Mutations and polymorphisms

lecture 4

What is an endogenous mutation?

mutation that occurs during replication and/or repair

What is a silent mutation?

a mutation that does not change the function of the resulting polypeptide

What hypothesis explains silent mutations?

the wobble hypothesis → the third base in a codon “wobbles” or can have multiple variations in which the same amino acid is produced

What are the physiological consequences of a silent mutation?

usually none

What is the loss of heterozygosity?

When an individual inherits a susceptible gene, but then a second mutation kicks that susceptible gene into a diseased gene

ex. cancer susceptibility genes turns into actual cancer

What is a missense mutation?

When another amino acid is produced in a polypeptide

What are the two kinds of missense mutations?

1. conservative: Asp → Glu

2. nonconservative: Arg → Gly

What is a nonsense mutation?

When a base indel creates a STOP codon, makes truncated proteins

What is a frameshift mutation?

When a base indel shifts the entire frame of a polypeptide, usually making a completely different protein with dysfx/nonfx

What is a restriction fragment length polymorphism (RFLP)?

When there is a mutation in a restriction site in which an endonuclease uses to detect areas of sequence to cut

• if a site is missed, only one side might be cut, and a longer fragment is created

How do we detect RFLP?

southern blots

What is VNTR?

variable number of tandem repeats

What are minisatellites in relation to VNTR?

10-60 bp repeats (short tandem repeats)

What are microsatellites in relation to VNTR?

<10 bp repeats

What is a trinucleotide repeat?

specific short tandem repeats that are three nucleotides long

What are some trinucleotide repeat disorders?

Friedrich’s ataxia, Fragile X syndrome, Huntington’s disease

What is the trinucleotide repeat of Friedrich’s ataxia? What are the symptoms?

GAA

symptoms: lack of muscle coordination, heart issues

What is the trinucleotide repeat of Fragile X? What are the symptoms?

CGG

symptoms: excess protein formation, mental disability in males

What is the trinucleotide repeat of Huntington’s? What are the symptoms?

CAG

symptoms: neurodegenerative disease

What is genomic imprinting?

the differential activation of genes (uniparental disomy)

What is angelmen syndrome?

The deletion of maternal chromosome 15

symptoms: congenital mental disability, muscular abnormality, uncontrolled laughing

What is Prader-Willi syndrome?

The deletion of paternal chromosome 15

symptoms: insatiable appetite, obesity, mental disability