MUTATIONS

What is a Mutation?

• A change in DNA

• Mutations are NOT

Teenage Mutant Ninja

Turtles or XMen!!!

• We are all mutants –

products of the mutations

in all of our ancestors before us

How Do Mutations Occur?

• During DNA replication when bases are substituted, deleted, or added

• During mitosis and/or meiosis when chromosomes don’t divide properly

• During crossing over when chromatids “get lost” instead of being incorporated into its homolog’s DNA

• Aging causes mutations when segments of DNA are degraded (telomeres)

• Exposure to chemicals in the environment called mutagens (such as UV radiation, Xrays, some food dyes)

Somatic vs. Germ Cell Mutations

• Somatic mutations affect cells of the body, such as skin, muscle, etc.

• Somatic mutations can not be passed to offspring

• Germ cells are cells that divide to make gametes

• Germ cell mutations are passed to offspring

Example of Germ Cell Mutation

• Queen Victoria had a germ cell mutation in cells that made her oocytes

• The mutation was in a gene that makes a protein for blood to clot

• She passed this mutation on to some of her children and they had hemophilia

• Gamete cells mutations can result in genetic disorders.

• If the parent survives with the disorder, it can be passed to another generation.

Example of Somatic Mutation

• UV radiation from the sun can mutate DNA in skin cells and cause cancer

• That cancer is not inherited

Gene vs. Chromosome Mutations

• Gene mutations affect one gene and therefore one protein (or polypeptide)

• Chromosome mutations affect a large part of a chromosome and all of the genes on that section of chromosome

Gene Mutations

• Can occur during DNA replication

• They are often point mutations, which affect a small number of bases or sometimes just one base pair

Types of Point Mutations

• Insertion (Addition)–one (or a few) bases is (are) inserted

• Deletion – one (or a few) base is (are) deleted

• Substitution – one base is substituted with another one

Deletion and Insertion Mutations Can Cause a Frameshift

Sickle Cell

• The mutation is in the gene for hemoglobin

• Malformed hemoglobin molecules cause red blood cells to “sickle”

• Red blood cells cause blood clots, which damage the kidneys and liver

• Severity varies from person to person

• Shortened life span (45 years is average)

• Pain due to blood clots

• Fatigue from lack of oxygen

Sickle Cell is Found in Certain Ancestral Groups

• Sickle cell evolved as a protection against malaria

• People with one sickle cell gene and one healthy gene don’t have sickle cell or get malaria!

Tay-Sachs• Children appear healthy at birth, but do

not progress as other children

• Child will stop smiling, sitting up, etc.

• Blindness and eventually complete paralysis

• Usually results in death by age 5

• There is no cure• Mutation in a gene for an enzyme that

processes lipids in the brain (Hex A)• The brain swells, crushing and killing

parts of the brain• Mutation occurred in central and

eastern Europe• Caused by a substitution mutation or a

deletion mutation

Cystic Fibrosis• Deletion in a transport protein that allows Cl-

to enter and exit cells • Causes thick mucus to build up in lungs,

which causes repeated lung infections• Mucus clogs up pancreatic duct so food isn’t

digested• Mucus causes intestinal blockage

• Breathing treatments can loosen mucus in lungs to increase lung function and decrease chance of infection

• Treated with antibiotics for

infections

• Use oral enzymes to digest food

(increase in food intake to make

up for undigested food)

The mutation is found here on chromosome 7

• CF occurs in all ancestral backgrounds and is the most common fatal genetic disorder (about 1 in every 20 people carries the gene)

• Severity of disease varies from person to person and they die from a respiratory infection or lung failure

Huntington’s• Named after

Dr. George Huntington

who first described it• Caused by an insertion

mutation (CAG is

repeated)

Nancy Wexler

• Causes jerky and uncontrolled movements

• Slurred speech

• Loss of memory

• Symptoms progress and get worse with time; caused by degeneration of nerve cells

• Symptoms usually appear between the ages of 35-40, but can be earlier

• Found in all major ethic groups

• Death is usually from pneumonia or choking

• Can live 10-20 years after the onset of the symptoms; some die earlier

Albinism

• Mutation in one

of the genes for

producing melanin

which gives hair,

skin, and eyes

their color

• Albinos often

have vision defects

Nondisjunction Mutations (Type of Chromosome Mutation)

• Occur when chromosomes fail to separate during meiosis

• Results in a cell with an extra chromosome or a chromosome missing

• The person wouldn’t have 46 chromosomes, but 45 or 47

An Example of a Nondisjunction MutationDown’s

• Named after Dr. Down that first described it

• Caused by 3 copies of the 21st chromosome (trisomy 21)

• Causes heart defects, mental retardation, unclear speech, rounded face, almond shaped eyes, poor muscle tone, fold in the eyelid

Notice the 3 21st chromosomes

Another Example of NondisjunctionKlinefelter’s

• An extra X chromosome (XXY) in males

• Usually sterile, some have enlarged breasts, delayed learning, may be tall and thin, symptoms vary and may be undetectable

Notice the 3 sex chromosomes

How Klinefelter’s Occurs

And Another Example of NondisjunctionTurner’s

• Have 1 X chromosome (XO) - females• About 98% of fetuses with Turner’s are

spontaneously aborted (miscarried)• Short, swelling of hands and feet, sterile,

and other symptoms vary from person to person