Combined Genetics HMX

QQ: A population can be defined as individuals who have a common characteristic, such as ____________. (Select all that apply.) 1. geography 2. ancestry 3. culture 4. Society

1. geography 2. ancestry 3. culture 4. Society

Mitochondrial disease (which stems from variations in mitochondrial DNA and nuclear DNA) affects 1 in _____________ people

5,000

_________________ _____________ elicit unintended physiological responses outside of the intended purpose of the drug

Off-target effects

________________ promotes the formation of blood vessels which can promote tumor growth by increasing the supply of oxygen and nutrients delivered to the tumor from the blood

VEGF (vascular endothelial growth factor)

Between treatment and control groups in the traditional approach of treatment, there can be variability between groups where some groups respond favorably and others do not. Few even have adverse reactions. This could be because of differences in __________________, ___________________ or ___________________

genetics environment lifestyle

If the length of the repeat continues to increase across generations, then this will __(increase/decrease)__ severity of symptoms

increase

Fragile X is an X-linked dominant condition, and DNA methylation of the pathogenic allele is the same in males and females. However, the phenotypes of the disease are often more severe in males than females. Which of the following explanations is most likely? 1. Females are mosaics for the FMR1 gene due to X-inactivation. 2. The FMR1 gene has an important mitochondrial function. 3. The FMR1 gene is imprinted in females but not males. 4. The FMR1 gene is imprinted in males but not females.

1. Females are mosaics for the FMR1 gene due to X-inactivation.

Variants in an individual's DNA sequence: 1. can be identified by comparing the aligned sequence reads to the reference genome. 2. will be found on all of an individual's sequence reads that span the variant. 3. are easier to identify as sequencing coverage decreases. 4. are usually pathogenic in nature.

1. can be identified by comparing the aligned sequence reads to the reference genome.

Within the mitochondrial matrix exists the mitochondrial genome. On average, there are about ____ copies of the mitochondrial genome

5

______________________ adds an acetyl group to an area on the histone. If we add this group to K9 on H3, then we __________________ transcription

Acetylation promote

_______________ factors and _________________ histone modifications leads to active genes which promotes transcription

Activating activating

_________________________ is the increase of symptom severity across generations

Anticipation

_______________________ is the cytological description of the inactive X, which appears as a small, highly condensed structure in the nucleus

Barr body

CRISPR uses the _____________ protein (which has nuclease properties so it can cut DNA), and ______________ _________ (which associates with the protein and determines where in the genome that the complex binds).

CAS9 guide RNA

Researchers are interested in repairing the CFTR variants at the DNA level using genome editing. Name one of the genome editing tools mentioned in this lesson that could be used for this purpose.

CRISPR

In addition to histone modification, ___________ __________________ can occur. This is when methyl groups are added directly to cytosine bases in the DNA sequence which acts as a silencing mark

DNA methylation

______________________ __________________ is caused by unstable GAA repeats in the FXN gene. These repeats occur in an ____________, so they do not occur in a protein coding region and therefore cannot effect protein function. However, they effect transcription efficiency. So as the length of the intron increases, the time to _______________ increases, so the RNA polymerase is more likely to fall off. This means that longer repeats lead to __(increased/decreased)__ levels of FXN mRNA, which ultimately causes the disease. Less than 33 repeats is the _____________ range 34-43 repeats is the _________________ range 44-65 repeats is the _____________________ range 66+ repeats is the _______________________ range

Friedreich ataxia intron transcribe decreased benign intermediate premutation mutation

______________________ _____ ____________________ is an important phenomenon within epigenetics. It states that the environment may influence epigenetic changes. The only way to study this is by following _______________ that are exposed to conditions of interest

Nutrition and disease cohorts

_____________________ looks at one gene and how it relates to pharmacology

Pharmacogenetics

_____________________ looks at many genes and the environment and how they relate to pharmacology

Pharmacogenomics

______________________________ optimizes drug treatments with genomic data. This includes maximizing efficiency of the treatment and minimizing harmful side effects

Pharmacogenomics

______________ ______________ is a blood vessel that carries blood from the GI system and other organs to the liver

Portal vein

________________________ approach to treatments involves a collection of extensive data on genetics, environment and lifestyle to tailor preventions and interventions to the individual

Precision

____________ is a tumor suppressor gene that encodes a protein important for mitochondrial production of energy. Loss of this gene's function results in increase growth of blood vessels, which can promote tumor growth. The SDHB protein is part of the succinate dehydrogenase enzyme (SDH)

SDHB

_________________________ approach to treatments involves a clinical trial with a group of affected individuals. Some receive the treatment and others receive a control. We evaluate if the treatment, on average, improves the outcome of the treatment group.

Traditional

_____________ ________________ (which are repeats of codons in a genetic sequence) are prone to errors in DNA replication and repair, which causes expansion and contraction of repeats. Increasing the length can lead to increased risk of disease phenotypes

Unstable repeats

The process of X-inactivation occurs independently in each cell in the developing embryo. This means that females are effectively ____________ for the X chromosome, meaning that different cells in their body effectively have different genotypes.

X mosaics

Females are ______ _________________, which means that some cells have the maternal X chromosome expressed and others have the paternal X chromosome expressed because of random inactivation. This is important when considering _____-________________ _________________ because if some cells express the maternal X and others express the paternal X then some cells will be affected and others will be unaffected (whereas males only express one X and therefore would be affected if their mother is affected). This means females can be __________________ ____________________

X mosaics X-linked diseases manifesting carriers

___________________________ produces equal expression of X-linked genes in males and females. This means that one of two X copies in females is silenced to bring down the expression of those genes to the level of the single X in males

X-inactivation

___________ is a proto-oncogene that encodes a signaling protein called a receptor tyrosine kinase. This protein transmits extracellular signals to activate pathways that promote growth and survival of the cell.

c-KIT

Unstable repeats can cause disease because the codons that are repeated code for an amino acid. Repeating these amino acids over and over along a sequence can affect the net ______________. This can cause amino acid sequences to be more ____________ and thus cause them to aggregate

charge sticky

After fertilization, any histone modifications and DNA methylation is reset so the chromosomes are unmodified. After this, random inactivation occurs where random chromosomes in random cells can be ____________________. The paternal and maternal chromosomes have an ________________________ ________________. This center has a gene called __________ which is transcribed to mRNA, but not translated to protein. This RNA binds specifically to the chromosome that produced it, leading to silencing of that chromosome. There is a _____________________ mechanism in this system so once one of the chromosome starts expressing the gene, it will produce more and more of it.

inactivated X-inactivation centers xist feedback

IGF2 encodes a growth factor. The larger IGF2, the __(larger/smaller)__ the baby is at birth. Both sperm and egg have imprinting centers downstream of the IGF2 gene. In the _________________ copy, the center is methylated, whereas in the ________________ copy, the center is unmethylated. This means that in the maternal copy, a protein can bind to the imprinting center which prevents the enhancer from acting upstream of it. this means the IGF2 gene is turned __(on/off)__ in the maternal copy. In the _________________ copy, the methylation on the imprinting center silences a downstream gene which allows the enhancer to act farther upstream on IGF2 and __(increase/decrease)__ transcription of the gene.

larger paternal maternal off paternal increase

Mitochondrial disease is caused by __(gain/loss)__ of function (which can cause tissue failure because they won't have the energy needed to function) and is __(multisystem/single system)__ (effects a number of different systems in the body)

loss multisystem

Whole genome sequencing occurs by first collecting cells, then ____________ them to collect genomic DNA. This DNA is processed and produces a _______________ ______________. The genomic DNA is ____________________ into a smaller pieces. This library undergoes __________________ __________________ ________________ which is when each fragment is sequenced at the same time. This produces millions of different sequences called ________________ _____________ (the A, T, C and Gs) which each span a different short segment of the genome. A _______________ ________________ is used to align our sequencing reads. This is a difficult step because of the _________________ sequences, like in the centromeres and telomeres, which make it challenging to align our reads. Because of this repetition, there can be _______________ between reads, which means we can have multiple sequences that span the same region. The number of reads that span a particular region of the genome is called the _________________. The more coverage you have, the __(more/less)__ reliably you'll be able to identify variation at a particular region. This variant identification allows us to extrapolate the individual's genome sequence

lysing genomic library fragmented massively parallel sequencing sequence reads reference genome repetitive overlap coverage more

Both protein core and DNA can be chemically modified via ______________________ and __________________, which alters the chromatin environment and thus influences gene expression.

methylation acetylation

The inactive chromosome, after X-inactivation, tends to have more DNA __________________, _________________ histone modification and ___________________ factors. The active chromosome has less DNA ________________ and more __________________ histone modifications

methylation repressive silencing methylation active

In mitochondrial replacement therapy, the vast majority of the child's DNA will come from the mothers __________________ DNA, and a small portion will come from the donors ___________________ DNA (which does not contain the pathogenic variant). This allows the children to inherit DNA from three sources: the father's nuclear DNA, the mother's nuclear DNA and the donor's mitochondrial DNA

nuclear mitochondrial

The precision approach uses _____________, which are comprehensive studies that study a particular field, and ________________ which take physiologic measurements, like activity level blood sugar level, heart activity, etc.

omics werables

A pharmacological genetic trait can be caused by _________ gene (Mendelian) or it can be caused by ________ genes with the combination of the environment (complex)

one many

A ________________________ is a group of people who can be defined by a common characteristic

population

The nucleosome has a ___________ core consisting of _____ histone proteins, which have a globular core and tails. The tails are part of the protein and therefore are composed of amino acids (i.e. lysine). The nucleosome also has _______ which is wrapped around the core

protein 8 DNA

A cellular ____________ can cause a single gene to switch back and forth between active and silenced genes. This signal is executed by ______________ ________________

signal chromatin modifiers

Problems with CRISPR include ________________ (instead of cutting at your region of interest, CAS9 might cut off-target in other regions in the genome, creasing new undesirable variants), _______________ (CAS9, guide RNA and DNA of interest for repair are all required to enter the cell you would like to edit. They can be delivered via __________________ or by inserting DNA encoding CAS9 and guide RNA into the cell and allowing the cells transcription and translation machinery to produce them. This is done by _______________ or ____________________)

specificity delivery microinjection transfection transduction

There are many challenges and important considerations in treating CF patients by using genome editing to repair the variant in their lung epithelial cells. Identify the statement below that does NOT describe an important consideration in using this type of approach. 1. Genome editing will affect the germline and may have consequences for the next generation. 2. Delivering the genome editing machinery to the necessary tissues can be difficult. 3. Off-target effects of the genome editing can increase risk of other problems. 4. Getting the genome editing machinery into cells can be difficult.

1. Genome editing will affect the germline and may have consequences for the next generation.

Which of the following statements about CRISPR are true? (select two answers) 1. The Cas9 protein can cut DNA but requires a guide RNA complementary to the region of interest. 2. The Cas9 protein is solely responsible for identifying and cutting DNA at the desired region. 3. Researchers designed and created the CRISPR machinery for genome editing. 4. CRISPR was discovered in bacteria where it acts as an immune response.

1. The Cas9 protein can cut DNA but requires a guide RNA complementary to the region of interest. 4. CRISPR was discovered in bacteria where it acts as an immune response.

In rare cases, Fragile X syndrome can be caused by DNA sequence changes other than the expansion of the CGG repeats at FMR1. Based on what you know about the cause of the disease, which of the following types of variation might be pathogenic and cause Fragile X syndrome? (select two answers) 1. a missense variant in FMR1 that abolishes protein activity 2. a regulatory variant that leads to overexpression of FMR1 3. a duplication of FMR1 4. a deletion of FMR1

1. a missense variant in FMR1 that abolishes protein activity 4. a deletion of FMR1

A ____________ is a set of short DNA fragments that will be subjected to massively parallel sequencing in order to produce ____________, which are the DNA sequences of those fragments. 1. genomic library; sequence reads 2. sequence reads; genomic library 3. genomic DNA; sequence reads 4. genomic DNA; genomic library

1. genomic library; sequence reads

The characteristics that can define a population include: 1. 2. 3. 4.

1. geography 2. ancestry 3. society 4. culture

Hemophilia A is a condition characterized by an inability of the blood to clot, which can cause profuse bleeding even after a minor injury. It is often caused by recessive pathogenic variants in the X-linked FVIII gene, which encodes factor VIII, a protein produced in the liver and released into the bloodstream to facilitate blood clotting. There are many possible pathogenic variants in the FVIII gene, which reduce the function or level of factor VIII. In some cases, females can be manifesting carriers of this disorder, which means that ____________ individuals ____________. 1. heterozygous; may have defective blood clotting 2. homozygous; may have defective blood clotting 3. heterozygous; all have normal blood clotting 4. homozygous; all have normal blood clotting

1. heterozygous; may have defective blood clotting

Leigh syndrome, a mitochondrial disease that typically manifests in the first year of life and includes the signs and symptoms such as neurological decay or decline, hypotonia, movement disorders and increases risk of hypertrophic cardiomyopathy, can be caused by many different pathogenic genetic variants that interfere with mitochondrial function. Variants that interfere with mitochondrial function can be found ____________. 1. in the mitochondrial genome or the nuclear genome 2. only in the mitochondrial genome 3. only in the nuclear genome

1. in the mitochondrial genome or the nuclear genome

Using the traditional approach to identifying and evaluating interventions, a treatment would be considered effective if there were no dangerous side effects and: 1. the individuals in given the treatment on average responded better than the individuals in the control group. 2. all the individuals given the treatment responded better than all the individuals in the control group. 3. most of the individuals in the treatment group responded favorably. 4. all the individuals given the treatment responded favorably.

1. the individuals in given the treatment on average responded better than the individuals in the control group.

These questions are focused on the pharmacogenetics of warfarin dosing. Warfarin is a blood thinner used preventatively in individuals with conditions that put them at a high risk of blood clotting, such as atrial fibrillation, and as a treatment for individuals with acute problems with blood clotting, such as deep vein thrombosis or pulmonary embolism. It is particularly important to ensure that the levels of the drug remain in the therapeutic range, because too low a dose will be ineffective, and too high a dose can lead to bleeding. Environmental factors can also play a role in determining warfarin dosing. VKORC1 requires a cofactor called vitamin K to form active blood clotting factors, so increasing levels of vitamin K in the body leads to increased production of blood clotting factors. Leafy greens, such as kale and spinach, are rich in vitamin K. If someone on a consistent therapeutic dose of warfarin who typically does not eat a lot of leafy greens suddenly eats a giant kale salad, which of the following statements are true? 1. She is not at risk of any warfarin related side effects. 2. She is at increased risk of blood clotting. 3. She is at increased risk of bleeding.

2. She is at increased risk of blood clotting.

QQ: Which of the following populations is likely to have the the lowest level of shared genetic history? 1. a group of individuals who recently moved from the same region of Eastern Europe who now live in diverse locations 2. a community comprised of recent immigrants from diverse locations 3. a group of individuals living in the same region of Western Africa 4. a tight-knit religious community that tends to intermarry

2. a community comprised of recent immigrants from diverse locations

Leigh syndrome has several modes of inheritance and is incompletely penetrant and has variable expressivity, so it is possible for an individual to be affected with mild signs and symptoms, yet have children with a more severe form of the disease. Which of the following individuals would be at risk of having a child affected by Leigh syndrome? Leigh disease is rare, so assume in all cases that the individual's partner carries no pathogenic variants related to Leigh disease. (select all that apply) 1. a mildly affected female homozygous for a pathogenic autosomal recessive variant 2. a mildly affected female homozygous for a pathogenic X-linked recessive variant 3. a mildly affected female with a pathogenic mitochondrial variant 4. a mildly affected male with a pathogenic mitochondrial variant

2. a mildly affected female homozygous for a pathogenic X-linked recessive variant 3. a mildly affected female with a pathogenic mitochondrial variant

The current version of the reference genome (select two answers) 1. has a comprehensive set of sequence and variation and no longer needs to be updated. 2. allows aligned sequences to be compared across different studies. 3. is a sequence corresponding to a single individual. 4. includes common sequence variation.

2. allows aligned sequences to be compared across different studies. 4. includes common sequence variation.

Liver cells expressing normal amounts of functional factor VIII in a manifesting carrier would have extensive ___________ on the copy of the chromosome encoding the pathogenic FVIII allele. (select all that apply) 1. transcription of the FVIII gene 2. chromatin compaction 3. DNA methylation 4. Xist binding

2. chromatin compaction 3. DNA methylation 4. Xist binding

Normally the FMR1 locus does not have DNA methylation in the gene or promoter region. However, copies of the FMR1 gene with mutation length CGG repeats are modified; they have DNA methylation extending into the promoter region. This leads to ____________ expression of that copy of the FMR1 gene. 1. no change in 2. decreased 3. increased

2. decreased

These questions are focused on the pharmacogenetics of warfarin dosing. Warfarin is a blood thinner used preventatively in individuals with conditions that put them at a high risk of blood clotting, such as atrial fibrillation, and as a treatment for individuals with acute problems with blood clotting, such as deep vein thrombosis or pulmonary embolism. It is particularly important to ensure that the levels of the drug remain in the therapeutic range, because too low a dose will be ineffective, and too high a dose can lead to bleeding. Allan, who is African American, is being prescribed warfarin because of his atrial fibrillation. His doctor orders variant-specific testing for the CYP2C9*2 and the CYP2C9*3 alleles, and finds that he has neither. This means that: 1. he has no variants in the CYP2C9 gene that lower warfarin metabolism but might in other genes. 2. he could have variants in CYP2C9 or other genes that lower warfarin metabolism. 3. he has no variants that decrease warfarin metabolism. 4. he can safely be given a standard dose of warfarin.

2. he could have variants in CYP2C9 or other genes that lower warfarin metabolism.

These questions focus on the genetics of Beckwith-Wiedemann syndrome and Russell-Silver syndrome. Beckwith-Wiedemann syndrome is characterized by high birth weight, rapid growth, and increased risk of certain cancers; Russell-Silver Syndrome is characterized by low birth weight, slow growth, and developmental delay. Both Beckwith-Wiedemann and Russell-Silver syndrome are associated with the locus on chromosome 11 that includes IGF2 and another gene called H19. This region includes an enhancer downstream of H19 and an imprinting center between the two genes. When the imprinting center is not imprinted, it acts as an insulator, meaning that it prevents the enhancer from activating the upstream genes, including IGF2, though the enhancer can activate transcription of H19, which is downstream. However, when this region is imprinted, meaning that the imprinting center is modified with DNA methylation, this affects the H19 promoter, leading to the silencing of H19. It also removes the insulator activity, allowing the enhancer to act on upstream genes; this leads to activation of IGF2. Normally, this region is imprinted in the sperm, but not the egg. This means that the DNA on the ____________ copy of the chromosome will be methylated at the imprinting center, while the DNA on the ____________copy of the chromosome will not be methylated in this region. 1. maternal; paternal 2. paternal; maternal

2. paternal; maternal

An individual is going to have her genome sequenced with the goal of identifying all of her protein coding variants. All of the following approaches would help to maximize the sequence coverage of the regions necessary to make these identifications, EXCEPT 1. decreasing the portion of the genome sequenced to only the protein coding regions. 2. performing whole genome sequencing instead of whole exome sequencing. 3. using a sequencing protocol that produces longer reads. 4. using a sequencing protocol that produces more reads.

2. performing whole genome sequencing instead of whole exome sequencing.

The F508del protein normally does not make it to the cell membrane due to its misfolding. However, if misfolding can be alleviated by a drug treatment, the protein does reach the membrane, but still is not fully stable and active. As a result, a combination therapy of two drugs can be more effective than a single drug alone. Which of the drugs below could be used in combination to treat this type of CF? (select two answers) Potentiator treatments increase the chloride transport activity of the CFTR channel at the membrane of the cell. Read-through treatments increase the ability of the translational machinery to read-through stop codons. Corrector treatments promote correct folding of proteins. Class I variants: No full length CFTR protein produced Class II variants: Misfolded CFTR protein produced Class III variants: CFTR protein produced; but transport activity reduced 1. read-through drug 2. potentiator drug 3. corrector drug

2. potentiator drug 3. corrector drug

Individuals with premutation length repeats in FMR1 may have some of the phenotypes of Fragile X but not others, which is _____________; for example, some individuals may have cognitive deficiencies, while others might have late onset ataxia. In addition, some individuals will have no phenotypes of the condition at all, due to ____________. 1. incomplete penetrance; variable expressivity 2. variable expressivity; incomplete penetrance 3. complete penetrance; variable expressivity 4. variable expressivity; complete penetrance

2. variable expressivity; incomplete penetrance

The most common Class II variant is the F508del variant, which is missing the 508th amino acid in the protein but has an otherwise normal sequence. Loss of this amino acid leads to misfolding of the protein, and the misfolded protein is not properly transported to the membrane. Based on this information, how many nucleotides are deleted in the CFTR allele encoding this variant? Enter your answer in numeric form.

3

DM1 is caused by an unstable CTG repeat in the DMPK gene. This repeat is downstream of the stop codon in the mRNA transcript, thus it is in the ____________, and will affect ____________ sequence. 1. coding region; mRNA, but not protein 2. coding region; mRNA and protein 3. 3' UTR; mRNA, but not protein 4. 5' UTR; mRNA, but not protein 5. 3' UTR; mRNA and protein 6. 5' UTR; mRNA and protein

3. 3' UTR; mRNA, but not protein

____________ is an example of a genomic sequencing approach, while ____________ is an example of genotyping. 1. Genome sequencing; exome sequencing 2. A gene panel; genome sequencing 3. Exome sequencing; a gene panel 4. A SNP microarray; a gene panel

3. Exome sequencing; a gene panel

Which of the following best describes the mechanism of dosage compensation in humans that ensures that males and females have the same expression levels of X-linked genes? 1. Expression of both copies of X-linked genes are decreased two-fold in females. 2. No mechanism is necessary; they naturally have the same expression levels. 3. Expression of one copy of each X-linked gene is silenced in females. 4. Expression of X-linked genes are increased two-fold in males.

3. Expression of one copy of each X-linked gene is silenced in females.

These questions are focused on the pharmacogenetics of warfarin dosing. Warfarin is a blood thinner used preventatively in individuals with conditions that put them at a high risk of blood clotting, such as atrial fibrillation, and as a treatment for individuals with acute problems with blood clotting, such as deep vein thrombosis or pulmonary embolism. It is particularly important to ensure that the levels of the drug remain in the therapeutic range, because too low a dose will be ineffective, and too high a dose can lead to bleeding. The rates of warfarin metabolism by the protein encoded by the different CYP2C9 alleles vary. The warfarin metabolism rate of the proteins encoded by CYP2C9*2 and the CYP2C9*3 alleles are decreased 30-40% and 80-90%, respectively, compared to the common version of the protein, encoded by CYP2C9*1. Below, the genotype of five individuals at the CYP2C9 gene are shown, with both alleles indicated. Which of the following individuals would need the lowest dose of warfarin to maintain warfarin levels in the therapeutic range? 1. Individual 1: CYP2C9*1 / CYP2C9*1 2. Individual 2: CYP2C9*2 / CYP2C9*2 3. Individual 3: CYP2C9*3 / CYP2C9*3 4. Individual 4: CYP2C9*2 / CYP2C9*3 5. Individual 5: CYP2C9*1 / CYP2C9*3

3. Individual 3: CYP2C9*3 / CYP2C9*3

This assessment will focus on Fragile X syndrome. Fragile X syndrome is a developmental neurological disorder characterized by cognitive impairment and an array of other developmental problems. Fragile X syndrome is caused by a pathogenic variant in the FMR1 gene, and is a highly penetrant X-linked dominant condition. Based on what you know about Fragile X syndrome so far, which of the following statements are true of a female who has one premutation allele of FMR1? (select two answers) 1. She may have affected children, but only if her partner also has a premutation allele. 2. She will not be affected if her other copy of FMR1 has a shorter repeat length. 3. She may or may not be affected with some of the phenotypes of Fragile X. 4. She may have affected children.

3. She may or may not be affected with some of the phenotypes of Fragile X. 4. She may have affected children.

Which of the following individuals has a risk of having a child with Leigh syndrome that could be alleviated by mitochondrial replacement therapy? 1. a mildly affected female homozygous for a pathogenic autosomal recessive variant 2. a mildly affected female homozygous for a pathogenic X-linked recessive variant 3. a mildly affected female with a pathogenic mitochondrial variant 4. a mildly affected male with a pathogenic mitochondrial variant

3. a mildly affected female with a pathogenic mitochondrial variant

These questions are focused on the pharmacogenetics of warfarin dosing. Warfarin is a blood thinner used preventatively in individuals with conditions that put them at a high risk of blood clotting, such as atrial fibrillation, and as a treatment for individuals with acute problems with blood clotting, such as deep vein thrombosis or pulmonary embolism. It is particularly important to ensure that the levels of the drug remain in the therapeutic range, because too low a dose will be ineffective, and too high a dose can lead to bleeding. Warfarin acts by inhibiting the activity of the VKORC1 protein, which helps to produce functional clotting factors. There is a variant in the VKORC1 gene that lowers the dose of warfarin required for treatment, and individuals with this variant have increased risk of bleeding when they are treated with warfarin. This variant is found 1639 base pairs upstream of the translational start site. This variant likely: 1. decreases the activity of the VKORC1 protein. 2. increases the activity of the VKORC1 protein. 3. decreases expression of the VKORC1 gene. 4. increases expression of the VKORC1 gene.

3. decreases expression of the VKORC1 gene.

Different cell types and tissues express different sets of genes; for example, some genes are expressed primarily in the heart, others primarily in the brain, and still others primarily in the liver. This is possible because all of these cell types have ____________. 1. different sequence variants that control gene expression 2. different ordering of genes on chromosomes 3. different histone and DNA modifications 4. different sets of genes

3. different histone and DNA modifications

Insulin is an important hormone that regulates glucose levels in the blood. The insulin protein is encoded by the INS gene, which is expressed primarily by the β-islet cells of the pancreas. These cells produce the insulin protein and secrete it into the bloodstream. Other cells in the pancreas do not produce insulin. If you examined the chromatin in the regulatory region of the INS gene in different cell types, you would expect to observe ____________ in the β-islet cells and ____________ in the other pancreatic cells. 1. DNA methylation; histone H3K9 methylation 2. histone H3K9 methylation; histone H3K4 methylation 3. histone H3K4 methylation; DNA methylation 4. histone H3K4 methylation; histone H3K9 acetylation

3. histone H3K4 methylation; DNA methylation

Leigh syndrome is considered a multisystem disease because ____________. 1. it is caused by variants in the mitochondrial genome 2. it can be caused by multiple different variants 3. it affects multiple tissues and organs 4. it has multiple inheritance patterns

3. it affects multiple tissues and organs

While researchers try to improve molecular treatments for CF, it is possible to improve a patient's health in other ways by treating specific symptoms. Individuals with CF can often contract respiratory infections that can negatively impact their lung health; they are particularly susceptible to infections with particular types of bacteria and fungi. Researchers are conducting comprehensive ____________ studies to characterize the different species present in the respiratory systems of individuals with CF. 1. transcriptomic 2. metabolomic 3. microbiomic 4. genomic

3. microbiomic

These questions focus on the genetics of Beckwith-Wiedemann syndrome and Russell-Silver syndrome. Beckwith-Wiedemann syndrome is characterized by high birth weight, rapid growth, and increased risk of certain cancers; Russell-Silver Syndrome is characterized by low birth weight, slow growth, and developmental delay. Both Beckwith-Wiedemann and Russell-Silver syndrome are associated with the locus on chromosome 11 that includes IGF2 and another gene called H19. This region includes an enhancer downstream of H19 and an imprinting center between the two genes. When the imprinting center is not imprinted, it acts as an insulator, meaning that it prevents the enhancer from activating the upstream genes, including IGF2, though the enhancer can activate transcription of H19, which is downstream. However, when this region is imprinted, meaning that the imprinting center is modified with DNA methylation, this affects the H19 promoter, leading to the silencing of H19. It also removes the insulator activity, allowing the enhancer to act on upstream genes; this leads to activation of IGF2. Given this information, which of the following statements best describes IGF2 gene expression? 1. Both copies of IGF2 are activated and produce similar amounts of IGF2 mRNA. 2. Both copies of IGF2 are silenced and neither produces IGF2 mRNA. 3. The maternal copy of IGF2 produces most of the IGF2 mRNA. 4. The paternal copy of IGF2 produces most of the IGF2 mRNA.

4. The paternal copy of IGF2 produces most of the IGF2 mRNA.

Efficient genome editing requires all of the following, EXCEPT 1. a system to deliver the editing components into cells. 2. machinery to cut the genome at the site of interest. 3. a DNA fragment encoding a sequence change. 4. a pathogenic variant to repair.

4. a pathogenic variant to repair.

β-islet cells always express the INS gene to some degree, but after a large meal, glucose levels in the blood rise and increased levels of insulin are required to stimulate cells to take up this glucose and convert it into energy. Which of the following events is likely to occur at the regulatory region of INS in response to increases in glucose in the blood stream? 1. decreased levels of H3K4 methylation 2. increased levels of DNA methylation 3. binding of repressive proteins 4. binding of activating proteins

4. binding of activating proteins

Individuals with Beckwith-Wiedemann have an above-average risk of developing certain types of cancers. This is because there is ____________ expression of IGF2, which is ____________. 1. decreased; a tumor suppressor gene 2. increased; a tumor suppressor gene 3. decreased; an oncogene 4. increased; an oncogene

4. increased; an oncogene

These questions are focused on the pharmacogenetics of warfarin dosing. Warfarin is a blood thinner used preventatively in individuals with conditions that put them at a high risk of blood clotting, such as atrial fibrillation, and as a treatment for individuals with acute problems with blood clotting, such as deep vein thrombosis or pulmonary embolism. It is particularly important to ensure that the levels of the drug remain in the therapeutic range, because too low a dose will be ineffective, and too high a dose can lead to bleeding. Warfarin is metabolized by the CYP2C9 protein. The common allele of this gene is CYP2C9*1, and an individual with two copies of this allele metabolizes warfarin at a rate that is typical of most people. The CYP2C9*2 and CYP2C9*3 alleles are also present in European populations. Each variant allele produces CYP2C9 proteins with a single amino acid change. These changes to the DNA sequence can be described as ____________ variants. 1. frameshift 2. regulatory 3. nonsense 4. missense 5. silent

4. missense

Genes encode enzymes that are involved in the metabolism of drugs. For example, _____________ encodes a liver enzyme that is important for breaking down many types of drugs. Knowing the __________________ of someone can allow us to adjust the dosage of drugs accordingly or determine if we should avoid taking a certain drug

CYP2D6 genotype

__________ __________________, _________________ factors and ________________________ histone modifications leads to silenced genes which inhibits transcription

DNA methylation silencing repressive

_____________________ is a reference to a genetic syndrome caused by a specific deletion chromosome 22 (q refers to the long arm and 11 refers to the position of that arm), and which is characterized by heart defects, a cleft palate and distinctive facial features as well as a large range of other complications

Deletion 22q11

___________________ is anything heritable that is not directly coded in the DNA sequence

Epigenetics

Many different types of studies are used in precision medicine. The descriptions below list examples of the type of data that might be collected. Select the correct study type (epigenomics, genomics, metabolimics, microbiomics, proteomics, transcriptomics, wearables) for each description given in the table below. 1. Assessing DNA methylation patterns in a cancer cell 2. Identifying the gut bacteria present in an individual 3. Monitoring heart activity continously using a portable electrocardiogram device 4. Identifying a disease variant using whole-exome sequencing 5. Measuring global mRNA levels in a tissue sample taken from a healthy lung 6. Measuring biochemical byproducts excreted in urine that can serve as indicators of kidney cancer 7. Identifying proteins that are specifically found in sperm cells

Epigenomics Microbiomics Wearables Genomics Transcriptomics Metabolomics Proteomics

___________________ _________________ can be performed by cutting the genome at a specific site to allow repair with a different sequence. We can cut a genome at a specific site with ________________ __________________ __________________ (which are proteins that bind and cut specific DNA sequences), ________________ (which mimic plant transcription factors so they can bind DNA and cut it at specific sequences) or __________________ (which is the leading approach to genome editing)

Genome editing zinc finger nucleases TALENs CRISPR

__________________________ _______________________ is the specific silencing of the paternally or maternally inherited copy of a gene. The regions that can escape the reset of chromatin modifications and DNA methylation marks 5 days after fertilization, and instead hold on to the modifications that they were originally given are _____________ ___________________

Genomic imprinting imprinting centers

________________________ is a dense region of chromatin which are usually silenced. These are characterized by repressive histone modifications, binding of silencing factors and a condensed chromatin structure

Heterochromatin

________________________ disease is caused by unstable CAG repeats in the HTT gene. Less than 26 repeats is the ________________ range 27-35 repeats is the ____________________ range, where you are likely to be asymptomatic and where you might pass on a pathogenic allele 36-40 repeats is the _____________________ range, where you are likely to develop the disease, but it is not fully penetrant 40+ repeats is the __________________ range, where you are pretty certain to develop the disease (about 100% penetrance)

Huntington Benign Intermediate Premutation Mutation

________________, also called Gleevec, targets some receptor tyrosine kinases and is often highly effective in treating GIST with c-KIT driver mutations

Imatinib

_________________________ adds a methyl group on an area on the histone. If we add this group to K4 (lysine 4) on the tail of H3 (histone 3), then we _________________ transcription. If we add this group on K9 on H3, then we _____________________ transcription

Methylation promote silence

_________________ has its own genome and is maternally inherited

Mitochondria

___________________ _________________ _______________ uses a donor egg (which has its own mitochondria, but no nucleus). The nucleus of the mother can be transferred into the donor egg right before or after in vitro fertilization

Mitochondrial replacement therapy

The ____________________ ____________________ is the 3-D structure that organizes DNA. The basic unit of organization in this environment is the _______________________, which is composed of protein and DNA

chromatin environment nucleosome

Mitochondrial DNA is __(circular/linear)__, _____ kB and has ____ protein coding genes

circular 17 14

In an active gene, if we change gene function/expression to make it silenced, then there would be no change in DNA sequence. If this change is heritable, then it is a ____________________ change

epigenetic

_______________________ is the study of an individual's genome sequence _______________________ is a characterization of our chromatin structure, including DNA methylation, histone modification, etc. ________________________ is a measurement of RNA levels ________________________ is a measurement of protein levels ________________________ studies the different metabolites in our bodies ________________________ studies all of the microbes that live in our gut and other parts of our bodies

genomics epigenomics transcriptomics proteomics metabolomics microbiomics

Because mitochondrial DNA is maternally inherited, the probability of inheriting a mitochondrial disease is __(higher/lower)__ if the mother has it than if the father has it

higher

Methylation and acetylation add their specific groups to different areas on the histone. This is called ___________________ __________________

histone modification

If someone is affected with a condition and they take a drug to treat the condition, they will take a dose of that drug which will _____________ over time and break down until it is ultimately removed from the body. _____________ ____________ are designed to provide a set dose of specific time intervals to improve the exposure of the drug. However, the ________________ rate of the drug can vary between people. This means that the drug regimen has to be tailored to the individual.

metabolize Drug regimens metabolism