LESSON 11: Chromosome Abnormalities

• chromosome - consists primarily of DNA and proteins (histones) and is duplicated and transmitted (via mitosis or meiosis) to the next cell generation
• heterochromatin - stains darkly and mostly DNA repeating sequences
• euchromatin - light staining and contains many protein-encoding genes
• parts of a chromosome

  1. telomeres
  2. origin of replication sites
  3. centromere
• telomeres - chromosome tips
• origin of replication sites - where replication forks begin to form
• centromere - largest construction of a chromosome
• examples of chromosome rearrangements:

  1. inverted square
  2. exchange of parts
• methylation - addition of methyl group to histones; causes nucleosomes to pack tightly together

  • deactivates transcription factors
• histone acetylation - adding acetyl groups; results in loose packing of nucleosomes
• DNA probes - labeled piece of DNA that binds to its complementary sequence on a particular chromosomes
• Any cell other than a mature RBC (which lacks nucleus) can be used to examine chromosomes
• To identify blood-borne cancers, chromosomes from bone marrow which give rise to blood cells may be examined
• Amniocentesis procedure


  1. Remove fetal cells and fluids

  2. Culture cells for a week to 10 days

  3. Karyotype typically 20 cells

  4. Examine amniotic fluid for abnormalities
• Amniotic fluid examination


  Examined for deficient, excess, or abnormal biochemical that could indicate an inborn error
• Amniocentesis can detect approx. 800 of more than 5000 known chromosomal and biochemical problems
• The most common abnormality detected is one extra chromosome (trisomy)
• Performed between this age of gestation

  14-16 weeks
• amniocentesis (1966) - doctor removes a sample of fetal cells and fluids from the uterus with a needle passed through the pregnant woman's abdominal wall

  • first fetal karyotype was constructed through this method
  • cells are cultured for a week to 10 days and typically 20 cells are karyotyped
• amniotic fluid - examined for deficient, excess or abnormal biochemical that could indicate an inborn error of metabolism
• amniocentesis - can detect approx. 800 of more than 5000 known chromosomal and biochemical problems

  • most common chromosomal abnormality detected is trisomy
  • performed between 14-16 weeks age of gestation
• amniocentesis - recommended if the risk of the fetus having a detectable condition exceeds risk that the procedure will cause a miscarriage

  • most common candidate is a pregnant woman over age 35 because this is "advanced maternal age"
• Another reason to do amniocentesis is if the blood test of a pregnant woman reveals low levels of a fetal liver protein called alpha fetoprotein (AFP) and high levels of human chorionic gonadotrophin (HCG)
• chorionic villus sampling - cells are obtained from the chorionic villi during the 10th-12th week of pregnancy

  • a karyotype is prepared directly from the collected cells
  • slightly less accurate than amniocentesis
  • transverse limb defects - halt development of feet and/or hands
• chorionic villus sampling - test for inborn error of metabolism are not possible

  • greater risk of spontaneous abortion
  • 0.8% added risk of miscarriage
• fetal cell sorting - newer technique that separates fetal cells from the woman's bloodstream

  • traces its roots in 1957
• karyotyping - indicated for:

  • suspected chromosome abnormality
  • sexual disorders
  • multiple congenital anomalies and/or developmental retardation
  • undiagnosed learning disabilities
  • infertility or multiple miscarriage, stillbirth and malignancies
• karyotyping - human chromosomes are categorized based on position of centromere
• metacentric chromosome - centromere is located in the middle

  • chromosomes 1, 3, 16, 19, and 20
• acrocentric chromsome - the centromere near one end

  • chromosomes 13, 14, 15, 21, and 22
• sub-metacentric chromosome - close to the center
• Chromosome arms are defined by:

  1. region number
  2. band
  3. sub-band
  4. sub-sub-band
  5. numbers
• Convenient Methods of Chromosome Banding

  1. G- (Giemsa)
  2. R- (Reverse)
  3. C- (Centromere)
  4. Q- (Quinacrine)
• phytohemagglutinin - speeds up mitosis
• colchicine and hypotonic saline - slows down mitosis
• Fluorescence In Situ Hybridization - applied to provide specific localization of genes on chromosomes

  • used to check the cause of trisomies, microdeletion syndromes, etc.
• 1923 - Theopilus Painter's chromosome sketches are published; human chromosome number thought to be 48
• 1951 - method to detangle chromosomes discovered by accident
• 1953 - Albert Levan and Joe-Hin Tjio develop "squash and stain" technique for chromosome preparation
• 1956 - using tissue culture cells, Levan, Tjio, and Biesele determine chromosome number to be 46