Genetics Exam 2 Diseases

Phenylketonuria (PKU) (symptoms, inheritance, molecular, fun fact)

Symptoms: Intellectual disability, musty odor of urine caused by accumulation of phenylalanine derivative

Inheritance: Recessive

Molecular: Gene that converts phenylalanine to tyrosine is mutated

Fun Fact:

• Test in newborns.

• Symptoms alleviated with diet.

• Disease not caused by absence of tyrosine but by excess of phenylalanine.

• At birth there are no symptoms because mother’s enzyme controls phenylalanine levels in the fetus.

• Mother with PKU that has genetically healthy baby, can have offspring with disease if she
  does not control diet during
  pregnancy

Genetic goitrous cretinism (symptoms, inheritance, molecular, fun fact)

Symptoms: Intellectual disability, enlarged thyroid gland

Inheritance: Recessive

Molecular: Gene that codes for enzyme that transforms tyrosine into thyroxin is mutated

Fun Fact:

• In this case, instead of accumulation of substance causing the disease, it is failure to synthesize an essential product, thyroid hormone.

• At birth there are no symptoms because mother’s enzyme provides thyroid in the fetus. (Would a mother with genetic goitrous
  cretinism that has genetically healthy baby, have offspring with disease if she does not control diet during pregnancy)

Albinism (symptoms, inheritance, molecular, fun fact)

Symptoms: No pigment

Inheritance: None

Molecular: Gene that codes for enzyme that transforms DOPA (neurotransmitter) into melanin is mutated

Fun Fact: Why are cave organisms albino? Could it be that it makes their brain work differently?

Galactosemia (symptoms, inheritance, molecular, fun fact)

Symptoms: Intellectual disability

Inheritance: Recessive

Molecular: Enzyme that breaks galactose-1-phosphate is missing or has half of the normal activity. Three alleles

Fun Fact: Test in newborns. Symptoms alleviated with diet

Lactose Intolerance (symptoms, inheritance, molecular, fun fact)

Symptoms: Bloating, cramps, gas, and diarrhea

Inheritance: Recessive

Molecular: Lactase levels decline with age

Fun Fact:

• Caused by variation of gene expression

• Variable among human population ie. maybe natural selection

Sickle Cell Anemia (symptoms, inheritance, molecular, fun fact)

Symptoms: Anemia and sickle shaped red blood cells

Inheritance: Recessive

Molecular:

• Beta-globin gene has aa six change from glu to val.

• Insoluble hemoglobin molecules stick together and form long tubular structures that distort cells

Fun Fact:

• Heterozygous are resistant to malaria.

• Allele frequent among west Africans due to natural selection.

• Can be treated with drugs that activate the production of fetal hemoglobin

Marfan Syndrome (symptoms, inheritance, molecular, fun fact)

Symptoms: Tall with long limbs. Sometimes excel in basketball and volleyball. Aorta is enlarged and can split open causing death

Inheritance: Dominant

Molecular: Fibrillin protein is part of the connective tissue

Fun Fact: Lincoln may have had it

Cystic Fibrosis (symptoms, inheritance, molecular, fun fact)

Symptoms: Multiple glands produce thick mucus clogs. They can make cysts in pancreas or block airways. Premature death.

Inheritance: Recessive

Molecular: Cystic fibrosis transmembrane conductance regulator (CFTR) gene has deletion of single amino acid. Makes chloride ion membrane channel fold wrongly, and therefore reduces amount of fluid added to glandular secretions.

Fun Fact: Gene therapy may cure it.

Color blindness (symptoms, inheritance, molecular, fun fact)

Symptoms: Red or green blindness

Inheritance: X-linked recessive

Molecular: Protein binds to visual pigments in retina

Fun Fact: Affects 8% of all male population

Duchene muscular dystrophy (symptoms, inheritance, molecular, fun fact)

Symptoms: Weakness and loss of muscular tissue. Individuals use distinctive set of maneuvers to get up. Premature death

Inheritance: X-linked recessive

Molecular: Dystrophin attaches to membrane of muscle cells to stabilize them. When absent or defective, membranes are torn apart

Fun Fact: Since it causes death, it would appear that natural selection should keep frequencies very low, but since mutation rates are high, mutation replaces the allele lost. There is a balance between alleles introduced by mutation and alleles removed by death

Hemophilia (symptoms, inheritance, molecular, fun fact)

Symptoms: Bleeding, defects with blood clotting

Inheritance: X-linked recessive

Molecular: None

Fun Fact: Queen Victoria was a carrier. Her offspring were part of the European royalty and disease changed the world history. For example, Russian Czar’s son had hemophilia and Rasputin was hired to cure him.

Mitochondrial disorders (symptoms, inheritance, molecular, fun fact)

Symptoms: Tissues with high energy requirements are affected most: muscle and nervous system

Inheritance: Mitochondria 1

Molecular: Mitochondria have DNA independent of the nucleus. The genes are mostly involved in respiration

Fun Fact: Mitochondrial DNA is inherited only by the ovule. Therefore mitochondrial DNA in inherited maternally

Huntington’s Disease (symptoms, inheritance, molecular, fun fact)

Symptoms: Progressive degeneration of the nervous system, uncontrolled jerky movements of the head and limbs. Phenotypic expression starts late in
age (30-50 years). Death after 5-15 years of onset

Inheritance: Dominant

Molecular: None

Fun Fact:

• If a parent has it, you have 50% probability of having it

• Gene has been sequenced and diagnostic tests are available

Camtodactyly (symptoms, inheritance, molecular, fun fact)

Symptoms: Unmovable, bent little finger

Inheritance: Dominant, but with low penetrance and expressivity

Molecular: None

Fun Fact:

• People that have dominant allele, not always show phenotype (penetrance)

• Sometimes little finger of both hands is affected, sometimes only one, sometimes none (expressivity)

Tay-Sachs (symptoms, inheritance, molecular, fun fact)

Symptoms: Fatal in early childhood

Inheritance: Recessive

Molecular: None

Fun Fact: Despite being selected against when homozygous, frequencies in some populations remain high because heterozygotes are more resistant to tuberculosis

Patau syndrome (symptoms, inheritance, molecular, fun fact)

Symptoms: Very early death. Facial and body structures malformations

Inheritance: Trisomy 13

Molecular: None

Fun Fact: None

Edwards syndrome (symptoms, inheritance, molecular, fun fact)

Symptoms: Very early death. Clenched fists with fingers overlapping and other body structures malformations

Inheritance: Trisomy 18

Molecular: none

Fun Fact: none

Downs Syndrome (symptoms, inheritance, molecular, fun fact)

Symptoms: Mental retardation and “Down” morphology

Inheritance: Trisomy 21

Molecular: None

Fun Fact:

• Most frequent chromosomal abnormality in newborns. Only autosomal aneuplody that is not lethal. Maternal age is the leading risk factor.

• Two possible reasons are being studied: a) Age of oocytes stopped at meiosis prophase I. b) Reduced maternal selection from embryo-uterine interactions leading to miscarriage of defective embryos

Turner Syndrome (symptoms, inheritance, molecular, fun fact)

Symptoms: Female, sterile, no significant mental retardation, short and plump

Inheritance: 45, X

Molecular: None

Fun Fact: The absence of an X chromosome has very little effect when compared with autosomal monosomy

Klinefelter syndrome (symptoms, inheritance, molecular, fun fact)

Symptoms: Male, low fertility, no significant mental retardation

Inheritance: 47, XXY

Molecular: None

Fun Fact: The excess of an X chromosome has very little effect when compared with autosomal trisomy

XYY (symptoms, inheritance, molecular, fun fact)

Symptoms: Male, no proven antisocial behavior

Inheritance: 47, XYY

Molecular: None

Fun Fact: The excess of a Y chromosome has very little effect when compared with autosomal trisomy

Cri-du-chat syndrome (symptoms, inheritance, molecular, fun fact)

Symptoms: Infants cry sounds like a cat meowing, mental retardation and multiple malformations

Inheritance: Deletion of short arm of chromosome 5

Molecular: None

Fun Fact: Deletions in autosomes have large effects. This is one of the few that is not immediately lethal, and even then it has large impact

In patients with this disorder it was discovered that the urine reacted with ferric chloride to produce a green color, indicating the presence of __________

phenylpyruvic acid

About _______ of the phenylalanine we eat is converted to tyrosine by this reaction; the rest is incorporated into proteins.

2/3

About 1 in every _______ newborns has PKU.

12,000

In almost all cases, PKU is caused by a mutation in a gene for the enzyme ____________, which normally converts phenylalanine to _______.

phenylalanine hydroxylase (PAH), tyrosine

In people with PKU, phenylalanine from dietary proteins cannot be converted to tyrosine and builds up to high levels in the ______ and _______ of the body

blood and tissues

If untreated, newborns with high levels of phenylalanine develop _________, have reflexes that cause their arms and legs to move in a jerky fashion, have epileptic seizures, and never acquire language skills.

severe intellectual disabilities

Because the skin pigment melanin is also a product of the blocked metabolic pathway, most people with PKU usually have ______ hair and skin color than their siblings or other family members.

lighter

The first sign of PKU in newborns is ___________ levels of __________ in the blood and urine

abnormally high

phenylalanine

Infants with PKU develop _______ before birth because the heterozygous mother has enough of the ______ enzyme in her body to break down the excess phenylalanine that accumulates in the fetus during prenatal development.

Normally

PAH

To avoid the consequences of PKU, a well-defined dietary treatment must be started in _________ after birth. After __ days, the brain is damaged beyond repair and treatment is less effective.

the first month

30 days

What is the major struggle with the PKU diet?

PKU is in most protein sources and it is not recommended to eliminate protein from a persons diet. The diet must allow there to be enough phenylalanine for the body to produce enough proteins for normal nervous system development but low enough to prevent intellectual disability.

Newborn homozygotes with genetic goitrous cretinism are unaffected because, during prenatal development, _________ hormones from the mother cross the placenta and promote normal growth. In the weeks after birth, physical development is slow, intellectual disability begins, and the thyroid gland greatly _______

thyroid

enlarges

__________ is an autosomal recessively inherited disorder caused by the inability to break down galactose, one of the two sugars found in lactose

Galactosemia

Galactosemia occurs with a frequency of 1 in ______ births and is caused by mutations in the gene that encodes the enzyme _________ (GALT). When GALT is missing or inactive, galactose metabolism is disrupted, and a compound called galactose-1-phosphate accumulates and reaches toxic levels in the body.

57,000

galactose-1-phosphate uridyl transferase

Unlike PKU, a lifetime dietary treatment for ___________ does not prevent long-term complications.

galactosemia

Like the ABO blood type, galactosemia is an example of a __________. In addition to the normal allele, G, and the recessive mutant allele, g, a third allele known as G^D

multiple allele system

Those with low _____ levels cannot digest lactose in milk and other dairy products.

lactase

Lactose intolerance is not considered a genetic disorder but only a variation in_________

gene expression

The mutation in sickle cell anemia affects the ________ component of hemoglobin

beta globin

The only difference between normal hemoglobin (HbA) and sickle cell hemoglobin (HbS) is the substitution of ________ for another at _______ in the beta chain; this change is the molecular basis of sickle cell anemia

One amino acid

Position 6

Marfan syndrome affects the body’s ___________ and causes visual problems, blood vessel defects, and loose joints.

connective tissue

Like Abraham Lincoln, those with Marfan syndrome are _____ and _____ , with long arms and legs and long, thin fingers.

tall & thin

Marfan syndrome affects males and females with _____ frequency and is found in all ethnic groups, with a frequency of about 1 in _____ individuals

equal

10,000

About _____% of affected individuals appear in families with no previous history of Marfan syndrome, indicating that this gene has a _________.

25%

high mutation rate

The gene responsible for Marfan syndrome, called ____, is located on chromosome ____ and encodes a protein, _______, which is a component of connective tissue

FBN1

15

fibrillin

Cystic fibrosis is a disabling autosomal recessive genetic disorder that affects the glands that produce ________, ____________, and ________

mucus

digestive enzymes

sweat

The most common form of color blindness, known as _______ blindness, affects about __% of the male population in the United States

red-green

8%

A rare form of blue color blindness is inherited as an autosomal ______ condition that maps to chromosome ___.

dominant

7

Muscular dystrophy is a group of inherited diseases characterized by progressive _________ and loss of ________ tissue.

weakness

muscle

The most common form of muscular dystrophy is _____________, which affects 1 in ______ males in the United States.

Duchenne muscular dystrophy

3500

DMD males appear healthy at birth but develop symptoms between ____ and ____ years of age. ______________ is one of the first signs of DMD, and the disease progresses rapidly. Affected individuals are usually confined to wheelchairs by 12 years of age because of muscle degeneration. Death usually occurs by age 20 as a result of _______ or _________.

1 and 6 years

Progressive muscle weakness

respiratory infection

cardiac failure

The DMD gene encodes a protein called _________

dystrophin

Hemophilia, an X-linked recessive disorder, is characterized by defects in the mechanism of _________

blood clotting

This form of hemophilia, called hemophilia A, occurs with a frequency of 1 in _______ males. Because only ______ recessive females can have hemophilia, the frequency in females is much lower—on the order of 1 in 100 million.

10,000

homozygous

Although Tay Sachs is a rare disease in most populations, Ashkenazi Jews have a _____ higher incidence of the disease than members of the general population.

tenfold

In favor of selection, there is indirect evidence that Tay-Sachs heterozygotes may be more resistant to ______, a disease endemic to cities and towns where most European Jews lived in the past

tuberculosis

Only 1 in ______ live births have trisomy 13, and the condition is lethal. _______ of all affected individuals die in the first month.

10,000

Half

The phenotype of ________ includes facial malformations, eye defects, extra fingers or toes, and feet with large protruding heels.

trisomy 13/ patau syndrome

Infants with trisomy ___ are small at birth, grow very slowly, and have intellectual disability.

18

In the United States, Down syndrome occurs in about 1 in _____ live births and is a leading cause of childhood intellectual disability and heart defects

800

Turner syndrome is the only viable monosomy in humans and occurs with a frequency of 1 in _____female births

10,000

Some people associated this disease with aggressive or violent behavior

XYY