Advanced BiologyChapter 13Genetic Disorders

• Autosomes – 22 perfectly matched chromosomes.

• #s 1-22

• Sex Chromosomes – 23rd pair

• XX = Female• XY = Male

• Monosomic – Lost one copy of a chromosome

• Usually fatal, especially if on an autosome

• Trisomic – Extra chromosome• 13, 15, 18 can have an extra

and survive for a short time• 21, 22 can survive into

adulthood

• Down Syndrome – Trisomy 21

• Extra copy of the 21st chromosome

• Primary Nondisjunction – Failure of chromosomes to separate during Meiosis

• Failure to separate is correlated to age:

• >20 – 1:1700 births• 20-30 – 1:1400• 30-35 – 1:750• 35-45 – 1:16

• Barr Body – One of the X chromosomes is inactivated

• Y Chromsome – Possesses some active genes, contains features associated with maleness

• Contains 78 genes

NONDISJUNCTION IN SEX CHROMOMSOMES• Triple X syndrome - XXX• One functional X, two Barr

Bodies• Female is sterile but normal

in other respects

NONDISJUNCTION IN SEX CHROMOMSOMES• Klinefelter Syndrome – XXY• Sterile Male• Has many female characteristics• May have diminished mental

capacity• 1:500

NONDISJUNCTION IN SEX CHROMOMSOMES• Turner Syndrome – XO• Sterile Female• Short in stature, webbed neck• Sex organs never fully mature• Low mental abilities• 1:5,000

NONDISJUNCTION IN SEX CHROMOMSOMES• Nonviable – OY• Fails to develop• Humans cannot survive

without the genes on the X chromosome

• Multiple alleles – Some traits possess multiple alleles for that specific trait

• Blood types.

GENETIC DISORDERS• Cystic Fibrosis• Autosomal• Occurs mainly in the white

population• 1:20 carry the allele• 1:1800 are homozygous recessive

GENETIC DISORDERS• A malfunction in a channel

protein causes a thick mucus to be produced in the lungs

• Can also affect ducts in the pancreas

• Most affected individuals die in their teens

GENETIC DISORDERS• Sickle Cell Anemia• Autosomal Recessive• Occurs more frequently in the

black pop.• 1:1600

GENETIC DISORDERS• Hemoglobin is defective;

doesn’t carry enough Oxygen

GENETIC DISORDERS• Phenylketonuria (PKU)• Autosomal recessive• 1:15,000

GENETIC DISORDERS• Inability to breakdown

phenylalanine (aa)• Can be controlled by

nutrition

GENETIC DISORDERS• Tay-Sachs Disease• Autosomal Recessive• 1:3600 if of Jewish decent• 1:300,000 in U.S

GENETIC DISORDERS• Affected individuals lack an enzyme that

breaks down gangliosides in the brain• These accumulate in the lysosome and

burst• Resulting in the destruction of brain

cells

GENETIC DISORDERS• Sex-linked recessive• Inability of blood to clot• Missing a clotting factor

GENETIC DISORDERS• Huntington’s Disease• DOMINANT• 1:10,000• Gene gets turned on in middle

age

GENETIC DISORDERS• Deterioration of brain cells

due to the inhibition of brain cell metabolism

GENETIC DISORDERS• High risk pregnancies• Parents who are:

–Heterozygous for a disease–OlderOR have a family history

GENETIC COUNSELING• Ultrasound – position of fetus• Amniocentesis• Withdraw fluid containing fetal

cells

GENETIC COUNSELING• Chorionic Villi Sampling• Take a sample of placental

tissue

GENE THERAPY• Gene Transfer Therapy• 1st done in 1990• 2 Girls had a rare blood disorder

due to a defective gene• Scientists isolated working

copies of the gene

GENE THERAPY• Introduced them into bone marrow

cells taken from each girl• Gene modified bone marrow cells

were allowed to proliferate (make more)

• Injected back into body• Both girls healthy

GENE THERAPY• Use of vectors (1995)• Attach gene to a virus –

adenovirus (cold)• Like a piggyback ride• Tried it with mice and the cf

gene

GENE THERAPY• Worked, tried it with humans• Worked for awhile, but

eventually immune system attacked virus

• Caused the loss of the good gene

GENE THERAPY• Problems with the vector:

–Adenovirus elicits a strong immune response (everyone has had a cold)

–Adenovirus can produced a severe immune reaction and be fatal

GENE THERAPYProblems with the vector:–Adenovirus inserts its DNA

into cell at a random location causing mutations

GENE THERAPY• Few years later, found new

vector• Use Parovirus called Adeno-

Associated Virus (AAV)• Has only two genes and needs

the adenovirus to replicate

GENE THERAPY• Scientists removed the two

genes and insert human genes in their place to take them into the cell

• Does not cause the problems that the adenovirus did

GENE THERAPY• In 1999, AAV cured anemia in

rhesus monkeys.• Also cured dogs of retinal

degeneration• In 2000 first human trial