Human Genetic Disorders and Genetic Abnormalities

Autosomes

• 22 pairs of matching homologous chromosomes

• (2 chromosomes in a homologous pair look exactly alike.)

Dominant Autosomal Heredity

• Simple dominant traits: free earlobes, tongue rolling, curly hair, long eyelashes, dimple, chin cleft, freckles, Widow’s peak, Polydactyly (having more than 5 fingers or toes).

* Dominant traits are always expressed in a person’s phenotype.

• Ex. Huntington’s disease

Huntington’s Disease

• Lethal genetic disorder caused by rare autosomal dominant allele (causes death)

• Dominant allele on chromosome 4 is the culprit

• deterioration of nervous system, particularly the brain

• results in uncontrolled, jerky movements of head and limbs

• no effective treatment• occurs between ages of 30 and

50• Mutation causing the disorder

changes a protein necessary for normal development of brain cells (called an expansion mutation-multiple repeats in the same DNA fragment)

Achondroplasia• Form of dwarfism• Inherited as an autosomal dominant

disorder• Affects approximately 1 in 10,000

people• Skeletal cartilage does not form

properly• Have abnormally short arms & legs

relative to other body parts

Hutchinson-Gilford progeria syndrome

• Mutation that disrupts interactions among genes that bring about growth and development

• Observable appearances start before age 2 – skin starts to thin, skeletal muscles weaken, hair loss is pronounced

• There are no documented cases of progeria running in families, so they suspect it arises from spontaneous mutations. Probably the mutated gene is dominant over a normal allele on the homologous chromosome

• Most die in their early teens from strokes or heart attacks

Dyslexia

• People see and write letters or parts of words backward

Recessive Autosomal Heredity

• Simple recessive traits: attached earlobes, straight hair, non-tongue roller, short eyelashes, no dimples

• Most genetic disorders are caused by recessive alleles.

Galactosemia• Inherited as a recessive

autosomal allele• About 1 in 100,000 newborns are

homozygous for the recessive allele

• Do not have working copies of one of the enzymes that digest lactose (See page 174)

• High galactose levels causes malnutrition, diarrhea, vomiting, and damages to the eyes, liver, and brain

• When untreated, galactosemics die early. If placed quickly on a restricted diet excluding dairy products, they grow up symptom free

Ex. Cystic fibrosis• most common lethal genetic

disorder among White Americans

• gene for this is located on region of chromosome 7

• Mucus accumulates in digestive tract and in lungs; breathing is difficult, thickened mucus slows secretion of digestive enzymes, so food cannot be digested properly.

• Treatments: Physical therapy, special diet, and new drug therapies

Ex. Sickle cell anemia – inherited as autosomal recessive trait

• most common in black Americans whose families originated in Africa and white Americans whose families originated in countries surrounding Mediterranean Sea

• Red blood cells are shaped like a sickle (half moon), not round

• Life span of sickled cells is shorter, therefore affected person suffers from anemia

• Clog small blood vessels causing tissue damage and deprivation of oxygen and nutrients

• Treatments: Blood transfusion and drug therapy

Ex. Tay Sachs: autosomal recessive disorder

• Affects on central nervous system • Recessive allele results in

absence of enzymes that normally breaks down a lipid produced and stored in tissues of central nervous system, therefore lipid accumulates in the brain.

• Results in blindness, loss of movement, mental deterioration

• Symptoms begin within 1st year of life.

• Results in death before age 5.• Allele is common among

Pennsylvania Dutch people and Ashkenazie Jewish people.

Ex. Phenylketonuria (PKU)

• Results from absence of enzymes that converts amino acids, phenylalanine, to tyrosine.

• Phenylalanine accumulates in body and damages central nervous system.

• Tests are given at birth –so infants affected by PKU are given a diet low in phenylalanine until brains are fully developed

Ex. Albinism

• Have no skin pigment.• Have very pale skin and white-

blonde hair• Affects all races

X-Linked Inheritance

• X-linked gene is found only on the X chromosome

• Examples: Colorblindness Hemophilia

Colorblindness

• Inability to distinguish among some or all colors

• Mutant forms of the X-linked genes change the light-absorbing capacity of sensory receptors inside the eyes

• Normally, humans can detect differences among 150 colors. One with red-green colorblindness sees fewer than 25 colors

Hemophilia

• Blood-clotting disorder• About 1 in 7,000 males are

affected• Treatments: Plasma, gene

cloning, Factor VIII drugs

MISTAKES IN MEIOSIS (Genetic Disorders)

• During meiosis, sister chromatids are to pull apart from each other. If they do not pull apart, you have an extra chromosome or a missing chromosome.

Aneuploidy – cells usually have one extra or one less chromosome

Autosomal aneuploidy is usually fatal form humans and is linked to most miscarriages.

Polyploidy

• Cells have 3 or more of each type of chromosome

• Half of all species of flowering plants, some species of insects, fish & other animals are polyploid

Nondisjunction

• Nearly all changes in chromosome number arise through nondisjunction whereby homologous chromosomes fail to separate properly

• Can be trisomic (3 of one type of chromosome and 2 of every other type)

• Can be monosomic – lacking a chromosome

Trisomy

• Have three of an autosome, instead of 2

• have 47 chromosomes

Examples:

• Down syndrome – Trisomy 21(extra chromosome 21)

• Only autosomal trisomy in which affected individuals survive to adulthood.

• 95% of all cases arise through nondisjunction at meiosis

• Occurs once in every 800 to 1000 births

• Affects more than 350,000 people in the U.S.

• Affected individuals have upward-slanting eyes, somewhat flattened facial features, fold of skin that

starts at the inner corner of each eye, have moderate to severe mental impairment and heart defects, skeleton develops abnormally, muscles and reflexes are weak, speech & other motor skills develop slowly

Klinefelter’s syndrome

• affects 1/500 males • Genotype is XXY• Sterile (Sperm count is low)• Taller than average, tend to be

overweight• Exhibit some degree of mental

retardation

• Testes and prostate gland are smaller than average

• They make less testosterone & more estrogen than normal males, with feminizing effects

• Hair is sparse, voice is high pitched, & the breasts are a bit enlarged

• Testosterone injections starting at puberty can reverse the feminized effects

XYY– affects 1/1000 males

• During anaphase II, 2 Y chromatids fail to separate and sperm cell containing 2 Y chromosomes is formed

• Normal intelligence• Fertile• Taller than average

XXX Syndrome

• Occurs at a frequency of 1 in 1000 live births

• Adults are fertile• Have slight learning difficulties

Monosomy• About 1 in 2500 to 10,000

newborn girls are XO• Lack a chromosome• Example: Turner’s syndrome• Genotype is XO• Lack functional ovaries and sex

characteristics are not fully developed

• Sterile• At least 98% XO embryos may

spontaneously abort early in pregnancy.

• Only 4’8’’ tall

Karyotype

• Chart of chromosome pairs used to identify an aneuploidy (photograph of all an organism’s chromosomes)

• Metaphase chromosomes are photographed and chromosome pictures are enlarged, cut apart, and arranged in pairs on a chart according to length and location of centromere.

• Allows researchers to study differences in chromosome shape, structure, and size.

Karyotype