45. Molecular diseases. Mutations as a reason for the development of molecular diseases. Consequences from the existence of point mutations that affect enzymes of the pathway for synthesis of hemoglobin. Defects that affect enzyme activities. Molecular diseases due to defects in the DNA repair mechanisms.

Introduction

Molecular diseases are caused by a change in a gene or in the protein it encodes. Most often the change is a mutation in the DNA sequence that alters a protein's structure, amount or regulation. This topic links the general types of mutation with their consequences for haemoglobin synthesis and enzyme activity, and with defects in DNA repair.

Mutations as the cause of molecular disease

• A mutation is a change in the DNA sequence. It can be inherited (germline) or acquired in a single cell (somatic).
• Point mutations are base substitutions. Missense mutations change one amino acid, nonsense mutations create a stop codon, and silent mutations change the codon without changing the amino acid.
• Small insertions and deletions cause frameshifts when their length is not a multiple of three. Splice-site and promoter mutations alter the processing or amount of transcripts, and expansions of trinucleotide repeats cause some neurological disease.
• Consequences depend on the protein. A mutation may cause loss of function (often recessive, because one normal allele is usually enough), gain of function, a dominant-negative effect in which the mutant subunit disrupts a multimeric complex, or altered regulation.
• The same gene can cause different diseases depending on where and how it is altered.