Molecular Pathology & Diagnostics

Question 1

Pathology

Answer 1

Study of disease

Question 2

Molecular Pathology

Answer 2

Application of techniques of molecular biology to the study of disease

Question 3

Factors in Human diseases

Answer 3

Genetically determined
Environmentally determined
Almost all combination of genetics and environmental factors

Question 4

Major categories of genetic disorders

Answer 4

Mendelian disorders-single gene defect
Polygenic-multifactorial (most diseases)
Chromosomal (cytogenetic)-change in large amount of DNA

Question 5

Inherited diseases / germline

Answer 5

Autosomal dominant
Autosomal recessive
X-linked
Multifactorial (polygenic)

Question 6

Acquired / somatic

Answer 6

Not inherited
occurs in subset of cells
not passed to children

Question 7

Alteration to DNA sequences

Answer 7

Absent gene product
Abnormal gene product
Disorder of gene regulation

Question 8

Types of genetic lesions

Answer 8

Chromosomal deletions
Chromosomal translocations
Mutations–from insertions, deletions, point mutations
Gene amplification –copies of gene

Question 9

Cytogenetics

Answer 9

Identifies: extra, missing, abnormal chromosomes
Translocations
Large insertions and deletions

Question 10

FISH

Answer 10

Visualizes proximity or separation of two sequences

Question 11

FISH–Advantages

Answer 11

Higher sensitivity for specific alteration

Can use interphase cells

Question 12

FISH–Disadvantages

Answer 12

Only detects targeted alterations

Question 13

Molecular detection methods

Answer 13

PCR
Restriction enzyme fragment analysis
Sequencing
Proteomics-protein fragment analysis

Question 14

Molecular detection methods applications:

Answer 14

Heritable diseases
Cancer
Infectious diseases
Pharmacogenomics

Question 15

Heritable Diseases Examples:

Answer 15

Cystic fibrosis-mutation in CFTR gene
Sickle Cell disease-mutation in beta globin gene
Huntington’s chorea- gene amplification
Common chromosomal abnormalities

Question 16

Common chromosomal abnormalities:

Answer 16

Autosomal trisomies: 21, 18, 13
Digeorge syndrome : 22q11 deletion
Sex Chromosome abnormalites:
XO-Turner syndrome
XXY-Kleinfelter Syndrome

Question 17

`Down syndrome increases risk of

Answer 17

leukemia, Alzheimer’s Disease (in 40s)–3 copies of Alz-linked genes

Question 18

Cystic fibrosis

Answer 18

Inherited CFTR defect (chloride channel)

Produces abnormal thick secretions–in lung, pancrease

Question 19

CF screening detects

Answer 19

Mutations occur all over gene.
delta-F508 most common CFTR mutation
(recessive autosomal)

Question 20

Molecular diagnostics applied to cancer

Answer 20

Initial diagnosis
Classification for prognosis
Evaluation for residual disease
Monitor for relapse
Identify most appropriate therapy

Question 21

Molecular techniques to infectious disease

Answer 21

Diagnosis
Monitoring therapy–viral loads
Genotyping-characterize organism
Epidemiology–common origins

Question 22

Pharmacogenomics

Answer 22

Identification of genetic markers response to pharmacologic agents

Question 23

SNP

Copy number variants are common

Answer 23

Not a dysfunctional mutation or genetic lesion

Alleles-variation in human population

Question 24

Xenobiotic metabolism depends on six genes:

Answer 24

CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4

Question 25

CYP alleles can result in ___, ___, or increased enzyme activity, thereby affecting the rate of drug metabolization

Answer 25

absent, decreased

Question 26

CYP alleles variation lead to;

Answer 26

Normal metabolizers
Poor metabolizers
Ultrafast metabolizers

Question 27

Short term anticoagulation

Answer 27

Heparin

Question 28

Long term anticoagulation

Answer 28

Coumadin

Question 29

Coumadin CYP gene

Answer 29

CYP2C9

Question 30

Coumadin targets

Answer 30

VKORC1–vitamin K epoxide reductase

Question 31

CYP2C9*2 or *3 poor metabolizers

Have trouble with?

Answer 31

over-anticoabulation when on Coumadin

Question 32

VKORC1 A requires a much lower dose of ___

Answer 32

Coumadin

Question 33

Coumadin-related complication of CYP2C9 polymorphisms

Answer 33

Under anticoagulation–can lead to pulmonary embolism (fatal)

Question 34

Coumadin-related complication of CYP2C9 polymorphisms

Answer 34

Over anticoagulation–leads to hemorrhage

Question 35

Chronic myelogenous leukemia

Answer 35

Translocation between abl and bcr genes

Philadelphia chromosome: t(9;22)(q34;q11)

Question 36

Diagnostics for CML

Answer 36

cytogenetics, FISH, PCR

Question 37

Specific therapy for CML

Answer 37

Gleevec (Imatinib) TK inhibitor, other TK inhibitors

Question 38

HER2/neu

Answer 38

Proto-oncogene on Chromosome 17

Question 39

Her2

Answer 39

Gene amplification (2copies) leads to cancer.
Poor response to Tamoxifen

Question 40

Her 2 is treated with

Answer 40

Herceptin-Traztuzumab