Genes and Genetic Defects

In which we examine normal genetic transmission and genetic defects.

Part 1: Genes

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Genes and DNA A gene is the unit of heredity. A gene contains hereditary information

encoded in the form of DNA, which is located at a specific position on a chromosome.

Genes determine many aspects of anatomy and physiology by controlling the production of proteins.

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Genotype & Phenotype Allele: Any of the alternate forms of a given gene. A

gene is a code that produces a protein. The alternate forms of a gene produce slightly different proteins.

The alleles for blood type are A, B, and O. Genotype: The pair of alleles for a given gene.

The six possible genotypes for blood type are:

AB BB

AA BO

AO AO

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Genotype & Phenotype Phenotype: The physical trait produced by a

genotype.The genotypes for blood type and their phenotypes are:

genotype phenotypeAB ABAA AAO ABB BBO BOO O

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Dominant & Recessive Alleles Dominant: produces the same phenotype

whether it is paired with same or different allele Recessive: produces the same phenotype

only if it is paired with the same allele Codominant: when neither of two alleles

dominate the other

For blood type: A is dominant over OB is dominant over Otherefore, O is recessiveA and B are codominant

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Why do some alleles dominate over others?

A gene contains code for producing a protein. The different alleles for a gene produce slightly

different versions or different amounts of that protein.

Note: some alleles are code that fail to produce the protein. (e.g., hemophilia)

The protein produced by one allele may be stronger than the protein produced by other alleles. The allele producing the stronger protein is dominant.

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Example of proteins The exact color of the human eye is determined by

the amount of a single pigment called melanin that is present in the iris of the eye.

Melanin is a dark brown pigment that is deposited on the front surface of the iris.

If a lot of melanin is present, the eye will appear brown or even black.

If very little melanin is present the iris appears blue. Intermediate amounts of melanin produces gray,

green, hazel or varying shades of brown.

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Some Examples of Dominance

Dominant Recessive

brown eyes gray, green, hazel, blue eyes

gray, green, hazel eyes blue eyes

blue eyes albino (pink) eyes

dark hair blonde hair, light hair

non-red hair red hair

curly hair straight hair

full head of hair baldness

widow’s peak normal hairline

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More Examples

Dominant Recessive

dimples no dimples

unattached ear lobes attached ear lobes

Roman nose straight nose

rolling tongue into a “U” non-rolling tongue

curved thumb straight thumb

curved pinky straight pinky

right handed left handed

hair on fingers hairless fingers

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Heterozygous & Homozygous

Rh factor: a protein found on the surface of red blood cells, which produces an antigenic reaction

There are 2 alleles for the Rh factor: + (produces the protein) and - (does not produce protein)

+ is dominant over -

Genotype:Phenotype:

+ + Homozygous Dominant Rh+- - Homozygous Recessive Rh-+ - Heterozygous Rh+

Part 2: Genetic Defects

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What is a Genetic Disorder?

Genetic disorder: a disorder that is caused by a a faulty allele that programs the body to be built in a maladaptive way.

Hemophilia: normal allele produces proteins that cause the blood to clot; faulty allele does not produce the blood-clotting proteins.

Sickle Cell Anemia: the faulty allele causes a mutation of a blood protein (beta globin), which in turn causes red blood cells to be sickle-shaped, stiff, and sticky, which cause severe organ damage.

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Types of Genetic DisordersGenetic disorders carried on the autosomes

Dominant genetic disorder: A genetic disorder in which the faulty allele is dominant. A person with just one faulty allele will have the disorder.

Recessive genetic disorder: A genetic disorder in which the faulty allele is recessive. Only people with two faulty alleles will have the disorder.

Genetic disorders carried on the X chromosome Sex-linked genetic disorder: The faulty allele is

recessive. A female must have two faulty alleles in order to have the disorder; a male will have the disorder with only one faulty allele.

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Dominant Genetic Disorders Caused by a gene on one of the autosomes, the

faulty allele is dominant. Anyone who has the faulty allele will get the

disorder.

Genotype: Phenotype:D D Homozygous Dominanthas disorderN N Homozygous Recessive

normalN D Heterozygous has disorder

N = normal allele, D = faulty allele

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Examples of Dominant Disorders

Huntington’s Chorea: faulty allele produces an abnormal protein that in middle age begins to destroy brain cells that control movement. (1 in 10,000 births)

Adult Polycystic Kidney Disease: faulty allele results in growth of fluid-filled cysts in kidneys, which replace healthy tissue and eventually cause kidney failure and death.

Neurofibromatosis: faulty allele results in growth of benign tumors on nerve cells throughout body. (1 in 2500 births)

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Example 1: Parents NN & NN

N N

NNN

normalNN

normal

NNN

normalNN

normal

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Example 2: Parents NN & ND

N N

NNN

normalNN

normal

DND

disorderND

disorder

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Example 3: Parents ND & ND

N D

NNN

normalND

disorder

DND

disorderDD

disorder

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Recessive Genetic Disorders Caused by a gene on one of the autosomes, the

faulty allele is recessive. Anyone who has the faulty allele will get the

disorder. Person with one faulty allele will not have

disorder, but will be a carrier.

Genotype: Phenotype:N N Homozygous DominantnormalD D Homozygous Recessive has

disorderN D Heterozygous carrier

N = normal allele, D = faulty allele

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Examples of Recessive Disorders

Sickle Cell Anemia: found in populations descended from Africa. Incidence among African-Americans, 1 in 375 births.

Tay-Sachs Disease: faulty allele does not produce protein needed to break down gangliosides in nerve cells, which accumulate and destroy the nerve. Incidence among Ashkenazi Jews, 1 in 27 are carriers. General population, 1 in 250 are carriers.

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Another Example Phenylketonuria: faulty allele that produces

mutated enzyme, which in turn fails to metabolize phenylalanine, which accumulates in the brain, causing retardation and epilepsy.

PKU test: blood test given to infants shortly after birth to determine if there is abnormally high level of phenylalanine in the blood.

Incidence: U.S. Caucasians, 1 in 8,000. U.S. Blacks: 1 in 50,000.Irish, 1 in 4500. Japanese, 1 in 143,000. Countries with low immigration from Celtic countries have low rates in Phenylketonuria.

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Example 1: Parents NN & NN

N N

NNN

normalNN

normal

NNN

normalNN

normal

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Example 2: Parents NN & ND

N N

NNN

normalNN

normal

DND

carrierND

carrier

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Example 3: Parents ND & ND

N D

NNN

normalND

carrier

DND

carrierDD

disorder

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Example 4: NN & DD

N N

DND

carrierND

carrier

DND

carrierND

carrier

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Sex-Linked Genetic Disorders Caused by a gene on the X chromosome, the

faulty allele is recessive. Males who have the faulty allele in their X

chromosome will have the disorder Females who have the faulty allele on one X

chromosome will be carriers; those who have the faulty allele on both X chromosomes will have the disorder.

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How do we know the faulty allele is on the X chromosome?

Traits on X chromosome

Traits on Y chromosome

29 of 37Besides male sex determining gene, only other trait found on Y chromosome

Come to class to see slide!

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Sex Differences in Sex-Linked Genetic Disorders

Y chromosome only has genes for male sex differentiation (and hairy ears).

Therefore, for all traits on X chromosome, males have only one gene. The single allele of a gene determine phenotype for males:

Genotype: Phenotype:

XNY normal

XDY disorder

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Sex Difference, continued

Females have two X chromosomes. Thus, for all traits on X, females have two genes.

Disorders on X are recessive. Therefore, to have disorder, females must have two faulty alleles. A female with one faulty and one normal allele is a carrier.

Genotype: Phenotype:

XN XN normal

XN XD carrier

XD XD disorder

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Examples of Sex-Linked Disorders

Hemophilia: faulty allele is mutation of blood-clotting gene. Persons with disorder have blood that clots very slow or does not clot at all. Incidence: 1 in 4000 males, 1 in 16,000,000 females.

Duchenne Muscular Dystrophy: faulty allele fails to produce muscle protein, dystrophin, the lack of which causes muscle cells to die. 70% of cases are inherited, 30% are spontaneous mutations. Incidence: 1 in 3500 males, 1 in 12,500,000 females (theoretical).

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Example 1: XNXN & XNY

XN Y

XN X

N X

N

normalX

N Y

normal

XN X

N X

N

normalX

N Y

normal

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Example 2: XNXD & XNY

XN Y

XN X

N X

N

normalX

N Y

normal

XD X

N X

D

carrierX

DY

disorder

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Example 3: XNXN & XDY

XD Y

XN X

N X

D

carrierX

N Y

normal

XN X

N X

D

carrierX

NY

normal

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Example 4: XNXD & XDY

XD Y

XN X

N X

D

carrierX

N Y

normal

XD X

D X

D

disorderX

DY

disorder

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Chromosomal Abnormalities vs. Genetic Defects

Genetic DefectsChromosomal Abnormalities

correct number of genes

too many or too few chromosomes

Number of units

faulty allele is abnormal

chromosomes are normal

Normalcy of units

one direct symptom (may be many indirect)

many symptomsNumber of symptoms directly caused