Genetics Chapter 3: Chromosomal Diseases

Questions and Answers

What biological process results in cells having half the number of chromosomes found in somatic cells?

Fertilization

Mitosis

Meiosis (correct)

Spermatogenesis

Which type of twins share the same genome?

Identical twins

Monozygotic twins (correct)

Dizygotic twins

Fraternal twins

In which phase of cell division are chromosomes most highly condensed and visible for inspection?

Prophase

Metaphase (correct)

Telophase

Anaphase

What significant factor determines the sex of the offspring during fertilization?

The sperm cell Signup and view all the answers

What is the diameter range of DNA molecules compared to mitotic chromosomes?

2 nanometers to over 1000 nanometers Signup and view all the answers

What term best describes alterations in the number or structure of chromosomes?

Chromosomal diseases Signup and view all the answers

What significant contribution did Tijo and Albert Levan make in 1955?

They established the accurate number of human chromosomes. Signup and view all the answers

Which chromosome type is NOT found in the human genome?

Telocentrics Signup and view all the answers

What is the primary purpose of using hypotonic solutions in karyotyping?

To allow chromosomes to move apart for analysis. Signup and view all the answers

Which staining method was the first introduced to clinical practice for chromosome banding?

G Banding Signup and view all the answers

During karyotyping from a tissue biopsy, why is it necessary to culture the cells before analysis?

To stimulate mitosis for better yield of metaphases. Signup and view all the answers

What distinguishes R banding from other chromosome banding techniques?

It employs heat denaturation followed by Giemsa staining. Signup and view all the answers

How are chromosomes sorted in the construction of a karyotype?

By size and shape using specific software. Signup and view all the answers

What is the primary result of Q banding in chromosomal analysis?

Differentiation of AT-rich and GC-rich regions Signup and view all the answers

Why is software reconstruction important in karyotype analysis?

It simplifies the interpretation of complex karyotypes. Signup and view all the answers

How can chromosomal diseases be classified based on gene dosage alterations?

Balanced and unbalanced alterations Signup and view all the answers

What characterizes a somatic anomaly in chromosomal alterations?

The alteration appears only in some tissue cells. Signup and view all the answers

Which chromosomal alteration typically correlates with serious phenotypic consequences?

Unbalanced translocation Signup and view all the answers

What is the minimum detectable alteration size in chromosomes through standard karyotype analysis?

4 million bases Signup and view all the answers

Which describes a balanced chromosomal situation?

May predispose carriers to have affected offspring. Signup and view all the answers

What can be inferred about trisomies in humans?

They can be compatible with live births in some cases. Signup and view all the answers

How is a balanced translocation visually represented in karyotype analysis?

It appears with a standard number of chromosomes but with some rearranged positions. Signup and view all the answers

Which chromosomal abnormality is most commonly associated with Down syndrome?

Trisomy 21 Signup and view all the answers

What is a primary cause of numerical chromosome anomalies in humans?

Non-disjunction during meiosis Signup and view all the answers

At what stage does non-disjunction primarily occur in human female meiosis?

During meiosis 1 Signup and view all the answers

What is the frequency of trisomy 21 in the newborn population?

1.25 in 1000 Signup and view all the answers

In terms of karyotypes, 45, X represents which condition?

Monosomy X Signup and view all the answers

Which of the following chromosomal trisomies is generally compatible with birth but has a poor prognosis?

Trisomy 18 Signup and view all the answers

What happens to fetuses with monosomy 45, X during embryonic development?

They develop as females Signup and view all the answers

What is the estimated prevalence of the unbalanced structural chromosomal alterations in the general population?

0.4 in 1000 Signup and view all the answers

Which chromosomal alteration is most commonly associated with leukemia?

Translocation between chromosome 9 and chromosome 22 Signup and view all the answers

What is the likely outcome for an embryo with a chromosomal monosomy?

High likelihood of not completing embryonic development Signup and view all the answers

What characterizes a balanced chromosomal translocation?

No alteration in gene dosage for the carrier Signup and view all the answers

What is an outcome of the formation of unbalanced gametes during fertilization?

They often lead to zygotes that are unable to complete embryonic development. Signup and view all the answers

Which type of chromosomal alteration is considered very rare and often incompatible with birth?

Triploidy Signup and view all the answers

Which situation leads to a zygote with partial trisomy and partial monosomy?

Fertilization of an unbalanced gamete with a normal gamete Signup and view all the answers

What is the primary impact of chromosomal abnormalities on gene expression?

Often leads to increased severity of conditions when many genes are affected Signup and view all the answers

What happens during tumorigenesis related to chromosomal alterations?

Common alterations include deletions and duplications within somatic cells. Signup and view all the answers

What defines a Robertsonian balanced translocation?

It involves an exchange between non-homologous chromosomes Signup and view all the answers

Which type of chromosome alteration is least likely to be compatible with birth?

Triploidy of any chromosome Signup and view all the answers

Which statement correctly describes the role of meiosis in sexual reproduction?

Meiosis produces gametes with half the number of chromosomes. Signup and view all the answers

What is the significance of observing chromosomes during metaphase?

Metaphase provides a stage where chromosomes exhibit the highest compaction. Signup and view all the answers

How do monozygotic twins differ from fraternal twins on a genetic level?

Monozygotic twins develop from a single fertilized egg that splits. Signup and view all the answers

What can be inferred about the structure of chromosomes during the process of DNA compaction?

Chromosomes require more than one type of compaction mechanism. Signup and view all the answers

Which characteristic is most likely associated with serious phenotypic consequences of chromosomal alterations?

Numerical alterations, such as aneuploidies. Signup and view all the answers

What is the significance of the year 1955 in cytogenetics?

Determination of 46 as the number of chromosomes in humans Signup and view all the answers

What is the primary stage during which non-disjunction occurs more frequently in human females?

Meiosis 1 during oogenesis Signup and view all the answers

Which chromosome type has a terminal position of the centromere?

Acrocentrics Signup and view all the answers

Which of the following trisomies has the highest prevalence in the general population?

Trisomy 21 Signup and view all the answers

What distinguishes Giemsa staining from R banding in chromosome analysis?

Giemsa staining results in dark bands corresponding to G and C rich areas. Signup and view all the answers

What is a commonly observed consequence of unbalanced gametes during fertilization?

Unbalanced zygote formation Signup and view all the answers

Which step is crucial before preparing a karyotype from a tissue biopsy?

Culturing the cells to enrich metaphases Signup and view all the answers

Which sex chromosome anomaly is the only one compatible with birth in humans?

45 X Signup and view all the answers

Why is it important to use a hypotonic solution in the karyotyping process?

To allow chromosomes to move apart for better analysis Signup and view all the answers

Why is maternal age a significant factor in the incidence of numerical chromosome anomalies?

It influences the likelihood of non-disjunction occurring. Signup and view all the answers

Which chromosomal abnormality is characterized by the presence of three copies of a specific chromosome?

Trisomy Signup and view all the answers

What is typically a consequence of structural chromosomal alterations?

Congenital pathologies Signup and view all the answers

What chromosomal alteration is specifically associated with the Philadelphia chromosome?

Robertsonian translocation Signup and view all the answers

Which type of chromosomal imbalance is likely to prevent the completion of embryonic development?

Monosomy Signup and view all the answers

In cases of balanced translocation, what can the resulting zygotes be?

Balanced or unbalanced Signup and view all the answers

Which numerical alteration involves having four copies of each chromosome?

Tetraploidy Signup and view all the answers

What typically happens to gametes formed from a carrier of an unbalanced translocation?

They can be unbalanced Signup and view all the answers

Which type of chromosomal condition is noted to be very rarely compatible with birth?

The majority of triploidies Signup and view all the answers

How does the severity of chromosomal abnormalities relate to affected genes?

More affected genes correlate with increased severity Signup and view all the answers

What is one notable exception to the compatibility of monosomies with birth?

Monosomy 45, X is sometimes compatible Signup and view all the answers

What is the expected phenotype outcome of a balanced chromosomal alteration?

Normal phenotype with potential risks to offspring Signup and view all the answers

In karyotype analysis, what is the consequence of trisomy involving chromosome 21?

It results in conditions like Down syndrome. Signup and view all the answers

How does a somatic anomaly differ from a constitutional anomaly?

Somatic anomalies occur in a genetic mosaic pattern. Signup and view all the answers

What limitation exists with traditional karyotyping in detecting chromosomal alterations?

It can only detect changes larger than 4 million bases. Signup and view all the answers

Which of the following statements about unbalanced chromosomal situations is correct?

They correlate with significant phenotypic consequences or malformations. Signup and view all the answers

What type of classification refers to chromosomal alterations that affect some cells and not others?

Somatic anomalies Signup and view all the answers

Which chromosomal condition is referred to as a balanced translocation in karyotype analysis?

There is a missing chromosome present in a normal phenotype. Signup and view all the answers

Study Notes

Overview of Chromosomal Diseases

Chromosomal diseases stem from gross alterations in chromosome number or structure affecting gene expression.
Metaphases provide a clear view of chromosomes during mitosis for study and analysis.
DNA compaction varies from 2 nanometers (DNA) to over 1000 nanometers (mitotic chromosome).

Cell Division Mechanisms

Chromosomes are duplicated during mitosis, while meiosis produces sperm and egg cells, each containing half the chromosome number.
Sperm carries either X or Y chromosome, determining offspring sex.
Monozygotic twins share identical genomes; fraternal twins share similar genetic similarity to siblings.

Technological Advances in Chromosomal Analysis

The year 2008 marked significant progress in identifying new classes of chromosomal alterations due to advances in cytogenetics.
Tijo and Levan established the human chromosome number (46) through analysis of non-transformed lymphocytes in 1955.

Chromosome Classification

Morphologically, chromosomes can be acrocentric, submetacentric, or metacentric; telocentrics are absent in humans.
Karyotyping creates photographs of chromosomes arranged by size and shape, usually extracted from blood or tissue samples.

Karyotype Preparation

Karyotypes are prepared from blood, involving centrifugation, hypotonic solutions to swell cells, and fixation for microscopic analysis.
Tissue biopsies require cell culture and specific chemicals to enrich mitotic phases for analysis.

Chromosome Banding Techniques

Giemsa staining (G-banding) is the most common chromosomal banding technique.
R-banding uses heat denaturation followed by Giemsa staining; dark bands indicate GC-rich areas.
Q-banding employs fluorescent dye (Quinacrine) for distinguishing band patterns.
C-banding targets constitutive heterochromatin for specific identification.

Trisomies and Chromosomal Anomalies

Trisomies involve three copies of a chromosome and are the most frequent chromosomal anomalies, often lethal during embryogenesis.
Example of trisomy: three copies of chromosome 15 have significant developmental issues.

Classification of Chromosomal Diseases

Gene Dosage Alterations: Balanced (no phenotype change) vs. Unbalanced (associated with disease).
- Balanced translocation might not disrupt gene dosage, while unbalanced settings correlate with serious conditions.
Presence in Body Cells:
- Constitutional anomalies affect all body cells.
- Somatic anomalies occur in a subset of cells, leading to genetic mosaicism.
Type of Anomaly:
- Numerical alterations: trisomies, monosomies, triploidies, tetraploidies.
- Structural alterations: translocations, inversions, deletions, duplications.

Notable Genetic Conditions

Philadelphia chromosome (translocation between chromosome 9 and 22) is significant in specific types of leukemia.
Severity of chromosomal abnormalities is closely linked to the extent of affected genes; more serious imbalances usually lead to early embryonic death.

Gamete Formation and Genetic Risks

Carriers of balanced translocations may create unbalanced gametes, leading to potential zygotes with chromosomal abnormalities.
Example: Robertsonian balanced translocation (chromosomes 14 and 21) has implications for offspring viability and disease risk.### Chromosomal Abnormalities and Nondisjunction
Monosomies of autosomes are incompatible with birth; trisomy 21 (Down syndrome) is an exception.
Frequency of numerical chromosome anomalies correlates with maternal age and inversely with gestational age.
Nondisjunction during meiosis leads to abnormal chromosome numbers; primarily occurs in meiosis I.
Gametes from nondisjunction can be n+1 or n-1 in meiosis I; in meiosis II, they can be normal, n+1, or n-1.
Altered gametes lead to unbalanced zygotes upon fertilization with a normal gamete.
Many factors potentially influence nondisjunction events; the list is not yet comprehensive.

Maternal Age and Chromosomal Anomalies

Increased maternal age is closely linked to higher incidence of numerical chromosomal anomalies, particularly trisomy 21.
Oogenesis involves prolonged meiotic arrest, increasing risk of chromosome errors once meiosis resumes.
Spermatogenesis occurs continuously post-birth to puberty, showing no correlation between paternal age and chromosomal anomalies.

Trisomy Statistics

Trisomy 21: Prevalent at approximately 1.25 per 1000 births; compatible with life.
Trisomy 18 (Edwards syndrome): Prevalence is around 0.1 per 1000, presents with severe health issues.
Trisomy 13 (Patau syndrome): Even rarer at 0.07 per 1000 births, also associated with high mortality rates.
Sex chromosome aneuploidies (47 XXY, 47 XYY, 47 XXX): Each occurs in about 1 in 1000 births; 45 X presents as Turner syndrome—0.1 in 1000 females.

Down Syndrome Phenotype and Pathogenesis

Down syndrome results from three copies of chromosome 21, leading to gene dosage imbalance.
Symptoms include:
- Mental retardation (100% prevalence); risk of Alzheimer's by age 35.
- Muscular hypotonia (100%) and short stature (70%).
- Distinct physical features: brachycephaly (75%), epicanthic fold, Brushfield spots (55%), protruding tongue (45%).
- Limb and hand abnormalities: short limbs (65%), short fingers (60%).
- Congenital cardiac defects (40% prevalence) and gastrointestinal anomalies.
- Increased risk of myeloproliferative disorders and leukemia.

Genotype-Phenotype Correlations

Gene mapping from the Human Genome Project aids in associating specific genes on chromosome 21 with phenotypes.
Known genes involved include:
- SOD1: Overexpression linked to aging and immune function.
- COL6A1: Possible link to heart defects.
- Other implicated genes: ETS2, CAF1A, CBS, DYRK, CRYA1, leading to various phenotypic outcomes.

Management of Down Syndrome

Regular health assessments include cardiac function (echocardiograms), ophthalmological and hearing evaluations.
Emphasis on prevention of obesity and periodontal disease; monitoring for celiac disease, thyroid issues, and other comorbidities.
Addressing behavioral and developmental needs, reproductive health, and potential for behavior problems.

Additional Chromosomal Disorders

Turner syndrome (45 X): Characterized by short stature, unique physical features, and lacks correlation with parental age.
Edwards syndrome (trisomy 18): Rare with distinct phenotypes like crossed legs, prominent heels, and significant health complications.
Patau syndrome (trisomy 13): Associated with severe developmental challenges including blindness and cleft lip.
Down syndrome also includes occurrences from Robertsonian translocations and rare mosaic forms, each with varying implications for maternal age and risk of recurrence.