I85PREP
⌘ K
ABMGG LGG study materials
ABMGG LGG study resources

ABMGG LGG practice questions

One question at a time. Build your ABMGG LGG understanding.

First 50 of 200 questions. Each one lists the choices, the correct answer, and an explanation. The checker at the top of this page saves progress in this browser when it is available.

Continue in the practice tool above to load more questions, 50 at a time.

Question 1Laboratory Genetics and Genomics

A peripheral blood karyotype reports 46,XX. Which technique would best detect a submicroscopic 200 kb deletion that is suspected clinically?

  1. Southern blot analysis
  2. Chromosomal microarray Correct answer.
  3. G-banded karyotype at 550-band resolution
  4. Standard FISH with a locus-specific probe

Explanation

Chromosomal microarray detects copy-number changes at kilobase resolution, far below the megabase scale resolvable by G-banding. Karyotype and single-locus FISH only detect abnormalities at lower resolution or at predefined loci.

Question 2Laboratory Genetics and Genomics

Which specimen source is generally preferred for constitutional cytogenetic analysis when a patient is available for a fresh sample?

  1. Peripheral blood lymphocytes Correct answer.
  2. Serum
  3. Bone marrow aspirate
  4. Formalin-fixed paraffin-embedded tissue

Explanation

Peripheral blood lymphocytes are easily obtained, yield high-quality metaphases after culture, and reflect the constitutional genotype. Other sources are used when blood is unsuitable or a tissue-specific mosaicism is suspected.

Question 3Laboratory Genetics and Genomics

A newborn screening result shows elevated immunoreactive trypsinogen, and CFTR sequencing reveals the variant c.1521_1523delCTT (p.Phe508del) on one allele with no second variant identified by sequencing. What is the most appropriate next step to identify a second allele?

  1. Methylation analysis of the CFTR promoter
  2. Deletion/duplication analysis of CFTR Correct answer.
  3. Karyotype of chromosome 7
  4. Repeat expansion testing of CFTR

Explanation

A substantial proportion of CFTR pathogenic alleles are copy-number variants not detected by sequencing, so deletion/duplication analysis is the standard reflex test. CFTR is not subject to repeat expansion or imprinting, making those approaches inappropriate.

Question 4Laboratory Genetics and Genomics

In a family with an autosomal dominant disorder, a pathogenic variant is identified in the proband. Which testing strategy is most appropriate for an asymptomatic adult sibling?

  1. Chromosomal microarray
  2. Methylation-specific PCR
  3. Whole-genome sequencing as a first-tier test
  4. Targeted familial variant testing after genetic counseling Correct answer.

Explanation

Once a familial pathogenic variant is known, targeted testing of at-risk relatives is the standard, most efficient, and most interpretable approach. Broad genomic testing in this setting adds cost and uncertain variants without improving detection of the known allele.

Question 5Laboratory Genetics and Genomics

A bone marrow karyotype in a patient with suspected myelodysplastic syndrome shows 46,XY,t(1;3)(p36;q21)[18]/46,XY[2]. How should the clonal finding be interpreted?

  1. A constitutional abnormality requiring parental studies
  2. Normal because fewer than 20 metaphases were abnormal
  3. A culture artifact of no clinical significance
  4. A clonal abnormality present in most analyzed cells, consistent with the clinical suspicion Correct answer.

Explanation

Detection of the same structural abnormality in multiple metaphases establishes clonality; 18 of 20 cells meets this criterion. Constitutional studies are not indicated when the abnormality is confined to marrow in an appropriate clinical context.

Question 6Laboratory Genetics and Genomics

Which laboratory practice most directly reduces the risk of specimen misidentification in a genetics laboratory?

  1. Two independent patient identifiers verified at accessioning and at each processing step Correct answer.
  2. Batching specimens by collection date
  3. Reading labels only at the time of reporting
  4. Using only the medical record number as the identifier

Explanation

Misidentification is prevented by confirming at least two independent identifiers at accessioning and at critical handoff points. Single identifiers and delayed checks increase the chance of an undetected swap.

Question 7Laboratory Genetics and Genomics

A patient with developmental delay has a karyotype showing a small supernumerary marker chromosome. Which approach is most useful to characterize its origin?

  1. Standard G-banding alone
  2. Repeat-primed PCR
  3. Sanger sequencing of a single candidate gene
  4. Chromosomal microarray combined with FISH using centromeric probes Correct answer.

Explanation

Microarray defines the copy-number content of the marker, and FISH with centromeric probes identifies the chromosome of origin. Together these clarify whether the marker contains clinically significant euchromatin.

Question 8Laboratory Genetics and Genomics

Which finding in a peripheral blood sample should raise concern for maternal cell contamination in a prenatal product-of-conception specimen?

  1. A normal female karyotype
  2. Presence of a maternal-specific allele in the fetal specimen Correct answer.
  3. Absence of a paternal allele at a highly polymorphic locus
  4. Homozygosity at multiple unlinked short tandem repeat loci

Explanation

Maternal cell contamination is detected by identifying alleles in the fetal sample that are unique to the mother at informative polymorphic loci. Comparison with maternal genotype is required to interpret such results.

Question 9Laboratory Genetics and Genomics

A laboratory validates a next-generation sequencing panel. Which metric best describes the proportion of the target region with adequate read depth to call variants reliably?

  1. Analytical specificity
  2. Positive predictive value
  3. Limit of detection
  4. Coverage uniformity Correct answer.

Explanation

Coverage uniformity reflects the fraction of targeted bases meeting a minimum depth threshold, which determines the callable region. Analytical specificity, limit of detection, and positive predictive value describe other performance characteristics.

Question 10Laboratory Genetics and Genomics

A patient with short stature and a suspected imprinted disorder has a methylation study showing loss of methylation at a maternally imprinted locus. Which mechanism is most consistent with this finding?

  1. A balanced reciprocal translocation
  2. Paternal uniparental disomy of the region Correct answer.
  3. A heterozygous deletion of the maternal allele
  4. A polygenic cause of short stature

Explanation

Loss of methylation at a maternally imprinted (paternally expressed) locus is characteristic of paternal uniparental disomy or a paternal imprinting defect. A maternal deletion would remove the silenced allele and typically leave the paternal active allele intact.

Question 11Laboratory Genetics and Genomics

Which of the following is the primary purpose of running a no-template control in a PCR-based assay?

  1. To detect reagent or environmental contamination Correct answer.
  2. To confirm primer specificity
  3. To quantify the input DNA concentration
  4. To assess the efficiency of the DNA extraction

Explanation

A no-template control contains all reagents but no DNA; amplification in this tube indicates contamination. It does not assess specificity, DNA quantity, or extraction efficiency.

Question 12Laboratory Genetics and Genomics

A fragile X syndrome test shows an FMR1 repeat of approximately 90 CGG repeats. How should this result be classified?

  1. Normal
  2. Full mutation
  3. Premutation Correct answer.
  4. Gray zone

Explanation

Premutation alleles range from about 55 to 200 CGG repeats; 90 repeats falls in this range. Full mutations exceed roughly 200 repeats, normal is below about 45, and the gray zone is intermediate.

Question 13Laboratory Genetics and Genomics

A lab reports a variant of uncertain significance in a cancer predisposition gene. Which approach best supports reclassification over time?

  1. Discarding the variant from the report
  2. Reporting the variant only if it is novel
  3. Periodic review of updated population, segregation, and functional data Correct answer.
  4. Immediate reporting as pathogenic if the patient has cancer

Explanation

VUS classification evolves as allele frequency, segregation, and functional evidence accumulate, so structured periodic review is best practice. Assigning pathogenicity based on the patient's phenotype alone is a known source of misclassification.

Question 14Laboratory Genetics and Genomics

Which cytogenetic finding is characteristic of a Robertsonian translocation?

  1. Ring formation of a single chromosome
  2. Inversion of a pericentromeric segment
  3. Fusion of two acrocentric chromosomes at their centromeres Correct answer.
  4. Reciprocal exchange between two nonhomologous chromosome arms

Explanation

Robertsonian translocations arise from centric fusion of two acrocentric chromosomes, producing a derivative chromosome with loss of short arms. Reciprocal translocations, inversions, and ring chromosomes involve different mechanisms.

Question 15Laboratory Genetics and Genomics

A prenatal sample from a pregnancy with a male fetus shows a karyotype of 46,XX on cultured amniocytes. Which explanation should be considered first?

  1. Maternal cell contamination of the specimen Correct answer.
  2. Complete hydatidiform mole
  3. Laboratory misidentification of the sample
  4. A true 46,XX male

Explanation

When fetal sex by ultrasound or cell-free DNA indicates male but cultured amniocytes are 46,XX, maternal cell contamination is the most common explanation and should be excluded by genotyping. Sample misidentification is also possible but is evaluated after contamination is ruled out.

Question 16Laboratory Genetics and Genomics

Which statement best describes the analytical sensitivity of a sequencing assay?

  1. The proportion of samples correctly identified as negative
  2. The number of genes included in the panel
  3. The probability that a reported variant is truly present
  4. The lowest variant allele fraction the assay can reliably detect Correct answer.

Explanation

Analytical sensitivity in variant detection refers to the lowest detectable variant allele fraction, often established with dilution series. Specificity, negative agreement, and panel size describe different parameters.

Question 17Laboratory Genetics and Genomics

A patient has a balanced reciprocal translocation t(11;22)(q23;q11.2) identified by karyotype. Which testing should be offered to a partner before conception?

  1. Repeat expansion testing
  2. Tumor sequencing
  3. Methylation analysis
  4. Karyotype of the partner Correct answer.

Explanation

Partner karyotyping identifies whether a balanced rearrangement is present that could affect reproductive risk. The other tests address unrelated mechanisms such as imprinting, repeat expansion, or somatic mutation.

Question 18Laboratory Genetics and Genomics

A laboratory observes a single metaphase with a random chromosome loss in an otherwise normal study of 20 cells. How should this be interpreted?

  1. As a clonal abnormality requiring FISH
  2. As a sign of maternal contamination
  3. As a technical artifact not meeting criteria for mosaicism Correct answer.
  4. As evidence of a constitutional monosomy

Explanation

Random single-cell loss is common and does not establish a clone; the International System for Human Cytogenomic Nomenclature requires multiple cells with the same abnormality. Additional cells or FISH may be added if there is clinical suspicion.

Question 19Laboratory Genetics and Genomics

In a newborn with ambiguous genitalia, which test provides the fastest assessment of the presence of the SRY gene?

  1. Whole-genome sequencing
  2. Chromosomal microarray
  3. Methylation analysis
  4. FISH or PCR for SRY Correct answer.

Explanation

Targeted FISH or PCR for SRY gives rapid, specific information about the presence of the testis-determining gene. Broader genomic tests are slower and less directed for this specific question.

Question 20Laboratory Genetics and Genomics

Which quality metric best reflects the ability of a laboratory to correctly identify a variant that is present in a specimen?

  1. Report completeness
  2. Analytical sensitivity Correct answer.
  3. Turnaround time
  4. Analytical specificity

Explanation

Analytical sensitivity is the probability of detecting a variant when it is present. Specificity addresses correct negatives, while turnaround time and report completeness are operational metrics.

Question 21Laboratory Genetics and Genomics

A patient with colorectal cancer has tumor testing showing loss of MLH1 and PMS2 by immunohistochemistry and BRAF V600E mutation. What is the most likely interpretation?

  1. A germline PMS2 pathogenic variant
  2. Sporadic MLH1 promoter hypermethylation rather than Lynch syndrome Correct answer.
  3. A germline MLH1 pathogenic variant
  4. Lynch syndrome due to MSH2 loss

Explanation

Combined MLH1/PMS2 loss with a BRAF V600E mutation strongly favors sporadic MLH1 hypermethylation over Lynch syndrome. Germline testing may still be considered depending on clinical features, but the molecular pattern points to a somatic mechanism.

Question 22Laboratory Genetics and Genomics

Which specimen type is most appropriate for detecting a low-level somatic mosaicism that may be missed in blood?

  1. Saliva only
  2. Serum
  3. Buccal swab without further testing
  4. Affected tissue such as skin fibroblasts Correct answer.

Explanation

When a mosaic variant is confined to a specific tissue, testing the affected tissue increases the likelihood of detection. Blood and saliva may not reflect the mosaic fraction in the affected lineage.

Question 23Laboratory Genetics and Genomics

A laboratory reports a homozygous apparent variant in a region with a nearby pseudogene. Which approach best reduces the risk of a false-positive result?

  1. Increasing the number of PCR cycles
  2. Using a single primer pair without validation
  3. Reporting the variant without confirmation
  4. Designing assays that avoid pseudogene homology and confirming with an orthogonal method Correct answer.

Explanation

Pseudogene homology can cause co-amplification and false calls, so homology-avoiding design with orthogonal confirmation is standard. Additional cycles or unvalidated primers would not resolve the ambiguity.

Question 24Laboratory Genetics and Genomics

Which of the following best describes the purpose of a proficiency testing program in a genetics laboratory?

  1. To replace internal quality control procedures
  2. To determine reimbursement rates
  3. To validate new instruments before purchase
  4. To provide an external assessment of analytical performance across laboratories Correct answer.

Explanation

Proficiency testing compares a laboratory's results with peer laboratories using common specimens, providing external quality assessment. It complements, rather than replaces, internal quality control.

Question 25Laboratory Genetics and Genomics

A patient has a pathogenic variant in a gene showing autosomal recessive inheritance, and only one variant is detected by sequencing. Which additional testing is most appropriate?

  1. Karyotype at 400-band resolution
  2. Methylation analysis
  3. Repeat expansion testing
  4. Deletion/duplication analysis of the gene Correct answer.

Explanation

A second recessive allele may be an intragenic deletion or duplication missed by sequencing, so copy-number analysis of the gene is the standard next step. Repeat expansion and methylation testing apply to different disease mechanisms.

Question 26Laboratory Genetics and Genomics

Which chromosome banding pattern is produced by Giemsa staining after trypsin digestion in a standard G-banded karyotype?

  1. Staining restricted to telomeres
  2. Fluorescent bands only at centromeres
  3. Uniform staining of all chromosomes
  4. Light and dark bands along each chromosome Correct answer.

Explanation

G-banding uses trypsin to digest chromatin proteins followed by Giemsa stain, producing a pattern of light and dark bands that allows chromosome identification and detection of structural abnormalities.

Question 27Laboratory Genetics and Genomics

Which type of variant is most reliably detected by routine G-banded karyotyping?

  1. A 5 Mb duplication Correct answer.
  2. A trinucleotide repeat expansion
  3. A 10 bp deletion
  4. A single nucleotide substitution

Explanation

G-banded karyotyping has a resolution of approximately 5–10 Mb, so large copy-number changes such as a 5 Mb duplication are visible, whereas smaller variants require molecular methods.

Question 28Laboratory Genetics and Genomics

Which molecular method is most appropriate for detecting a known point mutation when only a very small amount of DNA is available?

  1. Southern blot analysis
  2. Allele-specific PCR Correct answer.
  3. Fluorescence in situ hybridization
  4. Karyotype analysis

Explanation

Allele-specific PCR uses primers that discriminate single-base differences and can amplify from minute DNA quantities, making it well suited for detecting known point mutations.

Question 29Laboratory Genetics and Genomics

In a next-generation sequencing assay, which quality metric indicates the percentage of target bases covered by at least a specified number of reads?

  1. Transition/transversion ratio
  2. Allele fraction
  3. Depth of coverage Correct answer.
  4. On-target rate

Explanation

Depth of coverage (or coverage breadth) reports the proportion of target bases achieving a defined minimum read depth, which is critical for confidence in variant calling.

Question 30Laboratory Genetics and Genomics

Which finding on a peripheral blood smear suggests a need for cytogenetic evaluation for a hematologic malignancy?

  1. A left shift with band forms
  2. Presence of nucleated red blood cells Correct answer.
  3. A monoclonal gammopathy
  4. Toxic granulation of neutrophils

Explanation

Nucleated red blood cells in peripheral blood of an adult can indicate marrow stress or infiltration and may prompt cytogenetic analysis to evaluate for myelodysplastic syndrome or other malignancies.

Question 31Laboratory Genetics and Genomics

Which cytogenetic abnormality is characteristic of chronic myeloid leukemia (CML)?

  1. t(8;21)(q22;q22)
  2. inv(16)(p13.1q22)
  3. t(9;22)(q34;q11.2) Correct answer.
  4. t(15;17)(q22;q12)

Explanation

The Philadelphia chromosome results from a t(9;22)(q34;q11.2) translocation, which fuses BCR and ABL1 and is the defining cytogenetic abnormality of CML.

Question 32Laboratory Genetics and Genomics

A patient with a suspected inherited cancer syndrome is tested with a multigene panel, and a pathogenic variant is found in a gene for which the patient's family history is not suggestive. What is the most appropriate next step?

  1. Proceed directly to predictive testing of relatives without confirmation
  2. Repeat the same panel on a new specimen without additional review
  3. Dismiss the result as a false positive
  4. Confirm the variant in a CLIA-certified laboratory using orthogonal testing Correct answer.

Explanation

Unexpected pathogenic findings should be confirmed by an independent method in a CLIA-certified laboratory before clinical action or family testing, to exclude analytical error.

Question 33Laboratory Genetics and Genomics

Which mechanism best explains why uniparental disomy can cause an autosomal recessive disorder when only one parent carries a pathogenic variant?

  1. The other parent has a deletion of the entire gene
  2. A de novo mutation occurs on the maternal allele
  3. The carrier parent transmits two copies of the mutant allele through isodisomy Correct answer.
  4. The disorder is caused by a dominant-negative effect

Explanation

Uniparental isodisomy can result in two copies of a mutant allele from a single carrier parent, producing homozygosity for the variant and causing a recessive disorder even though only one parent is a carrier.

Question 34Laboratory Genetics and Genomics

Which test is most appropriate to detect a microdeletion that is below the resolution of G-banded karyotyping?

  1. Sanger sequencing
  2. Chromosomal microarray analysis Correct answer.
  3. Standard G-banded karyotype
  4. Southern blot

Explanation

Chromosomal microarray detects copy-number changes at kilobase resolution, far exceeding the ~5–10 Mb resolution of G-banded karyotyping, making it the method of choice for microdeletions.

Question 35Laboratory Genetics and Genomics

In a patient with developmental delay and dysmorphic features, a chromosomal microarray shows a 1.5 Mb deletion at 22q11.2. Which statement best describes the clinical utility of this finding?

  1. It indicates a need for immediate karyotype to confirm the deletion
  2. It is consistent with 22q11.2 deletion syndrome and warrants appropriate clinical evaluation Correct answer.
  3. It is a benign copy-number variant of no clinical significance
  4. It is a variant of uncertain significance requiring parental testing

Explanation

A 1.5 Mb deletion at 22q11.2 is the typical size for the recurrent deletion causing 22q11.2 deletion syndrome, and the finding should prompt syndrome-specific clinical evaluation.

Question 36Laboratory Genetics and Genomics

Which of the following is the primary reason for performing a chromosome analysis on products of conception after a miscarriage?

  1. To determine the cause of the miscarriage and provide recurrence risk information Correct answer.
  2. To assess the risk of neural tube defects in future pregnancies
  3. To diagnose a single-gene disorder in the fetus
  4. To identify maternal carrier status for a balanced translocation

Explanation

Chromosome analysis of products of conception can identify a chromosomal cause of pregnancy loss, which informs recurrence risk counseling and guides further testing if a parental rearrangement is suspected.

Question 37Laboratory Genetics and Genomics

A couple has had three first-trimester miscarriages. Karyotype of the products of conception from the most recent loss shows 46,XY,der(13;14)(q10;q10). What is the most likely explanation for the recurrent pregnancy loss?

  1. A de novo point mutation in the fetus
  2. A microdeletion on chromosome 13
  3. Maternal uniparental disomy of chromosome 14
  4. A balanced Robertsonian translocation in one of the parents Correct answer.

Explanation

The derivative chromosome der(13;14) in the fetus suggests a parental balanced Robertsonian translocation, which can produce unbalanced gametes and recurrent miscarriage.

Question 38Laboratory Genetics and Genomics

Which method is most suitable for detecting a low-level mosaicism that might be missed by conventional karyotyping of peripheral blood?

  1. Routine blood chemistry panel
  2. G-banded karyotype of peripheral blood lymphocytes
  3. Serum protein electrophoresis
  4. Interphase fluorescence in situ hybridization on a buccal smear Correct answer.

Explanation

Interphase FISH on a buccal smear can examine hundreds of cells from a different tissue and detect low-level mosaicism that might not be apparent in a limited number of blood metaphases.

Question 39Laboratory Genetics and Genomics

Which laboratory practice is essential to prevent contamination in a PCR-based assay for a highly sensitive mutation detection?

  1. Performing all steps in a single room
  2. Using separate pre- and post-amplification work areas with unidirectional workflow Correct answer.
  3. Using the same pipettes for all steps
  4. Increasing the number of amplification cycles

Explanation

Separate pre- and post-amplification areas with unidirectional workflow prevent amplicon carryover, which is a major source of false-positive results in sensitive PCR assays.

Question 40Laboratory Genetics and Genomics

In a quantitative PCR assay for a microdeletion, what does a relative quantification value of 0.5 indicate?

  1. Homozygous deletion of the target region
  2. Normal copy number
  3. Heterozygous deletion of the target region Correct answer.
  4. Duplication of the target region

Explanation

A relative quantification of 0.5 corresponds to one copy instead of two, consistent with a heterozygous deletion.

Question 41Laboratory Genetics and Genomics

Which of the following is a key limitation of Sanger sequencing for clinical variant detection?

  1. It requires whole-genome amplification
  2. It cannot detect single nucleotide substitutions
  3. It has low sensitivity for low-level mosaicism Correct answer.
  4. It cannot be used for targeted regions

Explanation

Sanger sequencing typically detects variant alleles present at roughly 15–20% or higher, so low-level mosaicism may be missed; more sensitive methods are needed for such cases.

Question 42Laboratory Genetics and Genomics

Which quality control measure is most important for ensuring the accuracy of a targeted next-generation sequencing panel?

  1. Reducing the sequencing depth to save costs
  2. Using only fresh-frozen samples
  3. Including a positive control with known variants in each run Correct answer.
  4. Increasing the number of samples per run

Explanation

A positive control with known variants verifies that the assay can detect expected variants and monitors analytical performance across runs.

Question 43Laboratory Genetics and Genomics

Which of the following best describes the purpose of a limit of detection (LoD) study in validating a molecular assay?

  1. To assess the cost-effectiveness of the test
  2. To establish the reference range for a biochemical marker
  3. To measure the turnaround time of the assay
  4. To determine the lowest analyte concentration that can be reliably detected Correct answer.

Explanation

The limit of detection is the lowest amount of analyte that can be detected with acceptable precision and accuracy, and it is a key validation parameter.

Question 44Laboratory Genetics and Genomics

A laboratory is validating a new assay and wants to ensure that results are consistent when the same sample is tested repeatedly. Which parameter is being assessed?

  1. Analytical specificity
  2. Analytical sensitivity
  3. Reportable range
  4. Precision Correct answer.

Explanation

Precision (or reproducibility) measures the agreement of repeated measurements of the same sample under specified conditions.

Question 45Laboratory Genetics and Genomics

Which of the following is an appropriate use of a proficiency testing (PT) program in a genetics laboratory?

  1. To provide an objective assessment of the laboratory's performance compared with peer laboratories Correct answer.
  2. To certify individual technologists
  3. To determine the clinical utility of a test
  4. To replace internal quality control procedures

Explanation

Proficiency testing evaluates a laboratory's performance against peer laboratories and is a required component of quality assurance, but it does not replace internal QC.

Question 46Laboratory Genetics and Genomics

A patient with a family history of Lynch syndrome has tumor tissue showing loss of MSH2 and MSH6 by immunohistochemistry. Which gene is most likely to harbor a germline mutation?

  1. MSH2 Correct answer.
  2. MLH1
  3. BRAF
  4. PMS2

Explanation

Loss of MSH2 and MSH6 expression typically reflects a germline mutation in MSH2, as MSH2 is an obligate partner of MSH6 and loss of MSH2 leads to degradation of both proteins.

Question 47Laboratory Genetics and Genomics

In a patient with a known pathogenic variant in a BRCA1, which test is most appropriate for a relative who wishes to know her carrier status?

  1. Chromosomal microarray
  2. Targeted testing for the known familial variant Correct answer.
  3. Full sequencing of BRCA1
  4. Karyotype analysis

Explanation

Once the familial pathogenic variant is known, targeted testing for that specific variant is the most efficient and appropriate approach for at-risk relatives.

Question 48Laboratory Genetics and Genomics

A laboratory reports a variant as pathogenic based on multiple lines of evidence. Which criterion is most important to avoid a false-positive classification?

  1. The variant is predicted to be damaging by in silico tools
  2. The variant is observed in at least one affected individual
  3. The variant is confirmed by orthogonal testing and segregates with disease Correct answer.
  4. The variant is absent from population databases

Explanation

Confirmation by orthogonal testing and segregation with disease in families provide strong evidence for pathogenicity and reduce the risk of a false-positive classification.

Question 49Laboratory Genetics and Genomics

Which of the following is the most appropriate method to detect a large deletion encompassing multiple exons of a gene?

  1. Sanger sequencing of the exons
  2. Southern blot with a single exon probe
  3. Multiplex ligation-dependent probe amplification (MLPA) Correct answer.
  4. Karyotype analysis

Explanation

MLPA quantifies exon copy number and is specifically designed to detect deletions and duplications of one or more exons.

Question 50Laboratory Genetics and Genomics

A patient is found to have a heterozygous pathogenic variant in a gene associated with autosomal dominant inheritance, but neither parent carries the variant. What is the most likely explanation?

  1. The variant is an artifact of testing
  2. The patient has a recessive disorder
  3. The variant is a benign polymorphism
  4. The variant is a de novo mutation in the patient Correct answer.

Explanation

A pathogenic variant present in the patient but absent in both parents is most likely de novo, especially for dominant disorders.