A karyotype from peripheral blood shows a normal human diploid chromosome count. How many chromosomes are present?
A. 44
B. 45
C. 46
D. 48

C. 46

A euploid embryo inherits equal chromosome sets from each parent. Which distribution is correct?
A. 23 maternal, 23 paternal
B. 22 maternal, 24 paternal
C. 24 maternal, 22 paternal
D. 46 maternal, 0 paternal

A. 23 maternal, 23 paternal

In humans, the number of autosomal chromosome pairs is:
A. 21 pairs
B. 22 chromosomes
C. 23 pairs
D. 22 pairs

D. 22 pairs

A couple asks who determines genetic sex at conception. The father can transmit:
A. X only
B. X or Y
C. Y only
D. Neither X nor Y

B. X or Y

A variant disrupts a DNA segment that encodes a functional product. This segment is a:
A. Locus
B. Gene
C. Allele
D. Chromatid

B. Gene

A report states “mutation at 7q31.” This describes a chromosomal:
A. Allele
B. Gene
C. Chromosome
D. Locus

D. Locus

Two siblings share the same locus but differ in sequence at that site. Each version is an:
A. Allele
B. Centromere
C. Chromatid
D. Telomere

A. Allele

A diploid individual’s genotype at one locus includes:
A. One allele
B. Three alleles
C. Two alleles
D. No alleles

C. Two alleles

A pedigree shows many affected males with carrier females. Best explanation?
A. X inactivation in males
B. Mitochondrial inheritance pattern
C. Y-linked transmission
D. Single X in males

D. Single X in males

A disorder appears in both sexes each generation with no sex bias. This pattern best fits:
A. X-linked dominant
B. X-linked recessive
C. Autosomal recessive
D. Mitochondrial inheritance

C. Autosomal recessive

A meiotic error causes sister chromatids to fail separation. This is:
A. Inversion
B. Nondisjunction
C. Translocation
D. Deletion

B. Nondisjunction

A newborn has an abnormal chromosome number due to meiotic segregation failure. This is:
A. Polyploidy
B. Mosaicism
C. Aneuploidy
D. Triploidy

C. Aneuploidy

Prenatal testing reveals autosomal aneuploidy. The most common outcome is:
A. Spontaneous abortion or disease
B. No phenotype
C. Isolated anemia
D. Always viable, mild symptoms

A. Spontaneous abortion or disease

Which is NOT a chromosomal structural alteration?
A. Inversion
B. Translocation
C. Deletion
D. Nondisjunction

D. Nondisjunction

A disorder appears in both sexes each generation with no sex bias. This pattern best fits:
A. X-linked dominant
B. X-linked recessive
C. Autosomal dominant
D. Mitochondrial inheritance

C. Autosomal dominant

A drug increases transcription by loosening chromatin via histone tail changes. Which mechanism?
A. DNA excision repair
B. Cytosine deamination
C. Histone acetylation
D. Splice-site mutation

C. Histone acetylation

A tumor shows stable DNA sequence but reduced gene expression via promoter modification. Most consistent with:
A. Histone ubiquitination
B. Replication slippage
C. Base substitution
D. Cytosine methylation

D. Cytosine methylation

A syndrome shows parent-of-origin effects without nucleotide change. This is:
A. Imprinting
B. Duplication
C. Translocation
D. Isochromosome formation

A. Imprinting

A disorder differs depending on whether the allele came from mother or father. This reflects imprinting being:
A. Random
B. Tissue-specific only
C. Sex-specific
D. Always paternal

C. Sex-specific

In a somatic lineage, an imprint typically:
A. Disappears after mitosis
B. Persists in progeny cells
C. Changes each cell cycle
D. Requires DNA sequence change

B. Persists in progeny cells

During gametogenesis, imprint marks are:
A. Reset
B. Permanently fixed
C. Randomly deleted
D. Converted to mutations

A. Reset

A researcher uses a population model to infer allele frequencies from genotype frequencies. This is:
A. Founder effect
B. Linkage analysis
C. Genomic imprinting
D. Hardy–Weinberg equilibrium

D. Hardy–Weinberg equilibrium

Hardy–Weinberg methods are best suited to analyze:
A. Mitochondrial disorders only
B. Autosomal and XLR disorders
C. X-linked dominant only
D. Chromosomal trisomies only

B. Autosomal and XLR disorders

A patient’s condition reflects multiple genes plus environment. This is:
A. Imprinting disorder
B. Single-gene disorder
C. Multifactorial disease
D. Aneuploidy syndrome

C. Multifactorial disease

A pedigree shows progressive severity across generations due to repeat expansion. Inheritance is usually:
A. Autosomal dominant
B. Autosomal recessive
C. X-linked recessive
D. Mitochondrial inheritance

A. Autosomal dominant

Earlier onset and worsening symptoms in later generations most directly correlates with:
A. Loss of imprinting
B. Decreased penetrance
C. Gene deletion size
D. Increasing repeat number

D. Increasing repeat number

A mutation removes cell-cycle “brakes,” enabling uncontrolled proliferation. The gene class is:
A. Growth factor genes
B. Ion channel genes
C. Tumor suppressor genes
D. Spliceosome genes

C. Tumor suppressor genes

Which is an epigenetic modification mechanism?
A. Gene translocation
B. Histone phosphorylation
C. Chromosome inversion
D. Nondisjunction

B. Histone phosphorylation

A pedigree shows vertical transmission of retinoblastoma-like cancer predisposition. Which statement best fits tumor suppressor inheritance?
A. Autosomal recessive; dominant mechanism
B. X-linked dominant; recessive mechanism
C. Autosomal dominant; recessive mechanism
D. Mitochondrial; dominant mechanism

C. Autosomal dominant; recessive mechanism

In a familial cancer workup, a tumor shows deletion of the remaining wild-type allele at a locus. This is:
A. Loss of heterozygosity
B. Variable expressivity
C. Anticipation
D. Imprinting

A. Loss of heterozygosity

A prenatal karyotype shows 47 total chromosomes. This abnormality is best termed:
A. Polyploidy
B. Triploidy
C. Tetraploidy
D. Aneuploidy

D. Aneuploidy

A newborn has streak ovaries and webbed neck; karyotype: 45,X. Diagnosis?
A. Klinefelter syndrome
B. Turner syndrome
C. Edwards syndrome
D. Patau syndrome

B. Turner syndrome

A fetus has 47,XY,+21. The diagnosis is:
A. Turner syndrome
B. Triple X syndrome
C. Patau syndrome
D. Down syndrome

D. Down syndrome

A lab orders a test to visualize chromosomes and detect trisomies and translocations. Best test?
A. Karyotype
B. PCR genotyping
C. Southern blot
D. Sanger sequencing

A. Karyotype

For karyotyping, cells are arrested when chromosomes are maximally visible. This stage is:
A. Prophase I
B. Mitotic metaphase
C. Anaphase II
D. Interphase

B. Mitotic metaphase

A genetics student asks when crossing over occurs. Correct timing is:
A. After metaphase I
B. After metaphase II
C. After replication, before metaphase I
D. Before DNA replication

C. After replication, before metaphase I

A traits lecture defines heritability. Which description is correct?
A. Genetic and environmental components
B. Only environmental contribution
C. Only genetic contribution
D. Only mitochondrial contribution

A. Genetic and environmental components

A trait has “genetic component 100%.” This implies:
A. Environment fully determines phenotype
B. Genes and environment equally contribute
C. Epigenetics dominates inheritance
D. No environmental influence on phenotype

D. No environmental influence on phenotype

A trait has “genetic component 10%.” This implies phenotype is mainly:
A. Mendelian segregation
B. Environmental
C. Chromosomal dosage
D. Imprinted alleles

B. Environmental

In counseling, “penetrance” refers to:
A. Disease severity among affected
B. Allele frequency in population
C. Probability phenotype expressed
D. Chromosome separation failure

C. Probability phenotype expressed

A mutation has 100% penetrance. This means:
A. All carriers express disease
B. Half of carriers express disease
C. No carriers express disease
D. Severity varies widely

A. All carriers express disease

A family shows incomplete penetrance. Which factor can explain penetrance <100%?
A. Nondisjunction events only
B. Modifier genes or epigenetics
C. Tight junction disruption
D. Crossover frequency changes

B. Modifier genes or epigenetics

Two relatives carry the same mutant allele and both are affected, but one is mild and one is severe. This is:
A. Anticipation
B. Incomplete dominance
C. Loss of heterozygosity
D. Variable expressivity

D. Variable expressivity

A disorder shows 100% penetrance, yet affected relatives have different clinical pictures. This best reflects:
A. Variable expressivity
B. Germline mosaicism
C. Allelic heterogeneity
D. X-inactivation

A. Variable expressivity

A clinician asks why expressivity varies within families. Most consistent causes are:
A. Only nondisjunction rates
B. Only imprint resetting
C. Environment and modifier genes
D. Only crossover differences

C. Environment and modifier genes

Which disorder is a classic example of variable expressivity?
A. Achondroplasia
B. Marfan syndrome
C. Down syndrome
D. Turner syndrome

B. Marfan syndrome

A heterozygous affected parent has an autosomal dominant disorder. Risk each child is affected:
A. 25%
B. 10%
C. 75%
D. 50%

D. 50%

A patient has café-au-lait spots and neurofibromas (Neurofibromatosis type 1). Inheritance pattern is most classically:
A. Autosomal recessive
B. X-linked recessive
C. Autosomal dominant
D. Mitochondrial

C. Autosomal dominant

Short-limbed dwarfism with FGFR involvement suggests:
A. Achondroplasia
B. Osteogenesis imperfecta
C. Marfan syndrome
D. Neurofibromatosis type 1

A. Achondroplasia

An adult develops progressive neurodegeneration with a family history across generations; the listed autosomal dominant example is:
A. Cystic fibrosis
B. Huntington disease type 2
C. Tay-Sachs disease
D. Duchenne muscular dystrophy

B. Huntington disease type 2

Achondroplasia is caused by mutation in which gene class?
A. Tumor suppressor gene
B. Ion channel gene
C. FGF receptor gene
D. Collagen gene

C. FGF receptor gene

Why is mitotic metaphase optimal for karyotyping?
A. Homologs pair and synapse
B. Spindle absent, DNA relaxed
C. Chromatids segregate to poles
D. Chromosomes most condensed, easily seen

D. Chromosomes most condensed, easily seen

A patient develops progressive chorea and cognitive decline. Testing reveals a triplet-repeat expansion in which gene?
A. NF1
B. HTT
C. CFTR
D. FBN1

B. HTT

A tall patient with lens subluxation has a mutation in a fibrous protein. The gene product is:
A. Fibrillin
B. Dystrophin
C. Tyrosinase
D. Factor VIII

A. Fibrillin

A child with café-au-lait spots has a mutation in a GTPase-activating protein. The mutated gene is:
A. HTT
B. DMD
C. NF1
D. OTC

C. NF1

Two carrier parents have a child. In autosomal recessive inheritance, expected outcomes are:
A. 25% affected
B. 50% affected
C. 75% affected
D. 25% carriers

A. 25% affected

A drug increases transcription by loosening chromatin via histone tail changes. Which mechanism?
A. DNA excision repair
B. Cytosine deamination
C. Histone acetylation
D. Splice-site mutation

C. Histone acetylation

A child has generalized hypopigmentation due to loss of melanin synthesis. Defective enzyme:
A. Phenylalanine hydroxylase
B. Melanocyte tyrosinase
C. Ornithine transcarbamylase
D. Hexosaminidase A

B. Melanocyte tyrosinase

A newborn has recurrent lung infections and pancreatic insufficiency. The mutated protein is:
A. Dystrophin
B. CFTR
C. Fibrillin
D. Neurofibromin

B. CFTR

A screening test suggests PKU. The most common deficiency is:
A. Homogentisate oxidase
B. Phenylalanine hydroxylase
C. Branched-chain dehydrogenase
D. Porphobilinogen deaminase

B. Phenylalanine hydroxylase

A patient has sickle cell disease. The causative mutation is:
A. E6V in β-globin
B. E6K in α-globin
C. V6E in α-globin
D. Frameshift in γ-globin

A. E6V in β-globin

A pedigree shows affected males only, with no male-to-male transmission. This suggests:
A. Autosomal dominant
B. Autosomal recessive
C. X-linked recessive
D. X-linked dominant

C. X-linked recessive

In X-linked recessive disorders, females are typically:
A. Asymptomatic
B. Always affected
C. More affected than males
D. Embryonic lethal

A. Asymptomatic

A conceptus has monosomy of chromosome 7. The expected outcome is:
A. Viable, mild phenotype
B. Embryonic lethal
C. Always mosaic survival
D. Causes only anemia

B. Embryonic lethal

Trisomies most compatible with limited survival involve:
A. 1, 2, 3
B. 5, 7, 9
C. 12, 16, 20
D. 13, 18, 21

D. 13, 18, 21

To balance gene expression in females, one X chromosome undergoes:
A. Random deletion
B. Inactivation and condensation
C. Complete replication failure
D. Translocation to Y chromosome

B. Inactivation and condensation

The condensed inactive X chromosome in female somatic cells is called:
A. Nucleolus organizer
B. Barr body
C. Sex vesicle
D. Chromatid bridge

B. Barr body

Which is an X-linked recessive disorder?
A. Hemophilia A
B. Cystic fibrosis
C. Marfan syndrome
D. Huntington disease type 2

A. Hemophilia A

Hemophilia A results from mutation in:
A. Factor IX
B. Factor VIII
C. Factor V
D. Factor XI

B. Factor VIII

Duchenne muscular dystrophy is most often due to:
A. Point mutation in NF1
B. Large deletions in DMD
C. Trisomy of chromosome 21
D. Expansion in HTT

B. Large deletions in DMD

Red-green color blindness most directly reflects:
A. Rod degeneration
B. Cone dysfunction
C. Lens opacification
D. Optic nerve transection

B. Cone dysfunction

The most common inborn error of the urea cycle is:
A. CPS1 deficiency
B. OTC deficiency
C. ASS deficiency
D. ASL deficiency

B. OTC deficiency

A child has exercise intolerance and lactic acidosis. A pathogenic mtDNA mutation most directly impairs:
A. Glycolysis
B. Oxidative phosphorylation
C. DNA replication
D. Beta oxidation

B. Oxidative phosphorylation

A muscle biopsy shows mixed normal and mutant mtDNA within the same cell. This is:
A. Polyploidy
B. Homoplasmy
C. Imprinting
D. Heteroplasmy

D. Heteroplasmy

A cell’s mitochondria all carry the same mtDNA genome (normal or mutant). This is:
A. Homoplasmy
B. Heteroplasmy
C. Aneuploidy
D. Mosaicism

A. Homoplasmy

A pedigree shows only affected mothers transmit a disorder. Mitochondria are inherited from the:
A. Father
B. Both parents
C. Mother
D. Paternal grandfather

C. Mother

A woman with a mitochondrial disorder has children. Expected penetrance among her children is:
A. All children affected
B. Half children affected
C. Only sons affected
D. Only daughters affected

A. All children affected

A man with a mitochondrial disorder has children with an unaffected partner. His children are most likely:
A. All affected
B. Half affected
C. Variable by sex
D. Unaffected

D. Unaffected

Two siblings from the same affected mother have different severities. Best explanation:
A. Anticipation
B. Reduced penetrance
C. Variable mutant mitochondria load
D. Uniparental disomy

C. Variable mutant mitochondria load

A mitochondrial disorder most prominently affects tissues with:
A. Low ATP demand
B. High energy requirement
C. Slow cell turnover
D. High melanin content

B. High energy requirement

A young adult has painless central vision loss consistent with Leber’s hereditary optic neuropathy (LHON). The typical genetic lesion is:
A. Mitochondrial rRNA mutation
B. Nuclear tRNA mutation
C. mtDNA large deletion
D. Mitochondrial protein-gene mutation

D. Mitochondrial protein-gene mutation

A patient has MERRF myoclonic seizures and ragged-red fibers. The lesion most classically involves:
A. Mitochondrial tRNA gene mutation
B. Mitochondrial protein-gene mutation
C. Autosomal dominant repeat
D. X-linked recessive deletion

A. Mitochondrial tRNA gene mutation

A patient has stroke-like episodes and lactic acidosis (MELAS). The mutation most often affects:
A. mtDNA deletion
B. Nuclear transcription factor
C. Mitochondrial tRNA gene mutation
D. PHEX gene mutation

C. Mitochondrial tRNA gene mutation

A teen has myopathy, cerebellar findings, and cardiomyopathy (Kearns–Sayre). Most likely mechanism:
A. mt rRNA point mutation
B. mtDNA deletion
C. NF1 loss-of-function
D. CFTR channel mutation

B. mtDNA deletion

A child has hypophosphatemic rickets with an X-linked dominant pedigree. The implicated gene is:
A. PHEX
B. HTT
C. NF1
D. CFTR

A. PHEX

A girl has blistering rash evolving into hyperpigmented streaks; males in family die early. The causal gene is:
A. PHEX
B. DMD
C. NF1
D. IKBKG

D. IKBKG

Incontinentia pigmenti type 1 is often:
A. Benign in males
B. Fatal in males
C. Fatal in females
D. Limited to males

B. Fatal in males

The IKBKG gene product primarily regulates a family of:
A. Ion channels
B. Structural collagens
C. Transcription factors
D. Mitochondrial ribosomes

C. Transcription factors

A trisomy results from a meiotic error. The process is:
A. Nondisjunction
B. Duplication
C. Insertion
D. Inversion

A. Nondisjunction

Nondisjunction is best defined as:
A. Two breaks with reversal
B. Unequal sorting in meiosis I/II
C. Extra segment copied twice
D. Reciprocal chromosome exchange

B. Unequal sorting in meiosis I/II

Which is a chromosomal structural alteration?
A. Aneuploidy
B. Penetrance
C. Inversion
D. Heritability

C. Inversion

An inversion involves:
A. Two breaks; segment inverted
B. One break; segment lost
C. One break; segment copied
D. Two breaks; chromosomes swapped

A. Two breaks; segment inverted

A duplication involves:
A. Segment inverted between breaks
B. Segment deleted entirely
C. Reciprocal exchange between chromosomes
D. Duplicated segment inserted same chromosome

D. Duplicated segment inserted same chromosome

A disorder caused by loss of a small chromosomal segment is best termed:
A. Heteroplasmy
B. Aneuploidy
C. Microdeletion syndrome
D. Homoplasmy

C. Microdeletion syndrome

A prenatal report notes an “insertion” without net DNA loss. Which description best fits an insertion?
A. Segment flipped within chromosome
B. Whole arm duplicated, other lost
C. Segment inserted into another chromosome
D. Reciprocal exchange between chromosomes

C. Segment inserted into another chromosome

A cytogenetics lab suspects an isochromosome. Which structure is most characteristic?
A. Two identical p arms or q arms
B. Two chromosomes mutually exchange arms
C. Small deletion under 5 Mb
D. Segment inverted between two breaks

A. Two identical p arms or q arms

In an isochromosome, the two arms are:
A. Randomly different in sequence
B. One maternal, one paternal
C. Complementary but nonidentical
D. Genetically identical to each other

D. Genetically identical to each other

A syndrome is linked to a small chromosomal deletion with complex, consistent phenotype. “Microdeletion” typically means:
A. Deletion larger than 20 Mb
B. Deletion under 5 megabases
C. Entire chromosome arm missing
D. Whole chromosome duplicated

B. Deletion under 5 megabases

A child’s phenotype suggests a microdeletion syndrome; standard karyotype is normal. A test often needed to localize the deletion is:
A. FISH
B. Karyotype
C. Western blot
D. Gram stain

A. FISH

A clinician suspects an even smaller deletion that FISH can miss. Which method is more sensitive for microdeletions?
A. Light microscopy banding
B. Standard karyotype
C. Single-gene PCR
D. Array-based genomic hybridization

D. Array-based genomic hybridization

Two main categories of chromosomal translocations are:
A. Inversion and duplication
B. Robertsonian and reciprocal
C. Insertion and deletion
D. Isochromosome and microdeletion

B. Robertsonian and reciprocal

A “balanced reciprocal translocation” is best described as:
A. One arm duplicated, other lost
B. Segment inverted within one chromosome
C. Mutual exchange between two chromosomes
D. Small deletion with complex phenotype

C. Mutual exchange between two chromosomes

A balanced reciprocal translocation is “balanced” because:
A. Entire chromosome number is normal
B. Extra copy compensates deletion
C. It always causes trisomy 21
D. No net genetic material loss

D. No net genetic material loss

A tall man has infertility and small testes. Which karyotype is most likely?
A. 45,X
B. 47,XXY
C. 47,XYY
D. 47,XXX

B. 47,XXY

A patient has short stature and amenorrhea; karyotype shows monosomy X. Diagnosis?
A. Turner syndrome
B. Triple-X syndrome
C. Down syndrome
D. Edwards syndrome

A. Turner syndrome

A newborn has cleft lip/palate and polydactyly; karyotype is trisomy 13. Syndrome?
A. Down syndrome
B. Edwards syndrome
C. Patau syndrome
D. Turner syndrome

C. Patau syndrome

A neonate with low birth weight and a small, abnormally shaped head has trisomy 18. Syndrome?
A. Patau syndrome
B. Edwards syndrome
C. Down syndrome
D. Klinefelter syndrome

B. Edwards syndrome

A child has hypotonia, characteristic facies, and congenital heart disease; karyotype shows +21. Syndrome?
A. Patau syndrome
B. Edwards syndrome
C. Turner syndrome
D. Down syndrome

D. Down syndrome

A female has learning difficulties but no major physical anomalies; karyotype is 47,XXX. Diagnosis?
A. Klinefelter syndrome
B. Turner syndrome
C. Triple-X syndrome
D. Down syndrome

C. Triple-X syndrome

A boy has some learning/behavioral problems; karyotype is 47,XYY. Diagnosis?
A. XYY syndrome
B. Klinefelter syndrome
C. Patau syndrome
D. Turner syndrome

A. XYY syndrome

Which aneuploidy is associated with increased leukemia risk?
A. Turner syndrome
B. Down syndrome
C. Triple-X syndrome
D. XYY syndrome

B. Down syndrome

Severe CNS anomalies with polydactyly strongly suggests:
A. Edwards syndrome
B. Down syndrome
C. Turner syndrome
D. Patau syndrome

D. Patau syndrome

Low birth weight with heart defects and small malformed head most strongly suggests:
A. Down syndrome
B. Patau syndrome
C. Edwards syndrome
D. Klinefelter syndrome

C. Edwards syndrome

Turner syndrome is especially common among:
A. Miscarriages and stillbirths
B. Elderly fathers only
C. Premature male births
D. Maternal diabetes pregnancies

A. Miscarriages and stillbirths