Human Genetic Mutations

• Mutations are a result in a change in DNA sequence

– A protein with a different AA sequence could be produced.

– Germ Cell - If mutations occur in sex cells they may be passed on to the next generation.

– Somatic- A mutation occurring only in body cells may be a problem for the individual but will not be passed on to the offspring.

• Mutations may be classified as chromosomal alterations or gene mutations

– Chromosomal alterations are generally more severe because many genes are usually involved.

2 Main Types of Mutations

1.) Chromosomal Mutations

2.) Gene Mutations

Chromosomal Mutations

• Any change in the structure or number of chromosomes

• Large scale: Affect many genes

Gene Mutations

• Small scale: one gene is affected

• Any change to the DNA sequence of a gene:

Nucleotides/Bases may be added, missing, or changed

Significance of MutationsSignificance of Mutations• Most are neutral

• Eye color• Birth marks

• Some are harmful• Cystic Fibrosis• Down Syndrome

• Some are beneficial• Sickle Cell Anemia to Malaria• Immunity to HIV

What Causes Mutations?What Causes Mutations? There are two ways in which DNA can

become mutated:– Mutations can be inherited.

Parent to child– Mutations can be acquired.

Environmental damageMistakes when DNA is copied

5 Types

1. Deletion

2. Duplication

3. Inversion 1. Pericentric

2. Paracentric

4. Translocation

5. NonDisjunction

Chromosomal Deletion

One or more genes are removed

Causes: Wolf-Hirschhorn syndrome (severe mental retardation)

cri du chat syndrome (mewing sounds, mental retardation)

Chromosomal Duplication

A segment of genes is copied twice and added to the chromosome

Causes: Charcot–Marie–Tooth disease

(high arched foot, claw feet, confined to a wheelchair)

Chromosomal Inversion

a segment of genes flip end-to-end on the chromosomeCauses:

Four-Ring Syndrome(cleft pallate, club feet, testes don’t descend)

Chromosomal Translocation

Material is swapped with another chromosome

Causes: Burkitt’s Lymphoma

(cancer of the lymph nodes, in children)

Nondisjunction

• Chromosomes FAIL TO SEPARATE during meiosis

• Meiosis I Nondisjunction• Meiosis II Nondisjunction

Nondisjunction• Produces gametes (and therefore a

baby) with one missing chromosome or one extra chromosome

KEY POINT #1

Too much or too little DNA is bad!

Gene Mutations: 2 Types

Point Mutation Frameshift Mutation

• Point mutation

• Only one nucleotide changes, but it makes a different protein

Point Mutation

• One base (A, T, C, or G) is substituted for another

• 3 Possible Consequences:

– nonsense mutations: code for a stop, which can translate the protein

– missense mutations: code for a different amino acid

– silent mutations: code for the same amino acid

Gene MutationsGene Mutations Point Mutations – changes in one

or a few nucleotides– Substitution

THE FAT CAT ATE THE RAT THE FAT HAT ATE THE RAT

– Insertion THE FAT CAT ATE THE RAT THE FAT CAT XLW ATE THE

RAT– Deletion

THE FAT CAT ATE THE RAT THE FAT ATE THE RAT

Frameshift Mutation

• One or more bases (A, T, C, or G) are added or deleted

• Caused by: – Insertion: adding a base

– Deletion: removing a base

• Frameshift • Causes every codon in the DNA sequence to be changed after the

mutation:• Insertion- one or more bases are added• Deletion- one or more bases are removed

A

Causes of Mutations

• spontaneous

• occur during DNA replication

• Caused by MUTAGENS• physical, ex: radiation from UV rays, X-rays or

extreme heat • or chemical (molecules that misplace base pairs or

disrupt the helical shape of DNA).

Gene Mutations

• KEY IDEA: A mutated gene will make a mutated protein

• Mutant proteins are trouble!–They do not go where they are

supposed to go

–They do not do what they are supposed to do

KEY POINT #2

Mutation of a gene = Mutant protein

Dysfunctional proteins cause the symptoms of the disorder

Length of Telomeres

Telomeres are structures at the ends of chromosomes that shorten with each cell division. After 50 divisions, the shortened length of telomeres causes mitosis to stop.

telomeres telomeres