Last Exam COPY

Question 1

1. ) What do Biochemical Assays for Metabolic Diseases detect?
2. ) When must they be used?

Answer 1

1.) Detects abnormalities caused by any mutant allele that has a significant effect on protein function.
2.) May be the only option if the causative mutation in the family is unknown.
L25 #31

Question 2

1. ) What is the definition of Concordance?

2. ) What is the Rate of Concordance?

Answer 2

1.) When two individuals in a family share a trait or have the same disease.
2.) Proportion of pairs of individuals (e.g. twins) who share a trait or have the same disease.
L22 #18

Question 3

1. ) What is the inheritance pattern for cystic fibrosis?
2. ) What is the primary genetic defect?
3. ) Most common location of mutation?
4. ) What is the function of the mutated gene/protein?

Answer 3

1.) Autosomal recessive
2.) Mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene –chromosome 7.
3.) ∆F508 is the most common.
4.) CFTR protein functions as a chloride channel, important for salt and water balance – affects multiple organs (e.g. lungs, pancreas).
L20 #31

Question 4

What is the best method to detect location of mutation in individuals with Duchenne and Becker muscular dystrophy?

Answer 4

Multiplex PCR.

L21 #14

Question 5

What does the following information tell us about the influences on complex diseases among adopted children:

1. ) Increased frequency with adopted family.
2. ) Increased frequency in biological family.

Answer 5

1.) Strong evidence for environmental influence in developing the disease.
2.) Strong evidence for genetic contribution to disease.
L22 #13

Question 6

What are two major drawbacks of Fetal DNA and Fetal Genome Analysis?

Answer 6

1.) When the disorder in the patient is due to a mutation different from the one being sought, i.e. you must know what it is you’re looking for.
2.) May not be predictive of clinical presentation in disorders characterized by variable expressivity (e.g. neurofibromatosis type 1, mitochondrial disorders).
L25 #31, p.729 TT

Question 7

What are four way that genetic and environmental factors associated with complex diseases are identified? Explain.

Answer 7

1.) Familial risks: Incidence of a disorder in relatives compared with the incidence in the general population.
2.) Twin studies: What is the incidence in monozygotic twins compared with dizygotic twins?
3.) Adoption studies: What is the incidence in adopted children of the disorders which their biological parents had (same genetic background, but different environment)?
4.) Population and migration studies: What is the incidence in people from the same ancestry group when they move to a different geographic area (helps to identify the effect of the environment on the disease).
L22 #12

Question 8

If an individual has a disease that does not exhibit male-to-male transmission, what other familial inheritance pattern must be observed to confirm the disease inheritance as X-linked?

Answer 8

All daughters of an affected male must also be affected.

L20 #43

Question 9

1. ) Ultrasonography allows detection of structural fetal anomalies associate with which three types of genetic disorders? Give examples of each.
2. ) Multiple fetal abnormalities increase the likelihood of a ___________ fetus.

Answer 9

1.)
i.) Single-gene disorders: OI.
ii.) Multifactorial disorders: NTDs, congenital heart defects.
iii.) Specific syndromes: Down and Turner syndrome.
2.) Chromosomally abnormal fetus.
L25 #9

Question 10

1. ) ______ and ________ are essential before prenatal genetic testing.
2. ) What is the function of this (what what ISN’T)?
3. ) What are three key aspect of this role?

Answer 10

1.) Genetic counseling and informed consent.
2.) To provide information to support decision-making –NOT to dictate course of action
3.) Accurate diagnosis, communication, and non-directive presentation of options.
L25 #47

Question 11

According to the ACOG (American College of Obstetricians and Gynecologists), what test should be done when structural anomalies are detected on US?

1. ) When is it indicated?
2. ) Describe the level of genetic information given.
3. ) What can it ID?
4. ) Limitations (2)?

Answer 11

Chromosomal Microarray Analysis (CMA)
1.) Indicated when structural anomalies are detected on US.
2.) High resolution (yields more information than conventional karyotyping).
3.) Can ID chromosomal aneuploidy, as well as lesions too small to be detected by karyotyping.
4.) Limitations: Detects Variants of Unknown Significance (VUS), as well as adult onset diseases.
L25 #26, p.724 TT

Question 12

What is the definition of Pharmacogenomics?

Answer 12

Refers to the sum of all relevant genetic information affecting drug therapy.
-Is a much broader investigation of genetic variations at the level of the genome.
L24 #6

Question 13

During which weeks is α-fetoprotein highest in the fetal plasma, amniotic fluid, and maternal serum?

Answer 13

-Highest in fetal plasma and amniotic fluid at 10 weeks.
-Highest in maternal serum at ≈ 30-40 weeks.
L25 #37

Question 14

Which parameters used in 1st and 2nd trimester screening tests (4) are seen uniformly increased or decreased among the three major trisomy disorders (trisomy 13, 18, and 21)? Indicate whether increased or decreased and which trimester they are observed.

Answer 14

1.) Nuchal translucency (NT), 1st trimester: Increased
2.) PAPP-A, 2st trimester: Decreased
3.) uE3, 2nd trimester: Decreased
4.) AFP, 2nd trimester: Decreased
L25 #43

Question 15

Which genes encode for the proteins that allow (a) Green color vision, and (b) Red color vision?

Answer 15

(a) Green: OPN1MW (opsin-1 medium-wave-sensitive).
(b) Red: OPN1LW (opsin-1 long-wave-sensitive).
L21 #20

Question 16

Oncogenes may be introduced by _____ or ______.

Answer 16

DNA or RNA viruses.

Week 8 review, #4

Question 17

What is the normal base pair length of CFTR gene on PCR? Abnormal?

Answer 17

Normal = 63 bp
Abnormal = 60 bp
L20 #33

Question 18

1. ) For treatment of adenosine deaminase deficiency (ADA), what is used as a vector for gene therapy?
2. ) What are three alternative treatments for ADA?

Answer 18

1.) Retrovirus used as a vector.
2.) BM transplant (matched donor), RBC transfusion from healthy donors, enzyme replacement therapy.
L26 #37

Question 19

What is the overall purpose of the phase I and phase II reactions of drug metabolism? What happens in each phase?

Answer 19

Phase I and II: Makes drugs more polar and, therefore, more easily excreted by the kidneys.
-Phase I: Oxidation and reduction.
-Phase II: Conjugation reaction.
L24 #11

Question 20

What is the new aneuploidy screening modality and what is the method?

Answer 20

Non-invasive prenatal screening testing (NIPS), through sequencing of cell-free DNA (cfDNA) in maternal plasma.
L25 #44

Question 21

Drugs exert their effects by interacting with _________.

Answer 21

Specific target proteins.

L24 #24

Question 22

In Huntington disease, what is the correlation between the number of repeats and the age of onset? What term applies to this relationship?

Answer 22

More CAG repeats correlated with EARLIER age of onset – This is called “ANTICIPATION.”
L20 #13

Question 23

What are two limitations that apply to chorionic villus sampling (CVS)?

Answer 23

1.) No amniotic fluid, thus, NTDs cannot be assessed (via [AFP]) – NTD requires AF or maternal serum alpha-fetoprotein levels (MSAFP).
2.) 1% of samples yield ambiguous results due to chromosomal mosaicism, follow up amnio is required.
L25 #15

Question 24

If all (or almost all) affected individuals are males, and the affected individual does not have an affected parent, what is the inheritance pattern of the disease?

Answer 24

X-linked recessive.

L20 #43

Question 25

What is the pattern of inheritance for the offspring of X-linked dominant affected males?

Answer 25

All daughters affected, no sons affected (i.e. no male-to-male transmission).
L21 #26

Question 26

1. ) Describe Cell-Free Fetal DNA (cfDNA) screening and timeframe.
2. ) What type of screening is it?
3. ) What type of diagnostic test is used?

Answer 26

1.) After 7 weeks gestation, maternal serum contains free fetal DNA derived from placental trophoblasts.
2.) Highly accurate, noninvasive prenatal screening (NIPS) for common autosomal and sex chromosome aneuploidies.
3.) cfDNA isolation followed by high-throughput sequencing.
L25 #19

Question 27

For 1st degree family relationships, give the type(s) of family members, and % of genes in common.

Answer 27

Parents, siblings, children —> 50% genes in common.

L22 #15

Question 28

1. ) What is the drug 6-mercaptopurine (6-MP) used for?
2. ) Reduced function in which gene increases the toxicity of 6-mercaptopurine (6-MP)?
3. ) Rate the three genetic polymorphisms of this gene from most active to least active.

Answer 28

1.) 6-MP is a chemotherapy drug used to treat acute lymphocytic leukemia.
2.) Thiopurine methyltransferase (TPMT)
3.) Wild type (wt/wt) = Most active
-Heterozygous wild type/variant (wt/v) = Intermediate activity
-Homozygous variant (v/v) = Least active
L24 #19

Question 29

In Huntington disease, how many repeats are required for…

1. ) Unaffected/normal
2. ) Pre-mutation/unaffected
3. ) Reduced penetrance
4. ) Full penetrance/mutation

Answer 29

1.) 10-26 = Normal; unaffected.
2.) 27-35 = Pre-mutation; unaffected.
3.) 36-40 = Reduced penetrance; (+/-) affected.
4.) >40 = Full mutation/penetrance; affected.
L20 #13

Question 30

In which ethnic groups is cystic fibrosis (an autosomal recessive disease) seen with increased frequency (4)?

Answer 30

Non-hispanic white, Ashkenazi Jewish, Native American (Zuni, Pueblo).
L25 #48

Question 31

What is the definition of penetrance?

Answer 31

The proportion of individuals carrying a variant (mutation) of a gene that ALSO express the associated phenotype.
L20 #13

Question 32

What are the characteristics of an ideal viral vector (5)?

Answer 32

1.) Adequate gene carrying capacity
2.) Undetectable by the immune system
3.) Efficiently/sufficiently correct the disease phenotype
4.) Long duration of expression
5.) Safe to administer
L26 #35

Question 33

1. ) What are iPSCs?

2. ) What are they used for?

Answer 33

1.) Induced pluripotent stem cells.
2.) Can be taken from a patient in need of a transplant and induced to form the organ tissue and the organ itself.
L26 #28, p.549 TT

Question 34

What is the most common source of achondroplasia mutations? What is the mutation?

Answer 34

≈ 75-88% of cases due to NEW (de novo) MUTATIONS, while ≈ 12-25% are inherited from an affected parent.
MUTATION = Gly —> Arg substitution (380)
L20 #19

Question 35

Give five examples of common human, adult-onset diseases with complex pattern of inheritance.

Answer 35

*1.) DM Type II
*2.) Alzheimer disease
3.) Arthritis
4.) Asthma
5.) Cancer
L22 #8

Question 36

What does the “Common disease-Common variant theory” state? What does it suggest?

Answer 36

That susceptibility alleles confer moderate risk and occur at relatively high frequency in the population (>1%).
-Suggests that association studies in large cohort populations (e.g. unrelated individuals sharing the common disease) will be fruitful —> Look for segregation of disease with a particular genotype.
L22 #24

Question 37

1. ) What is preimplantation genetic diagnosis (PGD), what does it allow for?
2. ) What diagnostic tests can be done (3)?

Answer 37

1.) Testing of embryos during in vitro fertilization (IVF) for the purpose of selecting unaffected embryos for transfer to the uterus. Allows couples at high-risk for a specific genetic disorder in their offspring to avoid pregnancy termination
2.) PCR (for single gene disorders), FISH, chromosomal microarray (CMA).
L25 #17

Question 38

1. ) What is the main goal of CRISPR/Cas9? What is this process called? What is the future possibility for CRISPR?
2. ) How does it correct a mutant gene?
3. ) Where can this process take place that makes it so useful? Example?

Answer 38

1.) To modify sequences in the genome in a site-specific (targeted) manner. Possibility of permanently curing disease
2.) Creates a double-strand break (endonucleases), and repairs using homology-directed repair.
3.) Can be done in vivo, e.g. Genetic editing works in mice with Duchenne muscular dystrophy —> DMD gene mutation is corrected and dystrophin expressed in muscles.
L26 #44-45

Question 39

What dietary manipulations must be made in the case of PKU (3)?

Answer 39

Restrict Phe, supplement with branched-chain AAs (Leu, Ile, Val), supplement with Tyr and Trp.
LIV–TT
L26 #9

Question 40

How often does an autosomal dominant abnormal phenotype appear throughout the course of many generations?

Answer 40

Abnormal phenotype appears in EVERY generation.

L20 #10

Question 41

1. ) Explain the threshold model for complex diseases.

2. ) In a graphical representation, what portion of the curve represents the number of individuals affected?

Answer 41

1.) In multifactorial disorders, there is a threshold (of genetic and environmental factors), above which a person will develop the multifactorial disorder.
2.) The area under the curve to the right of the threshold line.
L22 #7

Question 42

What are two variations that may be exhibited in postaxial polydactyly?

Answer 42

1.) May exhibit reduced penetrance.
2.) May exhibit variable expressivity (i.e. extra digit may vary from a small skin tag to a fully formed digit).
L20 #18

Question 43

Define High Throughput Screening. What is it used for?

Answer 43

Test/assay a large number of potential compounds at the same time (use of automaton/robotics). Used to evaluate small molecules for small molecule therapy.
L26 #18

Question 44

What are four outward physical manifestations of familial hypercholesterolemia?

Answer 44

1.) Thickened achilles tendon
2.) Cholesterol deposits in soft tissues leading to xanthelasmas, xanthomas, and arcus cornealis.
L20 #15

Question 45

1. ) Describe Massively Parallel Sequencing using cell-free fetal DNA including timeframe.
2. ) Who is it recommended for?
3. ) What are its clinical applications (3)?

Answer 45

1.) After 7 weeks gestation, cfDNA released from trophoblast can be detected in maternal serum.
Sequence fetal DNA using Massively Parallel Sequencing (a non-invasive prenatal screening –NIPS)
2.) Not recommended for the general population because not enough genetic counsellors to handle a large burden, thus, only recommended for women at high risk for having a child with Down’s syndrome.
3.) Rh genotype, gender determination, detection of autosomal trisomies.
L25 #28

Question 46

In HNPCC, what other type of cancer (besides colon cancer) is there a high probability of developing?

Answer 46

Endometrial cancer.

L20 #17

Question 47

1. ) What causes NTDs and when?
2. ) What three conditions does it result in?
3. ) When and how do you screen for NTDs?

Answer 47

1.) Failure of the neural tube to close by the 27th day after conception.
2.) Anencephaly, encephalocele, spina bifida.
3.) Screening at 15-20 weeks (2nd trimester) utilizing maternal serum α-fetoprotein (MSAFP)
L25 #33

Question 48

1. ) cfDNA is a _______, _________ screening for common _______ and _________.
2. ) Not a _____ test; provides a _________.
3. ) What should be done if abnormal?

Answer 48

1.) cfDNA is a highly accurate, non-invasive screening for common autosomal and sex chromosome aneuploidies.
2.) Not a definitive test; provides a risk assessment.
3.) If abnormal, invasive diagnostic testing should be done to confirm results.
L25 #20

Question 49

For 3rd degree family relationships, give the type(s) of family members, and % of genes in common.

Answer 49

First cousins, great grandchildren/-parents, great aunt/uncle/niece/nephew —> 12.5% genes in common.
L22 #15

Question 50

1. ) When is Chorionic Villus Sampling (CVS) performed?
2. ) Performed to assess _________ (__-__ days).
3. ) Risk of pregnancy loss similar to _______ with ________ approach.
4. ) What is a major advantage of CVS compared to amniocentesis?
5. ) Drawback compared to amniocentesis?

Answer 50

1.) 10-13 weeks
2.) Performed to assess fetal karyotype (7-10 days)
3.) Similar to amnio with transabdominal approach.
4.) Major advantage compared to amniocentesis is that CVS allows the results to be available at an early stage in pregnancy, thus reducing the period of uncertainty and allowing termination, if it is elected, to be performed in the first trimester.
5.) Not able to measure [AFP] and, thus, cannot evaluate for NTDs.
L25 #13, p.707 TT

Question 51

1. ) What mutation causes hemophilia A?
2. ) What are five consequences?
3. ) What is the inheritance pattern?

Answer 51

1.) Caused by mutations in Factor VIII (F8) gene.
2.) Fibrin formation affected, prolonged bleeding from wounds, bruising, hemorrhages in joints and muscles, intracranial bleeding with head trauma.
3.) X-linked recessive.
L21 #18-19

Question 52

What dietary changes must be made in the case of Ornithine Transcarbamoylase Deficiency (OTC) (2)?

Answer 52

Protein restriction, citrulline supplementation

L26 #9

Question 53

1. ) Concerning PKU with allelic heterogeneity, how much residual enzyme activity must be present in order for high dose BH4 to increase enzyme activity? What enzyme?
2. ) Which drug that acts as cofactor/coenzyme supplementation also requires the same residual enzyme activity? What does it act as?

Answer 53

1.) at least 12.5% residual phenylalanine hydroxylase (PAH) enzyme activity.
2.) Sapropterin dihydrochloride (Kuvan) —> tetrahydrobiopterin (BH4) cofactor
-Effective in some PKU patients (requires 12.5% residual PAH enzyme activity).
L26 #10

Question 54

1. ) How many copies of a mutant allele is needed for phenotypic expression in an autosomal dominant disease?
2. ) What chance does a child of an affected + unaffected parentage have of being affected?

Answer 54

1.) One copy of mutant allele disease gene is sufficient for expression of the disease phenotype.
2.) 50% chance of being affected.
L20 #8

Question 55

What is the Lyon Hypothesis?

Answer 55

One of the X chromosomes in females is randomly inactivated early in embryonic development.
L21 #5, p.17 njp

Question 56

Give five examples of common human congenital malformations with complex patterns of inheritance.

Answer 56

1.) Cleft lip-palate
2.) Congenital hip dislocations
3.) Congenital heart defects
4.) Pyloric stenosis
5.) Neural tube defects
L22 #8

Question 57

Give 5 genetic diseases for which stem cell transplants have been beneficial —> three general groups (1, 2, 1)

Answer 57

1.) SCID
2.) Lysosomal storage diseases (Hurler syndrome)
3-4.) Hereditary blood disorders —> Thalassemias, sickle cell disease
5.) Osteogenesis Imperfecta (OI) —> Mesenchymal stromal cells for OI.
L26 #31

Question 58

1. ) What is the definition of Genetic Association?

2. ) What method of genomic analysis is used in this study?

Answer 58

1.) Correlation between SNPs/genotype/haplotype, and phenotype.
2.) SNPs have facilitated this type of study; use of SNP microarray.
L22 #24

Question 59

Describe complex diseases in terms of the following:

1. ) Number of genes involved to cause disease phenotype.
2. ) Frequency
3. ) Mendelian pattern of inheritance?
4. ) Recurrence rate

Answer 59

1.) Many genes involved to cause the disease phenotype.
2.) Common frequency
3.) No Mendelian pattern of inheritance.
4.) Low recurrence rate.
L22 #10

Question 60

The degree of red and green color perception depends on where the ________ occurs within the genes during ________.

Answer 60

Crossing over occurs within the genes during meiosis.

L21 #22

Question 61

1. ) What is the role of G6PD (2)?
2. ) What are the effects of G6PD deficiency (2)?
3. ) What is the G6PD deficiency inheritance pattern?

Answer 61

1.) (a) Regulated step in PPP/HMP shunt, (b) Protects RBCs from effects of reactive oxygen species (ROS).
2.) (a) Causes RBC destruction (hemolysis), (b) Results in hemolytic anemia.
3.) X-linked recessive.
L21 #15, p.18 njp

Question 62

Microdeletions in which gene regions (3) are observed in males with azoospermia (AZF), i.e. no measurable levels of sperm in semen?

Answer 62

DAZ, DDX3Y, and USP9Y genes.
D.U.D. genes
L21 #39

Question 63

Carriers of Type II DM risk variants are more likely to:

1. ) Fail which therapy as opposed to another?
2. ) Require what?
3. ) What two genes are commonly associated with risk variants for Type II DM? What is their significance?

Answer 63

1.) Fail sulfonylurea therapy than metformin.
2.) Require/are more likely to be on insulin than diet alone.
3.) (i) TCF7L2: Associated with “open chromatin sites,”’ i.e. regions that are bound by regulatory factors; identified important role of intergenic SNPs. (ii) SLC30A8: encodes for β-cell zinc transporter (ZnT-8) crucial for insulin secretion.
L22 #26-28

Question 64

1. ) What is the inheritance pattern of Familial Hypercholesterolemia?
2. ) What is the primary genetic defect in familial hypercholesterolemia?
3. ) What are the results and consequential predispositions?
4. ) What is the result if heterozygotic for this condition?

Answer 64

1.) Autosomal dominant
2.) Mutations in the LDLR gene in chromosome 19.
3.) Elevated blood LDL levels, predisposing to coronary artery disease (CAD) at a young age.
4.) Reduced number of functional LDL receptors.
L20 #15

Question 65

1. ) What is the inheritance pattern of Postaxial Polydactyly.
2. ) What is the primary genetic defect in Postaxial Polydactyly and what does it encode for?
3. ) What is the consequence of mutation?

Answer 65

1.) Autosomal dominant
2.) Mutations in the GLI3 gene in chromosome 7 —> Encodes for a TF involved in shaping/patterning of many organs and tissues during development.
3.) Extra fingers or toes.
L20 #18

Question 66

1. ) When is fetal blood sampling performed? What else is it called (2)?
2. ) Indications (3)
3. ) What type of diagnostic assessment can it rapidly provide and how long does it take?

Answer 66

1.) after 20 weeks —> aka cordocentesis or percutaneous umbilical blood sampling (PUBS).
2.) Fetal anemia, thrombocytopenia assessment, and fetal karyotype (KT) determination (e.g. cases of mosaicism after amnio or CVS).
3.) Rapid fetal karyotype (KT) in 24-48 hours.
L25 #16

Question 67

1. ) What is the formula for Relative risk ratio (λr)?
2. ) What does it mean if λr >1?
3. ) What does it mean if λr = 1?

Answer 67

1. ) λr = (Prevalence of disease in relatives of affected person/Prevalence of disease in the general population)
2. ) λr > 1 means a relative is more likely to develop the disease than any individual in the population.
3. ) λr = 1 means that a relative is NO MORE LIKELY to develop the disease than any individual in the population.

L22 #16

Question 68

Describe how X-linked dominant disorders affect the sexes/offspring differently (4).

Answer 68

-Affects either sex, but more females than males (because there are more possible situations in which a female can be affected).
-Females are often more mildly and variably affected than males (due to random X inactivation and the fact that males have only one X chromosome).
-Affected female + Normal male = 50% chance of affected son or daughter.
-Affected male + Normal female = All affected daughters, no affected sons.
L21 #26

Question 69

1. ) What is the target protein of Warfarin?

2. ) How would you manipulate the dosage of a patient with less of this target?

Answer 69

1.) VKORC1 (Vitamin K recycling factor 1): Blocked by Warfarin to cause anticoagulant effect.
2.) Patients with less VKORC1 should get LESS Warfarin because they are more sensitive to the drug.
L24 #31

Question 70

1. ) What three types of mutations activate oncogenes to produce abnormal (hyperactive) proteins?
2. ) What three types of mutations activate oncogenes to produce excess normal protein?

Answer 70

1. ) Point mutations, chromosomal translocations, local DNA rearrangements.
2. ) Gene amplification, chromosomal translocations, insertional mutagenesis.
   p. 1 njp

Question 71

1. ) What is the inheritance pattern of HNPCC?

2. ) What is the primary genetic defect in HNPCC (aka ________). Give four genes and their associated chromosome.

Answer 71

1.) Autosomal dominant
2.) Hereditary Non-Polyposis Colon Cancer (HNPCC), aka Lynch Syndrome.
1˚ genetic defect: Mutations in mismatch repair genes —> MLH1 (Ch3), MSH2 (Ch2), PMS1 (Ch2), and PMS2 (Ch7).
1322, 1227 - in alphabetical order, L to S
L20 #17

Question 72

How do you determine the number of repeats in Huntington disease?

Answer 72

PCR amplify to determine the number of CAG repeats.

L20 #13

Question 73

Which enzymes of phase I (2) and phase II (1) drug metabolism reactions are associated with genetic variations that alter drug effects?

Answer 73

Phase I: CYP2C9, CYP2D6
Phase II: TPMT
L24 #12

Question 74

Explain the biologic significance of SNPs in intergenic DNA segments in Type II DM (i.e. genes involved and consequences).

Answer 74

TCF7L2 gene associated with “open chromatin sites” –Regions that are bound by regulatory factors.
-High-risk T allele associated with greater enhancer activity, increased transcription of TCF7L2 (5-fold in individuals with Type II DM compared to controls
L22 #27

Question 75

What physical damage results from Huntington disease? What is the result (physical-2, mental-2)?

Answer 75

Damage to corpus striatum —> Causes abnormal, involuntary writhing movements (chorea), loss of motor control.
-Behavior, mood, and personality changes; loss of thinking ability.
L20 #12

Question 76

The speed of results in cytogenic analysis is related to what? Give two examples with timeframe.

Answer 76

Speed of results is related to how quickly the cells can grow in culture.
1.) Fetal blood cells = 24-48 hours.
2.) Amniotic fluid cells or Cultured chorionic villi = 7-10 days.
L25 #23

Question 77

Which parameter used in 1st and 2nd trimester screening tests is indicative of a neural tube defect (NTD); increased or decreased, and during which trimester?

Answer 77

Increased AFP during the second trimester (15-20 weeks).

L25 #43

Question 78

The tendency for repeat expansion in Huntington disease is greater when disease if of ________ origin.

Answer 78

PATERNAL origin.

L20 #13

Question 79

1. ) What is the pattern of inheritance for Rett syndrome?
2. ) What is the cause of Rett syndrome?
3. ) What is the function of the mutated gene? What do the mutations do?
4. ) What is the inheritance pattern?
5. ) What is the manifestation in affected males?

Answer 79

1.) X-linked dominant.
2.) Mutations in the MeCP2 (methyl CpG binding protein 2).
3.) To bind methylated cytosines and mediate gene silencing. Mutations allow improper activation of many genes which are methylated and should normally have been silenced
-Thus, Rett syndrome is a DNA methylation disorder.
4.) X-linked dominant.
5.) Affected males are miscarried (male lethal).
L21 #30

Question 80

What is the meaning of the following:

1. ) 100% concordance in MZ twins.
2. ) less than 100% concordance in MZ twins.

Answer 80

1.) Strong evidence that genotype alone is sufficient to develop disease, e.g. sickle cell disease (all genetic).
2.) Strong evidence that non-genetic factors (e.g. environment) play a role in the disease.
L22 #19

Question 81

Define diversion in the context of manipulating metabolism to treat metabolic enzyme deficiencies, give an example.

Answer 81

Diversion: Facilitates excretion and/or production of less toxic products –e.g. seek to mobilize NH3 excretion in individuals with OTC deficiency.
L26 #11

Question 82

1. ) Concerning modification of somatic genome by transplantation, what does a liver transplant treat?
2. ) What is this mode of therapy called?

Answer 82

1.) Treatment of transerythin-mediated amyloidosis
2.) Serves as a mode of “gene replacement therapy” —> The organ serves as the mode of gene replacement.
L26 #27

Question 83

1. ) What is the most active form of Warfarin?

2. ) What role does CYP2C9 play in the Warfarin pathway?

Answer 83

1.) S-Warfarin (100x more activity than R-Warfarin).
2.) Warfarin metabolizer, converts S-Warfarin to the inactive form, 7-OH Warfarin.
L24 #31

Question 84

Describe the four different kinds of drug metabolizers.

Answer 84

1.) Ultra-rapid metabolizers (UM): Individuals who have multiple copies of an active gene.
2.) Extensive metabolizers (EM): Individuals who have two normal genes and metabolize a drug normally.
3.) Intermediate metabolizers (IM): Individuals who have one active and one non-active allele for the same gene.
4.) Poor metabolizers (PM): Individuals with a non-functional or less functional gene that metabolize a drug very slowly.
L24 #13

Question 85

1. ) What is the inheritance pattern of achondroplasia?
2. )What is the primary genetic defect in achondroplasia?
3. ) What does the gene encode for?
4. ) Consequences of mutation (5)?

Answer 85

1.) Autosomal dominant
2.) Mutations in FGFR3 gene in chromosome 4.
3.) FGFR encodes for a transmembrane tyrosine kinase receptor that binds fibroblast growth factor.
4.) Bone growth disturbances —> short limbs relative to trunk (normal-sized torso), prominent forehead, flattened nasal bridge, and redundant skin folds in arms and legs.
L20 #19

Question 86

Define manifesting heterozygote

Answer 86

When a female has one mutant copy of an X-linked gene and shows signs of an X-linked recessive disorder.
-A female heterozygous for an X-linked disorder in whom, because of non-random X inactivation, the trait is expressed clinically, although usually not to the same degree of severity as in hemizygous affected males.
L21 #7, p.1108 TT

Question 87

Describe the two techniques used of preimplantation genetic diagnosis (PGD) and their timeframe.

Answer 87

1.) Blastomere biopsy: Single cell removed THREE DAYS after IVF, when embryo is 8-16 cells.
2.) Blastocyst biopsy: Five trophectoderm cells removed 5-6 days after IVF, when blastocyst has developed.
L25 #18

Question 88

What is the term of zygosity used for the X chromosome in males? Why?

Answer 88

HEMIzygous: Because only one X chromosome and, therefore, cannot be hetero- or homozygous.
L21 #6

Question 89

Give four characteristics of the X-linked recessive pattern of inheritance (e.g. who is affected, parents of affected individual, mother of affected individual, transmission).

Answer 89

1.) Mainly affects males.
2.) Affected males are usually born to unaffected parents.
3.) The mother is normally an asymptomatic carrier and may have affected male relatives.
4.) NO MALE-TO-MALE TRANSMISSION in the pedigree. Transmission occurs from an affected male THROUGH FEMALES to an affected grandson and/or great-grandson
L21 #8, p.251 TT

Question 90

What is the term for an inability to perceive green colors? red?

Answer 90

Green: Deuteranopia
Red: Protanopia
L21 #20

Question 91

1. ) What is the basic concept of “Modification of Somatic Genome by Somatic Gene Therapy?”
2. ) How is it done?

Answer 91

1.) Introducing normal genes into somatic cells.
2.) Introduce genes via viral vectors
L26 #34

Question 92

Define “manifesting heterozygote”

Answer 92

A female heterozygous for an X-linked disorder can potentially manifest the disease phenotype IF all of active X chromosome happen to be the one carrying the gene with disease-causing mutation, Xm.
-A female heterozygous for an X-linked disorder in whom, because of random X inactivation, the trait is expressed clinically, although not usually to the same degree of severity as in hemizygous affected males (p.1108 TT)
L21 #35

Question 93

Define the pseudoautosomal region (PAR) of the Y chromosome.

Answer 93

Region that shares homology with regions on X chromosome and is used for pairing with X chromosome during meiosis.
Site of recombination with X chromosome
L21 #39

Segment of the X and Y chromosome, located at the most distal portion of their respective p and q arms, at which crossing over occurs during male meiosis.
•Traits due to alleles at pseudoautosomal loci will appear to be inherited as autosomal traits despite the physical location of these loci on the sex chromosomes.
p.1117 TT

Question 94

Explain the pathway (w/ associated genes) and its associated genetic variant that causes an insulin secretory defect.

Answer 94

SLC30A8 gene encodes for β-cell zinc transporter, ZnT-8, which is expressed exclusively in pancreatic islet cells.
-Zn transporter localized in membranes of secretory vesicles that transport Zn from cytoplasm into insulin secretory vesicles;provides Zn to allow for insulin storage and secretion.
-Variant encodes for an Arg to Trp change in position 325, which causes an insulin secretion defect.
L22 #26

Question 95

1. ) When is amniocentesis used?
2. ) What three general things is it used to evaluate?
3. ) What are seven diagnostic tests performed on amniocentesis?

Answer 95

1.) 15-20 wks of gestation
2.) Fetal chromosome and genome analysis, in addition to [AFP].
3.) [AFP] for NTDs, fetal karyotype (FISH), genome analysis, enzyme measurements, fetal lung maturity tests, AF bilirubin, PCR for pathogens.
L25 #11-12, p.33 njp

Question 96

What is the definition of Pharmacogenetics?

Answer 96

The study of how the variations in a targeted gene or groups of functionally related genes affect individual’s responses to drug therapy.
L24 #6

Question 97

1. ) How are the results of screening for NTDs expressed?
2. ) What is the formula?
3. ) What is an abnormal result?
4. ) What are results adjusted for (6)?

Answer 97

1.) Results expressed as Multiple of the Median (MoM)
2.) MoM = (Patient [MSAFP] / Median [MSAFP])
same gestational age (which means what???)
3.) Abnormal = 2.0 –2.5 MoM
4.) Maternal weight, race, IDDM (???), multiples, gestational age, and fetal viability.
L25 #38

Question 98

A.) Concerning G6PD deficiency, what four things must one avoid? —> Three drug classes (1, 2, 1) and one food.
B.) What is the overall goal of these restrictions?

Answer 98

A.)
1.) Antimalarial drugs: Primaquine, but not chloroquine or quinine.
2.) Antibiotics: Sulfamethoxazole, chloramphenicol.
3.) Antipyretics: Acetanilide, but not acetaminophen.
4.) Fava beans.
Triple A, F (AAA-F)
B.) Substrate reduction
L26 #7

Question 99

1. ) ____________ in the promoter region for ALOX5 result in the expression of different amount of target protein.
2. ) There must be _________ to get an ALOX5 enzyme with the highest activity.

Answer 99

1.) Variable Number of Tandem Repeats (VNTRs)
2.) Five tandem repeats
L24 #27

Question 100

What organ systems can be affected by Marfan syndrome (3)? Give examples of each.

Answer 100

1.) Ocular: Myopia, displaced lens (ectopia lentis).
2.) Skeletal: Tall stature, unusually long and slender limbs, scoliosis, hypermobility of joints.
3.) Cardiovascular: Mitral valve prolapse, dilatation of the ascending aorta.
L20 #22

Question 101

What is the consequence of an absent, mutated, or non-functioning SRY gene?

Answer 101

Female sex differentiation pathway proceeds.

L21 #42

Question 102

1. ) Give an example of cofactor/coenzyme supplementation in manipulation of metabolism and what it’s for.
2. ) It’s efficacy is conditional on what?

Answer 102

1.) Sapropterin dihydrochloride (KUVAN) – BH4 cofactor effective in some PKU patients.
2.) Requires at least 12.5% residual enzyme activity.
L26 #10

Question 103

Mutations in how many genes are associated with X-linked disorders?

Answer 103

300 genes

L21 #6

Question 104

Define the sex-determining region of the Y chromosome (SRY), i.e. what does it encode for?

Answer 104

Encodes for testis-determining factor (TDF) that triggers testes formation.
L21 #39

Question 105

What are the three steps to cytogenic analysis?

Answer 105

1.) Colcemid treatment + harvest.
2.) Hypotonic treatment (allows cell membrane to stretch, but not to break) + fixation.
3.) Metaphase spreading + DNA staining.
L25 #24

Question 106

Concerning the Human Genome:

1. ) How many nucleotides?
2. ) ≈ How many protein-coding genes?
3. ) How many proteins?
4. ) Where do the majority of differences between individuals in their genomes occur?
5. ) ≈ one in how many nucleotides do people differ in their genome?

Answer 106

1.) 3 billion
2.) ≈ 21,000
3.) ≈ 100,000
4.) SNPs
5.) 1 in every 1,000 nucleotides
L24 #7

Question 107

Anti-asthma drug _______ decreases airway inflammation by inhibiting the enzyme _______, which is encoded by the gene _______.

Answer 107

Zileuton, 5-lipoxygenase, ALOX5

L24 #26

Question 108

With regards to Autosomal Dominant inheritance pattern:

1. ) What is the correlation between affected persons and parents?
2. ) Gender?
3. ) Transmission and gender?

Answer 108

1.) An affected person usually has at least one affected parent.
2.) Affects either sex.
3.) Transmitted by either sex.
L20 #7

Question 109

What type of relation have the same alleles in every locus?

Answer 109

Monozygotic twins.

L22 #16

Question 110

What Y-linked gene mutation causes hearing loss? What is the transmission pattern?

Answer 110

DFNY1 gene mutations cause hearing loss –Transmission is EXCLUSIVELY male-to-male (i.e. Holandric transmission –gene occurring on the Y chromosome).
Mnemonic —> Hearing loss = Deaf = DF in NY = DFNY1
L21 #43

Question 111

Rett syndrome is a _________ (not a pattern of inheritance) disorder observed mainly in _________.

Answer 111

DNA methylation disorder observed mainly in females.

L21 #30

Question 112

Give two examples of depletion in the context of metabolic manipulation.

Answer 112

Direct removal of a compound
1.) Use of apheresis to remove LDL from the circulation in patients with homozygous familial hypercholesterolemia (Apheresis: a medical technology in which the blood of a donor or patient is passed through an apparatus that separates out one particular constituent and returns the remainder to the circulation).
2.) Use of phlebotomy to decrease iron overload in patients with hereditary hemochromatosis.
L26 #16

Question 113

1. ) What is the definition of locus heterogeneity? Give example of genetic disease that exhibits this.
2. ) Mutations in which genes cause a predisposition for this disease (4)?

Answer 113

1.) Same phenotype caused by many different genes.
e.g. Hereditary Non-Polyposis Colorectal Cancer (HNPCC).
2.) Mutations in mismatch repair genes —> MSH2, MLH1, PMS1, and PMS2.
L20 #38

Question 114

1. ) What is umbilical blood a source of (2)?

2. ) What are the advantages (3) and disadvantages (1)

Answer 114

1.) Hematopoietic stem cells and mesenchymal stromal cells.
2.) Advantages: Faster availability, 1-2 HLA (human lymphocyte antigen) mismatches out of six tolerated (i.e. better toleration of mismatches), lower incidence and severity of acute graft versus host. Essentially, less of an immune response
Disadvantages: Limited/lower number of hematopoietic stem cells.
L26 #32

Question 115

What is the definition of pleiotropism?

Answer 115

When a single gene affects a number of phenotypic traits in the same organism. These pleiotropic effects often seem to be unrelated to each other.

•Mutations in a single gene results in defects in several organ systems (multiple phenotypes)

•Multiple phenotypic effects of a single gene.
L20 #38

Question 116

1. ) Describe Cytogenic Analysis by FISH
2. ) Give timeframe and what it’s performed on.
3. ) What does it provide information on?

Answer 116

1.) Rapid method for screening fetal cells for common aneuploidies (chromosomes 13, 18, 21, X, and Y).
2.) Can be done in 1-2 days on interphase nuclei (no culture).
3.) Only provides information on the chromosome or gene of interest.
L25 #25

Question 117

Give an example of small molecular therapy in order to increase amount of functional protein. Which disorder is it used for?

Answer 117

Vitamin B6 for pyridoxine-responsive homocystinuria –Only if there is residual enzyme activity
L26 #18

Question 118

What are three methods by which evaluation for possible NTDs can be conducted?

Answer 118

1. ) Maternal serum alpha-fetoprotein (MSAFP) screening.
2. ) Amniocentesis for amniotic fluid alpha-fetoprotein (AF-AFP).
3. ) Ultrasonography (US).
   p. 707 TT

Question 119

Why do complex diseases cluster in families?

Answer 119

Because relatives of an affected individual are more likely to have disease-predisposing alleles in common.
L22 #16

Question 120

1. ) What accounts for the fact that Warfarin doses can significantly differ from patient-to-patient?
2. ) Rank the dosage level from highest to lowest based on the three VKORC1 genotypes (AA, GG, and GA).

Answer 120

1.) Dose depends on level-of-function of drug metabolism enzyme (CYP2C9), as well as the amount of drug target protein (VKORC1). Both of which can vary widely among patients due to their genotypes.
2.) GG = highest dose, GA = intermediate dose, AA = Lowest dose.
L24 #32

Question 121

1. ) On which tissues is cytogenic analysis used?
2. ) What does it detect and how?
3. ) Limitations (3)?

Answer 121

1.) Any tissue containing cells capable of dividing is suitable.
2.) Conventional G-banding of metaphase chromosomes detect aneuploidies and large structural changes
3.) Cells must be cultured, doesn’t ID microscopic defects.
L25 #23

Question 122

1. ) What disorder does ATTR stand for and what is its pattern of inheritance?
2. ) What mutations does it result in (i.e. in what product and what does the product do)?
3. ) What is the result?
4. ) What is the current common treatment?
5. ) What is an experimental drug treatment?

Answer 122

1.) Transerythrin-mediated amyloidosis (ATTR): Autosomal dominant disorder.
2.) Missense mutations in transerythrin (produced mainly in the liver), which transports retinol and thyroxine.
3.) Results in deposition of amyloid in peripheral nerves and heart = Neuropathy and cardiomyopathy.
4.) Liver transplant
5.) Patisiran (an RNAi).
L26 #25

Question 123

The more closely related two individuals are, the more _______ they have in common.

Answer 123

Alleles.

L22 #16

Question 124

1. ) What is the zygosity of each parent in autosomal recessive diseases?
2. ) Affected individual?
3. ) After birth of an affected individual, each subsequent child has a ___% chance of being affected.

Answer 124

1.) Each parent is a heterozygote (carries altered allele of gene).
2.) Affected individual is a homozygote (requires two copies of mutant gene to be affected).
3.) 25% chance
L20 #26

Question 125

What are the Approaches to aneuploidy studying during:

1. ) 1st trimester – ____ wks (3)
2. ) 2nd trimester –____ wks (4)
3. ) Integrated screening

Answer 125

1. ) 1st trimester (11-14 wks): Ultrasound (US) of nuchal translucency (NT), and two maternal serum metabolites —> β-hCG and PAPP-A).
2. ) 2nd trimester (15-20 wks): Quadruple screen –MSAFP, β-hCG, unconjugated estriol, inhibin A.

3.) Integrated screening: Combined 1st and 2nd trimester screening.
L25 #41

Question 126

Give two diseases that exhibit pleiotrophy. What is their inheritance pattern?

Answer 126

1.) Marfan syndrome (FBN1 mutation): Autosomal dominant.
2.) Phenylketonuria – PKU (PAH mutation): Autosomal recessive.
L20 #38

Question 127

1. ) What is the inheritance pattern of classical phenylketonuria (PKU)?
2. ) What is the primary genetic defect in classical phenylketonuria (PKU)? What is the function of the gene?
3. ) Result?
4. ) What causes the associated hypopigmentation?
5. ) Dietary treatment, i.e. limitations (1), supplementation (5)?

Answer 127

1.) Autosomal recessive
2.) Mutations in phenylalanine hydroxylase (PAH) gene, chromosome 12. PAH responsible for conversion of Phe to Tyr
3.) Complete or near complete deficiency of enzyme activity.
4.) Hypopigmentation due to lack of Tyr
5.) Limiting dietary Phe, along with supplementation of Tyr, Trp, and branched-chain amino acids (Leu, Ile, Val).
Mnemonic —> TT-LIV
L20 #34, p.16 njp

Question 128

1. ) What is the effect of Warfarin on poor metabolizers?
2. ) What enzyme is responsible for metabolism of Warfarin to its inactive form?
3. ) How would their dose differ from that of an effective metabolizer?

Answer 128

1.) Poor metabolizers have good efficacy with Warfarin, but this could result in Warfarin build-up and potential toxicity.
2.) CYP2C9
3.) Decrease the dose.
L24 #31

Question 129

1. ) What is the inheritance pattern of Marfan syndrome?
2. ) What is the primary genetic defect in Marfan syndrome?
3. ) What does the gene encode for?
4. ) What type of mutation is observed in the most severe phenotype?
5. ) What type of effect is observed in certain phenotypes? Describe.

Answer 129

1.) Autosomal dominant
2.) Mutations in FBN1 gene in chromosome 15.
3.) Encodes for fibrillin in connective tissue; affects the deposition of elastin.
4.) Missense mutations.
5.) Dominant negative effect: Mutant fibrillins bind to and disable normal fibrillins.
L20 #21

Question 130

1. ) What is the pattern of inheritance for Fragile X Syndrome?
2. ) What is the cause of Fragile X Syndrome?
3. ) Give the normal and abnormal versions (# of repeats).
4. ) On Southern blot, how many kb for the normal gene and gene with full mutation.

Answer 130

1.) X-linked dominant
2.) Trinucleotide repeat expansion (CCG) in the 5’ UTR of the FMR1 gene.
3.) Normal = 6-50 repeats, Abnormal > 200 repeats (due to duplication).
4.) Normal = 5.2kb, Full mutation = 5.7kb
L21 #32

Question 131

1. ) An association has been made between low MSAFP values and __________.
2. ) Overall risk of this increases ≈ 2.5x at what maternal age?
3. ) All women who present for prenatal care before ____ weeks should be offered screening.

Answer 131

1.) Down syndrome
2.) Maternal age > 35 years old
3.) 20 weeks
L25 #40

Question 132

What are the two ways in which the final phenotype of a complex disease can be classified? Describe.

Answer 132

1.) Qualitative –i.e. present or absent.
2.) Quantitative –height, weight, body mass, etc.
L22 #6

Question 133

Genetic counseling must address which SIX aspects (first three related to providing information, second three related to providing support)?

Answer 133

1.) Risk of affected fetus
2.) Consequences of condition
3.) Procedure-related risk
4.) Waiting for results
5.) Need for repeat procedure
6.) Possible inconclusive results
L25 #49

Question 134

Concerning Autosomal Recessive Inheritance of Disease:

1. ) An affected person is usually born to ________ parents.
2. ) Parents of an affected person are usually ______________.
3. ) Parental _________ increases the incidence.
4. ) Which sexes do they affect?

Answer 134

1.) Unaffected parents.
2.) Asymptomatic carriers.
3.) Consanguinity.
4.) Affects either sex.
L20 #25

Question 135

What are three problems that arise in Prenatal Chromosome Analysis?

Answer 135

1.) Pseudomosaicism (occurrence of a cytogenically abnormal cell that arose after the tissue was put into culture; generally considered to be artifactual and of no clinical signififance –p.1118 TT).
2.) Culture failure
3.) Unexpected adverse findings
L25 #27

Question 136

What type of transmission pattern likely reflects mitochondrial inheritance?

Answer 136

If transmission occurs through affected mothers and NEVER through affected sons.
L21 #44

Question 137

1. ) What is the inheritance pattern of Huntington disease?
2. ) What is the genetic basis for Huntington disease?
3. ) What are the functions of the gene (3)?

Answer 137

1.) Autosomal dominant
2.) Trinucleotide expansion (CAG) in the huntingtin (HTT) gene in chromosome 4.
3.) HTT may be involved in signaling, transport, and protection from apoptosis.
L20 #12

Question 138

What occurs in the gonads during development when the Y chromosome is present and absent?

Answer 138

Y chromosome present: The SRY encoding for TDF increases the transcription factor SOX9, which promotes the development of the testes and, subsequently, male internal/external genitalia.

Y chromosome absent: Absence of Y chromosome = absence of TDF/SRY = No male genitals = Female internal/external genitalia.
L21 #40

Question 139

1. ) How are hematopoietic stem cells and mesenchymal stromal cells harvested (three steps)?
2. ) What is this used to treat (2)?

Answer 139

1.) Bone marrow aspirate —> Apheresis of growth factor-mobilized hematopoietic stem cells (HSC) —> HSC infused into patients.
2.) Hereditary blood disorders, lysosomal storage diseases.
L26 #31

Question 140

For 2nd degree family relationships, give the type(s) of family members, and % of genes in common.

Answer 140

Aunt, uncle, niece, nephew, grandparents/grandchildren, and half-siblings —> 25% genes in common.
L22 #15

Question 141

What is the principal behind Induction of Exon Skipping, i.e. what does it use and what is the result? What is it being used to treat experimentally?

Answer 141

Use of antisense oligonucleotides to result in an in-frame mRNA.
-Used to treat Duchenne Muscular Dystrophy.
L26 #26

Question 142

1. ) What are two disorders of sexual development (and their genotypes) caused by SRY gene and sex reversal? What is a characteristic of both?
2. ) How do they occur?

Answer 142

1.)
i.) Incomplete masculinization (XY female).
ii.) Virilization (XX male).
Both exhibit ambiguous genitalia
2.) When errors occur during meiosis where crossing over occurs outside of the PAR region –it is likely to involve the SRY gene since it is relatively close to the PAR (see image on L21 #41). If the SRY gene does cross over to the X chromosome – potential for XX males and XY females
L21 #41

Question 143

How is nuchal translucency seen? What is it an indicator of?

Answer 143

Nuchal translucency seen on fetal ultrasound (US); predictive of increased risk for Down syndrome.
L25 #42

Question 144

1. ) Where is α-fetoprotein synthesized and where is it abundant in the fetus (3)?
2. ) In NTDs, where is α-fetoprotein found (2)?

Answer 144

1.) Fetal yolk sac, GI tract, and liver –abundant in the fetal serum.
2.) Amniotic fluid and maternal serum.
L25 #36

Question 145

1. ) What is Tamoxifen for?
2. ) What is the prodrug and active drug?
3. ) Genetic variations in which enzyme(s) influence the extent of metabolism and clinical outcome?

Answer 145

1.) Estrogen receptor positive breast cancer.
2.) Prodrug = Tamoxifen, Active drug = Endoxifen.
3.) CYP2D6
L24 #15

Question 146

Describe single gene diseases in terms of the following:

1. ) Number of genes involved to cause disease phenotype.
2. ) Frequency
3. ) Mendelian pattern of inheritance?
4. ) Recurrence rate

Answer 146

1.) One gene involved to cause disease phenotype.
2.) Rare frequency
3.) Follows Mendelian pattern of inheritance
4.) High recurrence rate
L22 #10

Question 147

In X-linked recessive disorders, how is the disorder transmitted between successive generations?

Answer 147

A disorder is transmitted from an affected male through FEMALE obligate carriers (unaffected daughters) of the following generation (meaning the expressed disorder effectively “skips” a generation) to grandsons and great-grandsons of the aforementioned affected male.

i. e. Transmitted from an affected male through females to an affected grandson and great-grandson (if the daughter of an obligate carrier, herself and obligate carrier, transmits the disorder to her son).
p. 252 TT

Question 148

What genetic disorder is often the result of a new mutation?

Answer 148

Achondroplasia –Affected person may be the first person in the family with the condition.
L20 #36

Question 149

1. ) 11% of known genetic mutations are _________. What do they result in?
2. ) What treatment can be used to rectify this type of mutation?
3. ) What is the ultimate result?

Answer 149

1.) Nonsense mutations –results in a premature stop codon.
2.) Small molecule therapy: small molecules encourage misreading of stop codon by tRNA during translation.
3.) Results in a functional protein.
L26 #19

Question 150

1. ) What is the inheritance pattern of Duchenne Muscular Dytrophy (DMD)?
2. ) What causes Duchenne Muscular Dystrophy (DMD)?
3. ) What is the result (3)?
4. ) What is the early diagnostic indicator? Explain.

Answer 150

1.) X-linked recessive
2.) Caused by mutations in dystrophin (DMD) gene in the X chromosome.
3.) (a) Degeneration of muscle fibers (normal fiber replaced by fat and connective tissue; seen as pseudohypertrophy of calf muscles), (b) presence of chronic inflammatory cells, (c) heart and respiratory muscles affected and eventually fail (usual cause of death by age 25).
4.) Creatine kinase released by muscle may be 20-fold higher.
L21 #13

Question 151

What is the definition of locus heterogeneity?

Answer 151

Where mutations in different genes result in the same phenotype.
L20 #17

Question 152

If an autosomal recessive phenotype appears more than once within a family, between which family members does it occur?

Answer 152

Usually occurs between siblings of proband (affected individual); NOT in parents, offspring, or other relatives.
L20 #28

Question 153

What are the three definitive parameters in 1st and 2nd trimester screening tests that would give a definitive diagnosis of Down syndrome (trisomy 21)? Indicate which trimester.

Answer 153

1st trimester: Elevated hCG (decreased in trisomies 13 and 18).
2nd trimester: Elevated hCG, elevated Inhibin A (only seen in trisomy 21).
L25 #43

Question 154

What % of genes and environment do monozygotic (MZ) and dizygotic (DZ) twins share?

Answer 154

1.) Monozygotic: Identical genotype (and gene expression patterns); usually share same environment.
2.) Dizygotic (two eggs fertilized by two sperm): Share 50% of genes; usually share same environment.
L22 #18

Question 155

Give four examples of X-linked recessive disorders

Answer 155

1.) Duchenne muscular dystrophy
2.) G6PD deficiency
3.) Hemophilia A
4.) Color blindness
L21 #23

Question 156

1. ) What is a complex disease?
2. ) What is the inheritance pattern?
3. ) In complex diseases, the influence of risk factors is ______.
4. ) Interaction of ________ and _________ confer both ________ and _________.

Answer 156

1.) A common disease with a complex inheritance pattern.
2.) Tend to cluster in families, but do not follow classic Mendelian inheritance patterns.
3.) Additive
4.) Interaction of genetic and environmental factors confer both susceptibility and protection.
L22 #4

Question 157

1. ) What are iPSCs? (i.e. where are they derived from, moral issues?)
2. ) How are they used?

Answer 157

1.) Induced pleuripotent stem cells: Derived from somatic cells, not subject to moral and ethical issues surrounding hESCs (human embryonic stem cells).
2.) Direct reprogramming of somatic cells using transcription factors to make tissue/organ of choice.
L26 #33

Question 158

1. ) Define “skewed X inactivation.” When/how does it occur?

2. ) What is the medical significance?

Answer 158

1.) Occurs when the inactivation of one X chromosome is favored over the other, leading to an uneven number of cells with each chromosome inactivated.
2.) This is of medical significance due to the potential for the expression of disease genes present on the X chromosome that are normally not expressed due to random X inactivation.
-i.e. Mutation is present, but individual is phenotypically normal due to inactivated chromosome.
L21 #34

Question 159

1. ) What is the definition for “recurrence risk?”
2. ) What is the usual recurrence risk for:
   a. ) Autosomal dominant traits
   b. ) Autosomal recessive traits

Answer 159

1.) The chance that an inherited disease that is present in a family will recur in that family, affecting another person orpersons.
2.)
a.) Autosomal dominant = 50%
b.) Autosomal recessive = 25%
L23 #25