Deck 18: Genomics: Genetics From a Whole-Genome Perspective

Question 1

When authors discuss whole genome-wide examination of genes,to what do they refer?

A)protein expression patterns
B)patterns of protein immunoprecipitation
C)RNA sampling techniques
D)comparison of conserved sequences
E)use of DNA microarrays

Answer 1

E

Question 2

It has been predicted that genes may be involved in smoking initiation and/or current smoking behavior.Previously,large twin and family studies have provided evidence of this and an estimate of heritability (genetic contribution)of 37-55% for initiation and 46-59% for current smoking,depending on gender.A large group of researchers from several institutions composed a pathway-or-systems-based series of studies including SNP analysis,cellular location and protein interaction,replication with other samples,statistical analysis,and bioinformatics.What is a likely result?

A)The study is unlikely to produce meaningful results because it is too diffuse in its methods.
B)The samples used also correlate with behaviors like depression,often associated with smoking,and they may be finding depression-associated genes.
C)Two specific genes,one for a transporter protein and one for an opioid receptor,are clearly shown to be causative in all members of each sample.
D)A group of genes that tend to code for proteins with similar biological function have been identified to contribute significantly.
E)Genome-wide association studies are of no practical use in studying human behaviors.

Answer 2

D

Question 3

Which of the following describes genome tiling arrays?

A)use of any DNA microchips
B)use of any RNA microchips
C)use of several microchips that together contain all sequences of a genome
D)use of an entire series of SNP comparisons,including at least one per chromosome
E)use of high-throughput technology

Answer 3

C

Question 4

A significant polymorphic inversion on chromosome 17,the MAPT inversion,is identified by marker SNPs that can now be used to screen large numbers in a population.The inverted region is large and extends for approximately 900 kb.The two haplotypes (one inverted and one not)are each associated with increased risk of a number of neurological conditions.How can the inverted region be used to find the most recent common ancestor of the inversion?

A)by typing SNPs from humans and from other primates
B)by assessing SNPs from a large number of human populations
C)by looking for heterozygotes for the two kinds of chromosome 17
D)by fertility studies on populations with each of the haplotypes
E)by using a BAC clone library to identify the ends of the inversion

Question 5

In an experiment designed to analyze the mRNAs present in a cell at a given time in the life cycle,it was found that about 50% of the mRNAs are of one type,less than 20% represent 8 other mRNAs,and the rest consist of several thousand different mRNAs.What does this information indicate?

A)Only the mRNA expressed at the highest level is of any importance to this cell type.
B)The pattern of expression of the low-level mRNAs is what makes the cell type unique.
C)The low-level expressed genes are from organelles.
D)Those genes expressed at low level are likely to be "housekeeping" genes found in many cell types.
E)The genes most specific to this cell type and life stage are the 8 found at an intermediate level.

Question 6

The splicing regulatory protein (SR)identifies exons to be included in mRNA.How might SR proteins regulate alternative splicing?

A)There are alternative binding regions for these proteins within each exon.
B)There are alternative SR proteins in different tissues at different stages of development.
C)The SR proteins lose the ability to bind to exon splice suppressors.
D)The SR proteins recruit the splicing small RNAs (U1,U2,…)or unusual ones.
E)The spliceosome complex can bind only to regions with bound SR proteins.

Question 7

When Warnecke and colleagues were looking for genes that are involved in the digestion of lignocellulose by termites,they needed genes

A)from the sequences of the termite genome.
B)of the primary strain of bacteria that inhabit the termites' bodies.
C)for the bacterial enzymes found in the lignocellulose-digesting part of the gut.
D)for the long-term maintenance of lignin-digesting microbial organisms.
E)that can be expressed in a lignocellulose-rich environment.

Question 8

Which of the following would likely exclude a sequence from being considered as an active gene?

A)a promoter with signals identical to the promoter of another gene
B)exons in different reading frames from one another
C)an exon followed by 3′ processing signals
D)only one exon with an in-frame stop codon
E)introns missing the GT-AG splice junctions appropriate for this gene

Question 9

A report of a newly identified syndrome in families of the Old Order Amish showed that the lethal condition that resulted from numerous,multisystem abnormalities is inherited as an autosomal recessive.SNP-based mapping showed that a portion of a region on chromosome 6p,namely the ICK gene (intestinal cell kinase),was homozygous in all autopsied patients but heterozygous in normal members of the affected families.The mutation seems so far to be specific only to the Amish.Which of the following would be a reasonable next step in studying this mutation?

A)sequencing to identify the abnormality in the ICK gene
B)use of a microarray to see whether the gene is expressed in heterozygotes
C)kinase activity assays in adult affected members of the families
D)development of a gene-based test for assessing carrier risk
E)development of a gene-based test for prenatal diagnosis

Question 10

Subtelomeres are blocks of homologous DNA sequences close to the ends of chromosomes.In a worldwide population of humans,when sequences of chromosomes 4q and 10q subtelomeres were analyzed only 17 4q and 8 10q haplotypes were found among African,European,and Asian groups.Which of the following might be among the results or conclusions of this analysis?

A)finding that few or no interchromosomal exchanges can occur among these chromosomes
B)a conclusion that all haplotypes were present before the human population migrated from Africa
C)reporting that haplotype polymorphism shows no response to natural selection
D)finding greater than 80% variation between homologous ends of chromosomes in humans
E)a conclusion that assigning chromosomal origin of repeat arrays by using specific restriction enzymes is possible only in a population with the same ethnic origin

Question 11

Celiac disease (CD)is a common,usually inherited human disorder of intestinal inflammation that is triggered by eating gluten,a major protein in wheat and other cereal grains.It is the most frequent food intolerance.One of the three genes involved is for SH2B3,a protein involved in innate,nonspecific immune response to bacterial pathogens.Celiac sufferers frequently have a particular allele of this gene.It is so common that which of the following might be hypothesized?

A)The gene must be common to all primate genomes.
B)The gene must be common in most mammalian genomes.
C)The allele must have been positively selected for during a period of especially frequent bacterial infections.
D)The wild-type allele must have been selected against during periods of frequent bacterial infections.
E)The gene must code for a T-cell receptor for a common bacterial component.

Question 12

What is the purpose of the two-hybrid system?

A)to study the nature of two hybrid organisms at a time
B)to study the interaction between an enhancer and a promoter
C)to explore a cDNA library to find interacting DNA sequences
D)to discover how and whether two proteins interact
E)to locate the chromosomal position of hybridized genes

Question 13

In looking for a gene responsible for albinism in humans,a group of researchers decided that at least one form of this condition was due to a lack of the enzyme tyrosinase.With this decision as a starting point,which of the following series of steps was most feasible?

A)Sequence the amino acids of the protein,use rabbits to make an antibody to the protein,purify and fluorescently label the protein,and hybridize the antibody to a cDNA library.
B)Sequence the protein,use the code table to figure out the best RNA sequence for it,synthesize the RNA,and use the RNA as a probe in cells from albino individuals.
C)Radioactively tag the enzyme and use it as a probe to identify the biochemical reaction in which it functions,work out the metabolic pathway involved,and find cells in albinos that cannot carry out these reactions.
D)Sequence the protein,work out the cDNA that codes for it,label the cDNA code,and use a FISH study to localize the gene on a karyotype.
E)Sequence the appropriate region from albino and non-albino cells and compare the sequences or do subtractive hybridization to see where there is a deletion.

Question 14

To study the maximum amount of genome diversity in the human species,which of the following provides the most information?

A)karyotyping
B)SNP variation
C)DNA fingerprinting
D)sequencing of one or more specific genes
E)ortholog comparisons

Question 15

In the 2009 article "Genomic Footprints of a Cryptic Plastic Endosymbiosis in Diatoms" (Science 324: 1724-26),Moustafa et al.described their search for possible gene transfer from organelles to the nucleus in diatom genomes.They assumed that diatomic plastids came from red algae.However,they found that most were from green algae.Which is most likely?

A)Diatoms once had green algal endosymbionts.
B)Red algae had green algal endosymbionts.
C)Red plastids were replaced by green plastids.
D)Cyanobacteria imported green plastid genes.
E)All red algal genes mutated to green algal genes.

Question 16

Although whole-genome duplications that result in polyploidy are fairly common in plant species,which of the following are common in other eukaryotes?

A)duplication of whole chromosome arms
B)segmental duplications of small gene regions
C)deletion of an entire haploid set of chromosomes
D)whole chromosome loss
E)miscellaneous aneuploidies in living members of a species

Question 17

Scientists studying the causes of a type of progressive hearing loss known as otosclerosis want to identify the genetic contribution to the disorder.By which of the following are they most likely to find a causative gene or genes?

A)a genome-wide association study with a large number of SNPs,using pooled DNA samples
B)genome-wide linkage analysis studies of families whose members have otosclerosis
C)a candidate gene case-control association study with genes known to be involved in ear development
D)comparison of gene expression among otosclerosis patients
E)allelic heterogeneity studies for a gene expected to be involved

Question 18

Transcomplementation is a name sometimes given for a test to see whether a gene from one organism can "rescue" a loss-of-function mutant of a different organism with a homologous gene.To which of the following processes might this term apply?

A)replacement of a nonfunctional globin gene with a globin pseudogene
B)substitution of a drought-resistant gene from potato plants with a drought-resistant gene from a cactus species
C)introduction of a human WEE1 gene into a yeast culture with wee1- mutants
D)replacement of a cdc25- with a cdc13+ gene to rescue a cell cycle dysfunction
E)use of Drosophila heat shock gene promoters to regulate heat shock genes in fugu

Question 19

Recombination between two Alu elements results in deletions.In humans these have often been associated with specific disorders.In a recent study,researchers compared Alu recombination-mediated deletions of humans and chimpanzees.They identified 492 human-specific deletions of this type.Why is this finding important?

A)It shows that humans are not as genetically close to chimpanzees as researchers previously thought.
B)It shows how much the chimpanzee genome has changed since the divergence of these two lineages.
C)It shows that the time of divergence of the two lineages is much older than was previously thought.
D)It shows that more deletions have occurred in humans than in chimps.
E)It demonstrates the importance of Alu recombination in shaping genome divergence.

Question 20

Which of the following defines the essential gene set of an organism such as a species of yeast?

A)genes that,when mutated,reduce the growth of a heterozygous organism
B)genes whose deletion alleles are not found among haploid offspring
C)the fewest genes that,when mutated,result in slow growth in optimal environments
D)genes whose mutations result in haploinsufficiency
E)genes that,when mutated,are either lethal or conditionally lethal in special environments

Question 21

Species whose ancestors might once have been free living may now be present as parasites.Would their genomes now tend to be larger,smaller,or approximately the same in size and complexity?

Question 22

Suppose that you have been able to partially sequence a significant number of cDNA clones from an as yet unsequenced insect genome.These clones are useful as what sequences that can help annotation?

Question 23

In humans,a large number of genes associated with immune function share sequence similarity and are evolutionarily related.These would be known as what kind of group?

Question 24

The karyotypes of several primate species,such as chimpanzee and gorilla,show two nearly telocentric chromosomes as opposed to the single large metacentric chromosome 2 in humans.Does this demonstrate chromosome breakage or fusion at the time of lineage divergence?

Question 25

An Alu sequence is a kind of retrotransposon,and approximately 1.4 million of them are found in the human genome.As they move about in the genome,they generate mutation by what mechanism?

Question 26

Genes can be assigned,relatively speaking,to the categories "essential" and "nonessential." In the identification of essential genes,a transposon can be inserted into a gene to inactivate it.The gene would then be identified as essential if the inactivation results in what?

Question 27

Conserved noncoding sequences (CNGs)are usually sequences involved in what kinds of functions?

Question 28

Suppose a geneticist sequences a specific gene region in two species,A and B,previously known to be closely related.He specifically wants to see which of the two species is closer to an ancestral species.The sequence comparison showed that this region in species B has an extra intron,unlike other near relatives,but that otherwise A and B are virtually the same for this region.Based on this data alone,he could reason that which species was more likely ancestral?

Question 29

Interspecific genome studies show us conserved sequences,but intraspecific comparisons identify what?

Question 30

Mammalian genomes all have a number of genes for globin polypeptides.Several of these genes are functional,but several are never expressed.What are the nonfunctional ones known as?

Question 31

A researcher has produced groups of contigs that are linked via paired end sequences,although these include some sequence gaps.What are these groups called?

Question 32

The BLAST program from NIH enables a researcher to look for homologous genes.It does so in general by searching for identity in what property?

Question 33

In a simple bioinformatics exercise,students are asked to locate the beginning of an ORF among the six possible reading frames for a hypothetical DNA molecule.The first step in their process should involve looking for what sequence?

Question 34

An inherited human disorder,familial dysautonomia,results from a nucleotide mutation in the gene IKAP that is expressed in the nervous system.The decreased IKAP protein leads to abnormal development,and the resulting disease is usually fatal by age 30.The nucleotide change alters splicing.If this change affects only the nervous system and not the immune system,in which the gene is also expressed,what feature must be found in this gene?

Question 35

Often,in the absence of experimental data,computerized algorithms are used to predict gene structures from large sequences.What is this approach known as?

Question 36

If a gene product is not a protein but a noncoding RNA,the sequence might be initially hypothesized from comparative genomics but must be confirmed how?

Question 37

Suppose that you use the sequence of the lacI gene,whose function you know is to encode a transcription factor,to find similar sequences in another bacterial strain.Are you more likely to find similar operons or similar transcription factors?

Question 38

In 2000,when then President Clinton along with Francis Collins of the Human Genome Project and Craig Venter of Celera announced the completion of a "draft" of the human genome,the event did not,in fact,represent true completion because most of what type of sequences were not included?

Question 39

A gene in a sheep-like species has been found to differ from that in related species by the inclusion of a variable number of tandem repeats of a short sequence.These repeats or duplications arise from what process?

Question 40

Very many related genes can be recognized by conserved protein domains.To what gene structures do these domains correlate?

Question 41

You are interested in sequencing the gene for Tangier disease (OMIM 205404).The disorder is rare,so it is feasible to obtain only very few samples.The approximate chromosomal location of the gene is known.How would you set about deciding on a model organism to use to study this disease,and what would you do once you had decided? (An outline of your procedure after the organism is chosen will be sufficient).

Question 42

If an entire genome is fragmented and then a large number of pieces are sequenced,the approach is known as the ________ approach.

Question 43

Under what circumstances is a metagenomic analysis preferable to analysis of a gene or genes from a single species?

Question 44

Now that small molecular-level deletions and subtle chromosomal rearrangements can be discovered using advanced cytogenetic techniques and microarrays,disorders whose causes had not previously been known can have their basis identified.However,since most of these are not widely publicized,being individually rare,it has been difficult to identify patients with shared chromosomal abnormalities who share phenotypic features.A new database,known as DECIPHER,is now available to search for patients with like phenotypes and/or like chromosomal abnormalities.If you are the clinical geneticist who has a patient whose data is entered into this database,suggest three or more ways in which this could be useful either to you or to the patient.

Question 45

The process of finding the location of genes and functional (e.g.,regulatory)sequences and their functions within a genome sequence is called ________.

Question 46

The whole-genome shotgun approach (WGS)was first used on which eukaryotic model organism?

Question 47

How and why is the two-hybrid system used to find where two proteins interact? Use a real example.

Question 48

Being able to do a BLAST search,among other things,assumes that you and every other researcher has access to known gene sequences.Some would prefer,however,that such sequence information should be "owned" by their discoverers.What are the pros and cons of such a position?

Question 49

Sequencing of DNA from a community of organisms rather than from a single individual is known as ________.

Question 50

A genome sequence is considered to be complete when all its ________ sequences are included,as well as reasonable amounts of repetitive sequences.