Genetic Disorders

Bio II

. 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?

Three Types of Chromosomal disorders• Monosomy - only one copy of one of the

chromosomes

• Trisomy – three copies of one of the chromosomes

• Missing or extra Sex Chromosomes (Monosomy of Trisomy of pair #23)

These disorders are caused byNondisjunction

Nondisjunction• The failure of homologous chromosomes to separate

properly during meiosis.

What should happen Nondisjunction

The results• If the abnormal gametes is fertilized the

results

Monosomy• The zygote is lacking a chromosome• Organisms lacking one or more chromosomes

rarely survive• There are no cases of autosomal monosomy.

This indicates humans require both members of each homologous pair of autosomes to survive.

• Some plants show monosomy

Trisomy• The zygote has an extra chromosome

• Organisms with an extra chromosome sometimes survive

Trisomy• Trisomy 8 (Warkany syndrome 2) • Trisomy 9 • Trisomy 12 (Chronic Lymphocytic Leukemia) • Trisomy 13 (Patau syndrome) • Trisomy 18 (Edwards syndrome) • Trisomy 21 (Down syndrome) • Trisomy 22

Downs Syndrome Female Karyotype

Down Syndrome

Male

Examples of trisomy in humans

• Trisomy 21: Downs Syndrome

• Trisomy 18: Edwards syndrome

• Trisomy 13: Patau syndrome

Polyploidy• The condition where cells have multiple sets of

chromosomes

• Usually 3-4 sets

• Most often found in plants, rare in animals

Examples of Polyploidy

Diploid & tetraploid many plants

Octoploidystrawberries

Triploid seedless watermelon

Monosomys and Trisomys of the sex chromosomes are often compatible with

life

Sex chromosome defects: Normally a man has XY and a woman XX. But the wrong combinations can arise with extra sex chromosomes or missing ones:

• Turner syndrome (XO syndrome, monosomy X, missing Y): This should just be called the "X syndrome" because the person has an X, but no second sex chromosome. Such people are female, as there is no male Y chromosome. It is a 1-in-5000 syndrome, involving some relatively minor conditions, but usually sterility.

• Klinefelter syndrome (XXY syndrome, also rarely XXXY): a 1-in-1000 disorder where the person is usually male (because of the Y chromosome), but has lower levels of testosterone and may have some female-like features (because there are two X chromosomes), and is usually sterile. The rarer XXXY syndrome may lead to retardation.

• Jacobs syndrome (XYY syndrome): The person has an extra Y male chromosome. He will be male and may be largely normal, or may suffer from minor features such as excess acne and may be very tall, and in some cases behavioral complaints such as aggression. Frequency around 1-in-2000.

• Triple-X (XXX, also XXXX or XXXXX): These people are females with an additional X chromosome. In rarer cases, there can even be 4 or 5 X chromosomes. They can be largely normal, or may suffer from problems such as infertility (some but not all), and reduced mental acuity. Occurs with a frequency around 1-in-700.

Sex Chromosome Abnormalities

Female Genotype Syndrome Male Genotype Syndrome

XX normal XY normal

XO Turner XXY Klinefelter

XXX Triple-X XYY Jacobs

Normal Male

Normal Female

Turner’s Karyotype

Kleinfelter Karyotype

More Types of Chromosomal disorders

• Deletion: A small section is missing. • Microdeletion: A minute amount of material (sometimes

only a single gene) is missing. • Translocation: A section of a chromosome is attached to

another chromosome. • Inversion: A section of chromosome is snipped out and

reinserted upside down. • Duplication: A section of a chromosome is duplicated, so

there is extra genetic material. • Ring chromosome: Material is deleted at both ends of a

chromosome, and the new ends join together to form a ring.

• Prader-Willi syndrome (deletion on chromosome 15): Affected children usually have mental retardation or learning disabilities, behavioral problems and short stature. They also may develop extreme obesity.

• Cri-du-chat (cat cry) syndrome (deletion on chromosome 5): Affected children have a cat-like high-pitched cry during infancy, mental retardation and physical abnormalities.

• Wolf-Hirschhorn syndrome (deletion on chromosome 4): This disorder is characterized by severe mental retardation, heart defects, poor muscle tone, seizures, high blood pressure and other problems.

• 22q11 deletion syndrome (deletion on chromosome 22): Deletions in a specific region of chromosome 22 cause a variety of problems that can include heart defects, cleft lip/palate, immune system abnormalities, characteristic facial features and learning disabilities. Certain combinations of these features are sometimes called DiGeorge or velocardiofacial syndrome. Individuals with this disorder have a 50 percent chance of passing the chromosomal abnormality on to their offspring with each pregnancy.

Additional Details

Examples of monosomy in humans

Monosomy X: Turners Syndrome