Duchene\'s muscular dystrophy is an X-linked disease characterized by gradual we

Question

Duchene's muscular dystrophy is an X-linked disease characterized by gradual weakening and wasting of muscle tissue. Usually the disease appears by 6 years of age and the patients are unable to walk by age 12. Death usually results from respiratory failure or infection, when the diaphragm muscles become affected. The gene for Duchene's muscular dystrophy has been cloned, and you are sequencing it to determine the defect. You obtain the following results- the coding stand sequence is shown.

Wild type:

5' CAG CTG CCC GAT TAT AGC GAG 3'

Mutant:

5' CAG CTG T AGC GAG CAA CAT 3'

What is the molecular defect (i.e. mutation) at the DNA level in this disease?

Using the codon chart, determine the amino acid sequence encoded by each gene segment.   For this problem, remember that the sequence above is the coding sequence; in other words, the sequence above is that of the mRNA (with Ts instead of Us).

Wild type:    

Muscular dystrophy:

What is the defect in muscular dystrophy at the protein level?

Explanation / Answer

Duchene's muscular dystrophy (DMD) is caused by a mutation of the dystrophin gene at locus Xp21, located on the short arm of the X chromosome. Dystrophin is responsible for connecting the cytoskeleton of each muscle fiber to the underlying basal lamina of extracellular matrix through a protein complex composed of many subunits. The inability of dystrophin production due to mutation allows excess calcium to penetrate the sarcolemma or muscle cell membrane) resulting in alterations in calcium and signalling pathways.

Wild type: 5' CAG CTG CCC GAT TAT AGC GAG 3'

Mutant:    5' CAG CTG TAG CGA GCA ACAT 3'

Completely different nucleotides occur in mutant compared to wild type gene.

Wild type: 5' CAG CTG CCC GAT TAT AGC GAG 3'

Protein:        Gln   Leu   Pro   Asp Tyr Ser   Glu

Mutant:    5' CAG CTG TAG CGA GCA ACAT 3'

Protein:       Gln   Leu STOP Arg Ala Thr

The stop codon is introduced in between the gene sequence in mutant gene and the nucleotides next to termination codon are entirely different in mutant gene than the wild type gene. Therefore, at protein levels the defect of DMD is described as gene termination inturrpting the sequence and alters the rest of gene with other nucleotides rather than nucleotides that are present in wild type gene.

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