements regarding cancer are correct?

1) The age-adjusted mortality of cancers as decreased by >70% since the seventies mainly due to personalized medicine

2) Carcinoma and cancer have identical meanings

3) A breast cancer is a carcinoma

4) Malignment tumors are called cancer

5) Liver cancer is the most frequent cancer in women

A) None is correct

B) Only 1 and 2 are correct

C) Only 1 and 4 are correct

D) Only 3 and 4 are correct

E) Only 3 and 5 are correct

40. In 2011 Hanahan and Weinberg added four features to the classical hallmarks of cancer. Which is NOT one of them?

A) P53 inactivation

B) Deregulated metabolism

C) Unstable DNAD) Inflammation

E) Evading the immune system

41. Which statement regarding cancer evolution are correct?

1) Most animal get cancer towards the end of their lifespan

2) Peto’s paradox describes the phenomenon that cancers of younger patients have more mutations than cancers of older patients

3) Recombination among the units of selection (individuals) does occur during the evolution of organisms, but it does not occur among the units of selection (cells) during the evolution of cancer

4) One estimates that almost 16 billion (16x109) cell division occur during the lifetime of a human

5) Species of different size and life expectancy evolve similar cancer susceptibility by adapting the number of cell divisions during their lifetime

A) None is correct

B) Only 2 is correct

C) Only 1 and 3 are correct

D) Only 1 and 5 are correct

E) Only 1, 2 and 4 are correct

42. Which statement regarding driver and passenger mutations are correct?

1) Driver mutations occur in oncogenes and passenger mutations occur in tumor suppressor genes

2) Driver mutations are frequent and passenger mutations are rare

3) Driver mutations occur by definition in driver genes

4) Driver mutations provide a selective advantage to cancer cells

5) Driver mutations are identified by observing them more often than expected across cancer samples

A) None is correct

B) Only 4 is correct

C) Only 2 and 5 are correct

D) Only 1 and 3 are correct

E) Only 3, 4 and 5 are correct

43. What is the main reason to sequence the genome or exome of a normal tissue (germline control) in addition to the cancer sample from a patient?

A) Because it allows to distinguish oncogenes from tumor suppressor genes

B) Because it allows to distinguish driver from passenger mutations

C) Because it allows to distinguish mutations that occurred in the cancer from mutations that were inherited

D) Because it allows to identify the inherited component of cancer in this patient

E) Because it allows to measure the patient-specific sequencing error rate

44. You sequence an autosomal gene by high-throughput sequencing from a cancer biopsy of a patient that is expected to contain largely cancer cells but also normal cells. You find that of 1000 reads

covering a particular site ~50% carry a mutation changing a conserved arginine to a histidine in the encoded protein. Which conclusion can be drawn?

A) It is likely a germline mutation

B) If the fraction of cancer cells is 100%, it cannot be a germline mutation

C) If the fraction of cancer cells is 50%, it is very likely a homozygous driver mutation

D) Since the frequency of the mutation is not 100%, it cannot be a germline mutation

E) The high frequency of this mutation among the reads is a strong indication that this is a driver mutation

45. Which statement regarding the identification of driver genes are correct?

1) Most mutations in a cancer sample are driver mutations

2) Mutations affecting the molecular function of a protein are usually driver mutations

3) The power to detect driver genes increases with an increasing number of patients

4) Driver genes listed in cancer genome papers are in most cases identified by a statistical enrichment of somatic mutation in patient samples of a particular cancer type

5) Driver genes listed in cancer genome papers are most cases experimentally validated by showing a growth advantage of their driver mutations in cell lines and/or mouse models

A) Only 3 and 4 are true

B) Only 3 and 5 are true

C) Only 1, 3 and 5 are true

D) Only 1, 2, 3 and 4 are true

E) Only 1, 2, 3 and 5 are true