Genetics Final

autosome

22 Paris of human chromosomes (1-22) code for structures and regulatory proteins

haploid

23 individual chromosomes

Diploid

23 pairs of chromosomes

What are CYP450 enzymes and what is their "job"? Know some examples of other (i.e. non-CYP) enzymes that metabolize drugs as well.

58 known CYP proteins metabolize about 60% of all Rxs o Controls how we metabolize 60% of drugs; slow, intermediate, extensive (NORMAL), or ultra-rapid o CYP3A = 50% of drugs; CCBs, benzos, statins, acetaminophen

aneuploid

more or fewer chromosomes for the species

null allele

non functional allele due to mutation

genomic nursing competencies

nurses must develop this. Will fail if all nurses are not on board due to how many nurses are in the workforce, competencies include knowledge, skills, and attitudes applied in practice

What is the up-and-coming next medication "right" to add to the current 6 rights?

o "Right drug for the right patient" has a whole new meaning

Alelle

Different forms of a gene

Heritability

The percent chance offspring of a carrier will also have the disorder

sex chromosome

XY, XX

oncongenes

cancer causing genes

Microarray

tests that looks for variations in DNA and RNA sequence

CRISP-Cas9

used to replace/repair DNA (genes) editing

genetic discrimination

"Discrimination faced by an asymptomatic individual who has a genetic mutation; excludes those with overt disease (discrimination on the basis of a disability) and no provisions for accomadation"

Der Yeshorim

"Grass roots" effort started by a rabbi who had several affected children Offers anonymous, voluntary screening of young Jewish people For TSD and other diseases common among Jews

Remember *3, *4, etc. symbols represent variants (most often SNPs but sometimes CNVs). Therefore, star nomenclature describes genotype that is associated with a particular phenotype, described as a metabolizer category (either poor, intermediate, extensive, ultrarapid). Be able to distinguish genotype and phenotype. What phenotype is represented by the *1 genotype for any CYP450 enzyme? What effect would a CNV in a CYP gene have on metabolism?

*2 and *3 = null allele, very poor metabolizers (loss-of-function) o Markedly decreased metabolism of: warfarin, diazepam, PPIs, propranolol, amitriptyline; required decrease in dosing to avoid toxicity o *17 increases expression; may need increased dose

Finally, pay close attention to the two slides entitled "Limitations/considerations of testing." Know some of the reasons we should perhaps resist doing a genetic test just because we can!

1. Genotype does not always predict phenotype !! 2. Variants of unknown significance (VUS) 3. Analytic validity > clinical validity >>> clinical utility 4. Redundant testing (e.g., NCAA and sickle cell testing) 5. Timing issues (e.g. pharmacogenomic testing) 6. ELSI issues (week 14) Incidental findings Patient notification Who owns the results Patents and licensing Resource utilization, access, and many, many more

What is the general mechanism of "three-parent" techniques to avoid inheritance of faulty mitochondria. Whose DNA does the child inherit?

3-parent-techniqe" mechanism: start by harvesting the ovum of the desiring maternal parent and gently removing the maternal spindle (containing the nucleus) and then implanted into a donor egg that has had its nucleus removed; then the new egg containing the nuclear DNA of the mother and the mitochondria DNA of the donor is fertilized with the sperm of the prospective mother's partner - pronuclear transfer (not legal in US)

What guidance do nurses have regarding their role in providing patient care that takes a genomic perspective?

Advocacy, protection, education. Nurses must develop competency bc of their strong presence in patient care

Compare a highly-penetrant gene mutation (e.g., the HTT mutation that causes Huntington's disease) with a risk allele for a more common condition.

A condition such as down syndrome is not caused by the production of a new protein, instead it is caused by an extra copy of chromosome 21

founder mutation

A genetic alteration observed with high frequency in a group that is or was geographically or culturally isolated, in which one or more of the ancestors was a carrier of the altered gene -small group of ppl leave larger population and settle somewhere else "founders effect"

Premutation

A genetic change that does not result in a phenotype itself but has a high probability of developing a second alteration—a full mutation—which does cause a phenotype.

What are features of diseases and health conditions that we (and our patients!) describe as "genetic"? How can nurses communicate effectively with patients who ask "is my condition genetic?"

A genetic condition is something that originates at the gene level and can be due to a mutation or changes in gene expression - error in ONE particular gene. Just bc it is hereditary does not mean it is genetic.

Haplotype

A group of alleles of different genes on a single chromosome that are closely enough linked to be inherited usually as a unit

How could a variation in DNA sequence ultimately affect health? Under what circumstance might a variation in DNA sequence not affect health?

A variation in DNA sequence could affect health by causing a mutation. On the other hand, if the variation in DNA does not change the structure of the protein, the health may be unaffected.

What are the #1 and #2 risk factors for developing breast cancer?

Age and sex

parens patriae

A legal doctrine that gives the state the authority to act in a child's best interest.

Know some mechanisms by which proteins encoded by tumor suppressor genes inhibit carcinogenesis.

A mutation that only affects one allele would inhibit carcinogenesis This is because tumor suppressor genes can still work with only one copy

How is a formal genetic risk assessment done by a genetic counselor different from a genetic assessment expected of generalist nurses?

A nurse is expected to pull information from family history, risk factors, and individual patient care and apply that to general understanding of genetics (example: family history of lung cancer, patient is a smoker, patient has chronic cough -- these are all increased risks/signs of lung cancer). This is a holistic approach. A formal genetic risk assessment done by a genetic counselor is a more specialized approach

X-linked inheritance

A pattern of inheritance in which a recessive gene is carried on the X chromosome, so that males are more likely to be affected

1. Personal genome services (PGS) have changed in the US over recent years with increasing regulation of direct-to-consumer genetic testing. How are PGS expected to evolve over the next several years?

As of now, PGS is a relatively niche market with services all over the internet. PGS allows a person to have their DNA thoroughly analyzed by experts. PGS could become part of routine clinical practice in the next few years as the technology rapidly advances.>> expected to expand capacity of genetic testing and reduce cost

Differentiate between autosomal aneuploidies and sex chromosome aneuploidies. Which type of aneuploidy is worse? Why?

Autosomal Aneuploidies: alteration in chromosomal number (gene dose) located on genes 1-22 (not sex chromosomes) i. Most are lethal with exceptions of trisomy 21, 18, and 13 Sex chromosome Aneuploidies: alteration in chromosomal number (gene dose) located on the sex chromosomes i. Much better tolerated Sex chromosome aneuploidies are much better tolerated than autosomal because of 2 reasons: (1) there is little genetic information on Y; and (2) X- inactivation - the material on X can be compressed so that females don't express the info twice

What are some of the barriers we face in making better use of FH in clinical practice?

Collecting and creating a pedigree takes time o Problems with HER compatibility o Lack of consensus re roles/responsibilities across providers and settings

Based on the framework of the central dogma, what are some potential approaches to treating or curing genetic diseases?

Based on the central dogma, some possible approaches for treating or curing genetic diseases include fixing a gene to make it function properly, or using gene therapy to cure a disease.

How could it be that something that happened to your grandmother (or great-grandmother) might affect your epigenome and health (and even that of your children and grandchildren)?

Bc it was present when the ovum that made you was formed when your grandmother was pregnant with your mother

If only maternal mtDNA is passed to the next generation, how is it possible that some mitochondrial disorders can be inherited from either parent?

Because ATP formation requires proteins encoded in both nuclear (ATP synthase) and mitochondrial DNA, it is possible that paternal affected nDNA was inherited by the child and caused the disruption in ATP production, causing a mitochondrial disorder to occur

11. Be able to explain how either nondisjunction or translocation may lead to a pregnancy with more (or less) than 46 chromosomes. When a baby is born with Down syndrome, why is it important to know if the extra chromosome is a result of nondisjunction or translocation?

Because nondisjunction has a far lower risk of recurrence than translocation

Fragile X - Males v. Females

Because this condition is X-linked dominant all males with the mutation will present however only females with the expanded trinucleotide repeat sequence on their dominant X chromosome will present

de novo mutation

an alteration in a gene that is present for the first time in one family member as a result of a mutation in a germ cell (egg or sperm) of one of the parents or in the fertilized egg itself

Review the example of genetics of the B2 receptor How does a common SNP in B2AR gene influence drug response? Is this PK or PD?

B2 receptor is the target of many asthma meds; encoded by ADRB2 on chromosome 5; protein has 417 amino acids o 2 common SNPs cause different proteins to be formed: Arg-16 (positive response to asthma meds) and Gly-16 (poor response to asthma meds)

difference between sickle cell and For yeshorim

sickle cell screening was govt mandated and for yeshorim was a choice

Turner syndrome/ Monosomy X (45, X): females experience effects of missing one X chromosome

Clinical manifestations: normal intelligence—may have some problems w/ spatial abilities, short stature, lack of ovarian development or early ovarian failure, delayed puberty, mild dysmorphic features (webbed neck, low posterior hairline, increased carrying angle of the elbow) ii. Important to identify this early in adolescence and can be supplemented with hormone replacement to give the pt height

Klinefelter syndrome (47, XXY): males with this condition contain an extra X chromosome

Clinical manifestations: tall stature, feminized body shape (smaller shoulders, wide hips), gynecomastia (male breast tissue), small testes with a low sperm count, lack of secondary sex characteristics (ex. Thin beards w/ minimal body hair), occasionally learning disabilities

Polysomy Y (47, XYY): males experience effects of extra Y chromosome

Clinical manifestations: tall stature, prone to acne (increased testosterone), normal intelligence levels (may be lower than siblings), prone to some types of learning disabilities/ behavioral problems ii. Although pts w/ this condition may be prone to behavioral problems there was no evidence for increased aggressiveness of propensity for violence - Richard Speck Defense proven incorrect

duty to warn and protect

Clinicians duty to warn of imminent harm to a duty to protect (Tarasoff rule)

What's wrong with cancer cells? (What are some of their features?)

Cancer cells are wrong in terms of their appearance, function, division, mutagenesis, intercellular communication, vascularity and migration These bad features are directed by proteins that are produced by mutated genes

Difference between Central Dogma and DNA replication

Central dogma is related to making a protein from DNA and RNA while DNA replication creates two identical sets of DNA to repair cells or make more

Given that most babies born with Trisomy 18 or 13 only live days, how is it possible for a child with this disorder to live years? How might you explain the concept of mosaicism to a pregnant woman or a new mom who learns of this diagnosis?

Children with Trisomy 18 or Trisomy 13 may live lears if they are mosaic Mosaicism means that a child only has the condition partially different cells in the same individual have different numbers or arrangements of chromosomes Only some cells are affected by the condition which could allow for a better chance of survival

Can you make sense of codeine as a prodrug metabolized by CYP2D6?

Codeine will be inactive when ingested and will stay that way until it reaches CYP2D6; where it is broken down/altered into an active form that will produce effects

genetic exceptionalism

Concept that 'genetic information is inherently different and should be treated differently than other forms of personal or medical information

analytic validity

how well does test determine genotype

• Aneuploidies—wrong # of chromosomes

Down syndrome o Klinefelter syndrome oTurner syndrome

Be able to distinguish the methods used in genetic testing. Which testing methodology focuses on phenotype rather than genotype? How do labs capitalize on DNA hybridization to develop tests that can find tiny variations in sequence? When is RNA testing useful?

DNA hybridization >> used to find single based variants and have probes that are specifically bind to genetic mutations and use the hybridization to find of the DNA they make probes that will bind to a patient's DNA if they have a particular mutation RNA testing is useful when looking for a differentiation in the transcriptome rather than the gene >> measures gene expression

histone modification

DNA is tightly wrapped around histones, if they leave the DNA can be relaxed

central dogma

DNA is transcribed into RNA, which is translated into protein

Recombinant DNA

DNA produced by combining DNA from different sources

What technology in the last 20 years has allowed genomic science to evolve so quickly?

DNA sequencing has allowed us to see how genes affect health and mechanisms of disease

How is it possible that all cells contain the same set of protein-encoding genes, yet make different proteins?

Different genes are activated in different parts of the body such as in the pancreas where genes that encode for insulin are activated and expressed

How is DNA structured?

Double stranded with weak hydrogen bonds holding the strands together. This is important bc it allows the strands to be separated easily

ELSI

Ethical, Legal, and Social Implications of Testing

What are some nursing interventions related to working with clients and families who have, or are at risk for sex chromosome or mitochondrial abnormalities?

Educate patient on full course of disorder and ensure their understanding about treatment plan Talk with the families and ensure they understand mosaicism as the cause of se chromosome abnormalities

EGAPP

Evaluation of Genomic Applications in Practice and Prevention: assess validity and utility of genetic tests, guide interventions, and predict risk using population screening -Use PICCO questions to answer if genetic tests for a specific disease have good analytical validity, clinical validity, and clinical utility. - Then recommend who should be screened/tested

How does ancestry apply to the topic of pharmacogenomics?

Everyone has 2 alleles - which means they could be *1*1 or *1*2 etc o Prevalence of *2*3 varies with ancestry - most common among Asian/African populations

6. Think about our discussions of using viral vectors, CRISPR-cas9, or mitochondrial transfer techniques to change genes. What is the difference between editing genes of somatic cells compared to germ cells? What is the difference between ex-vivo and in- vivo gene therapies?

Ex vivo is outside body modified and then put back in while in vivo is all inside the body

You should understand basic differences between FAP and Lynch syndrome. (For example, what kind of genes are mutated in these conditions?

FAP syndrome is caused by one singular mutated gene (APC gene) and leads to hundreds-thousands of polyps. These polyps are found in the rectum and colon. With this condition, you would want to test a child before age 18 because these patients may have hundreds of thousands of polyps by age 20 Lynch syndrome is caused by many mutated genes (MLH1, MSH2, MSH3, MSH6, etc). This syndrome is associated with endometrial and other cancers as well as colon cancer. There are fewer polyps with this condition

What are some of the screening and prevention options for people identified with elevated risk for FAP? Lynch syndrome? Breast cancer?

FAP: Sigmoidoscopy and Colonoscopy Lynch Syndrome: Colonoscopy, Endometrial aspiration, transvaginal ultrasound Breast Cancer: Mammogram, Self Checks

How does X-inactivation mitigate the effects of polysomy X conditions? What does it mean when we say females are mosaic for the 800+ genes on the X chromosome?

Females are "mosaic" for 800+ genes meaning that they could potentially express the same gene too many times because they have two copies of the X from maternal and paternal sides; this explains why some genetic diseases can be way worse than others depending on the individual affected

Where can a nurse find out which enzymes metabolize particular drugs? How should the nurse use that information?

Flockhart table

Tumor profiling

Gene expression profiles are used to see if chemotherapy would be beneficial; actual tissue is needed

What is a good definition of a gene, given what we currently understand about gene structure and function

Gene is comprised of DNA and reside on chromosomes; each is a blueprint for encoding multiple proteins

5. Genetic "engineering" currently applies two method to repair/edit or replace genes. Be able to compare gene transfer using viral vectors and gene editing using CRISPR-Cas9. What is the current regulatory landscape in the US re germline and somatic gene editing?

Gene transfer using viral vectors involves viruses being modified and used to infect cells to deliver the new gene. CRISPR involves a protein (Cas9) that works as an enzyme that can cut out molecular strands of DNA. Germline editing is not currently approved in the USA, but somatic editing is legal to treat diseases.

What are major sources of human genetic variation and how could each contribute to variation in drug response? Consider both PK and PD mechanisms.

Gene variants/polymorphisms/SNPs/mutations (variations in DNA sequence) o Copy number variants (variations in gene dose) o Variation in gene function/expression (how much protein the gene is making)

GINA

Genetic Information Nondiscrimination Act, essentially says that genetic information is different than other health information, and that people cannot be treated differently by insurance companies or employers because they have a genetic mutation

How are genetic tests evaluated?

Genetic tests are evaluated for >> sensitivity, specificity, analytic validity, clinical validity, clinical utility, and ELSI (ethical, legal, social implications

Genetic vs Genomic Disease

Genetic- error in one particular gene, very linear progression ex: Huntingtons, cystic fibrosis Genomic- effects of multiple genes and environment ex: HTN, cancer, asthma

Be able to describe how maternal serum screening has changed over the years. What events or policies drove the use of this testing approach? Why is the issue considered to be a population health problem?

Genome science makes advances but increases complexity. Historically, screening measured risks for NTD, DS, and trisomy 18; now there are markers tested and improved ultrasounds that allow for testing of many more conditions. Some populations are more inclined to have positive tests for certain conditions

What is the focus of Mendelian genetics, and how has that restricted the framework through which the public, students, and even many health professionals think about genetics?

Gregor Mendel began looking into phenotypes in the 1860s and determined how physical traits are passed down from parents to kids- theorized that these traits were determined by one single gene. His idea of the unit of inheritance was not true, but it developed a framework of how genes are passed down.

• Complex/ multifactorial—caused by multiple genes + environment

HTN o Heart disease o Type 1 DM o Alzheimer's do o Tourette syndrome o Breast cancer

When is high sensitivity desired? How about high specificity?

High sensitivity is desired in screening tests, high specificity is desired in diagnostic tests. Specificity is usually higher than sensitivity

In the course reading week 13, why was the genetic counselor so surprised that Shonnie Medina had the BRCA1,185delAG mutation? Be able to trace Shonnie's mutation over 2500 years of Jewish exile—from Palestine to Babylonia to Spain, then to Mexico and eventually Colorado

Hispanic woman surprised about BRCA mutation -- very unlikely to have the mutation

Somewhat philosophically, what are some ways that genetic testing differs from non- genetic testing? What do YOU think about the concept of genetic exceptionalism? What does HIPAA say? What does the state of South Carolina say? What does GINA (a federal law that trumps state laws) say?

I think that genetic information should be treated differently because it is far more personal and specific than other information HIPAA and SC say that genetic information is the same as other information GINA says that genetic information is different >> this trumps what all other organizations say

How would you advise a patient whose genetic test results for inherited cancer mutations was negative? What can you tell him or her about their risk to develop cancer?

I would advise them that they still are at a risk for cancer, I would inform them about the carcinogens that may cause them to develop mutations that could lead to cancer.

14. How would you provide anticipatory guidance to a new mom as you do her newborn's heelstick to collect NBS blood spots? What would you say?

I would inform the mother of the process of the heelstick procedure. I would also inform her that this is a screening test with a high false positive rate, so if her baby has a positive screen result they will need to come back for further testing

race

Identity with a group of people descended from a common ancestor. skin color

Ethnicity

Identity with a group of people that share distinct physical and mental traits as a product of common heredity and cultural traditions. -cultural, socioeconomic, religious, language, diet, customs

What is the rule of hypodescent and how did it influence legal and political definitions of race?

If someone is of mixed descent, they are assigned to the race w the lowest socioeconomic status When applied to legal and political definitions of race it lead to a hierarchy based in no facts

Do health care professionals have a "duty to warn" family members at risk for genetic conditions? Could that duty conflict with their responsibility to protect the patient privacy?

If their results indicate their family members may also be at risk for a condition, we must let them make the decision to notify them (if they do not wish to tell their family, we as nurses cannot call them and break the confidentiality of the patient's genetic tests)

what is the genetic component to morbidity and mortality of conditions like infection and trauma?

In each disease progression, the environment and genetics both relatively have contributions to the development another example - AIDS is almost entirely environmental, but a mutation within a gene can prevent the HIV disease from progressing into AIDS

How did the Human Genome Project 'open the molecular black box' and offer new strategies to diagnose and treat cancer? Be able to describe a clinical example of genomics informing cancer care.

In looking at the human genome project, we can now tell when changes in our genome have taken place that lead to cancer by comparing. Knowing this information also allows us to intervene more quickly to try and treat or minimize the effects of this cancer

What are some unintended consequences of genetic testing?

Incidental findings >> discovering information/risks/conditions that were unrelated to the original purpose of testing

What is the association between maternal age and risk for Down syndrome and how does that influence prenatal testing for DS for young women? older women? Which screening approach is most sensitive to maternal age?

Increasing maternal age increases the risk for having a child with down syndrome. Prenatal testing for young women is not done unless risk is 1/270 (unlikely for younger patients) and false negatives are a problem with this test. Prenatal testing for older women is done very frequently, especially over the age of 35. False positives are an issue with testing. This is because maternal age is weighed heavily in the algorithm used and skew the results.

Early attempts at gene therapy, e.g., the case of Jesse Gelsinger, used viruses to insert functional genes into a patient's genome. What kinds of problems were associated with using viral vectors and how does CRISPR-Cas9 avoid those problems?

Inserting viruses is very risky (i.e. Jesse Gelsinger died in a clinical trial; first death directly related to gene therapy) because the patient can have a severe immune response CRISPR-Cas9 is an enzyme that can basically be used like scissors to edit DNA

What are the potential benefits of NBS?

It identifies potential genetic disorders in babies If a baby is diagnosed with a genetic disorder shortly after birth, it allows for preventative measures/ treatments to begin at a young age

How is it possible for 21,000 genes to encode more than 400,000 proteins?

It is due to alternative splicing. Alternative splicing can split the gene in multiple ways (1,2,4,5 vs 2,3,4,5, vs 1,3,5,4)

Why is penetrance an issue in genetic testing?

Penetrance is an issue in genetic testing because it is often based on the white/european ethnicities, and it cannot give people a definitive answer on whether or not they will express the genes

Know how to communicate or discuss prenatal genetic test results with a patient/family.

It is important not to say that the baby tested "positive" or "negative" but instead say "the test put your pregnancy at a low risk for ___" or for a positive result, "the test result put your pregnancy at an increased risk for ___ but further testing is needed to actually diagnose"

What does it mean that carcinogenesis "takes multiple hits?" Be able to explain how an inherited mutation can speed up carcinogenesis.

It means that having a single mutation is not enough to cause cancer and carcinogenesis For carcinogenesis to occur, there are multiple mutations involved

What are some key features of mitochondrial diseases?

Key features: heterogenous group of disorders, usually progressive, and involves multiple systems; disrupted ATP production

6. What was the outcome of the Supreme Court ruling re Myriad Genetics and gene patents? Is there any type of DNA that can be patented in the US?

NATURALLY occurring genes are not patentable Synthetic DNA (i.e. cDNA or rDNA) is still eligible (see vocab)

does GINA still apply if patient already has manifestations of disease?

NO

In a condition (such as neurofibromatosis) with variable expressivity, how closely do people resemble each other at the phenotypic level? How about at the genotype level?

Neurofibromatosis type 1 >> highly variable expression Some have mild symptoms >> small light brown macules Some have severe symptoms >> large nodules Phenotype level >> resemblance varies greatly among others with the disorder Genotype level >> have the same gene so in that regard have a almost identical resemblance

Newer technology has led to expanded Newborn Screening (NBS) panels. What are some of the concerns? Be able to identify an advantage and a disadvantage to mandated NBS for Krabbe disease.

New technology makes it easy to add new test, but each new tests adds a new set of false positives Krabbe disease Advantage >> the treatment for Krabbe is a bone marrow transplant and it is more effective prior to onset of symptoms Disadvantage >> there is poor genotype-phenotype correlation

If a proto-oncogene has a loss-of-function mutation, does it become an oncogene?

No The mutations that cause oncogenes are point mutations, gene amplification, or chromosomal translocation

ancestry

family descent

protooncogenes

Normal cellular genes that regulate cell proliferation and differentiation that can become oncogenes.

Should we test for conditions with no available treatment/management plan?

Not entirely sure, on one had it would allow parents with positive children to prepare themselves mentally, but it's difficult if there is no plan to treat or manage the disorder

How has nucleic acid (i.e., DNA or RNA) testing impacted the practice of clinical microbiology? Nucleic acid tests for pathogens are rapid, sensitive and specific but we give something up. What is it, and how might that affect treatment options?

Nucleic acid (NA) tests identify DNA or RNA unique to various pathogens Used to identify specific pathogens

precision medicine

Obama committed to put funds towards human genome project

Why is an individual with an autosomal dominant disease presumed to be heterozygous for the mutation?

Often heterozygous because homozygous autosomal dominant embryos are often miscarried

How much of total DNA in a human genome is not related to genes and protein formation?

Only 5% of the DNA in each nucleus actually codes for genes

4. How do the trillions of microbes that live in our bodies contribute to our genome?

Our genome helps produce these microbes that can be traced through genome sequencing.

What is overdiagnosis? When is it tolerable? When could it be harmful?

Overdiagnosis is when an individual is diagnosed with a disorder that they do not have or are asymptomatic of, therefore do not require treatment Tolerable when the treatment is not harmful >> ex. Dietary modifications Harmful when the treatment can cause illness or death >> ex. Bone marrow transplant for Krabbe

Be able to apply the ACCE model to a PICO question to support evaluation of a genetic test.

PICO question: Does genetic testing in newly diagnosed individuals with colorectal cancer reduce M/M from lynch syndrome in relatives Population: relatives Intervention: testing in newly diagnosed individuals with CRC Control: no testing/ people that chose not to get tested Outcome: reduced M/M from lynch syndrome

What roles do proteins play in pharmacogenomics?

PK must be successful so that the drug reaches the target (while maintaining a high enough constant level in the blood or tissue) to produce the action which in turn will reflect the PD of the drug

Is FHH a genetic test? A screening test? A diagnostic test? In legal issues, is FH information considered to be genetic information?

Particularly useful genetic test, as it reflects not only shared genes, but also shared environments, lifestyles and habits

anticipatory guidance

Patient/family counseling which includes information, advice, and suggestions about expected health-related life occurrences, health maintenance, and preventive plans.

If a particular condition (e.g., polydactyly) is 80% penetrant, what does that mean?

Polydactyly >> if you have the mutation you have an 80% chance of having the disorder/expressing the gene

What is different about precision medicine?

Prcision medicine is individualized based care and it focuses on an understanding of molecular mechanisms of disease

Be able to describe which conditions the various prenatal tests are able to detect.

Prenatal tests are able to do karyotyping, mutation panels, microarrays, and DNA sequencing. Most commonly these tests are used to identify NTD and aneuploidies. Mutations can be detected, but very rare mutations will be missed.

Given a metabolizer category (i.e. ultrarapid) you should be able to predict the response to both a prodrug and an active drug

Prodrug; ingested as inactive until it is metabolized by a CYP enzyme o If CYP enzyme is ****ed, the person won't have any effects because it will just pass through their system Active drug; ingested as an active drug until it is metabolized by a CYP enzyme to inactivate/prepare for elimination oIf CYP is ****ed, then the drug will stay in their system a lot longer

What is a potential risk of including race as part of health assessment? What is a possible benefit?

Pros Race is a cornerstone of health disparity research Race has some clinical utility in health practice Ex. White child w abdominal pain/ fever >> thinking hot appendix Ex. Black child w abdominal pain/ fever >> thinking maybe sickle cell crisis Race has utility in unraveling the genetic basis for human variation including variation in disease risk Cons There is a lack of a clear definition of race How can you use race in health assessment and research if it is not measurable? The insufficiency of race to accurately identify populations Lack of scientific basis for race Risk of basing clinical decision on erroneous info The risk of perpetuating racism Ex. Story of Lena w CF not dx until age 8 because she was black

7. What does it mean when you see "rDNA origin" on a drug label?

Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in the genome

How is the risk information conveyed? Be able to differentiate between relative risk and absolute risk. What does it mean when a patient's RR is 2.5? How about 0.5?

Relative risk (RR) compares the likelihood of an event (i.e. developing a disease) between two groups (most often, an individual's risk compared to the population's) o "Given your FHH, your risk to develop _____ is about 2x the risk of other women your age" o Absolute risk (does not = precise) o"Your risk to have a major cardiac event in the next 10 years is 20%"

Be able to distinguish the various forms of prenatal testing currently offered. Which tests are screening tests? Which are diagnostic? Which are noninvasive? Invasive? Which tests directly examine fetal cells or the fetal genome? How early in pregnancy can prenatal testing be done and what are the implications of early testing? Where can nurses and their patients find current, credible information about prenatal testing?

Screening: noninvasive - maternal blood draw (NIPT, not fetal cells - 10 weeks), ultrasound (does not test fetal cells) Diagnostic: invasive - CVS (tests fetal cells at 10-13 weeks), amniocentesis (tests fetal cells at 15-20 weeks)

What does it mean that "Race is a surrogate for a surrogate for a surrogate for surrogate.

Self-identified race/ ethnicity is comprised of Environmental exposure Education Access the HC Culture Socioeconomic status stress Ancestral geographic origins Genome variation Variants in disease genes Genome variation And leads to health or disease

How is sex reversal an example of genotype-phenotype mismatch? What are some causes of sex reversal?

Sex reversal: individuals with the genotype of one gender and the phenotype of the other gender w/o undergoing surgery, hormonal manipulation or any other phenotypic manipulation i. Males as (46, XX) and Females as (46, XY)

Review public health genetics initiatives conducted in the US related to sickle cell carrier screening in 1972 and again with the 2010 NCAA policy. What are some of the issues with those policies? Compare them to Dor Yeshorim's approach to reduce Tay Sachs disease in a different population.

Sickle cell carrier screening National Sickle Cell Anemia Control Act 1972 targeted African American youth by testing them for sickle cell carrier status, was mandatory in some states NCAA 2010 >> mandatory testing for sickle cell trait among all D1 student athletes gene-based , personalized risk prevention program Prevented 7 deaths in 10 years Issues Could cause athletes not to be recruited because of their carrier status Mandates more water breaks in heat ect >> why not implement for all athletes

Gene sequencing of people around the globe has uncovered two common sources of genetic variation. What are they?

Single-base substitutions (SNPs) Single bases are substituted—common point shift mutation that varies according to ancestry Copy number variants (CNVs) Extra or missing genes that explain much more human variation than SNPs

• Mendelian Conditions-- monogenic/ single gene disorders

Tay sacs o HD o CF o Hemophilia o Osteogenesis imperfect o Thallasemia o Achondroplasia o Fragile X o Stromme S o Pfeiffer (2 genes) o Treacher Collins (3 genes) oColor vision deficiency (3 genes)

What is the problem with a "one size fits all" approach to drug selection/dosage from genomic viewpoint? Which patients may suffer?

Some people have good efficacy with no adverse reactions o Some people have good efficacy with adverse reactions o Some people have poor efficacy with adverse reactions o Some people have poor efficacy with no adverse reactions

alternative splicing

Splicing of introns in a pre-mRNA that occurs in different ways, leading to different mRNAs that code for different proteins or protein isoforms. Increases the diversity of proteins.

Note the relative prevalence of different types of colon cancer (i.e., sporadic, familial, inherited) as presented in a pie chart. These relative prevalences are similar for other human cancers!

Sporadic: 60% Familial: 30% Rare Syndromes: 4% MAP: 1% FAP: 1% HNPCC: 3-5%

What is the prevailing hypothesis about the variations in human skin color found around the globe?

States that dark skin offers protection from skin cancers but increases risk for vitamin D deficiency The closer you are to the equator does not necessarily determine how dark your pigment is but rather your exposure to more IV radiation Explain Australia as an outlier in terms of proximity to equator determining skin pigmentation

What would you tell a patient who asked you about inheritance of Down syndrome or another aneuploidy?

That it depends whether or not it was caused by nondisjunction or translocation Nondisjunction >> chromosome doesn't split during anaphase Translocation >> when a chromosome or a piece of a chromosome attaches to another chromosome If its because of translocation the chance of it happening again is a lot higher

(Once again) what are the promises of genomic healthcare?

The human genome promises to change how diseases are diagnosed, prevented, and treated.

genetic determinism

The belief that genes are the major determining factor in human behavior.

Overdiagnosis

The diagnosis of a disease that an individual does not actually have

What is the purpose of public health genomics and why is it more appropriately described as population genomics? What are two key emphases?

The emphasis is on populations and translational research. It should be called population genomics because a population is defined as "a collection of individuals who share at least one common or organizing characteristic"

Distinguish the genetic code and DNA sequence. Which was understood first?

The genetic code is the set of rules used by living cells to translate information from genetic material into proteins. Genetic code was understood first

Contrast a highly heritable condition (such as schizophrenia at 85%) with a condition with a lower heritability estimate (such as peptic ulcer at 37%). What do the heritability percentages mean and how would you explain them to a patient?

The heritability percentage is the proportion of variance attributed to inherited factors You would explain to the patient that if there's a high risk there chance may be high but they can help with reduction of risk by reducing environmental factors, and if their risk is low you will need to still take into consideration that there is a risk of contracting the disorder

Be able to identify the neurobehavioral phenotype associated with Williams syndrome. (This will be easy to remember if you watch the 5-minute video at http://www.youtube.com/watch?v=gF4DiqEdN3w!) What genetic change leads to the unique behaviors found in affected individuals

The neurobehavioral phenotype associated with William' Syndrome involves extreme friendliness and empathy for others. 25 genes out of 25,000 are deleted from the seventh chromosome-- Hypersocial--loquacity, unusual friendliness, ↑ social interest, lack of social inhibitions, prolonged gaze, musicality

intended use

The purpose of genetic tests includes predicting risk of disease, screening newborns, directing clinical management, identifying carriers, and establishing prenatal or clinical diagnoses or prognoses in individuals, families, or populations

How has the "intended use of FHH changed over the last few decades?

The traditional purpose of FH was to inform reproductive decision making o The current, expanded purpose of FH is to stratify risk to inform individualized care

If only 5-10% of cancer is inherited, why do we say cancer is a genetic disease? What do the genes involved with processes of carcinogenesis (and the proteins they encode) have in common?

We say cancer is a genetic disease because mutations that lead to cancer can be inherited

Recall that for two decades, Myriad Genetics held patents on the genes BRCA1 and BRCA2. What effect did that have on the availability of testing? What was Myriad's defense re preventing other laboratories for developing BRCA tests?

This decreased the availability of testing -- they charged $4,000 to analyze 2 genes and had exclusive rights to it "Myriad invested a great deal of money to figure out the sequence and develop synthetic molecules based on that sequence that can be used to test the variants in a patient. We think it's right for a company to be able to own its discoveries, earn back its investment, and make a reasonable profit" -- their reasoning

risk allele

altered allele that increases the risk of getting a genetic disorder. The allele itself does not cause the disorder it just increases the risk

What do Klinefelter syndrome, Turner Syndrome, and polysomy Y have in common?

They all are missing or have an extra sex chromosome

What is the nursing role in promoting social justice as it relates to genome science? (How can we avoid disparities and treat people fairly?) What are some ethical issues related to newly emerging technologies such as CRISPR-Cas9 or mitochondrial DNA engineering?

Think about designer babies >> genetic technology is expensive (financial disparities), and there are disparities with the knowledge of conditions (there is more genetic information about conditions/diseases common in certain races compared to others)

Using the CF example discussed in class, what are some of the issues around mutation analysis

Using the CF example from class there were a lot of different mutations that cause CF all of varying risk levels, so there is a lot of genetic code to look through in a healthy individual and then their risk level differs based on the specific mutation

Understand PK and PD (CYP2C9 and VKORC1) effects on warfarin response and some issues around warfarin genotyping.

Warfarin effects vary a lot person to person; the dose is highly individualized o *1 = wild type, *2 = 40% reduced metabolism, *3 = 90% reduced metabolism o VKORC1 genotype = 25% o CYP2CP = 15% Issues Lack of robust clinical outcome data o Cost ... benefit o Who will pay? o Timing of testing o Knowledge of HCPs

What does it mean when a gene is expressed

Whether or not a gene is "turned on" >> being transcribed, or to what degree a gene is being transcribed

how does the relative contribution of genetics and environment vary between different conditions

While some individuals may or may not have genetic abnormalities that increase the likelihood of developing a condition, certain conditions rely heavily on the environmental contributions to the progression of the conditions - for example, infection; a person may have an increased likelihood of developing infections, but ultimately the person's lifestyle choices and hygiene mechanisms will lead to or prevent the development of infections

What is the purpose of X-inactivation?

X-inactivation serves to equalize the gene dose (2) in males and females by compressing one of the female X's so that they cannot express the same gene twice despite inheriting two X sex chromosomes

dominance

a dominant mutation or allele is one that alters the phenotype regardless of its homolog (i.e, corresponding allele)

What sort of mutation causes Fragile X syndrome?

a trinucleotide (CGG) expansion in the promoter area of the FMRI gene on chromosome X

Pharmacokinetics

actions of the body that change the physical and chemical properties of a drug → absorption, metabolism, elimination

intron

additional sequences of gene that do not code for protein

DNA methylation

adds methyl groups (CH4) to cytosines in the gene promotor to silence the gene

human genome

all genes within human

genetic test

analysis of human chromosomes, DNA, RNA, genes, and/or gene products (e.g., enzymes and other types of proteins), which is predominately used to detect heritable or somatic mutations, genotypes, or phenotypes related to disease and health

ACCE

analytic validity, clinical validity, clinical utility, ELSI

What is the preferred approach to categorizing people in healthcare settings today?

ancestry described by geographical, geopolitical, cultural, and shared gene variants Reflects shared environmental pressures and gene variants

phg

applies findings from genome science to improve health of a population

What proportion of DNA sequence is identical between unrelated people?

approx 99%

How to identify a mitochondrial inheritance pattern in a pedigree.

ask when looking at pedigree i. Are both males and females affected? ii. Is every generation affected? iii. Is there direct inheritance? iv. Is the disorder only passed down by females? 1. If this is yes and all the other questions are yes, it is mito

what is the difference between a balanced and unbalance translocation?

balanced translocations do not usually cause signs or symptoms

In what way does variable expressivity limit the usefulness of genetic testing?

bc we can predict the genotype, but can't predict how its expressed so the patient won't know the severity of the disorder

Pharmacodynamics

body responses induced by a drug; including the intended action and side effects; involve the drug and its target

How has the definition of a genetic test changed over the last decade, and how does the evolving definition reflect the transition from traditional Mendelian genetics to genomics?

broadened to include non-inherited changes, and changes associated with environment >> not all genetic disorders are necessarily inherited

obligate carrier

carries the gene but does not have the trait

mendelian

caused by an error/mutation in one particular gene

complex

caused by direct/indirect effects of multiple genes AND environment

cffDNA

cell-free fetal DNA; this is the circulating fragments of fetal DNA found in maternal blood; this is what is collected and tested during NIPT

microbiome

combined genomes of trillions of microorganisms hosted in our body- many proteins come from this

Warfarin Pharmacogenomics

common anticoagulant; individualization of warfarin dosing is already the standard of care due to the extreme variations in warfarin response -depending on the level of metabolism occurring (which is determined by genotype of CYP2C9) a person could experience severe bleeding/clotting

XY Females

commonly caused by AIS (androgen insensitivity syndrome) in which all tissues, including the masculine tissues are missing androgen receptors. In this condition the patient undergoes normal gonad formation in embryonic development, but the testis is unable to completely develop due to the lack of androgen receptors and therefore the embryo develops mostly female genitalia

proteome

complete set of all proteins a person makes at a given time

Genome

complete set of genes for our species (20,000-25,000 individual genes

trancsriptome

complete set of mRNA

variable expressivity

conditions that affect people at a varying degree

What are the two kinds of genetic variations that contribute most to human variation ?

copy number variants affect the amount of protein produced, mutations alter proteins

How are mutations distinguished?

del = deletion ins = insertion _ (underscore) indicates range of bases Premature stop codon indicated by X or TER

copy number variants

deletions and duplications of tiny parts of a chromosome

What is the function of proteins in the body?

do most work in cells and are required for structure, function, and regulation

active drug

does not need to be metabolized to show therapeutic affects

clinical utility

does testing lead to improved health outcomes

clinical validity

does the test provide meaningful medical information

codominant

dominant and recessive allele working together (think eye color)

substrate

drug that is metabolized into a different form

Prodrug

drug that needs to be metabolized to be activated

dna replication

duplication of DNA resulting in two identical sets

secondary prevention

early detection/ prevention of getting worse (screening, tests, etc)

Fragile x manifestations

flat feet, muscle aches/pains, hip instability, delayed walking, poor balance/cognition, tremor, high incidence of autism, large ears, long-narrow face, prominent jaw, macrocephaly, mitral valve prolapse, reduced intelligence, poor verbal skills, social anxiety, attention deficit, etc.

anticipatory guidance

form of patient advocacy where nurse draws upon education and experience to anticipate intended and unintended consequences of healthcare and act pre-emptively

Noninvasive prenatal testing (NIPT)

fragments of fetal DNA were discovered in maternal blood (1997) so tests were developed to make inferences from this sample; used as a screening test and tests placental, not fetal DNA

Family Health History

genetic test that reflects shared genes, environments, lifestyles, and habits; the intended use is screening

direct to consumer

genetic testing that is not done by a healthcare provider but rather a 3rd party agency that does not clinically evaluate the patient only their DNA

How could the fact that "genotype does not always predict phenotype" limit the usefulness of a genetic test? Be able to describe a situation where a genetic test result might harm, rather than help, a patient.

genotype not always predicting phenotype limits genetic testing because there is not always a way to accurately ensure the patient with obtain the disease can be harmful when finding out you are at risk and have the mutation that is deathly with limited treatments and no cure

How would you explain the penetrance of BRCA gene mutations?

have to explain that with some of the mutations you have an 80% chance of contracting breast cancer along with a 25% change of contracting ovarian cancer

Explain the role of stop codons and the effects of premature stop codons on RNA translation. Why is the position of a premature stop codon within a gene significant?

he role of a stop codon is to signal the termination of translation into proteins The effect of premature stop codons can completely change the proteins that are being translated The position is significant because depending how premature the stop codon is, the larger the effect it will have on the translation of proteins

tertiary prevention

improve quality of life and reduce sx

expansion

increase of TNR within a gene

consanguinity

increased risk of disorder bc of familial ties (2nd cousins or closer)

high risk

individual has a family member with condition that is hereditary -intervention = referral for genetic evaluation with personalized prevention recommendations

moderate risk

individual has multiple family members with condition -intervention = personalized prevention recommendations

Sex Reversal

individuals with the genotype of one gender and the phenotype of the other gender w/o undergoing surgery, hormonal manipulation or any other phenotypic manipulation

Genetic "red flags:"

information that alerts the provider to the possibility of a genetic condition -remember F-GENES mnemonic (family history, groups of congenital anomalies, extreme presentation of common conditions, neurodevelopmental delay, extreme pathology, surprising lab values)

human genome project

international collaboration effort to map and sequence human DNA

Diagnostic test for aneuploidy

karyotype

eugenics

knowledge of genetics led to people deciding some should not reproduce due to poor genes

tumor suppressor genes

make proteins that stop cell division and kill cells

Transcription

making a strand of RNA that contains the same amino acid codes as gene for protein needed

mendelian vs sporadic inheritance

mendelian- inherited from parents sporadic-arise in new mutation

2 types of gene regulation

methylation and histone modification

epigenome

modification of DNA that does not alter sequence but adds methyl groups or wraps around histones to suppress the expression of gene

XX Males

most commonly caused by the translation of the SRY gene onto one of the X chromosomes (46, XX+SRY); men with this genotype share many characteristics of Klinefelter's syndrome (no sperm/ infertile)—except these men tend to have shorter-than-average stature, normal intelligence, and normal penile length

CYP450 enzymes

most important drug-metabolizing enzymes found in liver; specialized in inactivating foreign chemicals that have been ingested

incidental finding

mutation in the gene, not the mutation known to cause disorder

Trinucleotide Repeat (TNR)

mutation in which a sequence of 3 nucleotides repeats itself

genetic heterogeneity

mutations in different locations that result in the same phenotype (ex. 1700 mutations can cause cystic fibrosis)

recessive

need a copy of an allele from both parents to be expressed

What are the risk classifications designated for individualized care and how do they inform care recommendations?

o Average risk = standard prevention recommendations o Moderate ("familial") risk = personalized prevention recommendations o Considered moderate risk if: o 1 or more FDR with polyps (before or after age 60—affects reccs) o FDR with colon cancer dx age 60 or more o 5-year Gail (breast cancer risk) score > 1.66 o High (hereditary) risk = referral for genetic evaluation with personalized prevention recommendations o Considered high risk if: o >/= 3 relatives with HNPCC related cancers o >/= 3 relatives same side of family with the same cancer o >/= 2 relatives with BCC (1 w onset </= 50yrs) o >/= 1 relative with BC </= age 40

How common is it for people to have a positive/significant/actionable FHH? If your patient has a negative FHH (let's say for type II DM), what does that mean in terms of their risk to develop that condition? What would you tell the patient?

o FH is clinically actionable in 30-44% of people

chromatin

one of two identical parts of a chromosome

dominant

only need one copy of an allele from one parent for gene to be expressed

risk of consanguinity

parenting with a relative 6th degree or closer -increases risk of transmitting disorders

exome

part of DNA that encodes protein 1.5% of human DNA

What classification system is currently being applied to describe gene variants?

pathogenic likely pathogenic uncertain significance likely benign benign

diagnostic test

patient based → goal is to establish or rule out a diagnosis

mutational changes in DNA

permanent change that is harmful

variant changes in DNA

permanent change that is not harmful

proband

person in family who brought the genetic issue to the attention of a doctor

screening test

population based & meant for a whole group of people → goal is to identify people among entire group who are at risk for a condition

anticipation

phenotype of genetic disorder is expressed worse and earlier in each successive generation

karytope

picture of all chromosomes in a cell arranged in pairs from largest to smallest

chronic villus sampling

placental biopsy; diagnostic testing that is very invasive; occurs at 10-13 weeks

primary prevention

prevents onset of disease

carcinogenesis

process of cancer development - initiation, promotion, progression; occurs over years as mutations accumulate

codeine

prodrug that needs to be metabolized into morphine in order to experience therapeutic effects (typically pain relief) -metabolized by CYP 2D6

histones

protein that DNA wraps around to stay organized

Be able to describe the roles of proto-oncogenes, oncogenes, and tumor suppressor genes in carcinogenesis. What can happen if one of these genes is mutated, duplicated, deleted, or over- or under-expressed?

proto-oncogenes (gas pedal) code for proteins important in cell growth and cell division turn on cell cycle machinery oncogenes proto-oncogenes that become activated predispose us to cancer caused by OF, duplication, overexpression tumor suppressor genes (brakes) encode proteins that suppress cellular cycle LOF promotes carcinogenesis underexpression causes less of them but they can behave with only one copy

unknown genetic significance

prune belly syndrome condition characterized by a lack of abdominal muscles, causing the skin on the abdominal area to wrinkle and appear "prune-like"

sperms represent a more ________ epigenome

recent

diagnostic test for overexpression of oncogene

rna microarray

amniocentesis

sampling of amniotic fluid in fetal cells; occurs at 15-20 weeks

diagnostic test for susceptibility to common diseases

snp analysis

genomics

study of all genes in a genome together including interactions, environment, and influence of psychosocial and cultural factors

genetics

study of individual genes and their impact on rare single gene disorders

DNA hybridization-

take a double strand of DNA, heat it to separate it and attach another matching strand of DNA to the separated strand, useful in finding mutations

sensitivity (screening)

the ability of a test to detect all positive cases (expressed as %) -a measure of confidence that every negative is a true negative -critical for screening tests -how often the test is positive when the mutation is present 100% perfect- no false negatives

Specificity (diagnostic)

the ability of a test to never be wrong and exclude all negative cases -a measure of confidence that every positive is a true positive -how often the test is negative when the mutation is not present 100% perfect- no false positives

Utilitarianism

the doctrine that actions are right if they are useful or for the benefit of a majority.

What is the mechanism behind fragile X syndrome?

the expansion of the CGG sequence increases the hyper-methylation of the FMRI gene, silencing it's expression and leading to the manifestations of classic FXS

What is the significance of CGG repeats in Fragile X?

the number of CGG repeats is significant because the more repeats there are present leads to an increase in severity of the condition

Exon

the parts of a gene that belong in it

What important strategy should be applied when a family is affected by a genetic disease and the mutation is unknown? Who should be tested first? Why?

the pedigree should be used to find obligate carriers and those with the disorder a family member with the disorder should be tested first so they know that a mutation is present/ should be present

Penetrance

the percent of people with a genotype who express the condition

wild type

the phenotype for a character most commonly observed in natural populations

centromere

the point where two chromatids touch and microtubules attach

Paternalism

the practice of people with authority restricting the freedom and responsibility of those beneath them for their own benefits

variant of uncertain significance

they cannot determine risk associated with mutation

chromosome

threadlike structure of nucleic acids and protein that is encoded with genes, found in the nucleus

What tissues and body systems are most susceptible and what signs/symptoms would you anticipate in people with 'mito?'

tissues with high energy requirements are most vulnerable - LHON: bilateral, painless, blurred vision followed by progressive vision loss ii. MERRF: myoclonus (first sx), followed by generalized epilepsy, ataxia, muscle weakness, and dementia iii.MELAS: early childhood sx—generalized seizures, recurrent HA, , anorexia, weakness in limbs, and recurrent vomiting; by adolescence—impaired motor abilities,

When we talk about "thresholds" in reference to trinucleotide repeat disorders, what do we mean?

tne distinctive characteristic of TNR disorders is a threshold defined as a minimal repeat length that confers frequent mutations.

Mismatch repair genes

works to reverse DNA damage before it can accumulate -- accumulation results in cancer development

gene

unit of DNA that is blueprint for protein formation: resides on chromosome

translational research

use of lessons from basic research to develop and test applications to health care, psychotherapy, or other forms of treatment and intervention

Mercaptopurine

used to treat ALL/IBS; at toxic levels causes bone marrow suppression -metabolized by TPMT; there are several SNPs associated with low TPMT activity meaning it is common for individuals to have the SNP that could potentially lead to toxicity -genotyping for TPMT is now standard of care prior to administering this drug

euploid

when a cells nucleus contains normal diploid number of chromosomes for the species

When do we say a gene is expressed?

when it is activated at the promotor

diagnostic test for missense mutations

whole exam sequencing

diagnostic test for mutations that alter gene regulation

whole genome sequencing