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Genetics 6

front 1

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

back 1

C. Metaphase

front 2

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

back 2

A. Acrocentric

front 3

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

back 3

D. Metacentric

front 4

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

back 4

B. Telomeres

front 5

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

back 5

C. C-banding

front 6

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

back 6

A. Comparative genomic hybridization

front 7

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

back 7

D. Duplication of that region

front 8

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

back 8

B. Deletion of that region

front 9

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

back 9

C. Cytogenomic microarray (CMA)

front 10

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

back 10

A. Balanced chromosomal rearrangements

front 11

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

back 11

D. Trisomy compared with monosomy

front 12

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

back 12

B. Meiotic nondisjunction in meiosis I or II

front 13

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

back 13

C. Trisomy 21

front 14

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

back 14

B. AV canal defect and ventricular septal defect

front 15

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

back 15

D. Learning and memory deficits

front 16

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

back 16

A. APP (amyloid precursor protein)

front 17

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

back 17

C. Early-onset Alzheimer disease

front 18

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

back 18

B. Trisomy 18 (Edwards)

front 19

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)

back 19

D. Trisomy 13 (Patau syndrome)

front 20

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

back 20

A. Remain arrested in meiosis longer

front 21

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

back 21

C. 45,X

front 22

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

back 22

A. Bicuspid aortic valve

front 23

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

back 23

D. More SHOX copies increase stature

front 24

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

back 24

B. Klinefelter syndrome, 47,XXY

front 25

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

back 25

D. Distal Y pairing with X short arm

front 26

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

back 26

A. SRY gene translocated onto X

front 27

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

back 27

C. Normal phenotypic female with streak gonads

front 28

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

back 28

A. Robertsonian translocation

front 29

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

back 29

D. Cri-du-chat syndrome

front 30

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

back 30

B. Wolf–Hirschhorn syndrome

front 31

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

back 31

C. Interstitial deletion

front 32

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

back 32

A. Prader–Willi syndrome

front 33

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

back 33

D. Williams syndrome

front 34

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

back 34

B. Velocardiofacial (VCF) syndrome

front 35

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

back 35

C. Near telomeres, gene-dense region

front 36

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

back 36

D. Uniparental disomy

front 37

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

back 37

A. Heterodisomy

front 38

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

back 38

C. Isodisomy

front 39

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

back 39

B. Somatic mosaicism

front 40

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

back 40

B. Ring chromosome formation

front 41

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

back 41

B. ABD/CEF

front 42

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

back 42

A. Isochromosome

front 43

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

back 43

C. Philadelphia chromosome

front 44

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

back 44

C. Constitutive tyrosine kinase activity

front 45

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

back 45

D. MYC

front 46

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

back 46

D. Arrest cells in metaphase for karyotyping

front 47

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

back 47

B. The number and types of chromosomes

front 48

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

back 48

D. Metacentric, submetacentric, acrocentric

front 49

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

back 49

A. Contain 23-chromosome multiples (euploid)

front 50

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

back 50

C. To swell and rupture metaphase cells

front 51

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

back 51

B. Giemsa banding (G-banding)

front 52

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

back 52

D. Heat treatment, reversing dark–light pattern

front 53

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

back 53

A. Constitutive heterochromatin and acrocentric satellites

front 54

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

back 54

C. More extended, less condensed structurally

front 55

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

back 55

D. Fluorescence in situ hybridization

front 56

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

back 56

B. Labelled single-stranded DNA segment

front 57

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

back 57

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

front 58

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

back 58

C. Uses FISH with multiple colored probes

front 59

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

back 59

D. 50–100 kilobases per segment

front 60

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

back 60

B. Any chromosome count that is a multiple of 23

front 61

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

back 61

A. Triploid polyploid with extra full set

front 62

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

back 62

C. Dispermy at the time of fertilization

front 63

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

back 63

D. Aneuploid trisomy, not a 23 multiple

front 64

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

back 64

B. Nondisjunction in meiotic divisions

front 65

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

back 65

A. Structural congenital heart defect

front 66

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

back 66

C. Atrioventricular canal defect (AVSD)

front 67

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

back 67

D. Sensorineural hearing loss, hypothyroidism, eye abnormalities

front 68

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

back 68

B. Meiotic nondisjunction

front 69

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

back 69

D. Tissue-specific mosaicism

front 70

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

back 70

A. APP

front 71

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

back 71

C. Amyloid β precursor protein

front 72

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

back 72

D. 47,XY,+18

front 73

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

back 73

C. X inactivation masks mutant X alleles

front 74

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

back 74

B. Clinically more severe

front 75

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

back 75

C. Turner syndrome

front 76

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

back 76

B. Edema of ankles, wrists, webbed neck

front 77

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

back 77

D. 47,XX or XY,+21

front 78

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

back 78

D. Obstruction or atresia of esophagus, duodenum, anus

front 79

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

back 79

C. Patau syndrome

front 80

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

back 80

B. Secondary sex characteristics

front 81

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

back 81

C. Germline-restricted mosaicism

front 82

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

back 82

C. SHOX

front 83

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

back 83

A. Short arm, long arm

front 84

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

back 84

C. SHOX haploinsufficiency from single X copy

front 85

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

back 85

B. Pseudoautosomal region

front 86

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

back 86

D. Gonadal streak and poor secondary sex

front 87

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

back 87

A. 47,XXY

front 88

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

back 88

C. Sex chromosome aneuploidy

front 89

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

back 89

B. Higher incidence in prison populations

front 90

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

back 90

D. Chromosome abnormalities

front 91

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

back 91

A. Cause more severe clinical phenotypes

front 92

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

back 92

C. Clastogen

front 93

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

back 93

D. Translocation

front 94

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

back 94

A. Reciprocal translocation

front 95

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

back 95

B. Loss of p arms, fusion of q arms

front 96

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

back 96

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

front 97

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

back 97

D. Balanced, either normal or carrier

front 98

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

back 98

B. Unbalanced gametes with trisomy, monosomy

front 99

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

back 99

D. Microdeletions of 15q

front 100

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

back 100

B. Genetic imprinting

front 101

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

back 101

C. Williams syndrome

front 102

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

back 102

D. ELN

front 103

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

back 103

B. Visual–spatial cognition

front 104

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

back 104

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

front 105

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

back 105

C. Contiguous gene syndrome

front 106

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

back 106

A. Deletion of several adjacent genes

front 107

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

back 107

D. <5 Mb, need banding or molecular

front 108

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

back 108

B. Deletions or duplications in gene-rich telomeric regions

front 109

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

back 109

C. Isodisomy

front 110

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

back 110

A. Heterodisomy

front 111

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

back 111

A. Two identical maternal mutant alleles

front 112

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

back 112

B. Duplications of chromosomal segments

front 113

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

back 113

A. Ring chromosome

front 114

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

back 114

C. Inversion

front 115

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

back 115

B. Pericentric inversion

front 116

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

back 116

D. Deletions or duplications from abnormal recombination

front 117

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

back 117

A. Isochromosome

front 118

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

back 118

A. Lethal because of large deletions

front 119

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

back 119

A. Edwards syndrome phenotype

front 120

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

back 120

C. Developmental delay, dysmorphic facies, malformations

front 121

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

back 121

C. Philadelphia chromosome

front 122

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

back 122

D. ABL

front 123

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

back 123

B. Increased tyrosine kinase activity

front 124

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

back 124

B. Balanced translocation affecting regulatory sequences