Mutations

When something goes wrong…

Causes of Mutations

• Mutations are caused by changes in the nucleotide sequence of DNA (A, T, C, G) or of a gene (specific area of a chromosome)

• This can occur:– During DNA replication– During cell division– After cell division

Mutations Types• Germ-Cell Mutations

– Occur in an organism’s sex cells– Do not affect the organism itself but may

be passed to offspring• Somatic-Cell Mutations

– Take place in an organisms body cells and can affect the organism

– Cannot be inherited• Lethal Mutations

– Cause death, often before birth

Gene Mutations

Gene Mutations• Point mutations affect a single nucleotide

• Base pair substitutions switches a nucleotide– Silent mutation

• Does not change the amino acid– Missence mutation

• Change of a single amino acid– Nonsense mutation

• Changes amino acid to stop codon– Neutral mutation

• Changes amino acid to chemical similar amino acid

Gene Mutations• Frameshift Mutation

– Change in reading frame due to adding or deleting a nucleotide

AAT TGC CCG ACT TTT CGC CAT• Add A after 2nd nucleotide

AAAA TTG CCC GAC TTT TCG CCA T

Chromosomal

Mutations

Chromosomal Mutations• These mutations can be detected by karyotyping

– Nondisjunction• Homologous chromosomes or chromatids don’t split in

division– Deletion

• Loss of a piece of chromosome due to breakage– Duplication

• Portion of the chromosome can be duplicated– Inversion

• Part breaks off, then reattaches in reverse position– Translocation

• Part breaks off, reattaches to a non-homologous chromosomes

– Insertion• Extra DNA is inserted into a non-homologous chromosome

Effects of Mutations• Always result in changes to genotype

(DNA) but not always phenotype (what you see!)

– Neutral• No effect

– Beneficial• Enhances fitness

– Deleterious• Decreases fitness

Cystic Fibrosis

Cystic Fibrosis• Genetic disorder affecting the respiratory and

digestive system caused by defective gene on Chromosome 7– 1000 different mutations in this gene have been

identified– Most often caused by deletion of a single amino acid

• Body produces a mucous that clogs the airways and increases risks of infection

• Both parents must pass on the gene to their children– More than 10 million Americans carry the gene and

don’t know it• About 2,500 babies are born with cystic fibrosis

in the U.S. each year.

Turner Syndrome

Turner Syndrome• Caused by missing or incomplete X chromosome

often due to non-disjunction• Women with Turner syndrome are usually sterile

and cannot have children• Short in stature, stocky appearance, arms that turn

out slightly at the elbow, receding jaw line, short webbed neck, and low hairline

• Affects 60,000 females in the United States. This disorder is seen in 1 of every 2000 to 2500 babies born, with about 800 new cases diagnosed each year

• In 75-80% of cases, the single X chromosome comes from the mother's egg; the father's sperm that fertilizes the egg is missing its sex chromosome

Klinefelter Syndrome

Klinefelter Syndrome• Caused by an extra X chromosome (XXY) in

males due to by nondisjuction• Males are often tall and don’t develop secondary

sex characteristics (facial hair, underarm hair, etc)

• Often not diagnosed until puberty (less muscular body, more breast tissue, less hair) or when men try to have children due to sterility

• Treated with hormone replacement therapy – testosterone injections

• Klinefelter syndrome is one of the most common genetic abnormalities. It affects between 1 in 500 and 1 in 1,000 males.

Sickle Cell Disease

Sickle Cell Disease• Mutation on a gene on chromosome 11 that codes for the

shape• Blood cells get stuck in the blood vessels and cannot

transport oxygen, resulting in pain and damage to organs, leading to low red blood cell counts

• Both parents must pas a defective gene to their children• Daily penicillin to prevent infections, folic acid to build

new cells, blood transfusions, bone marrow transplant• Unlike normal red blood cells, which can live for 120

days, sickle-shaped cells live only 10 to 20 days.• In the United States, the disease most commonly affects

African-Americans. About 1 out of every 500 African-American babies born in the United States has sickle cell anemia