MUTATIONS How mistakes are made…

MutationsMutations are defined as “a sudden genetic change in the DNA sequence that affects genetic information”.

They can occur at the molecular level (genes) and change a single gene, or at the chromosome level and affect many genes.

Things that can cause mutations are called “mutagens”.

Known mutagens are ultraviolet light, cigarette smoking, some viruses, certain chemicals like PCB’s.

Mutagens often result in cancer.

Inheritability of Mutations

It depends on where it occursi.Germ mutations – occur in gametes. Inheritable (colorblindness, hemophilia)ii.Somatic mutations – affect body cell, not inheritable (CAN RESULT IN cancer)

Effects of MutationsNot all mutations have effects.Silent mutations - have no effect on the expression of the gene.

Causes for this type of mutation: It is in a non-coding region It does not change the amino acid sequenceThe change does not affect the folding of the

protein

Types of Mutations a) Point Mutations – effects a single gene

i. Substitutionii. Frameshift

a. deletionb. insertions

b) Chromosomal Mutations – most drastic, change in structure or # of chromosomes (affects many genes)

III. Point Mutationsa) Substitution – one base exchanges for another,

affects 1 amino acid(Ex. GCA-TCA GCT-TCA

The Effects of Point Mutations►A point mutation is a change in a single base pair in DNA.

A change in a single nitrogenous base can change the entire structure of a protein because a change in a single amino acid can affect the shape of the protein.

Normal

Point mutation

mRNA

ProteinStop

Stop

mRNA

Protein

Replace G with A

Effects of substitution mutations

Missense mutations – causes a change in the amino acid coded for

Nonsense mutations – causes a stop codon to occur prematurely

Sickle cell anemia

Tay-Sachs

Frameshift Mutations►What would happen if a single base were lost from a

DNA strand?►A mutation in which a single base is added or deleted

from DNA is called a frameshift mutation because it shifts the reading of codons by one base.As a result, every codon after the deleted base would

be different.

mRNA

Protein

Deletion of U

Frameshift – affects several amino acids

-Insertion – 1 base is inserted, affects several amino acids

Ex. (GCA-TCA GCA-GTC-A-Deletion – base is removed,

affects several amino acidsEx. (GCA-TCA GCT-CA

X

Cystic fibrosis

Chromosome mutationsNondisjunction – incomplete chromosome division during meiosis; results in gametes with too many or too few chromosomes. Ex: Down syndrome is caused by an extra #21 chromosome

AneuploidyPolyploidy

Down’s Syndrome•Trisomy 21

•1 in 700 births

•Mental retardation

•Vision problems

•Heart problems

Likelihood of chromosomal mutations

1 in 1700 for mothers under 20.1 in 1400 for mothers between 20 and 30.1 in 750 for mothers between 30 and 35.1 in 16 for mothers over 45.

Sex chromosome disorders – occurs as a result of nondisjunction of the sex chromosomesEx: Turner’s syndrome – X-; Klinefelter’s syndrome – XXY.

Klinefelter’s Syndrome

•XXY

•1 in 1,000

•Usually sterile because of low sperm count

•Tall, sparse body hair

•Suffer from gynecomastia- male breast tissue

•Testosterone treatments

Turner’s Syndrome•XO genotype—Monosomy X

•1 in 2,500 births

•Short, sterile

•75% result in non-disjunction from the father

XYY-Jacob’s Syndrome a.k.a. “Super Males”

• 1 in 1,000 men

•Normal appearance, very tall

•Low IQ, prone to violence

Patau’s Syndrome•1 out of 6,000 births

•Trisomy 13

•80-90% do not survive past 1 yr old

Edward’s Syndrome•Trisomy 18

•Second most common trisomy after down’s syndrome

•Only 5% live to age 1

•1 out of 8,000 births

•Severely retarded, many die from malformed heart

•Polydactyly or syndactyly

Other Chromosomal MutationsAffect many different genesCaused by errors in meiosis or environmental disturbances.

Translocation – occurs when a piece of one chromosome breaks off and attaches to a nonhomologous chromosomeInversion – occurs when a piece of one chromosome breaks off, flips, and reattaches to the same chromosome

Deletion – occurs when a piece of a chromosome breaks off and is lostDuplication – occurs when a segment of a chromosome is repeated

Cri du Chat“Cry of the Cat”

•1 in 50,000 births

•A piece of chromosome 5 is missing

•Severe mental retardation, nonverbal

•Does not run in families