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Questions and Answers
What occurs during a Robertsonian translocation?
What occurs during a Robertsonian translocation?
Which chromosomes are involved in a typical Robertsonian translocation that is associated with familial Down syndrome?
Which chromosomes are involved in a typical Robertsonian translocation that is associated with familial Down syndrome?
How does the presence of a Robertsonian translocation in a parent affect the risk of Down syndrome?
How does the presence of a Robertsonian translocation in a parent affect the risk of Down syndrome?
What is the typical karyotype for a carrier of a Robertsonian translocation related to Down syndrome?
What is the typical karyotype for a carrier of a Robertsonian translocation related to Down syndrome?
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What is the significance of having only 45 chromosomes in a person with a Robertsonian translocation?
What is the significance of having only 45 chromosomes in a person with a Robertsonian translocation?
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What is the primary cause of trisomies and monosomies in chromosome abnormalities?
What is the primary cause of trisomies and monosomies in chromosome abnormalities?
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Which technique is commonly used in cytogenetic analysis to visualize chromosomes?
Which technique is commonly used in cytogenetic analysis to visualize chromosomes?
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What distinguishes balanced from unbalanced chromosomal structural abnormalities?
What distinguishes balanced from unbalanced chromosomal structural abnormalities?
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What is the role of Robertsonian translocations in familial Down syndrome?
What is the role of Robertsonian translocations in familial Down syndrome?
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Which of the following syndromes is associated with a deletion of genetic material?
Which of the following syndromes is associated with a deletion of genetic material?
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What type of chromosome abnormality can result from improper chromosome recombination during meiosis?
What type of chromosome abnormality can result from improper chromosome recombination during meiosis?
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Which prenatal outcome is significantly associated with chromosomal abnormalities?
Which prenatal outcome is significantly associated with chromosomal abnormalities?
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What are the major phenotypic characteristics associated with trisomy 21?
What are the major phenotypic characteristics associated with trisomy 21?
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What type of structural abnormality typically leads to serious problems in both the carrier and offspring?
What type of structural abnormality typically leads to serious problems in both the carrier and offspring?
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What occurs during reciprocal translocations?
What occurs during reciprocal translocations?
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What is the most common characteristic of balanced chromosomal abnormalities?
What is the most common characteristic of balanced chromosomal abnormalities?
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What defines euploidy in humans?
What defines euploidy in humans?
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Which of the following is NOT a type of unbalanced chromosomal abnormality?
Which of the following is NOT a type of unbalanced chromosomal abnormality?
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Why are autosomal monosomies generally incompatible with life?
Why are autosomal monosomies generally incompatible with life?
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What are isochromosomes characterized by?
What are isochromosomes characterized by?
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What is a common cause of aneuploidy?
What is a common cause of aneuploidy?
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How can unequal crossing over during meiosis affect chromosomal structure?
How can unequal crossing over during meiosis affect chromosomal structure?
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Which of the following phenotypes is associated with trisomy 21?
Which of the following phenotypes is associated with trisomy 21?
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What characterizes the trisomic offspring from nondisjunction in Meiosis I?
What characterizes the trisomic offspring from nondisjunction in Meiosis I?
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What role do toxic agents play in chromosomal abnormalities?
What role do toxic agents play in chromosomal abnormalities?
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What phenotype is most commonly associated with trisomy 21?
What phenotype is most commonly associated with trisomy 21?
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How can Robertsonian translocations play a role in Down syndrome?
How can Robertsonian translocations play a role in Down syndrome?
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What effect does polyploidy generally have on human pregnancies?
What effect does polyploidy generally have on human pregnancies?
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What is a key difference between trisomy generated by nondisjunction in Meiosis I versus Meiosis II?
What is a key difference between trisomy generated by nondisjunction in Meiosis I versus Meiosis II?
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What is the karyotype associated with Trisomy 21?
What is the karyotype associated with Trisomy 21?
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What is the estimated frequency of Trisomy 21 in live births?
What is the estimated frequency of Trisomy 21 in live births?
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Which of the following is NOT one of the 5 A's of Down syndrome?
Which of the following is NOT one of the 5 A's of Down syndrome?
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What percentage of individuals with Down syndrome are expected to survive to age 50 with interventional care?
What percentage of individuals with Down syndrome are expected to survive to age 50 with interventional care?
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What is the most common cause of Trisomy 21?
What is the most common cause of Trisomy 21?
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Which gene is associated with causing intellectual disability when overexpressed in Down syndrome?
Which gene is associated with causing intellectual disability when overexpressed in Down syndrome?
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Which of the following developmental issues is more severe in Trisomy 18 than Trisomy 21?
Which of the following developmental issues is more severe in Trisomy 18 than Trisomy 21?
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What major developmental difficulty is more common in individuals with Trisomy 18 compared to those with Down syndrome?
What major developmental difficulty is more common in individuals with Trisomy 18 compared to those with Down syndrome?
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What characteristic is associated with Patau syndrome (Trisomy 13)?
What characteristic is associated with Patau syndrome (Trisomy 13)?
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How is mosaicism related to Trisomy 21?
How is mosaicism related to Trisomy 21?
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Study Notes
Chromosome Abnormalities
- Important contributor to morbidity and mortality
- Occur in approximately 1 in 150 live births
- Leading cause of intellectual disability, pregnancy loss
- 50% of first-trimester miscarriages
- 20% of second-trimester miscarriages
Types of Chromosome Abnormalities
-
Abnormalities in chromosome Number
- Trisomies, Monosomies
- Caused by nondisjunction during anaphase I or II of meiosis
-
Abnormalities in chromosome structure
- Translocations, Deletions, Duplications
- Caused by improper chromosome recombination during prophase I of meiosis
Euploidy
- Chromosome number is a multiple of 23 (in humans)
- Includes haploid gametes and diploid somatic cells
Polyploidy
- Individuals possess an extra complete set of chromosomes (triploid, tetraploid, etc.)
- Results in seedless fruits in plants but is lethal in humans (generally)
Aneuploidy
- Total chromosome number is NOT a multiple of 23
- Monosomy: one chromosome pair is present in only one copy.
- Trisomy: one chromosome pair is present in three copies
- Autosomal monosomies are usually incompatible with life
- Autosomal trisomies can be compatible with life (trisomies 21, 18, and 13 are the most common in live births)
- “The body can tolerate excess genetic material more readily than it can tolerate a deficit of genetic material.”
Nondisjunction
- Most common cause of aneuploidy
- Occurs during meiosis, causing unequal distribution of chromosomes to daughter cells
Trisomy 21 (Down Syndrome)
- Karyotype: 47, XY, +21 (sex is irrelevant)
- Frequency: 1 in 800 to 1000 live births (most common autosomal trisomy)
- Features:
-
5 A's of Down syndrome:
- Advanced maternal age
- Atresia (duodenal)
- Atrioventricular septal defect
- Alzheimer's disease (early onset)
- AML (acute myeloid leukemia)
- Accounts for 10% of intellectual disability cases in the US
- 80% survive to age 10, 50% to age 50 with medical intervention
- Males are usually sterile; females can reproduce but 40% fail to ovulate
- Females with Down syndrome have a 50% risk of producing trisomic offspring, but overall risk is lowered by increased risk of spontaneous abortion
-
5 A's of Down syndrome:
Mechanism of Trisomy 21
- 95% caused by nondisjunction, usually in the mother during meiosis I
- Mosaicism is possible, where the extra chromosome 21 is lost from some cells during early embryogenesis, leading to a milder phenotype
- Genes on chromosome 21:
- Up to 40% have no known purpose
- Candidate genes:
- DYRK1A: associated with intellectual disability and learning/memory problems in mice when overexpressed
- DSCR1 (Down syndrome critical region gene 1): overexpressed in Down syndrome fetal brains; plays a role in CNS development
- APP: amyloid beta precursor protein; associated with some Alzheimer's disease cases
Trisomy 18 (Edwards Syndrome)
- Karyotype: 47, XY, +18
- Features:
- SGA (small for gestational age) due to prenatal growth deficiency
- Distinctive facial features
- Hand abnormalities
- Small ears and mouth
- Short sternum
- Congenital heart defects (especially VSDs)
- Omphalocele
- Diaphragmatic hernia
- More severe developmental difficulties than Down syndrome, including inability to walk independently
- Second most common autosomal trisomy resulting in live births
Trisomy 13 (Patau Syndrome)
- Karyotype: 47, XY, +13
- Features:
- Oral-facial clefts
- Microphthalmia
- Postaxial polydactyly
- CNS, heart, and renal abnormalities
- Third most common autosomal trisomy resulting in live births
Structural Chromosome Abnormalities
- Occur due to unequal crossing over or exposure to toxic agents that cause chromosome breakage and rejoining
Types of Structural Abnormalities
-
Balanced: no gain or loss of genetic material
- Often does not affect the carrier but can cause issues in offspring
- Examples: Translocations, isochromosomes, inversions
-
Unbalanced: causes gain or loss of genetic material
- Problematic for both carriers and offspring
- Examples: Deletions, ring chromosomes, subtelomeric rearrangements, duplications
Translocations
- Exchange of genetic material between two nonhomologous chromosomes
-
Balanced translocations:
- Among the most common chromosomal abnormalities (up to 1 in 500)
- Reciprocal translocations: breaks in two different chromosomes, leading to mutual exchange; carriers are often phenotypically normal.
Robertsonian Translocations
- Short arms of two nonhomologous chromosomes are lost, and the remaining long arms fuse.
- Occurs only in acrocentric chromosomes (13, 14, 15, 21, and 22)
- Carriers have 45 chromosomes but are usually phenotypically normal.
Familial Down Syndrome
- Accounts for up to 5% of Down syndrome cases.
- Result of Robertsonian translocation of 14q and 21q
- Does not have a correlation with increased maternal age.
- Risk of Down syndrome in offspring is Mendelian, meaning carriers with a Robertsonian translocation have a higher risk of passing it down.
- Typical carrier karyotype: 45, XY, der(14;21)(q10,q10)
Familial Down Syndrome without a Robertsonian Translocation
- Occurs due to isochromosome formation, where a chromosome replicates one of its arms, leading to a duplication of a specific chromosome segment and a loss of other segments.
Isochromosome
- A chromosome with two identical arms, formed as a result of misdivision of centromere during mitosis or meiosis.
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Description
Explore the fascinating topic of chromosome abnormalities and their impact on human health. This quiz covers key concepts such as euploidy, polyploidy, and aneuploidy, as well as their consequences for intellectual disability and pregnancy outcomes. Test your knowledge on the types and causes of these genetic conditions.
