Class 12 and 13: Pedigree Analysis

Question 1

Pedigree

Answer 1

Charts of family histories that show phenotypes and family relationships of the individuals. Pedigrees are used to study human heredity of traits (usually disease) and to make predictions about an individual presenting the disease or be a carrier of the disease. They help: 1) establish how a disease is inherited, 2) to predict the risk of transmission of that genetic disease.

Question 2

Homozygous

Answer 2

Offspring is given the same allele for a particular gene from both parents. (example: RR, rr)

Question 3

Heterozygous

Answer 3

Offspring is given different alleles for a particular gene from both parents. (example: Rr)

Question 4

Hemizygous

Answer 4

A chromosome in a diploid organism is hemizygous when only one copy is present. Almost all X-linked genes are hemizygous in males with normal chromosomes because they have only one X chromosome.

Question 5

Autosomal Diseases

Answer 5

Diseases located on the non-sexual chromosomes (1-22)

Question 6

Autosomal Dominant

Answer 6

• Must have one affected parent.
• Does NOT skip generations.
• Just need one copy of the affected dominant allele (upper case letter) to control the phenotype.
• Homozygote (both upper case) and heterozygote organisms show the phenotype.
• Men and women roughly affected equally.

Question 7

Marfan Syndrome

Answer 7

• Affects the skeleton, the cardiovascular system, and the eyes. Individuals are tall, thin, long arms and legs + thin fingers. Heart defects.
• The gene responsible is called FBN1 and located on chromosome 15. It encodes the protein fibrillin-1, component of connective tissue.
• 1 in 5,000
• Fribrillin-1 = protein secreted outside of the cell. It binds together with other proteins to form elastic fibers that allow the skin, ligaments, and blood vessels to stretch. It provides support to some tissues such as nerves, muscles, and lenses of the eyes. Controls amount of TGF-B which stimulates cell proliferation.
• People with Marfan Syndrome express a mutant form of fibrillin -> therefore have defective connective tissue. Too much TGF-B is released and too many cells are made. There is an instability of tissue. High risk of rupture of the aorta wall, threatening life.

Question 8

Huntington Disease

Answer 8

• Disease associate with progressive neuronal degeneration and dementia. It develops symptoms at the adult stage, usually between 30-50 years old: They start having uncontrolled movements (muscle coordination), It progresses toward a total loss of the use of their limbs, Personality changes, and dementia (loss of cognitive capabilities).
• The gene called Huntington and located on chromosome 4 controls the disease. The mutant allele carries numerous repeates of the CAG tri-nucleotide.
  This is toxic for brain cells.
• More than 35 CAG repeats puts the individual at risk of developing Huntington Disease. The more repeats, the earlier the symptoms will appear.
• Transgenic mice have presented the same abnormal CAG repeats in the gene coding for Huntington. They show the same progressive behavioral changes and loss of musical control. These mice are a useful tool to develop drugs and treatment for Huntington disease.

Question 9

Autosomal Recessive

Answer 9

• Doesn’t have to affect parent to affect child.
• Skips generations.
• Need two copies of the affected recessive allele (lower case letter) to control the phenotype.
• Only the homozygous (two lower case letters) are affected by the disease.
• Men and women roughly affected equally.

Question 10

Cystic fibrosis

Answer 10

• Genetic disorder associated with abnormal secretions of the exocrine glands = thick and sticky mucus. The phenotype of this disease affects the lungs and digestive system. The mucus clogs the lungs and causes frequent lung infections. The mucus also obstructs the pancreas which lowers the efficiency of the digestive system.
• CFTR (Cystic Fibrosis Transmembrane Conductance) gene is the Cystic Fibrosis gene. Gene is located on chromosome 7. CFTR protein controls the movement of the chloride ions across the epithelial lining of the lungs and the pancreas. When CFTR protein is non functional: problem of balance of the salt and water in the lungs and pancreas which creates the thick mucus.

Question 11

Galactosemia

Answer 11

• Genetic disorder associated with the inability to metabolize galactose. Mostly caused by the lack of the enzyme GALT galactose-1-phosphate uridyl transferase, involved in galactose metabolism.
• These substances damage the liver, brain, kidneys, and eyes resulting in hepatomegaly (enlarged liver), cirrhosis (very advanced liver damage), renal failure, cataracts and mental retardation.
• 1 in 57,000 births. Without treatment, high levels of galactose-1-phosphate accumulate and mortality in infants is about 75%.
• 1 molecule of Lactose = 1 molecule of galactose + 1 molecule of glucose. When the lactose is catabolized, galactose is released. So people with galactosemia must avoid all products that contain lactose or galactose such as milk, milk-containing products for life. Infants screened as sick need to be fed with other lactose-free formula.

Question 12

X-linked Recessive

Answer 12

• Females must be homozygous (two lower case letters) to be affected, males must be hemizygous (receive affected x chromosome).
• Males get the disease from their mother and give it to all of their daughters and none of their sons.
• Men have it more than women.

Question 13

Hemophilia

Answer 13

• Group of hereditary genetic disorders that impair the body’s ability to control blood clotting, process that allow to stop bleeding when a blood vessel is broken.
• Hemophilia A (clotting factor VIII deficiency) is the most common form of the disorder, present in about 1 in 5,000-10,000 male births.
• Hemophilia B (factor IX deficiency) occurs in around 1 in about 20,000-34,000 male births.
• Females are almost exclusively asymptomatic carriers.

Question 14

Color Blindness

Answer 14

• Inability to perceive color differences. Most common : red-green blindness. ~8% of the US male population is affected. Caused by defects in the development of retinal cones that perceive color in light and transmit the info to the optic nerve.
• Other conditions that are not always genetically inherited that can lead to color blindness: brain damage, degenerative diseases of the eyes, retinal damages caused by diabetes.