Why are most identified human genetic diseases rare?

Sourav PanNovember 8, 2024

Answered

Most identified human genetic diseases are considered rare due to several factors related to their genetic origins, inheritance patterns, and the overall population dynamics. Here’s an overview of why these diseases are classified as rare:

Genetic Basis of Rare Diseases

1. Single-Gene Mutations: A significant proportion of rare diseases, estimated at 71.9%, are genetic in origin, often caused by mutations in a single gene. These mutations can lead to conditions such as cystic fibrosis or Huntington’s disease, which affect a relatively small number of individuals compared to more common diseases.
2. Sporadic Mutations: Many rare genetic diseases arise from sporadic or de novo mutations that occur in the germ cells (sperm or egg) of unaffected parents. This means that even if a disease is genetic, it may not be inherited from parents but rather occur as a new mutation in the offspring. For example, approximately one-quarter of cases of Marfan syndrome result from such spontaneous mutations .
3. Inheritance Patterns: The inheritance patterns of many genetic diseases contribute to their rarity:
   • Autosomal Recessive Disorders: These require two copies of the mutant allele for the disease to manifest, making it less likely for the disease to appear in the population unless both parents are carriers .
   • X-Linked Disorders: Many X-linked recessive disorders primarily affect males, as they have only one X chromosome. Females can be carriers without expressing the disease unless they inherit two copies of the recessive allele . This gender bias further limits the prevalence of these conditions.

Population Dynamics

1. Low Prevalence Rates: A disease is often classified as rare if it affects fewer than 200,000 people in the United States or has a prevalence of less than 1 in 2,000 individuals globally. With over 6,000 known rare diseases and many more being described, the low prevalence rates contribute to their classification as rare.
2. Diverse Genetic Disorders: The vast number of distinct genetic disorders means that while each individual disorder may be rare, collectively they affect a significant portion of the population. For instance, around 1 in 21 people may be affected by some form of genetic disorder classified as “rare”.
3. Underdiagnosis and Misdiagnosis: Many individuals with rare genetic conditions may go undiagnosed or misdiagnosed due to a lack of awareness among healthcare providers or insufficient access to genetic testing. This can lead to an underestimation of the prevalence of these diseases