63 Mutations Can Produce New Alleles

Key Idea: A mutation to the gene coding for the connexin 26 protein produces a new allele. The phenotype for the new allele is congenital deafness.

` Recall that mutations can produce new alleles. A single mutation to the gene coding for a protein called connexin 26 produces a new allele. ` If a person inherits two copies of the mutation (one from each parent) they suffer from a form of genetic hearing loss called non-syndromic recessive deafness (NSRD). ` Carriers (individuals with only one copy of the mutated gene) are unaffected. ` The mutation (shown below) involves the deletion of the 35th nucleotide base. It produces a shortened polypeptide chain and results in a protein that does not function correctly.

The image above shows a single connexin 26 protein. Connexin 26 is found in many areas of the body including the inner ear.

1

The gene that codes for the protein connexin 26 is on chromosome 13.

2

Polypeptide formed (amino acid sequence)

Leu Gly Gly Val Asn

28

C T G G G G G G

42

T G T G A A C

Normal DNA sequence The most common mutation in this gene is deletion of the 35th base (guanine (G)). Deleting the guanine changes the code and results in a short chain, which cannot function. The code is read in 3-base sequences called codons. One codon codes for one amino acid.

Connexin 26 polypeptide chains

Six connexin 26 proteins join together. They form a connection called a gap junction between cells which allows molecules, ions and electrical impulses to directly pass between cells. If these proteins are not made correctly, they cannot form the final structure.

3

Polypeptide formed

Leu Gly Val Stop

28

G

Mutation causes a short polypeptide chain

42

C T G G G G G T G T G A A C A

4

Mutated sequence TGA codes for stop

The deletion creates a recessive allele. A person is deaf when they carry two recessive alleles.

1. (a) Identify the type of mutation that produces the connexin 26 mutation:

(b) What phenotype does the connexin 26 mutation produce?

(c) How does the mutation stop connexin 26 from carrying out its biological role?

2. Why has the connexin 26 mutation not been eliminated from the population?