. Karyotype Analysis of Human Chromosomes
1. Karyotype preparation and analysis
Cells (from blood, amniotic fluid, etc) are grown in vitro (in a cell culture dish) to increase their number
Cell division is then arrested in metaphase with colchicine (prevents mitotic spindle from forming)
Cells are centrifuged and lysed to release chromosomes
Chromosomes are stained, photographed, and grouped by size and banding patterns
This is a photograph of the 46 human chromosomes in a somatic cell, arrested in metphase. Can you see that they are duplicated sister chromatids?
2. Normal male karyotype (a Cytogeneticist has lined these chromosomes up, matching homologues up and arranging them by size)
3. Normal female karyotype
II. Alterations in chromosome number:
Nondisjunction occurs when either homologues fail to separate during anaphase I of meiosis, or sister chromatids fail to separate during anaphase II. The result is that one gamete has 2 copies of one chromosome and the other has no copy of that chromosome. (The other chromosomes are distributed normally.)
If either of these gametes unites with another during fertilization, the result is aneuploidy (abnormal chromosome number)
A trisomic cell has one extra chromosome (2n +1) = example: trisomy 21. (Polyploidy refers to the condition of having three homologous chromosomes rather then two)
A monosomic cell has one missing chromosome (2n – 1) = usually lethal except for one known in humans: Turner’s syndrome (monosomy XO).
The frequency of nondisjunction is quite high in humans, but the results are usually so devastating to the growing zygote that miscarriage occurs very early in the pregnancy.
If the individual survives, he or she usually has a set of symptoms – a syndrome – caused by the abnormal dose of each gene product from that chromosome.
1. Human disorders due to chromosome alterations in autosomes (Chromosomes 1-22). There only 3 trisomies that result in a baby that can survive for a time after birth; the others are too devastating and the baby usually dies in utero.
A. Down syndrome (trisomy 21): The result of an extra copy of chromosome 21. People with Down syndrome are 47, 21+. Down syndrome affects 1:700 children and alters the child’s phenotype either moderately or severely:
characteristic facial features, short stature; heart defects
susceptibility to respiratory disease, shorter lifespan
prone to developing early Alzheimer’s and leukemia
often sexually underdeveloped and sterile, usually some degree of mental retardation.
Down Syndrome is correlated with age of mother but can also be the result of nondisjunction of the father’s chromosome 21.
Karyotype of a boy with Down Syndrome:
B. Patau syndrome (trisomy 13): serious eye, brain, circulatory defects as well as cleft palate. 1:5000 live births. Children rarely live more than a few months.
C. Edward’s syndrome (trisomy 18): almost every organ system affected 1:10,000 live births. Children with full Trisomy 18 generally do not live more than a few months.
