أسئلة المحاضرة الرابعة جينتكس (قبل التعديل)

Karyotype and Chromosome Analysis

• A karyotype is a description of the number and structure of chromosomes.
• Karyotyping is carried out in dividing cells halted in metaphase.
• The process involves culturing lymphocytes, stimulating their division, then arresting them in metaphase using colchicine.
• Chromosomes are then fixed, stained, examined, and photographed.
• Photographed chromosomes are matched into pairs.

Chromosome Structure

• Chromosomes are thread-like structures containing DNA tightly packed and coiled around histones.
• Telomeres are repetitive nucleotide sequences located at each end of a chromosome.
• Telomeres stabilize and protect chromosome ends from deterioration or fusion.
• Each chromosome is composed of two identical chromatids connected at the centromere.
• Each chromatid has a long arm (q arm) and a short arm (p arm).

Chromosome Classification

• By centromere position:
  • Metacentric: Centromere is in the middle, arms are equal in length.
  • Submetacentric: Centromere is between the center and the end, one arm is longer than the other.
  • Acrocentric: Centromere is close to one end, one arm is much shorter.
  • Telocentric: Centromere is at the end, only one arm is present (not in humans).
• By gene complement:
  • Autosomes: 22 pairs of identical homologous chromosomes.
  • Sex chromosomes: One pair of either identical homologues (XX, female) or unidentical homologues (XY, male).
• Denver classification:
  • Groups chromosomes based on length and centromere position into seven groups (A-G) in descending order.

Clinical Importance of Chromosomal Studies

• Diagnosis of diseases and syndromes such as Down syndrome.
• Diagnosis of malignant diseases like chronic myeloid leukemia.
• Prenatal diagnosis of diseases and determination of fetal sex.

Causes of Chromosomal Abnormalities

• Radiation can cause chromosomal damage.
• Family history of chromosomal abnormalities.
• German measles infection can fragment chromosomes.
• Pregnancy in older women can lead to congenital syndromes.
• Autoimmune diseases can cause chromosomal abnormalities.

Types of Chromosomal Abnormalities

• Numerical: Abnormal number of chromosomes:
  • Monosomy: One chromosome missing.
  • Trisomy: One extra chromosome.
• Structural: Part of a chromosome is missing, extra, or switched to another chromosome.

Specific Chromosomal Abnormalities

• Klinefelter's syndrome: 47,XXY
  • Non-separation of chromosomes in the first meiotic cell division in the mother during ova formation.
  • Ova contains two X chromosomes.
  • Fertilization by a Y sperm results in XXY chromosomes.
• Turner's syndrome: 45,X0
  • Non-separation of chromosomes in the first meiotic cell division in the mother during ova formation.
  • Ova contains no X chromosomes.
  • Fertilization by an X sperm results in X0 chromosomes.
• Down's syndrome (Trisomy 21):
  • Most common trisomy.
  • An extra chromosome 21.
• Cri-du-chat syndrome: Deletion of the short arm on chromosome 5.
  • Characterized by a cat-like cry in infants.
• Wolf syndrome: Deletion of the short arm on chromosome 4.
• Philadelphia chromosome: Translocation between chromosomes 9 and 22.
  • Occurs in chronic myeloid leukemia.

Karyotyping

• Karyotyping is the process of examining and describing the number and structure of chromosomes in a cell.
• The analysis is performed on cells in metaphase of the cell cycle.
• To obtain cells for analysis, a blood sample is collected and treated with an anticoagulant like heparin.
• Lymphocytes are separated from other cells in the blood by centrifugation.
• Lymphocytes are stimulated to divide by adding a mitogenic agent, phytohemagglutinin to the culture medium.
• Cell division is stopped at metaphase by adding colchicine.
• The cells are then treated with a hypotonic solution which causes them to swell.
• Finally, cells are spread on slides by the drop method and stained for analysis.

Chromosomes

• Chromosomes are thread-like structures located in the nucleus of eukaryotic cells that contain DNA.
• DNA is tightly coiled around a protein called histones.
• Telomeres are regions of repetitive nucleotide sequences located at the ends of chromosomes.
• Telomeres help stabilize and protect the ends of chromosomes from deterioration and fusion.

Structure of Human Chromosomes

• Each chromosome is composed of two identical chromatids joined by a centromere.
• Each chromatid has a long arm (q) and a short arm (p).
• The terminal ends of each chromatid are called telomeres.

Chromosome Classification

Classification By Centromere Position

• Metacentric: Centromere is located in the middle of the chromosome and both arms are the same length.
• Submetacentric: Centromere is slightly off center and results in one arm being slightly longer than the other.
• Acrocentric: Centromere is located near one end of the chromosome, making one arm much shorter than the other.
• Telocentric: Centromere is located at the end of the chromosome with only one arm. Telocentric chromosomes are NOT found in humans.

Classification By Gene Complement

• Autosomes: 22 pairs of chromosomes that are identical in males and females.
• **Sex Chromosomes:**One pair of chromosomes that determine sex.
  • XX - Female
  • XY - Male

Denver Classification

• Chromosomes are classified into seven groups based on length and centromere position.
• Groups are organized in descending order from largest to smallest.
• Group A: Chromosomes 1-3 (Largest)
• Group B: Chromosomes 4-5 and the X chromosome
• Group C: Chromosomes 6-12
• Group D: Chromosomes 13-15
• Group E: Chromosomes 16-18
• Group F: Chromosomes 19-20 and the Y chromosome
• Group G: Chromosomes 21-22 (Smallest)

Clinical Importance of Karyotyping

• Karyotyping is used to diagnose genetic diseases and syndromes.
• It can be used to diagnose cancers like Chronic Myeloid Leukemia (CML).
• Fetal karyotyping can aid in prenatal diagnosis of genetic diseases and determine the sex of the fetus.

Causes of Chromosomal Abnormalities

• Radiation exposure can cause chromosomal damage.
• Family history of chromosomal abnormalities can increase the risk.
• Infections like German measles can cause chromosomal fragmentation.
• Pregnancy in older women is associated with a higher risk of chromosomal abnormalities.
• Autoimmune diseases can also lead to chromosomal abnormalities.

Types of Chromosomal Abnormalities

• Numerical Abnormalities: Involve an abnormal number of chromosomes
  • Monosomy: One chromosome is missing from a pair.
  • Trisomy: One extra chromosome is present in a pair.
• Structural Abnormalities: Involve the structure of a chromosome.
  • Deletion: A part of a chromosome is missing.
  • Translocation: A part of a chromosome has been switched to another chromosome.

Examples of Chromosomal Abnormalities

• Sex Chromosome Abnormalities*
• Klinefelter's Syndrome: 47, XXY (Male - extra X chromosome)
• Turner's Syndrome: 45, XO (Female - missing X chromosome)
• Autosomal Abnormalities*
• Down Syndrome (Trisomy 21): 47, XX or XY +21 (Male or Female - extra chromosome 21)
• Wolf Syndrome: Deletion in the short arm of chromosome 4.
• Cri-du-chat Syndrome: Deletion of the short arm on chromosome 5.
• Philadelphia Chromosome: A translocation between chromosomes 9 and 22 associated with chronic myeloid leukemia (CML).

Karyotyping

• Karyotyping is the process of analyzing and describing the number and structure of chromosomes.
• It is typically carried out in dividing cells arrested in the metaphase stage of cell division.

Karyotyping Procedure

• A blood sample is collected and anticoagulant (heparin) is added.
• Blood is centrifuged to separate lymphocytes from other cells.
• Lymphocytes are incubated in a suitable culture medium, with phyto-haemagglutinin (mitogenic agent) added to stimulate division.
• Cultured lymphocytes are incubated for three days.
• Colchicine is added to stop cell division at metaphase.
• Cells are treated with a hypotonic solution.
• Samples are spread on slides using the drop method.
• Chromosomes are fixed, stained, examined, and photographed.
• Photographed chromosomes are cut and matched into pairs using an image analyzer.

Chromosome Structure

• Chromosomes are thread-like structures composed of DNA tightly packed and coiled around histones.
• Telomeres are regions of repetitive nucleotide sequences located at each end of a chromosome.
• Telomeres stabilize and protect chromosome ends from deterioration and fusion with neighboring chromosomes.
• Each chromosome is formed of two identical chromatids connected at the centromere.
• Each chromatid has:
  • A long arm called the "q" arm.
  • A short arm called the "p" arm.

Chromosome Classification

By Centromere Position

• Metacentric: Centromere is nearly in the middle, resulting in two arms of the same length.
• Submetacentric: Centromere is between the center and upper ends, resulting in one arm longer than the other.
• Acrocentric: Centromere is close to one end, resulting in one arm much shorter than the other.
• Telocentric: Centromere is at the end, resulting in only one arm (not present in humans).

By Gene Complement

• Autosomes (somatic): 22 pairs of identical homologues.
• Sex chromosomes: One pair of chromosomes:
  • Identical homologues (XX) in females.
  • Unidentical homologues (XY) in males.

Denver Classification

• Groups chromosomes based on their total length and centromere position in descending order:

Clinical Importance of Chromosomal Studies

• Diagnosis of diseases and syndromes:
  • Down syndrome.
• Diagnosis of malignant diseases:
  • Chronic myeloid leukemia.
• Prenatal diagnosis:
  • Detecting certain diseases and determining fetal sex.

Causes of Chromosomal Abnormalities

• Radiation: Can cause chromosomal damage.
• Family history: Parents or family members with chromosomal abnormalities increase the risk.
• German measles infection: The virus can fragment chromosomes.
• Older maternal age: Increases the risk of children with congenital syndromes.
• Autoimmune diseases: Can cause chromosomal abnormalities.

Types of Chromosomal Abnormalities

Numerical Abnormalities

• Abnormal number of chromosomes:
  • Monosomy: Missing a chromosome.
  • Trisomy: An extra chromosome in a normal pair.

Structural Abnormalities

• Alterations in chromosome structure:
  • Deletion: Part of a chromosome is missing.
  • Translocation: Exchange of material between non-homologous chromosomes.

Examples of Chromosomal Abnormalities

Numerical Abnormalities

Sex Chromosomes

• Klinefelter’s syndrome (47,XXY): Non-separation of chromosomes in the mother during the formation of ova, resulting in an ovum with two X chromosomes (XX). Fertilization by a sperm with a Y chromosome leads to a zygote with XXY chromosomes.
• Turner’s syndrome (45,XO): Non-separation of chromosomes in the mother during the formation of ova, resulting in an ovum with no X chromosomes. Fertilization by a sperm with an X chromosome leads to a zygote with XO chromosomes.

Autosomes

• Monosomy: Wolf syndrome (missing part of chromosome 4).
• Trisomy: Down syndrome (trisomy 21).

Structural Abnormalities

• Deletion:
  • Cri-du-chat syndrome: Deletion of the short arm on chromosome 5, characterized by a cat-like cry in affected infants.
• Translocation:
  • Philadelphia chromosome: Translocation between chromosomes 9 and 22, often observed in chronic myeloid leukemia.

Karyotyping

• Karyotyping is the description of the number and structure of chromosomes
• Karyotyping is performed on dividing cells arrested in metaphase

Karyotyping Procedure

• Collect blood sample
• Add anticoagulant like heparin
• Centrifuge blood to separate lymphocytes
• Incubate lymphocytes in a suitable medium
• Add phyto-haemagglutinin to stimulate division
• Culture for 3 days
• Stop cell division with colchicine
• Treat cultured cells with hypotonic solution
• Spread cells on slides using the drop method
• Fix, stain and examine chromosomes
• Photograph chromosomes and cut, then match pairs with image analyser

Chromosomes

• Thread-like structures
• Consists of DNA molecule tightly packed and coiled around histones

Telomere

• Region of repetitive nucleotide sequences at each end of a chromosome
• Stabilizes and protects chromosomes from deterioration and fusion

Structure of Human Chromosome

• Each chromosome is formed of two identical chromatids connected at their centromere
• Each chromatid has a long arm (q) and a short arm (p)
• Telomeres are the terminal ends of the chromatids

Chromosome Classification (based on position of centromere)

• Metacentric: Centromere is nearly in the middle, two arms are of equal length
• Submetacentric: Centromere is between the center and the upper end, one arm is longer than the other
• **Acrocentric:**Centromere is close to one end, one arm is much shorter than the other
• Telocentric: Centromere is at the end, only one arm (not present in humans)

Chromosome Classification (based on gene complement)

• Autosomes (somatic): 22 pairs of identical homologues
• Sex chromosomes: One pair of
  • Identical homologues (XX female)
  • Unidentical homologues (XY male)

Denver Classification

• Based on length and position of centromere into 7 groups in descending order:
  • Group A: Chromosomes 1-3
  • Group B: Chromosomes 4-5 and X chromosome
  • Group C: Chromosomes 6-12
  • Group D: Chromosomes 13-15
  • Group E: Chromosomes 16-18
  • Group F: Chromosomes 19-20 and Y chromosome
  • Group G: Chromosomes 21-22

Clinical Importance of Chromosomal Studies

• Diagnosis of diseases:
  • Down syndrome
  • Chronic myeloid leukemia
• Prenatal diagnosis:
  • Diagnose diseases
  • Determine fetal sex

Causes of Chromosomal Abnormalities

• Radiation: causes chromosomal damage
• Family history: hereditary factors
• German measles: virus causes fragmentation of chromosomes
• Pregnancy in older women: may result in children with congenital syndromes
• Auto-immune diseases: can cause chromosomal abnormalities

Types of Chromosomal Abnormalities

• Numerical: Abnormal number of chromosomes
  • Monosomy: Missing chromosome
  • Trisomy: Extra chromosome
• Structural: Part of an individual chromosome is missing, extra, or switched to another chromosome

Sex Chromosome Abnormalities

• Males:
  • Klinefelter’s syndrome (47, XXY): Non-separation of chromosomes occurs during the first meiotic cell division in the mother during the formation of ova, resulting in an ovum with two X chromosomes. Fertilization with a sperm containing a Y chromosome results in XXY chromosomes
• Females:
  • Turner's syndrome (45, XO): Non-separation of chromosomes occurs during the first meiotic cell division in the mother during the formation of ova, resulting in an ovum with no X chromosomes. Fertilization with a sperm containing an X chromosome leads to XO chromosomes

Autosome Abnormalities

• Monosomy: Wolf syndrome
• Trisomy: Down's syndrome
• Structural: Cri-du-chat syndrome, Philadelphia chromosome

Down's Syndrome (Mongolism or Trisomy 21)

• Most common chromosomal abnormality
• Trisomy 21: the addition of a chromosome to the pair
• Characterized by certain physical features and developmental delays

Deletion

• Detachment and loss of portions from chromosomal arms
• Cri-du-chat syndrome: Deletion of the short arm on chromosome number 5, characterized by a cat-like cry in babies
• Wolf syndrome: Deletion of the short arm on chromosome number 4

Translocation

• Exchange of material between non-homologous chromosomes
• Philadelphia chromosome: Translocation between chromosomes 9 and 22, commonly found in Chronic Myeloid Leukemia