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GH Coarsework 2023 > Techniques 3 And Genetic Testing > Flashcards

Techniques 3 And Genetic Testing Flashcards

1
Q

Characterise Sanger sequencing

A
  1. Developed by Frederick Sanger in 1977
  2. Sequence short pieces of DNA: 100bp up to 1000bp
  3. Sequencing only a few samples at a time.
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2
Q

Principle of Sanger sequencing.

A
  1. Chain termination sequencing
  2. Dideoxy nucleotides (ddNTPs) lack a 3’ hydroxyl on their deoxyribose required for the formation of a phosphodiester bond between two nucleotides. Unlike the deoxynucleotide (dNTP).
  3. Incorporation of ddNTP prevent the diction of another nucleotide because ddNTP cannot form a phosphodiester bond with 5’ phosphate group the next nucleotide.
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3
Q

Limitations of sanger sequencing

A
  1. Targeted analysis
  2. Short sequencing 100bp to 1000bp (quality degrades after 700bp)
  3. Poor sequencing in first 15 to 40 bases
  4. Expensive and labour intensive for multiple targets (works best for single gene disorders)
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4
Q

Alternatives to sanger sequencing : NGS, why is it better.

A
  1. Higher sequencing depth enables higher sensitivity
  2. Higher discovery power
  3. Higher pathogenic variant resolution
  4. More data produced with the same amount of input DNA
  5. Higher sample throughput
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5
Q

Current applications of Sanger sequencing

A
  1. Targeting smaller genomic regions
  2. Identifying know pathogenic variants
  3. Validation of variants identified through next generation sequencing (NGS)
  4. Filling ‘gaps’ in NGS data in difficult -to-sequence areas and where coverage depth is low. Like GC rich and repetitive regions
  5. Verifying plasmids sequences and inserts.
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6
Q

The process of sager sequencing

A
  1. PCR amplification
  2. Purification of PCR product
  3. Cycle sequencing
  4. Purification
  5. Capillary electrophoresis
  6. Analysis
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7
Q

Why do you do a PCR product check

A
  1. Determine if PCR amplification was successful
  2. Determine if correct region was amplified
  3. Determine if there was contamination
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8
Q

Different methods of purification

A
  1. Ethanol precipitation
  2. Magnetic beads
  3. Spin columns
  4. Size exclusion membrane filters
  5. Enzymatic
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9
Q

Required components for cycling sequencing during sanger sequencing.

A
  1. DdNTP
  2. DNTPs
  3. Polymerase
  4. Buffer.
  5. Primer (forward or reverse never both)
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10
Q

Describe cycle sequencing

A
  1. DNTPs are incorporated into a growing strand
  2. When a ddNTP is incorporated synthesis is terminated and no additional dNTPs can get incorporated.
  3. This process is repeated in a number of cycles
  4. DdNTPs are randomly incorporated at different positions = multiple. DNA fragments of different lengths
  5. A ddNTP would get incorporated at every position of the target DNA.
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11
Q

Why do sequencing purification during sanger sequencing

A
  1. Removes. Excess primers and dNTPs, so that it doesn’t interfere with sequencing reaction.
  2. Interfere with quality and signal strength of sequencing data.
  3. Dye blobs - obscure portions of sequences.
  4. Increases Base calling accuracy.
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12
Q

Explain capillary electrophoresis during sanger sequencing

A
  1. Fragments separated by size
  2. Genetic analyser
  3. Fluorescent dyes excited by laser and detected
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13
Q

Process of sequencing analysis and interpretation

A
  1. Check quality of sequence
  2. Alignment
  3. Analysis
  4. Report
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14
Q

Uses of genetic mapping approach/ tool

A
  1. Identify candidate genes -large contribution to disease
  2. Construction of physical maps
  3. Haplotype analysis in highly inbred/geographically confined Populations.
  4. Indirect testing; markers flanking disease gene, track mutation/high-risk chromosome in family.
  5. Rare, unknown genetic disease - no reliable test availed for families
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15
Q

Define linkage disequilibrium

A

Certain alleles of each gene inherited together more often than expected by chance.

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16
Q

Define crossover/recombination

A
  1. Exchange of genetic info
  2. 1st meiotic prophase
  3. Dependent on distance
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17
Q

Explain LOD score -

A

A statistical estimate of wether 2 genetic loci physically located near each other on a chromosome and are therefore likely to be inherited together.

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18
Q

What is recombination fraction (theta )

A

Proportion of recombinant between the 2 genes

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19
Q

Define linkage equilibrium

A

Two genes /traits/loci inherited completely independently in each generation

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20
Q

Linkage disequilibrium may be due to …

A
  1. Actual genetic linkage (genes closely located n same chromosome)
  2. Functional interaction (some combinations of alleles at two loci affect viability of potential offspring .
  3. Occurs in populations as a result of mutation, random genetic drift, selection, and population admixture.
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21
Q

What is direct testing

A

Targeted testing for mutation associated with disease.

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22
Q

What is indirect testing

A
  1. Compare and track DNA markers (SNPs, STRs )linked to disease But Do not cause the genetic condition
  2. Useful when no reliable test available for families with rare, unknown genetic disease.
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23
Q

Types of genetic markers

A
  1. RFLPs (restriction fragment length polymorphism)
  2. Microsatellites markers
    2.1 STRPs (short tandem repeat polymorphism)
    2.2 SNPs ( single nucleotide polymorphisms)
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24
Q

Techniques used to genotype people during linkage analysis

A
  1. PCR
  2. Agarose gel electrophoresis
  3. CaPillary electrophoresis
  4. Southern blot
  5. Sequencing
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25
Q

Linked marker analysis can be used for which diseases.

A
  1. X-linked
    - duchenne/Becker muscular dystrophy
    -Haemophilia A/B
  2. Autosomal recessive
    -infantile polycystic kidney disease
    -beta thalassaemia
    -cystic fibrosis
  3. Uni paternal disomy
    -prader-willi/ Angelman syndrome
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26
Q

Why are homozygous alleles uninformative during linkage analysis.

A
  1. You cannot tell which allele is associated with the disease locus.
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27
Q

Define genetic counselling

A

Genetic counselling is the process of helping people understand and adapt to the medical, psychological and familial implications of genetic contributions to disease.

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28
Q

What are the three parts of genetic counselling.

A
  1. Interpretation of family and medical histories to asses the chance of disease occurrence or recurrence.
  2. Education about inheritance, testing, management, prevention, resources and research.
  3. Counselling to promote informed choices and adaptation to the risk or condition.
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29
Q

What are some factors that lead to a referral to clinical genetics. (8)

A
  1. Family history of a genetic condition
  2. child with birth defect or development delay.
  3. Families with a strong cancer history
  4. Dysmorphic features
  5. Multiple miscarriages
  6. Abnormalities on fetal ultrasound
  7. Teratogen exposure
  8. Patient with a known genetic condition.
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30
Q

What are inborn errors of metabolism.

A
  1. Genetic disorder that results from a defect in a single gene that codes for an enzyme involved n a metabolic pathway.
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31
Q

What are the two types of metabolic pathways

A
  1. Catabolic: breakdown of energy containing sources such as protein, lipid and carbohydrates to produce energy.
  2. Anabolic: energy used to create molecules from smaller components
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32
Q

what type of inheritance pattern do we usually see when it comes to inborn errors of metabolism.

A
  1. Autosomal recessive: 50% of normal level of enzymes produced -generally More than sufficient to continue normal metabolism.
  2. Some are X-linked
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33
Q

Consequences of an enzyme defect/ enzyme block.

A
  1. Increase in substrate (may be toxic)
  2. Reduction in product (reduction of energy production)
  3. Increase in alternative product ( may be toxic)
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34
Q

What is neuroregression

A

Child initially develops milestone normally, then gradually loses skills and deteriorates. Usually relentless course ending in encephalopathy and premature death.

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35
Q

What causes neuroregression

A
  1. It’s an accumulation of waste products in cell over time, reaches a threshold and eventually results in cell death.
  2. It’s often due to a genetic defect in an enzyme that removes cellular waste.
  3. Examples are lysosomal storage diseases such as Tay-sachs.
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36
Q

What is the importance of making a diagnosis of inborn errors of metabolism.

A
  1. Appropriate clinical managements: some can be management with diet or enzyme replacement therapy or bone marrows transplants.
  2. Managing recurrence risks using prenatal, carrier testing and cascade family screening.
  3. Understanding the incidence in Local population.
  4. Bringing closure to a family by explaining the underlying cause.
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37
Q

What are some challenges when it comes to diagnosing Inborn errors of metabolism.

A
  1. IEM are rare conditions with complicated testing algorithms
  2. Incidence varies globally
  3. Mostly physicians do not see IEM regularly.
  4. Very long and expensive journey to get to a diagnosis
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38
Q

Diagnostic testing options for inborn errors of metabolism.

A
  1. Biochemical assay
  2. Enzyme assay
  3. Molecular genetic testing
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39
Q

Characterise and give examples of biochemical assay done for IEM

A
  1. Basically an indirect test the consequence of the missing enzyme likely causes accumulation of various biochemical substances in blood or urine.
  2. Simple, inexpensive, easily available and can guide emergency management.
  3. Example: urea cycle disorders
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40
Q

Characterise enzyme assay done for IEM

A
  1. More direct assay.
  2. Detection of presence or absence of enzyme of interest in blood.
  3. Useful for common IEM.
  4. Not all IEM have enzyme assay
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41
Q

Characterise molecular genetic assay done for IEM

A
  1. Sequencing the gene coding for enzyme of interest.
42
Q

What constitutes a good newborn screening program .

A
  1. The conditions included in the screening program are common in population.
  2. The screening program is sensitive in terms of detecting the conditions-limit false neg
  3. Need to know the difference between screening and diagnosing a condition. If you are going to screen a patient, you have to follow it up with a diagnosis.
  4. Effective treatment needs to exist
  5. Cost/benefit ratio
43
Q

Talk about how gametogenesis in females can lead to non-disjunction.

A
  1. Gametogenesis is the formation of gametes through meiosis.
  2. Meiosis 1 happens when the oogonium matures and becomes the primary oocyte, this occurs in the 1st few months of intrauterine life.
  3. At birth primary oocyte maturation arrests.
  4. Meiosis 2 resumes at age +-15 to 50.
  5. Delayed onset at puberty and completion at 50 leads to wear and tear of primary oocyte during arrest.
  6. This causes spindle damage which lead to non-disjunction.
44
Q

Primary and secondary nondisjunction

A

Primary- nondisjunction in meiosis 1
Secondary- nondisjunction in meiosis 2

45
Q

Examples of Aneuploidy in autosomes.

A
  1. Trisomy 21- Down syndrome
  2. Trisomy 13 - Palau syndrome
  3. Trisomy 18- Edward syndrome
46
Q

Examples in sex aneuplodies.

A
  1. Monosomy x or do -Turner syndrome
  2. XXY- klinegelter syndrome
  3. XXX- Triple X syndrome
  4. XYY-Jacob’s syndrome
47
Q

Principles of QF-PCR

A
  1. Uses fluorescently labelled primers, specific to STRs of interest.
  2. Each targeted STR marker is specific to the chromosome on which it is located.
  3. The copy number of the STR marker can be diagnostic of the copy number of the chromosome.
  4. PCR products are separated by capillary electrophoresis based on number of repeat units.
48
Q

What are the two non-polymorphic markers used in QF-PCR

A
  1. Amelogenin: amplifies chromosome X and Y
  2. SRY: chromosome Y
  3. TAF9L: sequences both chromosome 3 and X
49
Q

Advantage of QF-PCR for aneuploidy screening

A
  1. Relatively quick test
  2. High sensitivity for common trisomies
  3. Can be used to infer likely maternal cell contamination
  4. Rapid for XX/XY sexing
  5. Works on DNA from old/degraded samples-different types.
  6. Low DNA concentrations
  7. Diagnostic test and alternative to karyotyping.
50
Q

Disadvantage of QF-PCR for aneuploidy screening. (6)

A
  1. Mosaicism not always detected
  2. No coverage of other chromosomes 3. Translocations of tested chromosomes may not be detected
  3. Low concentration DNA may affect interpretation
  4. Maternal cell contamination, incl only” CVS result “maternal
  5. Confined placental mosaicism (abnormal CVS finding, but AFs or blood in normal ranges)
  6. Null alleles/primer binding mutations
51
Q

What is MLPA used for?

A

Techniques used for the quantification of copy number variants (CNVs) -deletions and duplications.

52
Q

Steps of MLPA ASSAY principle

A
  1. Sample DNA denature
  2. Probe hybridisation
  3. Probe ligation
  4. Amplification of lighted probes
  5. Fragment separation
  6. data analysis
53
Q

How does MLPA work?

A
  1. One probe consists of two oligonucleotides
  2. Hybridised probe Oligos are connected by ligation
  3. The lighted probes are amplified in a multiplex PCR. MLPA probes are amplified.
  4. PCR reaction is very reproducible, as only one pair of PCR primers is used for all the reactions.
  5. Each probe generates an amplification product of unique length
  6. Amplification products are analysed by capillary electrophoresis.
  7. Differences in relative amount of probe target sequences in the sample results in different relative peak heights between the patient sample and the reference sample.
54
Q

What would the DQ ratio be if the sample is identical to reference samples.

A

0.80-1.20

55
Q

What would the DQ ratio be if the sample has a heterozygous deletion.

A

0.40-0.65

56
Q

What would the DQ ratio be if the sample has a heterozygous duplication.

A

1.35-1.65

57
Q

What are some microdeletion and duplication syndromes.

A
  1. DiGeorgesyndrome (22q11.2 microdeletion)
  2. Williams-Beurensyndrome (7q11 microdeletion)
  3. Neurofibromatosis type 1 (17q11 microdeletion)
  4. Smith-Magenissyndrome (17p microdeletion)
58
Q

Limitations of genetic testing via MLPA.

A
  1. The probemixeshas a limited number of probes for each specific chromosomal region and will therefore not detect all possible causes of the syndromes included.
  2. MLPA cannot detect any changes that lie outside the target sequence of the probes. Even when MLPA did not detect any aberrations, the possibility remains that biological changes in that gene or chromosomal region do exist but remain undetected.
  3. Sequence changes (e.g. SNPs, point mutations, small indels) in the target sequence detected by a probe can cause false positive results.
59
Q

What is methylation sensitive MPLA useful for .

A

Methylation- sensitive MPLA has been developed to characterised imprinted regions in addition to the quantification of copy number variants.

60
Q

MLPA limitations

A
  1. Unable to detect balanced translocations- only karyotyping can
  2. Limited to the kit design. Probes are specific to target regions. only karyotyping can
  3. Comparative genomic hybridization ( aCGH )/ micro array is better at characterizing more regions. However this technique is not applicable for single gene disorders.
61
Q

Testing approach and consideration

A
  1. Limited resource lab:
    1.1 driven on basis of clinical phenotype of patient
    1.2 valuable in certain classic monogenic syndrome and families with previously attributed molecular cause.
  2. New advanced technology (WES,WGS,NGS) impractical for routine testing.
62
Q

Diagnostic test should be these 5 things.

A
  1. Robust
  2. Simple
  3. Cost effective
  4. Affordable
  5. Validity
63
Q

When Evaluating a diagnostic test what do you look for ?

A
  1. Analytical validity
  2. Clinical validity
  3. Clinical utility
64
Q

What is analytical validity

A
  1. Does test work in the lab?
  2. Measure of ability of molecule test to detect genetic variant/mutation.
  3. Analytical sensitivity (false-neg rate)
  4. Analytical specificity (false-positive Rate)
65
Q

Clinical validity

A
  1. Does test work in the talent population of interest?
  2. Ability to correctly classify individuals to disease status or risk.
  3. Test may be clinically valid when applied to individuals from high risk population, but not so when applied to general population.
66
Q

What is the ACCE framework and what does it ensure.

A
  1. Analytical validity
  2. Clinical validity
  3. Clinical utility
  4. Ethical, legal and social issues (ELSI)
    It ensures that genetic diagnostic tests are fit for clinical use.
67
Q

3 phases of Lab testing

A
  1. Preanalytical: Taking, labelling, transporting and receiving sample
  2. Analytic: lab test
  3. Post-analytical: reporting, within a specified turnaround time (TAT)
68
Q

A good quality assurance (QA) does 4 things

A
  1. Standard operating procedures (SOPs) for each Step, ranging from specimen handling to instrument performance validation.
  2. Defines administrative requirements eg record keeping
  3. Specifies corrective actions, documentation, and the persons responsible for carrying out corrective actions when problems and identified.
  4. Sustains high-quality employee performance
69
Q

The following test metrics are used to quantify the analytical and clinical validity of a test:

A
  1. Sensivity
  2. Specificity
  3. Accuracy
  4. Positive predictive value (PPV)
  5. Negative predictive value (NPV)
70
Q

Define Sensitivity

A
  1. Sensitivity describes how well a test can detect a specific disease or condition in people who actually have the disease or condition.
  2. Sensitivity = true positive / true positive + false negative
71
Q

Compare the analytical sensitivity and clinical sensitivity of genetic tests vs genomic tests.

A
  1. Analytical sensitivity: genetic test is high vs slightly lower for genomic test.
  2. Clinical sensitivity: genetic test is limited vs genomic test which is higher not 100%
72
Q

Define Specificity

A
  1. Specificity refers to the percentage of people who test neg for a specific disease among a group of people who do not have disease.
  2. True negative/ false positive + true negative
73
Q

Define accuracy

A
  1. Accuracy is the ability of a test to correctly differentiate patients and healthy people.
  2. (True positive +true negative)/(true positive + false positive + true negative + false negative)
74
Q

Positive predictive value

A
  1. The likelihood that a person with a positive test result does have the gene mutation or the disease.
  2. PPV = true positive / true positive + false positive .
75
Q

Negative predictive value

A
  1. The likelihood that a person with a negative test exult does not have the disease, or the gene mutation.
  2. NPV = true negative / false negative + true negative
76
Q

Equation for prevalence

A

(True positive + false negative ) /(true positive +true negative + false positive + false negative )

77
Q

Define clinical utility

A

Usefulness (clinical utility) includes other considerations, specifically:
1. What’s are the benefits and risk of test? This includes consideration of cost .
2. This should be considered in comparison with alternatives

78
Q

Why can genetic testing be more beneficial (more clinical utility ) than clinical tests.

A
  1. Genetic variants are present from conception (before the disease onset) thus genetic testing can therefore be used in different contexts:
  2. Prenatal diagnosis
  3. Carrier testing
  4. Early pre-symptomatic testing
79
Q

For what reasons, is research -based genetic testing not a substitute for clinical testing.

A
  1. Not subject to clinical validation; clinical sensitivity and specificity are often not known.
  2. Done when research funds allow thus there is no set turnaround time.
  3. Not subject to strict quality control.
80
Q

Benefits of direct to consumer testing.

A
  1. May allow people to be more proactive about their health.
  2. Patients often report a sense of satisfaction, empowerment.
  3. Raises public awareness of genetics
81
Q

Risks of direct to consumer testing.

A
  1. Especially regarding health related tests, concern about:
    - whether the tests have proven validity and utility
    - lack of genetic counselling at the feedback of results
  2. DTC companies often claim test validity and utility for their products (often false)
  3. Results may be misleading, and cause anxiety or confusion inappropriate modification to diet.
  4. Cost of test is likely unjustified.
82
Q

What is genetic screening

A
  1. Done for a particular condition
  2. In individuals, groups or populations
  3. Without family history of the condition
  4. Alters risk, may not be definitive
  5. Positive results require further follow up.
83
Q

What genetic testing can be done chromosomal analysis.

A
  1. MLPA analysis (micro deletion/duplication )
  2. Micro—array analysis
  3. Whole genome sequencing
  4. Karyotyping
  5. FISH.
  6. QF- PCR
  7. Array CGH
84
Q

What genetic testing can be done single gene analysis.

A
  1. Sequencing panels
  2. Exome sequencing
  3. Whole genome sequencing
85
Q

Indications for chromosome analysis (9)

A
  1. When we want to confirmation/exclusion of diagnosis for known chromosomal syndromes.
  2. Unexplained developmental delay
  3. Multiple congenital abnormalities
  4. Abnormal of sexual differentiation and development
  5. Infertility/sub fertility
  6. Recurrent miscarriages
  7. Family history of abnormalities
  8. Pregnancies at increased risk because of prenatal screening
  9. Neoplastic conditions for which chromosome abnormality ID will help diagnosis and/ or management.
86
Q

How can you analyse single gene using biochemical measures.

A
  1. Enzyme activity
  2. Amount of substrate
  3. Amount of product
  4. Alternative product
87
Q

Different types of mutation detection

A
  1. Testing for specific sequences changes such as southern blot, RFLP based on:
    1.1 Family specific
    1.2 common mutations
    1.3 population specific
    1.4 common mechanism
  2. Sanger sequencing
    3: next generation sequencing
88
Q

Single gene analysis is useful for definitive: (6)

A
  1. Clinical diagnosis
  2. Pre-clinical diagnosis
  3. Carrier testing
  4. Prenatal testing
  5. Phenotype prediction
  6. Directing therapy
89
Q

Pre-clinical diagnosis is important why?

A
  1. Identify ‘at-risk” individuals prior to onset of symptoms
    - for mutation neg individuals we can say no follow-up unnecessary
    - mutation positive individuals can be given early intervention, appropriate monitoring and improved management.
    (Note: positive test does not always indicate patient will develop disease)
90
Q

What are the types of carrier testing.

A
  1. Family specific: known genetic disease in family therefore we Test for specific mutation.
  2. Broad carrier screens -NGS panels
  3. Population specific testing for common disorders.
91
Q

Why should carrier testing be done?

A

To detect those at risk for genetic disease for themselves or their offspring so that they can make informed choices regarding their Reproductive options
(Enhance autonomy)

92
Q

What disease is carrier testing commonly carried out for and which populations are associated with these diseases.

A
  1. Beta-thalassaemia: mediterraneans and Indians
  2. Sickle cell anaemia: Sub-Saharan Africans and Indians
  3. Cystic fibrosis: north-west European
  4. Tay-Sachs: Ashkenazi Jews.
93
Q

Why would you do prenatal diagnosis.

A
  1. Detection of disease in utero/ preimplantation.
    -reproductive options
    -early management
94
Q

Limitations of DNA analysis (9)

A
  1. DNA analysis not always most appropriate test
  2. For many gene disorder there are no common mutations.
  3. Each patient has unique mutations therefore there is a need individual testing and even if ‘’ problem’’ genes are known testing is not quick.
  4. Mutation may be missed or multiple techniques required to detect different types of mutations.
  5. Variants with unknown effect (VUS).
  6. Unintended/secondary findings (What do we do???)
  7. Tests May be expensive
  8. Genetic complexity needs to be taken into account because it can cause misinterpretation.
  9. Potential for inappropriate testing for profit rather than science. Can cause false reassurance or incorrect risk.
95
Q

Purpose of population screening

A
  1. The purpose of screening is to identify people in an apparently healthy population who are at higher risk of a health problem or a condition, so that an early treatment or intervention can be offered. This may lead to better health outcomes for some of the screens individuals.
  2. In some cases, such as antenatal screening , the purpose of screening is to give people information about an increased risk or condition to help them make an informed decision about their care or treatment .
  3. Screening is not the same as early diagnosis.
96
Q

The aims of screening programmes look to…

A
  1. To reduce mortality by early detection and early treatment of a condition.
  2. To reduce the incidence of a condition by identifying and treatment is precursors.
  3. To reduce the severity of a condition by identifying people with the condition and offering effective treatment.
  4. To increase choice by identifying conditions or risk factors at an early stage in a life course when more option are available.
97
Q

Wilson and jungner’s 10 principles of screening.

A
  1. The condition should be an important health problem.
  2. There should be an accepted treatment for patients with recognised disease.
  3. Facilities for diagnosis and treatment should be available.
  4. There should be a recognisable latent or early symptomatic phase.
  5. There should be a suitable test or examination.
  6. The test should be acceptable to the population.
  7. The natural history of the condition, including development from latent to declared disease, should be adequately understood.
  8. There should be an agreed policy on whom to treat as patients.
  9. The cost of case-finding should be economically balanced in relation to possible expenditure on medical care as a whole
  10. Case- finding should be a continuous process and not a ‘once’ and for all’ project .
98
Q

Screening programmes follows what pathway. (6)

A
  1. Identify the population eligible for screening.
  2. Invitation and information
  3. Testing
  4. Referral of screen positives and reporting of screen negative
  5. Diagnosis
  6. Intervention, treatment and follow up
99
Q

What does population prevalence mean for positive predictive value.

A

When a Condition is less common in a country (low prevalence ), the positive predictive value is lower. This means that there will be more false positive than in a country with a higher prevalence of the condition, even though the sensitivity and specificity are the same.

100
Q

The benefits of screening

A
  1. Reduction in the incidence and mortality.
  2. Early intervention for newborns
  3. Providing parents with information in the antenatal period.
101
Q

The harm of screening

A
  1. Because most people who are screened do not have the condition, more people can be exposed to the harm of screening than may be able to benefit from it.
  2. Because screening tests are not 100% sensitive or specific, there will always be false positives and negatives.
  3. Earlier detection of condition can lead to over diagnosis: detecting conditions that would never cause that individual harm in their life.
102
Q

Reasons for overdiagnosis

A
  1. High-resolution technologies such as sensitive biomarkers or imaging technologies, which can detect very small occurrences of a condition, lower the detection threshold of the screening test, leading to detection of smaller, and often more benign, instances of a condition.

GH Coarsework 2023 (13 decks)

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