Question

Many genetic diseases are caused by mutations in a gene and often, it is a single nucleotide polymorphism (SNP) that has dramatic consequences (e.g. the E6V hemoglobin mutation in sickle cell disease). Other diseases are the result of multiple mutations, that have occurred within various genes (often in cancer).

My question is, are there also many (or any?) known diseases that only manifest if two or more particular mutations arise in the same gene? My assumption is that they exist, but are rather rare; an ideal answer would point me to a publication with quantitative data: how many known diseases are caused by a single mutation, how many by double, etc.

Regarding alleles: I am not asking whether mutations have to occur homozygously to manifest; I'm talking about mutations in the same copy of the gene; for coding sequences, we would be talking about a double (triple,...) mutant of a protein.

Answer 1

Diseases can manifest from multiple mutations within the same gene, known as complex allelic disorders, although such cases are less common than those arising from a single mutation. Examples of diseases caused by single mutations include cystic fibrosis and sickle cell disease. The exact numbers of diseases caused by different mutation patterns are not easily quantifiable due to variability and ongoing research.

Step-by-step explanation:

Yes, there are diseases that only manifest if two or more particular mutations arise in the same gene, though these cases may be less common than those caused by a single mutation. An example of such a disease would be complex allelic disorders, where multiple mutations within the same gene lead to a disease phenotype. These can contrast with diseases caused by a single mutation, like sickle cell disease, which results from an E6V hemoglobin mutation. Complex allelic disorders may require specific combinations of mutations to generate the disease phenotype and are often the result of intricate interactions between multiple variants in the same gene.

The number of diseases caused by single vs. multiple mutations may not be easily quantifiable as it varies widely and is subject to ongoing research. Autosomal recessive disorders such as cystic fibrosis are also often the result of mutations in a single gene, though two copies of the mutated gene (one inherited from each parent) are typically necessary for the disease to manifest. Yes, there are known diseases that only manifest if two or more particular mutations arise in the same gene. These diseases are generally rare and are caused by mutations that affect the same copy of the gene. One example of a disease caused by multiple mutations in the same gene is retinitis pigmentosa, which is a group of genetic disorders that lead to the progressive degeneration of the retina. An article published in the journal 'Human Molecular Genetics' titled 'The genetics and genomics of retinitis pigmentosa' provides detailed information about the disease and the genetic mutations associated with it.