Pedigree Detective
A pedigree shows affected individuals in every generation with male-to-male transmission.
A. X-linked dominant
B. Autosomal recessive
C.Y-linked
D. X-linked recessive
What is Y-linked inheritance?
This protein coats the inactive X chromosome during X-inactivation.
A. UBE3A
B. XIST RNA
C. DNA methyltransferase
D. Histone acetyltransferase
What is XIST RNA?
This autosomal dominant disorder results from mutations in the LDL receptor and causes markedly elevated LDL cholesterol and tendon xanthomas.
A. Marfan syndrome
B. Cystic fibrosis
C. Phenylketonuria
D. Familial hypercholesterolemia
What is familial hypercholesterolemia?
A heterozygous father has an autosomal dominant disorder. The mother is unaffected. What is the probability each child is affected?
A. 0%
B. 25%
C. 50%
D. 100%
What is 50%?
This inheritance pattern commonly skips generations and is more likely to affect siblings than parents.
A. Autosomal dominant
B. Autosomal recessive
C. X-linked dominant
D. Mitochondrial
What is autosomal recessive inheritance?
Addition of methyl groups to CpG islands generally has this effect on gene expression.
A. Increased translation
B. Increased transcription
C. Increased mRNA stability
D. Gene silencing
What is gene silencing (decreased transcription)?
This autosomal dominant connective tissue disorder is caused by mutations in FBN1 and is associated with aortic aneurysms and ectopia lentis.
A. Ehlers-Danlos syndrome
B. Marfan syndrome
C. Osteogenesis imperfecta
D. Neurofibromatosis type 1
What is Marfan syndrome?
A carrier mother and unaffected father have a son. What is the probability he has an X-linked recessive disease?
A. 0%
B. 25%
C. 50%
D. 100%
What is 50%?
An affected father passes the disorder to all daughters but none of his sons.
A. Autosomal dominant
B. X-linked recessive
C. X-linked dominant
D. Mitochondrial
What is X-linked dominant inheritance?
Different phenotypes in genetically identical female cells caused by random X-inactivation produce this phenomenon.
A. Somatic mosaicism
B. Genomic imprinting
C. Anticipation
D. Variable penetrance
What is somatic mosaicism?
This autosomal dominant connective tissue disorder is most commonly caused by mutations in type I collagen and presents with recurrent fractures and blue sclerae.
A. Marfan syndrome
B. Ehlers-Danlos syndrome
C. Osteogenesis imperfecta
D. Cystic fibrosis
What is osteogenesis imperfecta?
An affected father has an X-linked dominant disorder. What percentage of daughters inherit the disease?
A. 0%
B. 25%
C. 50%
D. 100%
What is 100%?
Carrier mothers have a 50% chance of producing affected sons.
A. X-linked recessive
B. Autosomal recessive
C. Mitochondrial
D. X-linked dominant
What is X-linked recessive inheritance?
Genes are expressed differently depending on whether they were inherited from the mother or father because of this process.
A. X-inactivation
B. Genomic imprinting
C. Anticipation
D. Codominance
What is genomic imprinting?
This connective tissue disorder results from defects in collagen synthesis and commonly presents with hyperextensible skin and hypermobile joints.
A. Marfan syndrome
B. Osteogenesis imperfecta
C. Neurofibromatosis type 1
D. Ehlers-Danlos syndrome
What is Ehlers-Danlos syndrome?
A woman with a mitochondrial disorder has four children. How many are at risk of inheriting the mutation?
A. None
B. One
C. Two
D. All four
What is all four children?
Only mothers transmit the disease to their offspring, while affected fathers transmit it to none of their children.
A. X-linked dominant
B. Mitochondrial
C. Autosomal dominant
D. X-linked recessive
What is mitochondrial (maternal) inheritance?
Loss of the maternal UBE3A allele causes this syndrome.
A. Angelman syndrome
B. Prader-Willi syndrome
C. Fragile X syndrome
D. Turner syndrome
What is Angelman syndrome?
This autosomal recessive disease results from mutations in the CFTR gene and causes recurrent pulmonary infections and pancreatic insufficiency.
A. Tay-Sachs disease
B. Phenylketonuria
C. Cystic fibrosis
D. Familial hypercholesterolemia
What is cystic fibrosis?
An affected male with mitochondrial disease has three children. How many inherit the mutation?
A. None
B. One
C. Two
D. All three
What is none?
The presence of father-to-son transmission rules out this inheritance pattern.
A. Autosomal dominant
B. Autosomal recessive
C. X-linked inheritance
D. Y-linked inheritance
What is X-linked inheritance?
Loss of the paternal chromosome 15q11-q13 region causes this syndrome.
A. Angelman syndrome
B. Prader-Willi syndrome
C. Fragile X syndrome
D. Williams syndrome
What is Prader-Willi syndrome?
This autosomal recessive lysosomal storage disorder results from hexosaminidase A deficiency and presents with developmental regression and a cherry-red macula.
A. Gaucher disease
B. Niemann-Pick disease
C. Tay-Sachs disease
D. Fabry disease
What is Tay-Sachs disease?
A mitochondrial disease shows different severity among siblings because of this phenomenon.
A. Anticipation
B. Genomic imprinting
C. Heteroplasmy
D. Incomplete penetrance
What is heteroplasmy?
A double horizontal line connecting two parents in a pedigree indicates this.
A. Dizygotic twins
B. Consanguinity
C. Adoption
D. Carrier status
What is consanguinity?
Familial hypercholesterolemia is an example of this dominant disease mechanism caused by insufficient LDL receptor production.
A. Dominant-negative effect
B. Gain of function
C. Haploinsufficiency
D. Loss of heterozygosity
What is haploinsufficiency?
This autosomal recessive disorder results from deficiency of phenylalanine hydroxylase and is treated with dietary restriction of phenylalanine.
A. Homocystinuria
B. Phenylketonuria (PKU)
C. Alkaptonuria
D. Maple syrup urine disease
What is phenylketonuria (PKU)?
Increasing disease severity in successive generations due to repeat expansion is called this.
A. Variable expressivity
B. Heteroplasmy
C. Genomic imprinting
D. Anticipation
What is anticipation?
An unaffected couple has multiple affected children, and males and females are equally affected.
A. Autosomal dominant
B. X-linked dominant
C. Autosomal recessive
D. Mitochondrial
What is autosomal recessive inheritance?
Mutations in collagen causing osteogenesis imperfecta commonly act through this dominant mechanism by interfering with normal collagen assembly.
A. Haploinsufficiency
B. Gain of function
C. Loss of heterozygosity
D. Dominant-negative effect
What is a dominant-negative effect?
This autosomal dominant disorder is caused by mutations in the NF1 gene and is characterized by café-au-lait spots, neurofibromas, and Lisch nodules.
A. Tuberous sclerosis
B. Neurofibromatosis type 1
C. Neurofibromatosis type 2
D. Von Hippel-Lindau disease
What is neurofibromatosis type 1?
Fragile X syndrome results when CGG repeats trigger this epigenetic modification.
A. Histone acetylation
B. DNA demethylation
C. RNA interference
D. CpG methylation
What is CpG methylation leading to gene silencing?
Females carrying one mutant allele usually do not express disease because they possess this genetic advantage.
A. Genomic imprinting
B. Uniparental disomy
C. A second normal X chromosome
D. Mitochondrial heteroplasmy
What is a second normal X chromosome (heterozygosity)
Individuals with the same mutation show different disease severity because of this concept.
A. Reduced penetrance
B. Variable expressivity
C. Genomic imprinting
D. Anticipation
What is variable expressivity?
Loss of the paternal chromosome 15q11-q13 region produces hypotonia, hyperphagia, obesity, and intellectual disability.
A. Angelman syndrome
B. Fragile X syndrome
C. Prader-Willi syndrome
D. Williams syndrome
What is Prader-Willi syndrome?
A disease appears only when inherited from one parent because the allele from the other parent is epigenetically silenced. This phenomenon is called:
A. Anticipation
B. X-inactivation
C. Genomic imprinting
D. Variable expressivity
What is genomic imprinting?
This individual is the first affected family member who comes to medical attention.
A. Consultand
B. Carrier
C. Proband
D. Founder
What is the proband (propositus)?
Individuals with a disease-causing mutation who never develop symptoms illustrate this concept.
A. Reduced penetrance
B. Pleiotropy
C. Variable expressivity
D. Genetic heterogeneity
What is reduced (incomplete) penetrance?
Expansion of CGG repeats leading to methylation and silencing of the FMR1 gene causes this inherited form of intellectual disability.
A. Huntington disease
B. Myotonic dystrophy
C. Friedreich ataxia
D. Fragile X syndrome
What is Fragile X syndrome?
A pedigree shows affected males and females. Every child of an affected mother is affected, but none of the children of affected fathers inherit the disease. Siblings show different severities of illness.
A. X-linked dominant inheritance with variable expressivity
B. Autosomal dominant inheritance with incomplete penetrance
C. Genomic imprinting with anticipation
D. Mitochondrial inheritance with heteroplasmy
What is mitochondrial inheritance with heteroplasmy?