Podcast
Questions and Answers
Which of the following karyotypes represents a female with Patau syndrome?
Which of the following karyotypes represents a female with Patau syndrome?
- 47, XY, +21
- 47, XX, +13 (correct)
- 45, XO
- 47, XX, +18
Aneuploidy is best defined as which of the following?
Aneuploidy is best defined as which of the following?
- A change in the number of one or more chromosomes. (correct)
- A normal chromosome number in somatic cells.
- The gain of an entire haploid set of chromosomes.
- The presence of three copies of each chromosome.
Which of the following best describes the genetic makeup of an individual with Triploidy?
Which of the following best describes the genetic makeup of an individual with Triploidy?
- 92 chromosomes
- 47 chromosomes
- 69 chromosomes (correct)
- 45 chromosomes
Nondisjunction in meiosis I results in which of the following?
Nondisjunction in meiosis I results in which of the following?
Which of the following is a key characteristic of aneuploidy of autosomal chromosomes, contrasting it with aneuploidy of sex chromosomes?
Which of the following is a key characteristic of aneuploidy of autosomal chromosomes, contrasting it with aneuploidy of sex chromosomes?
An individual with a 45, XO karyotype has which of the following conditions?
An individual with a 45, XO karyotype has which of the following conditions?
Which of the following is a typical characteristic of Klinefelter Syndrome?
Which of the following is a typical characteristic of Klinefelter Syndrome?
Which of the following is not a frequently observed feature of Down Syndrome?
Which of the following is not a frequently observed feature of Down Syndrome?
Which of the following is the most common cause for first trimester spontaneous abortions?
Which of the following is the most common cause for first trimester spontaneous abortions?
Which of the following is a common characteristic shared by Trisomy 13, Trisomy 18 and Trisomy 21?
Which of the following is a common characteristic shared by Trisomy 13, Trisomy 18 and Trisomy 21?
What is a key feature of Edwards Syndrome (Trisomy 18)?
What is a key feature of Edwards Syndrome (Trisomy 18)?
Which characteristic is most closely associated with Patau Syndrome (Trisomy 13)?
Which characteristic is most closely associated with Patau Syndrome (Trisomy 13)?
Which of the following best describes a Robertsonian translocation?
Which of the following best describes a Robertsonian translocation?
What is the most likely outcome of a fetus inheriting monosomy of an autosome?
What is the most likely outcome of a fetus inheriting monosomy of an autosome?
What is a key feature of a balanced translocation?
What is a key feature of a balanced translocation?
Cri-du-Chat syndrome is associated with what type of chromosomal abnormality?
Cri-du-Chat syndrome is associated with what type of chromosomal abnormality?
What is a key characteristic of individuals who carry a Robertsonian translocation?
What is a key characteristic of individuals who carry a Robertsonian translocation?
What genetic mechanism underlies Charcot-Marie-Tooth disease type 1A?
What genetic mechanism underlies Charcot-Marie-Tooth disease type 1A?
How does a paracentric inversion differ from a pericentric inversion?
How does a paracentric inversion differ from a pericentric inversion?
What is characteristic of an isochromosome?
What is characteristic of an isochromosome?
In reciprocal translocations, what typically occurs?
In reciprocal translocations, what typically occurs?
Which of the following best describes the mechanism by which polyploidy arises?
Which of the following best describes the mechanism by which polyploidy arises?
Which of the following best describes how a structural chromosomal aberration in a somatic cell may lead to cancer?
Which of the following best describes how a structural chromosomal aberration in a somatic cell may lead to cancer?
What is the relationship between translocation and gametogenesis?
What is the relationship between translocation and gametogenesis?
What role does the Philadelphia chromosome play in cancer?
What role does the Philadelphia chromosome play in cancer?
When does Trisomy 18 usually originate?
When does Trisomy 18 usually originate?
What statement is true about Robertsonian translocations?
What statement is true about Robertsonian translocations?
Which type of structural chromosome mutation results in genetic material being flipped, but no loss or gain of genetic material?
Which type of structural chromosome mutation results in genetic material being flipped, but no loss or gain of genetic material?
What is another name for the X-chromatin?
What is another name for the X-chromatin?
What can errors in chromosome maldistribution cause?
What can errors in chromosome maldistribution cause?
If there is an incident of nondisjunction at meiosis II, what cells are affected?
If there is an incident of nondisjunction at meiosis II, what cells are affected?
Which statement is true about the deletion
Which statement is true about the deletion
What is the process called when Barr body---or X-chromatin is rendered inactive?
What is the process called when Barr body---or X-chromatin is rendered inactive?
An individual has cells with both a 46,XY karyotype and a 47,XXY karyotype. What is the term for the presence of two or more genetically distinct cell lines in one individual?
An individual has cells with both a 46,XY karyotype and a 47,XXY karyotype. What is the term for the presence of two or more genetically distinct cell lines in one individual?
A geneticist identifies a family with a history of miscarriages. Karyotype analysis reveals that the mother carries a balanced reciprocal translocation between chromosomes 2 and 5. Although she is asymptomatic, how can this translocation affect her offspring?
A geneticist identifies a family with a history of miscarriages. Karyotype analysis reveals that the mother carries a balanced reciprocal translocation between chromosomes 2 and 5. Although she is asymptomatic, how can this translocation affect her offspring?
A researcher is studying a new genetic disorder. She observes that affected individuals have a partial deletion of chromosome 7, leading to the loss of the elastin gene (ELN). What is the term for this type of genetic abnormality?
A researcher is studying a new genetic disorder. She observes that affected individuals have a partial deletion of chromosome 7, leading to the loss of the elastin gene (ELN). What is the term for this type of genetic abnormality?
During a genetics lecture, a professor discusses a condition that arises from having three copies of each chromosome, resulting in a total of 69 chromosomes in humans. What term is the professor most likely describing?
During a genetics lecture, a professor discusses a condition that arises from having three copies of each chromosome, resulting in a total of 69 chromosomes in humans. What term is the professor most likely describing?
Aneuploidy in gametes are classified as:
Aneuploidy in gametes are classified as:
Imagine a scenario where a chromosome breaks, and the severed portion reattaches to the same chromosome but in the reverse orientation. This type of chromosomal abnormality is best described as which of the following?
Imagine a scenario where a chromosome breaks, and the severed portion reattaches to the same chromosome but in the reverse orientation. This type of chromosomal abnormality is best described as which of the following?
Which of the following conditions involves a chromosomal aberration that is often not detected until after puberty?
Which of the following conditions involves a chromosomal aberration that is often not detected until after puberty?
What is the likelihood that a fetus inheriting monosomy of an autosome will survive?
What is the likelihood that a fetus inheriting monosomy of an autosome will survive?
A couple, both carriers of a Robertsonian translocation between chromosome 14 and 21, seek genetic counseling. What is the chance that their child will inherit a normal karyotype?
A couple, both carriers of a Robertsonian translocation between chromosome 14 and 21, seek genetic counseling. What is the chance that their child will inherit a normal karyotype?
Which of the following is the most likely cause of tetraploidy in a human zygote?
Which of the following is the most likely cause of tetraploidy in a human zygote?
What distinguishes a paracentric inversion from a pericentric inversion?
What distinguishes a paracentric inversion from a pericentric inversion?
How could a seemingly balanced reciprocal translocation in a parent lead to unbalanced gametes?
How could a seemingly balanced reciprocal translocation in a parent lead to unbalanced gametes?
A researcher discovers a novel genetic mutation in a family with a high incidence of a particular cancer. Cytogenetic analysis reveals that the affected individuals have a specific chromosomal abnormality in their somatic cells, but not in their germline cells. Furthermore, this abnormality consistently involves the fusion of two previously distinct genes, resulting in a novel fusion protein with altered function. This scenario corresponds to which of the following mechanisms?
A researcher discovers a novel genetic mutation in a family with a high incidence of a particular cancer. Cytogenetic analysis reveals that the affected individuals have a specific chromosomal abnormality in their somatic cells, but not in their germline cells. Furthermore, this abnormality consistently involves the fusion of two previously distinct genes, resulting in a novel fusion protein with altered function. This scenario corresponds to which of the following mechanisms?
A human cell exhibits a karyotype with 92 chromosomes. Which of the following chromosomal aberrations is most likely responsible for this observation?
A human cell exhibits a karyotype with 92 chromosomes. Which of the following chromosomal aberrations is most likely responsible for this observation?
Consider a scenario where a cell undergoes meiosis, but during anaphase I, homologous chromosomes fail to separate properly. Assuming the resulting gamete is fertilized by a normal gamete, which condition is most likely to occur in the offspring?
Consider a scenario where a cell undergoes meiosis, but during anaphase I, homologous chromosomes fail to separate properly. Assuming the resulting gamete is fertilized by a normal gamete, which condition is most likely to occur in the offspring?
Which of the following best differentiates between paracentric and pericentric inversions in chromosome structure?
Which of the following best differentiates between paracentric and pericentric inversions in chromosome structure?
A researcher discovers a novel gene fusion resulting from a chromosomal translocation in a cancer cell line. This fusion event brings a strong enhancer sequence in close proximity to a proto-oncogene, leading to its overexpression. Which type of translocation event is most likely responsible for this phenomenon?
A researcher discovers a novel gene fusion resulting from a chromosomal translocation in a cancer cell line. This fusion event brings a strong enhancer sequence in close proximity to a proto-oncogene, leading to its overexpression. Which type of translocation event is most likely responsible for this phenomenon?
In a scenario involving a Robertsonian translocation between chromosome 14 and 21, which of the following gamete compositions would lead to a viable offspring with Down syndrome?
In a scenario involving a Robertsonian translocation between chromosome 14 and 21, which of the following gamete compositions would lead to a viable offspring with Down syndrome?
What is the most significant implication of an isochromosome formation involving the long arm of the X chromosome in a female?
What is the most significant implication of an isochromosome formation involving the long arm of the X chromosome in a female?
Which of the following mechanisms likely explains how a seemingly balanced translocation in a parent can result in offspring with partial trisomies or monosomies?
Which of the following mechanisms likely explains how a seemingly balanced translocation in a parent can result in offspring with partial trisomies or monosomies?
A researcher is studying a population with a high rate of consanguinity and discovers several individuals with a novel autosomal recessive disorder. Cytogenetic analysis reveals that affected individuals have a small deletion on chromosome 15, encompassing only a handful of genes. Non-affected carriers of the deletion exhibit no discernible phenotype. Which of the following mechanisms is most likely responsible for the observed inheritance pattern?
A researcher is studying a population with a high rate of consanguinity and discovers several individuals with a novel autosomal recessive disorder. Cytogenetic analysis reveals that affected individuals have a small deletion on chromosome 15, encompassing only a handful of genes. Non-affected carriers of the deletion exhibit no discernible phenotype. Which of the following mechanisms is most likely responsible for the observed inheritance pattern?
How does the presence of a ring chromosome typically lead to genetic instability and phenotypic consequences?
How does the presence of a ring chromosome typically lead to genetic instability and phenotypic consequences?
Why do autosomal monosomies typically result in more severe developmental defects compared to sex chromosome monosomies?
Why do autosomal monosomies typically result in more severe developmental defects compared to sex chromosome monosomies?
Individuals with balanced Robertsonian translocations are typically phenotypically normal. However, their offspring may not be. Why?
Individuals with balanced Robertsonian translocations are typically phenotypically normal. However, their offspring may not be. Why?
Why is aneuploidy of sex chromosomes generally less severe than aneuploidy of autosomes?
Why is aneuploidy of sex chromosomes generally less severe than aneuploidy of autosomes?
What is the most significant risk associated with reciprocal translocations in the context of gametogenesis?
What is the most significant risk associated with reciprocal translocations in the context of gametogenesis?
Which mechanism explains the significant variability in phenotypic expression observed in individuals with mosaic aneuploidy?
Which mechanism explains the significant variability in phenotypic expression observed in individuals with mosaic aneuploidy?
What is the underlying mechanism by which the Philadelphia chromosome leads to chronic myeloid leukemia (CML)?
What is the underlying mechanism by which the Philadelphia chromosome leads to chronic myeloid leukemia (CML)?
Which of the following is the primary reason why triploidy is almost always lethal in humans?
Which of the following is the primary reason why triploidy is almost always lethal in humans?
A genetic counselor is advising a couple where one partner is a carrier of a pericentric inversion on chromosome 8. What is the most significant risk regarding potential offspring?
A genetic counselor is advising a couple where one partner is a carrier of a pericentric inversion on chromosome 8. What is the most significant risk regarding potential offspring?
What is the most likely outcome of a conceptus with tetraploidy?
What is the most likely outcome of a conceptus with tetraploidy?
How does Cri-du-chat syndrome typically manifest, leading to its characteristic features?
How does Cri-du-chat syndrome typically manifest, leading to its characteristic features?
A researcher discovers a novel chromosomal rearrangement in a patient with a rare genetic disorder. The rearrangement involves the fusion of two acrocentric chromosomes at their centromeres, with the loss of the short arms. What type of chromosomal aberration is most likely responsible for this observation?
A researcher discovers a novel chromosomal rearrangement in a patient with a rare genetic disorder. The rearrangement involves the fusion of two acrocentric chromosomes at their centromeres, with the loss of the short arms. What type of chromosomal aberration is most likely responsible for this observation?
A child is diagnosed with a condition resulting from a chromosomal abnormality where there are three copies of chromosome 18 in every cell. What is the most appropriate term for this condition?
A child is diagnosed with a condition resulting from a chromosomal abnormality where there are three copies of chromosome 18 in every cell. What is the most appropriate term for this condition?
What is the primary mechanism through which maternal age increases the risk of chromosomal aneuploidies, such as Trisomy 21, in offspring?
What is the primary mechanism through which maternal age increases the risk of chromosomal aneuploidies, such as Trisomy 21, in offspring?
In an individual with a mosaic karyotype, where some cells are 46,XY and others are 47,XXY, what cellular process most likely caused this condition?
In an individual with a mosaic karyotype, where some cells are 46,XY and others are 47,XXY, what cellular process most likely caused this condition?
A chromosome has a segment that is relocated to a non-homologous chromosome. What is this aberration called?
A chromosome has a segment that is relocated to a non-homologous chromosome. What is this aberration called?
A scientist is investigating a novel genetic condition and determines that the affected individuals have 69 chromosomes per cell. Which term describes this condition?
A scientist is investigating a novel genetic condition and determines that the affected individuals have 69 chromosomes per cell. Which term describes this condition?
What is the most significant implication of uniparental disomy (UPD) with regard to Prader-Willi Syndrome and Angelman Syndrome?
What is the most significant implication of uniparental disomy (UPD) with regard to Prader-Willi Syndrome and Angelman Syndrome?
How can an isochromosome lead to genomic imbalance?
How can an isochromosome lead to genomic imbalance?
In the context of chromosome structure, what is the distinguishing feature of a paracentric inversion?
In the context of chromosome structure, what is the distinguishing feature of a paracentric inversion?
What is the risk for offspring of a mother with a 14;21 Robertsonian translocation?
What is the risk for offspring of a mother with a 14;21 Robertsonian translocation?
What best describes genetic mosaicism?
What best describes genetic mosaicism?
What accounts for the majority of spontaneous abortions that occur during the first trimester?
What accounts for the majority of spontaneous abortions that occur during the first trimester?
In the context of aneuploidy, what does the term 'nullisomic' refer to?
In the context of aneuploidy, what does the term 'nullisomic' refer to?
What is the process when X-chromatin is rendered inactive?
What is the process when X-chromatin is rendered inactive?
How can structural chromosomal aberrations in somatic cells potentially contribute to cancer development?
How can structural chromosomal aberrations in somatic cells potentially contribute to cancer development?
Which genetic abnormality is linked with Charcot-Marie-Tooth disease type 1A?
Which genetic abnormality is linked with Charcot-Marie-Tooth disease type 1A?
Why are balanced reciprocal translocations often clinically silent in carriers but pose significant risks to their offspring?
Why are balanced reciprocal translocations often clinically silent in carriers but pose significant risks to their offspring?
A researcher is investigating a novel mechanism of tumorigenesis involving structural chromosomal aberrations. They observe a case where a previously silent proto-oncogene is now constitutively expressed due to its relocation near a highly active enhancer region. This phenomenon is MOST consistent with which type of chromosomal rearrangement?
A researcher is investigating a novel mechanism of tumorigenesis involving structural chromosomal aberrations. They observe a case where a previously silent proto-oncogene is now constitutively expressed due to its relocation near a highly active enhancer region. This phenomenon is MOST consistent with which type of chromosomal rearrangement?
A genetic counselor encounters a family with several members affected by a rare disorder. Pedigree analysis suggests an autosomal dominant inheritance pattern with incomplete penetrance. Cytogenetic analysis reveals that affected individuals carry what appears to be a balanced translocation. What cytogenetic mechanism is MOST likely responsible for the observed inheritance pattern and variable expressivity?
A genetic counselor encounters a family with several members affected by a rare disorder. Pedigree analysis suggests an autosomal dominant inheritance pattern with incomplete penetrance. Cytogenetic analysis reveals that affected individuals carry what appears to be a balanced translocation. What cytogenetic mechanism is MOST likely responsible for the observed inheritance pattern and variable expressivity?
A clinician is evaluating a patient with multiple congenital anomalies, including heart defects and facial dysmorphism. Karyotype analysis reveals a ring chromosome derived from chromosome 14. Further investigation suggests that the ring chromosome is unstable during cell division. Which mechanism BEST explains the genetic instability and phenotypic variability associated with ring chromosomes?
A clinician is evaluating a patient with multiple congenital anomalies, including heart defects and facial dysmorphism. Karyotype analysis reveals a ring chromosome derived from chromosome 14. Further investigation suggests that the ring chromosome is unstable during cell division. Which mechanism BEST explains the genetic instability and phenotypic variability associated with ring chromosomes?
During a study on chromosome fragility, a researcher discovers a novel compound that significantly increases the occurrence of chromosomal breaks in vitro. After treating human lymphocytes with this compound, they observe a marked increase in the formation of isochromosomes through misdivision of the centromere. What checkpoint mechanism has MOST likely been compromised by this compound?
During a study on chromosome fragility, a researcher discovers a novel compound that significantly increases the occurrence of chromosomal breaks in vitro. After treating human lymphocytes with this compound, they observe a marked increase in the formation of isochromosomes through misdivision of the centromere. What checkpoint mechanism has MOST likely been compromised by this compound?
A genetics lab receives a sample from a phenotypically normal individual with a family history of multiple pregnancy losses and congenital anomalies. Karyotyping reveals a seemingly balanced reciprocal translocation between chromosomes 5 and 12. Advanced genomic sequencing identifies that the translocation breakpoint on chromosome 5 disrupts a non-coding regulatory RNA crucial for genomic imprinting on chromosome 12. Which of these consequences is MOST likely?
A genetics lab receives a sample from a phenotypically normal individual with a family history of multiple pregnancy losses and congenital anomalies. Karyotyping reveals a seemingly balanced reciprocal translocation between chromosomes 5 and 12. Advanced genomic sequencing identifies that the translocation breakpoint on chromosome 5 disrupts a non-coding regulatory RNA crucial for genomic imprinting on chromosome 12. Which of these consequences is MOST likely?
Flashcards
Numerical Chromosomal Abnormalities
Numerical Chromosomal Abnormalities
Changes in the number of chromosomes or entire sets of chromosomes
Euploidy
Euploidy
Normal chromosome number, 2N (46 chromosomes) for somatic cells, N (23 chromosomes) for gametes
Aneuploidy
Aneuploidy
A change in the number of one or more chromosomes (not in the entire set)
Polyploidy
Polyploidy
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Nondisjunction
Nondisjunction
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Trisomy
Trisomy
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Monosomy
Monosomy
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Turner Syndrome (45, XO)
Turner Syndrome (45, XO)
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Klinefelter Syndrome (47, XXY)
Klinefelter Syndrome (47, XXY)
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Down Syndrome (Trisomy 21)
Down Syndrome (Trisomy 21)
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Edwards Syndrome (Trisomy 18)
Edwards Syndrome (Trisomy 18)
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Patau Syndrome (Trisomy 13)
Patau Syndrome (Trisomy 13)
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Polyploidy
Polyploidy
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Triploidy
Triploidy
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Tetraploidy
Tetraploidy
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Structural Chromosome Abnormalities
Structural Chromosome Abnormalities
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Structural Chromosomal Aberrations
Structural Chromosomal Aberrations
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Deletion
Deletion
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Duplication
Duplication
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Inversion
Inversion
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Translocation
Translocation
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Chromosome Deletions
Chromosome Deletions
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Cri-du-Chat Syndrome
Cri-du-Chat Syndrome
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Wolf-Hirschhorn Syndrome
Wolf-Hirschhorn Syndrome
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DiGeorge Syndrome
DiGeorge Syndrome
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Williams Syndrome
Williams Syndrome
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Chromosome Duplication
Chromosome Duplication
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Charcot-Marie-Tooth Disease
Charcot-Marie-Tooth Disease
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Chromosomal Translocations
Chromosomal Translocations
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Reciprocal Translocation
Reciprocal Translocation
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BCR-ABL translocation
BCR-ABL translocation
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Robertsonian Translocation
Robertsonian Translocation
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Chromosome Inversion
Chromosome Inversion
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Hemophilia A
Hemophilia A
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Ring Chromosome
Ring Chromosome
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Isochromosome
Isochromosome
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Chromosome Disturbance
Chromosome Disturbance
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Chromosomal Abnormality Causes
Chromosomal Abnormality Causes
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Homologous Chromosomes
Homologous Chromosomes
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Sex Chromosomes (Gonosomes)
Sex Chromosomes (Gonosomes)
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Nullisomic Gamete
Nullisomic Gamete
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Disomic Gamete
Disomic Gamete
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X Chromosome Requirement
X Chromosome Requirement
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Y Chromosome Determination
Y Chromosome Determination
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Barr Body Formation
Barr Body Formation
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Lyonization
Lyonization
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Aneuploidy of Autosomes
Aneuploidy of Autosomes
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Autosomal Aberration Outcome
Autosomal Aberration Outcome
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Abnormal Division Risk
Abnormal Division Risk
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Trisomies Formation in Meiosis
Trisomies Formation in Meiosis
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Terminal Deletion
Terminal Deletion
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Interstitial Deletion
Interstitial Deletion
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Study Notes
Cytogenetics and Chromosomal Basis for Human Disease
- Substantial changes in chromosome structure or number can lead to disease.
- These changes can result from errors in cell division, non-disjunction of chromosomes, maternal age, or environmental factors.
- Changes in chromosome number or structure can lead to pregnancy loss or abnormalities found in live births.
Numerical Chromosomal Abnormalities
- Involve changes in the number of chromosomes or entire sets of chromosomes.
- Euploidy refers to the normal chromosome number: 2N (46 chromosomes) in somatic cells and N (23 chromosomes) in gametes.
- Aneuploidy involves extra or missing chromosomes, while polyploidy refers to extra sets of chromosomes
- Polyploidy can be triploidy or tetraploidy resulting from spindle failure during mitosis.
- Aneuploidy: change in the number of one or more chromosomes (not in the entire set)
- Gain or loss of one or more chromosomes (autosome or sex)
- Loss of autosome is not viable resulting in spontaneous abortion
- Gain of autosome can be compatible with life (Trisomies 13, 18, 21 are viable)
- Loss or gain of sex chromosome is viable (X0, XXY)
- Aneuploidies in gametes are classified as: nullisomic (n-1; lack of a chromosome) or disomic (n+1: extra copy of a chromosome)
- Polyploidy: Is the gain of an entire haploid set of chromosomes, chromosome is 3N, 4N etc and not viable (spontaneous abortion)
- Triploidy: usually resulting from fertilization of an ovum by 2 sperm cells, with 3 copies of each chromosome, resulting in 69 chromosomes prenatally
- Tetraploidy: 4 copies of each chromosome, 92 total.
- Euploidy, Aneuploidy, Polyploidy, Turner, Klinefelter, Trisomy 21, 18, 13, Edwards are all numerical chromosome abnormalities
- In humans, somatic cells (autosomes) have 23 pairs of homologous chromosomes
- Each pair of chromosomes has one member from a parent
- Human sex chromosomes are called gonosomes
- X and Y chromosomes differ in size and genetic composition
- The other 22 pairs of chromosomes are autosomes with the same size and genetic composition
- Euploids have a normal number of chromosomes
- Aneuploids have an extra or missing chromosome
- Polyploids have extra sets of chromosomes and spindle fails during mitosis
- Trisomy 16 is the most common cause of 1st trimester spontaneous abortion
Chromosome Maldistribution
- Changes in ploidy occur due to non-disjunction in meiosis during gamete formation
- Non-disjunction at Meiosis I affects all daughter cells (2 cells disomic, 2 nullisomic)
- Non-disjunction at Meiosis II affects half of daughter cells (1 disomic, 1 nullisomic, 2 monosomic)
- Nondisjunction most commonly occurs in meiosis I and less common in meiosis II
- May also affect somatic cells
- Juxtaposition of changed and unchanged cells, occurs via mitotic losses and formation of somatic mosaics
- Mosaicism is the presence of two or more genetically distinct cell lines in an individual derived from a single zygote.
- Nondisjunction-may lead to formation of abnormal numbers of individual chromosomes
- Mis-segregation of chromosomes during anaphase, and can be caused by failure of chromosomes to separate or from the lack of microtubule connections to one kinetochore
Aneuploidy: Abnormal Number of Chromosomes
- Trisomies of chromosome 13, 18, and 21 are consistent with life.
- Results from nondisjunction during anaphase I/II of meiosis or anaphase of mitosis
- Homologues or chromatids do not separate
- Risk of having a child with an aneuploidy increases as a woman ages.
Aneuploidies of the Sex Chromosomes
- Abnormal distribution usually results in minor impairment of mental and physical development
- Relatively common and less severe
- At least 1 X chromosome is required for survival
- If a Y chromosome is present, phenotype is male, with few exception
- If >1X chromosome present, all but one will become a Barr body
- Barr body/ X-chromatin is an inactive X chromosome in a cell with more than one X chromosome and it is rendered inactive in a process called lyonization.
Turner Syndrome, 45, XO
- Due to the aneuploidy of sex chromosome
- Caused by monosomy of the X chromosome
- Does not correspond to the age of the mother
- Features include: short stature, broad shield-like shape of chest, webbed neck and ovarian dysgenesis
- Does not affect life expectancy or mental development
Klinefelter Syndrome: 47, XXY
- Affects males usually not detected until after puberty.
- Features include: tall and thin stature, with long arms and legs
- Hypogonadism
- Underdeveloped secondary and sexual characteristics
- Gynecomastia is also present along with infertility and muscle tone
Aneuploidy of Autosomes
- A syndrome or disorder that is NOT a sex chromosome
- Leads to distinct mental and physical impairment
- The majority of autosomal aberrations lead to spontaneous miscarriage before the 12th week of gestation
- Risk of abnormal division is increased by the age of the mother at the time of division
Trisomy 21: Down Syndrome
- Chromosomal aberration characterized by the addition of chromosome 21
- Characterized by addition of chromosome 21
- 47, XY +21, it is one of the most common chromosomal aberrations involving autosomes
- Risk of nondisjunction increase with mother's age
Characteristics of Down Syndrome
- Impaired intelligence
- Specific phenotypic characteristic, flat face, epicanthus
- Small opened mouth w/ protruding tongue
- Small physical stature. Muscular hypotonia (reduced muscle tone)
- Organ systems risks Gastrointestinal tract, Heart, Respiratory
- Increased risk of leukemia and Alzheimer's
- Epicanthus: outward and upward slanting of eyes
Trisomy 18: Edwards Syndrome
- Second most common autosomal trisomy. 47, XX +18, correlates with the mother's age
- 80% female
- Low survival rate, the majority die before birth
- Of those affected 5-8% survive to 12 mo
- Full Trisomy 18 has the extra chromosome in every cell of the baby
- Partial Trisomy 18 has only part of an extra chromosome, an extra part may be attached to another egg or sperm
- Mosaic trisomy 18-extra chromosome only in some of cells of the baby
Edward Syndrome's Characteristics
- Impaired intelligence and Prenatal growth deficiency
- Low-set ears, rotated backwards, Long and narrow skull
- Clenched fist and Deformed feet "rocker-bottom feet"
- Middle and ring fingers are overlapped by index and little fingers
- Organ abnormalities
Trisomy 13: Patau Syndrome
- Chromosomal aberration characterized by the addition of chromosome 13 (47, XX +13)
- Correlates with mother's age
- ~ 95% of the affected children die before the age of 6 months
Patau Syndrome's Characteristics
- Microcephaly or abnormally small head
- Cleft lip, alveolar ridge and palate
- Polydactyly unusual number of fingers/toes
- Malformations of the central nervous system
- Organ Systems, Heart, kidneys, and/or the urinary tract
Structural Chromosomal Aberrations
- Structural chromosomal aberrations are typically characterized by: *Occurs when chromosomes are broken by clastogens like Radiation, Viruses, Chemicals
- Unbalanced alterations: gain or loss of genetic material and Balanced alterations: without loss or gain of genetic material
- Structural Alterations involve Germ cells (can be submitted to offspring), and Somatic cells (can alter genetic material cancer)
Types of Structural Chromosomal Aberrations
- *Deletion: loss of individual gene sequence
- Duplication: broken segment inserted into homologous chromosome
- Inversion: broken segment reattached in reversed, can be:
- Paracentric
- Pericentric
- Translocation: exchange between non-homologous chromosomes
- Associated Diseases: Cri-du-Chat, DiGeorge, and Turner
Chromosome Deletions
- Loss of a specific segment of the chromosome
- The loss of a segment may be accompanied by reunification or reconstitution with the same chromosome and or Segregation of the broken segment, without a centromere
- Categories of Deletions:
- Terminal: End of chromosome lost
- Interstitial: Material within the chromosome is lost
Cri-du-Chat Syndrome: Cry of the Cat
- Due to deletion of the distal short arm (p) of chromosome 5 (microdeletion)
- 46, XX, del (5p)
- Distinctive cry that becomes less obvious as the child ages. Most survive to adulthood
- Features include Excessive drooling and Feeding problems due to difficulty in swallowing and sucking
- Intellectual disability
- Occurs across all ethnicities and is more common in females
Wolf-Hirschhorn Syndrome
- Deletion occurs at 4p16.3
- Distinctive facial features of Small head, wide spaced eyes, and broad beaked nose
- Brain and muscles are also affected, in intellectual disability, seizures and low muscle tone/development
- Bones are also affected resulting in Short stature, malformations of hands and feet, chest, and spine
- Other organ defects or malformations to the heart, Urinary tract and genitals
DiGeorge Syndrome: Microdeletion Syndrome
- 22q11 deletion syndrome
- Most common microdeletion
- Defective embryonic migration of neural crest cells to developing structures of the neck
- Features include a number of congenital heart defects, and Cleft palate in 80% of those affected
- Developmental delay, ADD, anxiety, and autism spectrum disorder
- Includes Functional defects of the thymus and Hypoparathyroidism
Williams Syndrome: Microdeletion Syndrome
- 7q11.23 deletion
- Mild intellectual disability, cardiovascular defects, poor visuospatial abilities.
- Deleted region elastin gene (ELN potentially explaining the cardiovascular defects due to the large amount of elastin in blood vessels
- Deleted region also contains the LIMK1 gene, a kinase expressed in the brain
- Facial features include:
- Broad forehead, short opening between eyelids, low nasal bridge, full lips and cheeks, relatively large mouth
- May contribute to the visual-spatial deficiencies
Chromosome Duplication
- Chromosome that has two copies of a specific region of DNA
- Can occur by uneven crossing over, tends to be less harmful than deletions and leads to partial trisomy
Charcot-Marie-Tooth Disease
- Multiple variations of CMT disease arising from a different gene mutation and demyelinating peripheral polyneuropathy
- Type 1A is caused by a duplication of the gene encoding peripheral myelin protein 22 (PMP22) on chromosome 17
- Hereditary Motor and Sensory Neuropathy (HMSN)
- Symptoms include slow progressive muscle weakness and atrophy
- Upper extremity ataxia and tremor, GI Problems, and Scoliosis
- The extra gene leads to increased production PMP22 protein, an integral nervous system
- Overexpression of this gene causes the structure and function of the myelin sheath to be abnormal
Chromosomal Translocations
- Portion of one chromosome is transferred to another chromosome
- Two main types: Reciprocal and Robertsonian
- Can be balanced or unbalanced
- Balanced rearrangement will have no loss or gain of chromosome material
- Unbalanced rearrangement Causes a gain or loss of chromosomal material.*
Reciprocal Translocation
- Type of balanced translocation in which the genetic material of two different chromosomes is exchanged
- Translocation during gametogenesis →offspring will carry translocation in all cells (translocation carrier)
- Translocation carrier may transmit genetic material to offspring causing partial Trisomies and monosomies
- Typically pregnancy loss
- Occurs 1:500 in newborns
- translocation in somatic cells often has no clinical consequences
- When oncogene or tumor suppressor gene alteration occurs, it leads to abnormal growth: CML, AML, follicular lymphomas, Burkitt's lymphoma,
- 14: 21 carrier mother—10%risk of down syndrome
Balanced Translocation and Cancer
- balanced translocation between chromosomes 9 and 22
- Small hybrid chromosome of Philadelphia chromosome is produced
- Fusion point of the chromosome fragments creates a fusion protein consisting of the protein BCR with the ABL tyrosine kinase which the development of chronic myeloid leukemia (CML)
- Protooncogenes can be transformed into oncogenes through translocation events
- Causes of the origin of many tumors and types of cancer because in other environments they achieve different effects
- Can lead to pathogenic disorders
- When oncogene or tumor suppressor gene alteration occurs, it leads to abnormal growth
- CML, AML, follicular lymphomas, Burkitt's lymphoma.
Robertsonian Translocation
- Occurs only in acrocentric chromosomes (centromeres toward the end)
- Involves loss of short p arms and subsequent fusion of long q arms of chromosomes
- Carriers of Robertsonian translocations have a karyotype with only 45 chromosomes
Robertsonian Translocation of Down Syndrome
- 4-5% of Down syndrome cases are caused by inheriting the derivative chromosome from a Robertsonian translocation on chromosomes 14 and 21
- This leads to 3 copies of the 21-q arm, which mimics the consequences of trisomy of the full chromosome 21
- Remember that 95% of Down Syndrome is due to Trisomy 21
Chromosome Inversion
- Portion of the chromosome has broken off, turned upside down and reattached
- Paracentric inversion does not include centromere region
- Pericentric inversion includes the centromere region
- DO not lose any genetic material, carriers are almost always unaffected, but their offspring may have small partial trisomy
- Can lead to difficulties with homologous recombination during meiosis
Hemophilia A
- ~40% of cases of Hemophilia A are due to chromosome inversions
- Hemophilia A is caused by mutations in the gene for clotting factor VIII an X-linked recessive disease
Ring Chromosome
- A portion of a chromosome breaks and forms a circle or a ring
- Often lost with resulting monosomy
- Turner syndrome (XO) results from the loss of ring X chromosome
- Patients with ring X chromosome are associated with distinct dysmorphism and are likely intellectually impaired
Isochromosome
- Two copies of one arm, no copy of the other arm.
- Two copies of one arm, no copy of the other.
- Most common isochromosome occurs with the long arm of chromosome X, resulting in 20% Turner syndrome.
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