The human β-globin wild-type allele and a certain mutant allele are identical in sequence except for a single base-pair substitution that changes one nucleotide at the end of intron 2. The wild-type and mutant sequences of the affected portion of pre-mRNA are

                   Intron 2                        Exon 3        _
wild type     5′-CCUCCCACAG      CUCCUG-3′
mutant.       5′-CCUCCCACUG      CUCCUG-3′

This is one example of how DNA sequence change occurring somewhere other than in an exon can produce mutation. List other kinds of DNA sequence changes occurring outside exons that can produce mutation. In each case, characterize the kind of change you would expect to see in mutant mRNA or mutant protein.

Key Concepts

Introns and Exons

Introns are non-coding sequences in a gene that are transcribed into pre-mRNA but are removed during RNA splicing, while exons are coding sequences that remain in the mature mRNA. Mutations can occur in introns, potentially affecting splicing and leading to altered mRNA or protein products, even though the mutation is not in the coding region.

Splicing Mutations

Splicing mutations occur when changes in the DNA sequence affect the splicing of pre-mRNA. These mutations can lead to the inclusion of intronic sequences in the final mRNA or the exclusion of essential exonic sequences, resulting in a nonfunctional or dysfunctional protein. Such alterations can significantly impact gene expression and protein function.

Regulatory Elements

Regulatory elements, such as enhancers and silencers, are DNA sequences that control the transcription of nearby genes. Mutations in these regions can disrupt the binding of transcription factors, leading to changes in gene expression levels. This can result in altered mRNA and protein levels, potentially causing phenotypic changes or diseases.