Types of Types of MutatioMutatio

nsns

Chromosome Mutations

• May Involve:– Changing the

structure of a chromosome

– The loss or gain of part of a chromosome

– Ultimately they change either a gene or gene dosage

Chromosome Mutations

• Five types exist:–Deletion– Inversion–Translocation–Nondisjunction

–Duplication

Deletion

• Due to breakage• A piece of a

chromosome is lost

Angelman Syndrome• Caused by small

deletion on Ch 15 inherited from mom

• Paternal genes are normally suppressed

• Developmental delay• Happy and excitable• Hand flapping

Inversion

• Chromosome segment breaks off

• Segment flips around backwards

• Segment reattaches

• Usually do not lead to abnormalities

• Lead to decreased fertility

Consequences of Inversions

Duplication

• Occurs when a gene sequence is repeated

Charcot-Marie-Tooth Syndrome• Chr 17 duplication• Inherited• Weakness of foot

and lower leg muscles

• High arches, hammertoes, and other deformities

Translocation

• Involves two chromosomes that aren’t homologous

•Part of one chromosome is transferred to another chromosomes

Philadelphia Translocation

• Individuals develop leukemia

• Part of 8 and 22 go to Ch 9.

• Fusion event leads to misexpression of one gene

• Not inherited!

Philadelphia Chromosome

Translocation

Nondisjunction

•Failure of chromosomes to separate during meiosis

• Causes gamete to have too many or too few chromosomes

Symptoms of Klinefelter Syndrome (XXY)

• breast enlargement

• lack of facial and body hair

• likelihood to be overweight and taller than average males

• Infertile (no sperm)

Chromosome Mutation Animation

Gene Mutations

• Change in the nucleotide sequence of a gene

• May only involve a single nucleotide

• May be due to copying errors, chemicals, viruses, etc.

Point Mutation

• Change of a single nucleotide

• Includes the deletion, insertion, or substitution of ONE nucleotide in a gene

Point Mutation

•Sickle Cell disease is the result of one nucleotide substitution

• Occurs in the hemoglobin gene

Sickle Cell Disease Results from a Base Change in Beta Globin Gene

Figure 12.1

Frameshift Mutation

• Inserting or deleting one or more nucleotides

• Changes the “reading frame” like changing a sentence

•Proteins built incorrectly

Frameshift Mutation

• Original:–The fat cat ate the wee rat.

• Frame Shift (“a” added):– The fat caa tet hew eer at.

Amino Acid Sequence Changed

Gene Mutation Animation

Pedigree Analysis–figure out the

genetic basis of a disease or trait from its inheritance pattern

–predict the risk of disease in future offspring in a family (genetic counseling)

Basic patterns of inheritance

– autosomal, recessive– autosomal, dominant– X-linked, recessive– X-linked, dominant

(very rare)

• Trait is rare in pedigree

• Trait often skips generations (hidden in heterozygous carriers)

• Trait affects males and females equally

Autosomal recessive traits

Autosomal Recessive mutations

Autosomal Dominant

• Trait is common in the pedigree

• Trait is found in every generation

• Affected individuals transmit the trait to ~1/2 of their children (regardless of sex)

Autosomal Dominant

X-linked recessive

• Trait is rare in pedigree

• Trait skips generations

• Affected fathers DO NOT pass to their sons,

• Males are more often affected than females

X-linked recessive

Pedigree Analysis in real life

Remember: •dominant traits may be rare in population

• recessive traits may be common in population

• alleles may come into the pedigree from 2 sources

• mutation happens

• often traits are more complex

• affected by environment & other genes