USMLE Step 1 Genetics Practice Questions

A couple is undergoing genetic counseling. The man is affected by an autosomal dominant disorder with incomplete penetrance. They want to know the risk of having an affected child. If the penetrance of the disorder is 80%, and assuming the man is heterozygous and the woman is unaffected, what is the probability that their first child will be phenotypically affected by the disorder?

• (A) 40%
• (B) 50%
• (C) 80%
• (D) 100%

Prader-Willi syndrome and Angelman syndrome are distinct genetic disorders caused by the deletion or inactivation of genes on the long arm of chromosome 15 (15q11-q13). Which genetic phenomenon explains why deletion of the *paternally* derived chromosome 15 region causes Prader-Willi syndrome, while deletion of the *maternally* derived region causes Angelman syndrome?

• (A) Genomic imprinting
• (B) Anticipation
• (C) Mosaicism
• (D) Uniparental disomy

Cystic fibrosis is an autosomal recessive disorder caused by mutations in the CFTR gene. If the carrier frequency for cystic fibrosis in a specific population is 1/25, what is the approximate probability that a child born to two unrelated, asymptomatic individuals from this population will be affected with cystic fibrosis?

• (A) 1/2500
• (B) 1/25
• (C) 1/50
• (D) 1/100

Which type of mutation involves the change of a single DNA base pair that results in the substitution of one amino acid for another in the final protein?

• (A) Missense mutation
• (B) Nonsense mutation
• (C) Silent mutation
• (D) Frameshift mutation

Down syndrome (Trisomy 21) is most commonly caused by which type of chromosomal abnormality occurring during meiosis?

• (A) Nondisjunction
• (B) Translocation
• (C) Deletion
• (D) Inversion

Huntington disease is an autosomal dominant neurodegenerative disorder characterized by progressive motor, cognitive, and psychiatric symptoms. It exhibits anticipation, meaning the disease tends to have an earlier onset and increased severity in successive generations. This anticipation is primarily caused by:

• (A) Expansion of CAG trinucleotide repeats in the HTT gene
• (B) Deletion within the huntingtin gene
• (C) Point mutations leading to protein misfolding
• (D) Epigenetic silencing of the HTT gene

A couple has a child affected with an autosomal recessive condition. They are planning another pregnancy and want to know the probability that their next child will also be affected. What is the recurrence risk?

• (A) 25%
• (B) 50%
• (C) 75%
• (D) 100%

Which of the following inheritance patterns is characterized by transmission only from affected fathers to all of their daughters, and never from father to son?

• (A) X-linked dominant
• (B) X-linked recessive
• (C) Autosomal dominant
• (D) Y-linked

Hardy-Weinberg equilibrium describes the relationship between allele frequencies and genotype frequencies in a population under certain assumptions (e.g., random mating, no mutation, no migration, no selection, large population size). If the frequency of an autosomal recessive disease allele (q) in a population is 0.02 (2%), what is the expected frequency of heterozygous carriers (2pq) in that population?

• (A) 0.0392 (or approx. 1/25)
• (B) 0.0004 (or 1/2500)
• (C) 0.02 (or 1/50)
• (D) 0.9604

Which genetic term describes the phenomenon where mutations in different genes can cause the same or very similar phenotypes?

• (A) Locus heterogeneity
• (B) Allelic heterogeneity
• (C) Variable expressivity
• (D) Pleiotropy

Turner syndrome (45,X) is a chromosomal abnormality affecting females, characterized by short stature, ovarian dysgenesis, webbed neck, and other features. This condition results from the absence of:

• (A) One entire X chromosome
• (B) One entire Y chromosome
• (C) A portion of the short arm of chromosome 5
• (D) An extra copy of chromosome 18

Duchenne Muscular Dystrophy (DMD) is a severe X-linked recessive disorder causing progressive muscle degeneration. It is caused by mutations (often deletions) in the DMD gene, which encodes the protein dystrophin. Why are males typically affected much more severely and frequently than females?

• (A) Males have only one X chromosome, so a single recessive allele on that X is sufficient to cause the disease.
• (B) The gene is located on the Y chromosome.
• (C) Females have hormonal protection against the disease.
• (D) The mutation is dominant in males but recessive in females.

Which technique is commonly used to amplify specific segments of DNA exponentially, allowing for analysis even from very small starting samples?

• (A) Polymerase Chain Reaction (PCR)
• (B) Southern blotting
• (C) Northern blotting
• (D) Western blotting

Mitochondrial diseases are caused by mutations in mitochondrial DNA (mtDNA). What is the typical pattern of inheritance for these disorders?

• (A) Maternal inheritance
• (B) Autosomal dominant inheritance
• (C) Autosomal recessive inheritance
• (D) X-linked inheritance

A Robertsonian translocation involves the fusion of the long arms of two acrocentric chromosomes (chromosomes 13, 14, 15, 21, 22) at the centromere, with loss of the short arms. Carriers of a balanced Robertsonian translocation are phenotypically normal but are at increased risk of producing unbalanced gametes. A common example involves chromosomes 14 and 21. A carrier of a balanced t(14;21) translocation has an increased risk of having a child with which condition?

• (A) Down syndrome (Translocation type)
• (B) Patau syndrome (Trisomy 13)
• (C) Edwards syndrome (Trisomy 18)
• (D) Cri-du-chat syndrome

Which term describes the presence of two or more genetically distinct cell lines within a single individual, derived from a single zygote?

• (A) Mosaicism
• (B) Chimerism
• (C) Heteroplasmy
• (D) Polymorphism

Sickle cell disease is an autosomal recessive disorder caused by a specific missense mutation (Glu6Val) in the beta-globin gene. Individuals heterozygous for the sickle cell allele (sickle cell trait) are generally asymptomatic but may show some protection against malaria. This phenomenon, where the heterozygous state confers a selective advantage, is known as:

• (A) Heterozygote advantage (or Overdominance)
• (B) Founder effect
• (C) Genetic drift
• (D) Gene flow

What is the function of telomeres, the repetitive DNA sequences found at the ends of linear eukaryotic chromosomes?

• (A) Protect chromosome ends from degradation and fusion, and solve the end-replication problem
• (B) Serve as origins of replication
• (C) Encode ribosomal RNA
• (D) Regulate gene expression

Which enzyme is responsible for unwinding the DNA double helix at the replication fork, separating the two parental strands so they can serve as templates?

• (A) Helicase
• (B) DNA polymerase
• (C) Ligase
• (D) Topoisomerase

Fragile X syndrome, the most common inherited cause of intellectual disability, is caused by an expansion of a CGG trinucleotide repeat in the 5' untranslated region (UTR) of the FMR1 gene on the X chromosome. This expansion leads to hypermethylation and silencing of the FMR1 gene. This mechanism of gene silencing is an example of:

• (A) Epigenetic modification
• (B) Frameshift mutation
• (C) Missense mutation
• (D) Chromosomal deletion

A Barr body is an inactive X chromosome observed in the nucleus of somatic cells in female mammals. This process of X-inactivation ensures dosage compensation between males (XY) and females (XX). Which statement about X-inactivation is generally TRUE?

• (A) It is a random process, meaning either the paternal or maternal X can be inactivated in a given cell.
• (B) It occurs only in germline cells.
• (C) The entire X chromosome, including the pseudoautosomal regions, is inactivated.
• (D) Once inactivated, the X chromosome can be easily reactivated later in life.

Which type of RNA processing involves the removal of non-coding sequences (introns) from a primary RNA transcript and the joining together of the coding sequences (exons)?

• (A) Splicing
• (B) Capping
• (C) Polyadenylation
• (D) Editing

Li-Fraumeni syndrome is a rare autosomal dominant disorder characterized by a high predisposition to developing multiple types of cancers at an early age (e.g., sarcomas, breast cancer, brain tumors, leukemia). It is most commonly caused by germline mutations in which tumor suppressor gene?

• (A) TP53
• (B) BRCA1
• (C) RB1
• (D) APC

What is the genetic basis of Type 1 Neurofibromatosis (NF1), an autosomal dominant disorder characterized by cafe-au-lait spots, neurofibromas, Lisch nodules (iris hamartomas), and an increased risk of certain tumors?

• (A) Loss-of-function mutations in the NF1 gene, a tumor suppressor
• (B) Gain-of-function mutations in the RET proto-oncogene
• (C) Expansion of trinucleotide repeats
• (D) Chromosomal translocation

Which term describes a situation where a single gene mutation affects multiple, seemingly unrelated phenotypic traits?

• (A) Pleiotropy
• (B) Incomplete penetrance
• (C) Variable expressivity
• (D) Epistasis

The process of translation (protein synthesis) occurs on which cellular structures?

• (A) Ribosomes
• (B) Nucleus
• (C) Mitochondria
• (D) Golgi apparatus

A 'frameshift' mutation is typically caused by:

• (A) Insertion or deletion of a number of nucleotides not divisible by three
• (B) Substitution of a purine for a pyrimidine
• (C) Substitution of one amino acid codon for another
• (D) Conversion of an amino acid codon to a stop codon

What is the role of DNA ligase during DNA replication?

• (A) Joining Okazaki fragments on the lagging strand
• (B) Unwinding the DNA double helix
• (C) Synthesizing RNA primers
• (D) Adding DNA nucleotides to the new strand

Achondroplasia, the most common form of dwarfism, is an autosomal dominant disorder caused by a specific gain-of-function mutation in which gene, leading to inhibition of chondrocyte proliferation?

• (A) FGFR3 (Fibroblast Growth Factor Receptor 3)
• (B) COL1A1 (Collagen Type I Alpha 1)
• (C) FBN1 (Fibrillin-1)
• (D) CFTR (Cystic Fibrosis Transmembrane Conductance Regulator)

Which inheritance pattern often shows affected individuals in every generation, male-to-male transmission, and roughly equal numbers of affected males and females?

• (A) Autosomal dominant
• (B) Autosomal recessive
• (C) X-linked recessive
• (D) Mitochondrial

What is the purpose of adding a 5' cap (a modified guanine nucleotide) to eukaryotic mRNA transcripts?

• (A) Protect mRNA from degradation and facilitate ribosome binding
• (B) Signal termination of transcription
• (C) Facilitate splicing
• (D) Enable transport to mitochondria

Klinefelter syndrome is a genetic condition affecting males, typically characterized by tall stature, small testes, gynecomastia, and infertility. What is the most common karyotype associated with this syndrome?

• (A) 47,XXY
• (B) 45,X
• (C) 47,XYY
• (D) 47,XXX

Which technique uses fluorescently labeled DNA probes to detect the presence, absence, or location of specific DNA sequences on chromosomes, often used to identify chromosomal abnormalities like deletions or duplications?

• (A) Fluorescence In Situ Hybridization (FISH)
• (B) Karyotyping
• (C) PCR
• (D) Western blotting

What is meant by 'variable expressivity' in genetics?

• (A) Individuals with the same disease-causing genotype exhibit different severity or range of symptoms.
• (B) Individuals with the disease-causing genotype do not always develop the disease phenotype.
• (C) Mutations in different genes cause the same phenotype.
• (D) A single gene mutation causes multiple phenotypic effects.

The process of synthesizing RNA from a DNA template is catalyzed by which enzyme?

• (A) RNA Polymerase
• (B) DNA Polymerase
• (C) Reverse Transcriptase
• (D) Helicase

In the context of population genetics, what does 'genetic drift' refer to?

• (A) Random fluctuations in allele frequencies from one generation to the next, particularly significant in small populations.
• (B) Movement of alleles between populations due to migration.
• (C) Differential survival and reproduction based on genotype (natural selection).
• (D) Introduction of new alleles through mutation.

What is the primary function of the enzyme reverse transcriptase, famously used by retroviruses like HIV?

• (A) Synthesizing DNA from an RNA template
• (B) Synthesizing RNA from a DNA template
• (C) Synthesizing DNA from a DNA template
• (D) Degrading RNA

Which type of DNA repair mechanism corrects errors made during DNA replication, such as base mismatches or small insertions/deletions, that are missed by the proofreading activity of DNA polymerase?

• (A) Mismatch Repair (MMR)
• (B) Base Excision Repair (BER)
• (C) Nucleotide Excision Repair (NER)
• (D) Non-homologous end joining (NHEJ)

A 'silent' mutation is a point mutation that:

• (A) Changes a codon to one that encodes the same amino acid.
• (B) Changes an amino acid codon to a stop codon.
• (C) Changes a codon to one that encodes a different amino acid.
• (D) Causes a shift in the reading frame.

What is the role of the sigma factor in prokaryotic transcription?

• (A) Recognizes the promoter sequence and initiates transcription
• (B) Unwinds the DNA helix
• (C) Synthesizes the RNA transcript
• (D) Terminates transcription