A researcher adds colchicine and colcemid to cultured fibroblasts before karyotyping. Dividing cells are arrested primarily in:
A. Anaphase
B. Prophase
C. Metaphase
D. Telophase

C. Metaphase

A chromosome shows its centromere very close to one end, with a long and a tiny arm. This morphology is best termed:
A. Acrocentric
B. Submetacentric
C. Telocentric
D. Metacentric

A. Acrocentric

A human autosome has arms of roughly equal length with the centromere near the midpoint. It is classified as:
A. Acrocentric
B. Telocentric
C. Submetacentric
D. Metacentric

D. Metacentric

A student labels the chromosomal regions that cap the ends and maintain stability after replication. These structures are:
A. Centromeres
B. Telomeres
C. Pericentromeres
D. Satellites

B. Telomeres

A cytogeneticist wants to highlight constitutive heterochromatin adjacent to centromeres. Which banding method is most appropriate?
A. R-banding
B. G-banding
C. C-banding
D. Q-banding

C. C-banding

A patient’s tumor sample is tested using a technique that compares tumor DNA to reference DNA with red and green fluorochromes to detect chromosomal copy-number changes. This method is:
A. Comparative genomic hybridization
B. Targeted FISH panel
C. Cytogenomic microarray
D. Standard G-banded karyotype

A. Comparative genomic hybridization

In comparative genomic hybridization, a chromosomal region appears bright red when tumor DNA is compared to normal. This most strongly suggests:
A. Balanced translocation
B. Normal copy number
C. Large deletion present
D. Duplication of that region

D. Duplication of that region

In the same CGH experiment, a chromosomal segment appears predominantly green. This indicates:
A. Chromosomal inversion
B. Deletion of that region
C. Triplication of that segment
D. Balanced reciprocal translocation

B. Deletion of that region

A child with developmental delay undergoes high-resolution testing that can detect uniparental disomy and loss of heterozygosity, does not require dividing cells, and uses minimal DNA. The best test is:
A. Standard G-banded karyotype
B. Targeted FISH with probes
C. Cytogenomic microarray (CMA)
D. Conventional comparative genomic hybridization

C. Cytogenomic microarray (CMA)

Cytogenomic microarray is chosen over conventional karyotyping for subtle copy-number changes. A key limitation of CMA is inability to detect:
A. Balanced chromosomal rearrangements
B. Small interstitial deletions
C. Uniparental disomy events
D. Loss of heterozygosity

A. Balanced chromosomal rearrangements

Which type of autosomal aneuploidy is generally better tolerated and more compatible with live birth?
A. Monosomy for large autosomes
B. Monosomy for sex chromosomes
C. Balanced autosomal monosomy
D. Trisomy compared with monosomy

D. Trisomy compared with monosomy

The most common underlying mechanism for human autosomal aneuploidy (e.g., trisomies) is:
A. Deletions during DNA replication
B. Meiotic nondisjunction in meiosis I or II
C. Mitotic nondisjunction in somatic tissues
D. Translocations during spermatogenesis

B. Meiotic nondisjunction in meiosis I or II

A neonate has duodenal atresia with “double bubble” sign, hypotonia, recurrent respiratory infections, leukemia risk, and a complete AV canal defect. The most likely karyotype abnormality is:
A. Trisomy 13
B. Monosomy X
C. Trisomy 21
D. Trisomy 18

C. Trisomy 21

A term infant with Down syndrome is evaluated for congenital heart disease. Which combination best describes the typical cardiac defects in this condition?
A. PDA and coarctation of aorta
B. AV canal defect and ventricular septal defect
C. ASD secundum and pulmonary stenosis
D. Isolated muscular ventricular septal defect

B. AV canal defect and ventricular septal defect

In Down syndrome, overexpression of the DYRK1A gene on chromosome 21 primarily contributes to:
A. Duodenal atresia and stenosis
B. Hematologic malignancy risk
C. Atrioventricular canal malformations
D. Learning and memory deficits

D. Learning and memory deficits

A 39-year-old man with Down syndrome develops progressive cognitive decline and dementia. Which gene’s triplication on chromosome 21 best explains his early-onset Alzheimer pathology?
A. APP (amyloid precursor protein)
B. SHOX
C. SRY
D. DYRK1A

A. APP (amyloid precursor protein)

A child has partial A21 that does not include the APP locus. Which neurologic complication is notably unlikely even in adulthood?
A. Epilepsy
B. Autism spectrum disorder
C. Early-onset Alzheimer disease
D. Parkinsonian features

C. Early-onset Alzheimer disease

Among trisomy 13, trisomy 18, and trisomy 21, ventricular septal defect is most frequent (≈90%) in which syndrome?
A. Trisomy 13 (Patau)
B. Trisomy 18 (Edwards)
C. Trisomy 21 (Down)
D. Trisomy 8 mosaicism

B. Trisomy 18 (Edwards)

A newborn with severe growth restriction has microphthalmia, post-axial polydactyly of the hands, and very poor postnatal survival. The most likely diagnosis is:
A. Trisomy 18 (Edwards syndrome)
B. Trisomy 21 (Down syndrome)
C. Monosomy X (Turner syndrome)
D. Trisomy 13 (Patau syndrome)

D. Trisomy 13 (Patau syndrome)

A 42-year-old woman asks about recurrence risk of Down syndrome in future pregnancies. Age-related risk is primarily increased because her oocytes:
A. Remain arrested in meiosis longer
B. Undergo more mitotic divisions
C. Have fewer crossing-over events
D. Are exposed to higher estrogen levels

A. Remain arrested in meiosis longer

A short 15-year-old phenotypic female has primary amenorrhea, streak ovaries, webbed neck, and lymphedema at birth. Karyotype shows:
A. 47,XXY
B. 47,XXX
C. 45,X
D. 46,XY

C. 45,X

A girl with Turner syndrome is found to have a cardiac murmur. Which associated cardiac defect is most characteristic?
A. Bicuspid aortic valve
B. Complete atrioventricular canal
C. Tetralogy of Fallot
D. Large muscular ventricular septal defect

A. Bicuspid aortic valve

The SHOX gene encodes a transcription factor expressed in embryonic limb development. Its dosage effect is best summarized as:
A. SHOX dosage only affects gonads
B. More SHOX copies reduce stature
C. SHOX dosage only affects cognition
D. More SHOX copies increase stature

D. More SHOX copies increase stature

A tall, infertile male with testicular atrophy, low testosterone, gynecomastia, and learning difficulties is evaluated. The likely diagnosis and karyotype are:
A. Turner syndrome, 45,X
B. Klinefelter syndrome, 47,XXY
C. XYY syndrome, 47,XYY
D. Trisomy X, 47,XXX

B. Klinefelter syndrome, 47,XXY

The pseudoautosomal region, which undergoes obligatory recombination with X, is located on which chromosomal segment?
A. Long arm of X chromosome
B. Centromeric region of Y chromosome
C. Proximal long arm of Y chromosome
D. Distal Y pairing with X short arm

D. Distal Y pairing with X short arm

An individual with an XX karyotype presents as a phenotypic male with normal testes. This is most likely explained by:
A. SRY gene translocated onto X
B. Deletion of the SHOX gene
C. Mosaicism with 45,X cell line
D. Deletion of the APP gene

A. SRY gene translocated onto X

A newborn has karyotype 46,XY but lacks the SRY gene. Which phenotype is most likely?
A. Normal phenotypic male with testes
B. Ambiguous genitalia, normal male ducts
C. Normal phenotypic female with streak gonads
D. Normal phenotypic male, infertile later

C. Normal phenotypic female with streak gonads

A rearrangement causes loss of p arms from two nonhomologous acrocentric chromosomes and fusion of their q arms at one centromere. The individual has 45 chromosomes but appears normal. This describes:
A. Robertsonian translocation
B. Reciprocal balanced translocation
C. Pericentric inversion
D. Isochromosome formation

A. Robertsonian translocation

A 6-month-old with microcephaly, severe intellectual disability, and a characteristic high-pitched “cat-like” cry has karyotype 45,XY,del(5p). The diagnosis is:
A. Wolf–Hirschhorn syndrome
B. Prader–Willi syndrome
C. Williams syndrome
D. Cri-du-chat syndrome

D. Cri-du-chat syndrome

A child presents with a “Greek warrior helmet” facial appearance and severe developmental delay due to deletion of the distal short arm of chromosome 4. This condition is:
A. Monosomy 1p36 syndrome
B. Wolf–Hirschhorn syndrome
C. DiGeorge sequence
D. Williams–Beuren syndrome

B. Wolf–Hirschhorn syndrome

A normal chromosome readout is “ABCDEFG.” A proband shows “ABEFG.” This anomaly is best classified as:
A. Terminal deletion
B. Pericentric inversion
C. Interstitial deletion
D. Paracentric inversion

C. Interstitial deletion

A child with hypotonia, obesity, short stature, small hands and feet, and intellectual disability is found to have a microdeletion of 15q11–q13. The syndrome is:
A. Prader–Willi syndrome
B. Angelman syndrome
C. Williams syndrome
D. Monosomy 1p36

A. Prader–Willi syndrome

A patient with mild intellectual disability, supravalvular aortic stenosis, multiple pulmonary arterial stenoses, distinctive facies, dental anomalies, and hyperglycemia has a microdeletion of 7q11 including ELN and LIMK1. Diagnosis?
A. DiGeorge sequence
B. Wolf–Hirschhorn syndrome
C. Prader–Willi syndrome
D. Williams syndrome

D. Williams syndrome

A child has thymic hypoplasia, conotruncal cardiac defects, secondary hypocalcemia, and a 22q long-arm deletion. A clinically overlapping condition with similar deletion is:
A. Monosomy 1p36 syndrome
B. Velocardiofacial (VCF) syndrome
C. Kallmann syndrome
D. Cri-du-chat syndrome

B. Velocardiofacial (VCF) syndrome

A deletion of chromosome region 1p36 causes global developmental delay, seizures, and intellectual disability. This region is located:
A. At the centromere of chromosome 1
B. At the middle of the p arm
C. Near telomeres, gene-dense region
D. Near q-arm pericentromeric heterochromatin

C. Near telomeres, gene-dense region

A child inherits both copies of chromosome 15 from the mother and none from the father. This is an example of:
A. Heteroplasmy
B. Mosaicism
C. Segmental isochromosome
D. Uniparental disomy

D. Uniparental disomy

A karyotype shows two maternally derived homologs of chromosome 7, one from each maternal homolog. This pattern is specifically termed:
A. Heterodisomy
B. Ring chromosome
C. Isodisomy
D. Robertsonian disomy

A. Heterodisomy

Another patient has two identical copies of the same maternal chromosome 7 homolog with no paternal contribution. This pattern is:
A. Robertsonian translocation
B. Balanced reciprocal translocation
C. Isodisomy
D. Heterodisomy

C. Isodisomy

A girl with Turner features has mosaic karyotype 45,X/46,XX. This pattern best represents:
A. Germline mosaicism
B. Somatic mosaicism
C. Gonadal chimerism
D. Segmental isodisomy

B. Somatic mosaicism

A karyotype is reported as 46,Xr(X). Terminal deletions at both ends of one X chromosome have occurred, and the ends fused. This is an example of:
A. Dicentric chromosome
B. Ring chromosome formation
C. Isochromosome Xq
D. Balanced inversion

B. Ring chromosome formation

Compared to a normal chromosome arrangement ABC/DEF, which of the following represents a pericentric inversion?
A. ABC/DFE
B. ABD/CEF
C. ACB/DEF
D. AEC/DBF

B. ABD/CEF

Which structural abnormality produces a chromosome with two copies of one arm and complete absence of the other arm, often lethal due to missing information?
A. Isochromosome
B. Ring chromosome
C. Robertsonian fusion
D. Paracentric inversion

A. Isochromosome

A patient with chronic myelogenous leukemia has a shortened chromosome 22 containing most of BCR and a segment of ABL from chromosome 9. This derivative chromosome is known as the:
A. DiGeorge chromosome
B. Birkitt chromosome
C. Philadelphia chromosome
D. Robertsonian chromosome

C. Philadelphia chromosome

In chronic myelogenous leukemia, the ABL proto-oncogene is relocated from 9q to 22q. This translocation produces:
A. Loss of ABL expression
B. Defective DNA repair helicase
C. Constitutive tyrosine kinase activity
D. Absent immunoglobulin heavy chains

C. Constitutive tyrosine kinase activity

A child with a rapidly growing jaw mass is diagnosed with Burkitt lymphoma. A reciprocal translocation t(8;14) moves which proto-oncogene near the Ig heavy chain locus?
A. BCR
B. ABL
C. ELN
D. MYC

D. MYC

In early cytogenetics, spindle poisons such as colchicine and colcemid were added to cultured cells. Their primary effect was to:
A. Arrest cells in G1 phase
B. Arrest cells in anaphase
C. Arrest cells in S phase
D. Arrest cells in metaphase for karyotyping

D. Arrest cells in metaphase for karyotyping

In clinical cytogenetics, the karyotype of a patient best refers to:
A. The photographic layout of chromosomes
B. The number and types of chromosomes
C. The banding pattern of each chromosome
D. The total amount of nuclear DNA

B. The number and types of chromosomes

On a teaching slide, three human chromosomes are arranged left to right, showing centromeres progressively closer to the tip. The correct description from left to right is:
A. Acrocentric, submetacentric, metacentric
B. Metacentric, acrocentric, submetacentric
C. Submetacentric, metacentric, acrocentric
D. Metacentric, submetacentric, acrocentric

D. Metacentric, submetacentric, acrocentric

A normal human somatic cell and a normal human gamete are both considered karyotypically normal because they each:
A. Contain 23-chromosome multiples (euploid)
B. Contain at least one Y chromosome
C. Contain only somatic chromosomes, no sex
D. Contain 23 pairs of sex chromosomes

A. Contain 23-chromosome multiples (euploid)

During karyotyping, why are cultured metaphase cells exposed to a hypotonic saline solution before slide preparation?
A. To arrest cells in metaphase
B. To enhance Giemsa banding contrast
C. To swell and rupture metaphase cells
D. To fix chromosomes to glass slides

C. To swell and rupture metaphase cells

A modern laboratory wants to perform standard banding to identify each human chromosome by its characteristic dark–light pattern. The most commonly used technique is:
A. Q-banding with quinacrine dye
B. Giemsa banding (G-banding)
C. C-banding for centromeric regions
D. R-banding with heat pre-treatment

B. Giemsa banding (G-banding)

A lab performs reverse banding to visualize telomeric regions more clearly. This method, compared with G-banding, requires:
A. Enzymatic digestion of chromatin first
B. UV exposure to activate fluorochromes
C. Acid hydrolysis of DNA backbones
D. Heat treatment, reversing dark–light pattern

D. Heat treatment, reversing dark–light pattern

A cytogenetic workup includes both C-banding and NOR staining. These techniques are specifically used to detect:
A. Constitutive heterochromatin and acrocentric satellites
B. Telomeres and centromeric heterochromatin
C. Coding exons and tandem repeats
D. Imprinted loci and promoter methylation

A. Constitutive heterochromatin and acrocentric satellites

High-resolution banding in prophase or prometaphase increases total visible bands from ~300–450 to ~800 because chromosomes at these stages are:
A. Shorter, thicker, more condensed
B. Replicated but still in S phase
C. More extended, less condensed structurally
D. Unreplicated, containing single DNA strands

C. More extended, less condensed structurally

In cytogenetics, FISH is commonly used for targeted gene analysis. FISH stands for:
A. Fragmented in situ hybridization
B. Fluorometric interphase sequence hybridization
C. Fluorescent interphase segment hybridization
D. Fluorescence in situ hybridization

D. Fluorescence in situ hybridization

During FISH, the probe applied to the slide is best described as:
A. Double-stranded genomic DNA fragment
B. Labelled single-stranded DNA segment
C. Single-stranded RNA complementary probe
D. Unlabelled double-stranded PCR product

B. Labelled single-stranded DNA segment

Compared with high-resolution banding alone, a major advantage of FISH for microdeletion testing is:
A. Higher resolution, greater specificity, ~1 Mb detection
B. Ability to detect balanced translocations
C. Ability to quantify gene expression levels
D. Ability to assess triploidy in metaphase

A. Higher resolution, greater specificity, ~1 Mb detection

Spectral karyotyping (SKY) is a specialized karyotype method that:
A. Uses only Giemsa with high magnification
B. Detects point mutations within gene exons
C. Uses FISH with multiple colored probes
D. Uses electron microscopy for chromosomes

C. Uses FISH with multiple colored probes

A patient undergoes array comparative genomic hybridization (aCGH). This technique can reliably detect chromosomal duplications or deletions as small as approximately:
A. 1 gigabase per segment
B. 1 kilobase per segment
C. 10 megabases per segment
D. 50–100 kilobases per segment

D. 50–100 kilobases per segment

A cell biologist describes a human cell as euploid. Which karyotype pattern fits this definition?
A. 47 chromosomes, trisomy for one autosome
B. Any chromosome count that is a multiple of 23
C. Any chromosome count with exactly 46
D. Any karyotype with complete sex chromosomes

B. Any chromosome count that is a multiple of 23

A conceptus with karyotype 69,XXX is:
A. Triploid polyploid with extra full set
B. Aneuploid monosomic for one chromosome
C. Euploid diploid with X duplication
D. Haploid with one complete chromosome set

A. Triploid polyploid with extra full set

The most common mechanism producing human triploidy (e.g., 69,XXX or 69,XXY) is:
A. Retention of polar bodies
B. Mitotic nondisjunction post-fertilization
C. Dispermy at the time of fertilization
D. Fusion of two haploid zygotes together

C. Dispermy at the time of fertilization

A karyotype 47,XX,+21 is best described as:
A. Euploid polyploid with extra set
B. Balanced Robertsonian translocation carrier
C. Normal but with structural rearrangement
D. Aneuploid trisomy, not a 23 multiple

D. Aneuploid trisomy, not a 23 multiple

Across human conceptions, the single most common cause of aneuploidy such as monosomy or trisomy is:
A. Gene conversion during meiosis
B. Nondisjunction in meiotic divisions
C. Environmental clastogens during mitosis
D. Telomere shortening in germ cells

B. Nondisjunction in meiotic divisions

A 2-month-old with trisomy 21 is being evaluated for major comorbidities. The single most significant medical problem affecting these patients is:
A. Structural congenital heart defect
B. Severe primary immunodeficiency
C. Cystic lung malformations
D. Primary adrenal insufficiency

A. Structural congenital heart defect

A newborn girl with Down syndrome has a loud systolic murmur and failure to thrive. Echocardiography most likely shows:
A. Isolated secundum ASD
B. Isolated muscular VSD
C. Atrioventricular canal defect (AVSD)
D. Isolated patent ductus arteriosus

C. Atrioventricular canal defect (AVSD)

In addition to AV canal defects, which set of complications is especially common in individuals with trisomy 21?
A. Cystic kidneys, hyperthyroidism, cataracts
B. Hearing loss, hyperthyroidism, retinal tears
C. Obstructive sleep apnea, renal failure, glaucoma
D. Sensorineural hearing loss, hypothyroidism, eye abnormalities

D. Sensorineural hearing loss, hypothyroidism, eye abnormalities

More than 95% of Down syndrome cases arise from which mechanism?
A. Balanced Robertsonian translocation
B. Meiotic nondisjunction
C. Postzygotic mitotic deletion
D. Paternal uniparental disomy

B. Meiotic nondisjunction

A clinically normal woman under 30 has one child with trisomy 21 and normal parental karyotypes. The recurrence risk is partly explained by trisomy 21 confined to her germline. This pattern is:
A. Germline heteroplasmy
B. Confined placental mosaicism
C. General somatic mosaicism
D. Tissue-specific mosaicism

D. Tissue-specific mosaicism

A 40-year-old man with Down syndrome develops progressive memory loss and cognitive decline. The third copy of which gene on chromosome 21 is most implicated?
A. APP
B. DYRK1A
C. SHOX
D. SRY

A. APP

The APP gene product most directly involved in Alzheimer pathology is:
A. Tau microtubule protein
B. Synaptic vesicle transporter
C. Amyloid β precursor protein
D. Presenilin gamma-secretase subunit

C. Amyloid β precursor protein

A fetus is diagnosed with trisomy 18. Counseling notes that fewer than 5% of conceptions survive to term. The classic full karyotype notation in a male is:
A. 47,XY,+21
B. 45,X
C. 47,XXY
D. 47,XY,+18

D. 47,XY,+18

Which statement best explains why aneuploidy prevalence is lower in females than males?
A. Oocytes have fewer meiotic errors
B. Female gonads eliminate abnormal cells
C. X inactivation masks mutant X alleles
D. Female embryos never inherit lethal trisomies

C. X inactivation masks mutant X alleles

Compared with autosomal aneuploidy, sex chromosome aneuploidy tends to be:
A. Clinically less severe
B. Clinically more severe
C. Uniformly lethal in utero
D. Always neuroprotective

B. Clinically more severe

A girl with short stature and primary amenorrhea has karyotype 45,X. This monosomy is known as:
A. Patau syndrome
B. Edwards syndrome
C. Turner syndrome
D. Klinefelter syndrome

C. Turner syndrome

A neonate with Turner syndrome (45,X) is most likely to show which physical findings at birth?
A. Polydactyly and rocker-bottom feet
B. Edema of ankles, wrists, webbed neck
C. Holoprosencephaly and scalp defects
D. Macroglossia and omphalocele

B. Edema of ankles, wrists, webbed neck

A 6-month-old with trisomy 21 has upslanting palpebral fissures and a low nasal bridge. Which karyotype format correctly describes this condition?
A. 47,XX or XY,+13
B. 45,X
C. 47,XXY
D. 47,XX or XY,+21

D. 47,XX or XY,+21

A 2-year-old with Down syndrome presents with bilious vomiting; imaging shows duodenal obstruction. Which GI problems collectively affect about 3% of children with trisomy 21?
A. Pyloric stenosis only
B. Obstruction or atresia of foregut only
C. Inflammatory bowel disease variants
D. Obstruction or atresia of esophagus, duodenum, anus

D. Obstruction or atresia of esophagus, duodenum, anus

A 3-year-old girl is noted to have her index finger overlapping the middle finger at rest, along with growth restriction and congenital heart disease. This hand finding is characteristic of:
A. Turner syndrome
B. Down syndrome
C. Patau syndrome
D. Edwards syndrome

C. Patau syndrome

A teen with Turner syndrome is started on estrogen therapy. The main goal is to promote:
A. Linear growth only
B. Secondary sex characteristics
C. Closure of epiphyseal plates
D. Regression of aortic coarctation

B. Secondary sex characteristics

A liveborn infant with Turner syndrome is later found to have a normal 46,XX placenta with mixed 45,X/46,XX cells only in placental tissue. This is best described as:
A. Confined placental mosaicism
B. Somatic tissue mosaicism
C. Germline-restricted mosaicism
D. Maternal uniparental disomy

C. Germline-restricted mosaicism

In Turner syndrome, mutation or haploinsufficiency of which gene is strongly associated with short stature?
A. APP
B. DYRK1A
C. SHOX
D. SRY

C. SHOX

In cytogenetics, the p and q chromosome arms refer respectively to:
A. Short arm, long arm
B. Long arm, short arm
C. Centromeric arm, telomeric arm
D. Telomeric arm, centromeric arm

A. Short arm, long arm

Short stature in Turner syndrome is largely due to:
A. Complete loss of growth hormone
B. Inactivation of both SHOX alleles
C. SHOX haploinsufficiency from single X copy
D. Excessive SHOX expression on both X

C. SHOX haploinsufficiency from single X copy

The distal portion of the Y chromosome that pairs with X is called the:
A. SRY segment
B. Pseudoautosomal region
C. Testis-determining region
D. Nonrecombining Y segment

B. Pseudoautosomal region

An XY individual lacking SRY due to abnormal crossover typically has which gonadal finding?
A. Normal testes with oligospermia
B. Normal ovaries with infertility
C. Testes in inguinal canal
D. Gonadal streak and poor secondary sex

D. Gonadal streak and poor secondary sex

A tall, infertile man with atrophic seminiferous tubules and gynecomastia has which classic karyotype?
A. 47,XXY
B. 45,X
C. 47,XYY
D. 47,XXX

A. 47,XXY

Klinefelter syndrome (47,XXY) is best categorized as:
A. Balanced structural rearrangement
B. Polyploid, triploid condition
C. Sex chromosome aneuploidy
D. Autosomal trisomy disorder

C. Sex chromosome aneuploidy

The 47,XYY karyotype gained notoriety because of:
A. Extreme short stature in athletes
B. Higher incidence in prison populations
C. Very high childhood leukemia risk
D. Association with Turner-like features

B. Higher incidence in prison populations

Among known etiologies of pregnancy loss, the leading cause is:
A. Maternal autoimmune disease
B. Placental vascular malformations
C. Single-gene Mendelian disorders
D. Chromosome abnormalities

D. Chromosome abnormalities

Compared with balanced structural rearrangements, unbalanced chromosome abnormalities usually:
A. Cause more severe clinical phenotypes
B. Are always clinically silent
C. Only affect sex chromosomes
D. Only appear in mosaic form

A. Cause more severe clinical phenotypes

A substance that promotes chromosome breakage in experimental systems, such as ionizing radiation, is termed a:
A. Teratogen
B. Oncogene
C. Clastogen
D. Mutator enzyme

C. Clastogen

The exchange of chromosomal material between nonhomologous chromosomes is called:
A. Inversion
B. Duplication
C. Deletion
D. Translocation

D. Translocation

Which rearrangement preserves total genomic content via mutual exchange between two nonhomologous chromosomes?
A. Reciprocal translocation
B. Pericentric inversion
C. Telomeric deletion
D. Isochromosome formation

A. Reciprocal translocation

A Robertsonian translocation is characterized by:
A. Fusion of two homologous centromeres
B. Loss of p arms, fusion of q arms
C. Duplication of p arms only
D. Inversion around centromeric region

B. Loss of p arms, fusion of q arms

Robertsonian translocations typically involve which chromosome class?
A. Metacentric autosomes
B. Submetacentric sex chromosomes
C. Acrocentric chromosomes 13,14,15,21,22
D. All autosomes equally

C. Acrocentric chromosomes 13,14,15,21,22

In a Robertsonian carrier, alternate segregation during meiosis produces gametes that are:
A. Always lethal
B. Always aneuploid
C. Unbalanced for long arms
D. Balanced, either normal or carrier

D. Balanced, either normal or carrier

In a Robertsonian carrier, adjacent segregation during meiosis principally results in:
A. Balanced gametes only
B. Unbalanced gametes with trisomy, monosomy
C. Only normal disomic gametes
D. Only monosomic viable gametes

B. Unbalanced gametes with trisomy, monosomy

About 70% of Prader–Willi syndrome cases are due to:
A. Paternal UPD of 15q
B. Maternal UPD of 15q
C. Microdeletion of 7q11
D. Microdeletions of 15q

D. Microdeletions of 15q

The phenomenon in which phenotype depends on whether a deleted allele is maternal or paternal is:
A. Mosaicism
B. Genetic imprinting
C. Anticipation
D. Heteroplasmy

B. Genetic imprinting

Supravalvular aortic stenosis is a hallmark cardiovascular lesion in:
A. Turner syndrome
B. Prader–Willi syndrome
C. Williams syndrome
D. Wolf–Hirschhorn syndrome

C. Williams syndrome

SVAS in Williams syndrome is most directly linked to mutation of which gene?
A. LIMK1
B. SRY
C. SHOX
D. ELN

D. ELN

The LIMK1 gene in Williams syndrome is most associated with defects in:
A. Auditory processing
B. Visual–spatial cognition
C. Motor coordination
D. Language comprehension

B. Visual–spatial cognition

Patients with Wolf–Hirschhorn syndrome may show WAGR features, which include:
A. Wilms tumor, aniridia, GU anomalies, mental disability
B. Wilms tumor, asthma, gout, renal failure
C. Williams tumor, aniridia, goiter, rash
D. Wilms tumor, autism, GU anomalies, rigidity

A. Wilms tumor, aniridia, GU anomalies, mental disability

A child with Wilms tumor, aniridia, genitourinary anomalies, and developmental delay is diagnosed with WAGR syndrome. At the cytogenetic level, this is best classified as:
A. Telomeric microdeletion syndrome
B. Single-gene loss disorder
C. Contiguous gene syndrome
D. Balanced reciprocal translocation

C. Contiguous gene syndrome

Which description best defines a contiguous gene syndrome?
A. Deletion of several adjacent genes
B. Duplication of one critical exon
C. Inversion around a centromeric region
D. Trisomy of an entire chromosome

A. Deletion of several adjacent genes

Microdeletions are typically:
A. Larger than 10 megabases
B. Readily visible on simple karyotype
C. Undetectable by molecular techniques
D. <5 Mb, need banding or molecular

D. <5 Mb, need banding or molecular

Subtelomeric rearrangements usually involve:
A. Pericentromeric heterochromatin losses
B. Deletions or duplications in gene-rich telomeric regions
C. Balanced swaps between metacentric chromosomes
D. Loss of whole short arms only

B. Deletions or duplications in gene-rich telomeric regions

In uniparental disomy, two identical copies of one parental homolog define:
A. Trisomy
B. Monosomy
C. Isodisomy
D. Heterodisomy

C. Isodisomy

In uniparental disomy, two different homologs from one parent (one of each) define:
A. Heterodisomy
B. Isodisomy
C. Mosaicism
D. Polyploidy

A. Heterodisomy

A child of healthy parents manifests an autosomal recessive disease, and testing shows maternal uniparental isodisomy for that chromosome. What is the best explanation?
A. Two identical maternal mutant alleles
B. Two different maternal mutant alleles
C. One normal paternal and one mutant allele
D. Somatic mosaicism for a dominant variant

A. Two identical maternal mutant alleles

Unequal crossing over during meiosis most classically produces which structural abnormality?
A. Ring chromosomes
B. Duplications of chromosomal segments
C. Robertsonian fusions
D. Isochromosomes of short arms

B. Duplications of chromosomal segments

A chromosome with terminal deletions at both ends that subsequently fuses to itself is called a:
A. Ring chromosome
B. Dicentric chromosome
C. Robertsonian derivative
D. Isochromosome

A. Ring chromosome

Which structural change results when a chromosomal segment is excised and reinserted in reverse orientation?
A. Translocation
B. Duplication
C. Inversion
D. Deletion

C. Inversion

A karyotype report describes an inversion including the centromere. This is:
A. Paracentric inversion
B. Pericentric inversion
C. Terminal inversion
D. Interstitial inversion

B. Pericentric inversion

Phenotypically normal parents are found to carry a balanced paracentric inversion. Their reproductive risk is primarily due to gametes carrying:
A. Extra whole chromosomes
B. Ring chromosomes only
C. Balanced inversions only
D. Deletions or duplications from abnormal recombination

D. Deletions or duplications from abnormal recombination

A chromosome splits along the wrong axis, producing a chromosome with two long arms and no short arm. This rearrangement is termed:
A. Isochromosome
B. Robertsonian translocation
C. Paracentric inversion
D. Terminal duplication

A. Isochromosome

Isochromosomes are generally:
A. Lethal because of large deletions
B. Harmless, like balanced translocations
C. Always limited to sex chromosomes
D. Associated only with polyploidy

A. Lethal because of large deletions

A patient has an isochromosome 18q with three copies of 18q and loss of 18p. The clinical picture most closely resembles:
A. Edwards syndrome phenotype
B. Patau syndrome phenotype
C. Down syndrome phenotype
D. Turner syndrome phenotype

A. Edwards syndrome phenotype

Which constellation of findings is most typical of major chromosome abnormalities?
A. Isolated anemia only
B. Single organ failure, normal development
C. Developmental delay, dysmorphic facies, malformations
D. Normal development with mild anemia

C. Developmental delay, dysmorphic facies, malformations

A patient with chronic myelogenous leukemia has a shortened chromosome 22 with a 9;22 reciprocal translocation. This derivative is called the:
A. Robertsonian chromosome
B. Edwards chromosome
C. Philadelphia chromosome
D. Patau chromosome

C. Philadelphia chromosome

In the Philadelphia chromosome, which gene’s relocation is central to pathogenesis?
A. BCR only
B. MYC
C. ELN
D. ABL

D. ABL

The abnormal ABL fusion protein in CML most directly causes:
A. Loss of all kinase activity
B. Increased tyrosine kinase activity
C. Inhibition of all cell division
D. Exclusive activation in epithelial cells

B. Increased tyrosine kinase activity

The Philadelphia chromosome is best described cytogenetically as:
A. Unbalanced translocation with gene loss
B. Balanced translocation affecting regulatory sequences
C. Simple terminal deletion of 22q
D. Isochromosome formation of chromosome 22

B. Balanced translocation affecting regulatory sequences