Every one of us is carrying hundreds of broken genes - and the number is rapidly increasing
Excerpt: "Genetic variants predicted to severely disrupt protein-coding genes, collectively known as loss-of-function (LoF) variants, are of considerable scientific and clinical interest. Traditionally such variants have been regarded as rare and having a high probability of being deleterious, on the basis of their well-established causal roles in severe Mendelian diseases such as cystic fibrosis and Duchenne muscular dystrophy. However, recent studies examining the complete genomes of apparently healthy subjects have suggested that such individuals carry at least 200 and perhaps as many as 800 predicted LoF variants. These numbers imply a previously unappreciated robustness of the human genome to gene-disrupting mutations, and have important implications for the clinical interpretation of human genome sequencing data."
Excerpt: "The immune system is a sophisticated biological system dedicated to fight against foreign antigens, distinguish self from non-self-antigens and eliminate cells that are not growing properly. Consequently, organisms are protected from potentially damaging microorganisms and from infected or abnormally growing cells. The immune system is also designed to tolerate self-antigens and non-pathogenic microorganisms such as commensal microbiota. This concept is referred to as immune tolerance, which involves apoptosis of self-antigen-specific lymphocytes. This process can also be altered by specific genetic defects of the immune system. In consequence, inborn errors of immunity (IEI) or primary immunodeficiency disorders (PIDD) may drive increased susceptibility to infection, autoinflammation, autoimmunity, malignancy or allergy. They are caused by mutations that result in loss (LOF) or gain of function (GOF) of key molecules participating in the immune response. To date, defects in more than 450 genes have been described to cause different IEI phenotypes. These phenotypes are very heterogeneous including: antibody deficiency, T and B lymphocyte deficiency, complement deficiency, autoimmunity, lymphoproliferative syndromes or immune dysregulation. In some cases, immunodeficiency may concur with autoimmunity and/or immune dysregulation, especially when genetic defects compromise molecules that regulate the immune response or are involved in tolerance. Although IEI are considered rare diseases and defects in individual genes may be infrequent; collectively, they can affect a considerable number of individuals."
"The current version of DisGeNET (v7.0) contains 1,134,942 gene-disease associations (GDAs)
(My comment: This number is an update made on Jan. 2021, next update will increase that number close to two million), between 21,671 genes and 30,170 diseases, disorders, traits, and clinical or abnormal human phenotypes, and 369,554 variant-disease associations (VDAs), between 194,515 variants and 14,155 diseases, traits, and phenotypes."
Summary and conclusion:
- Every healthy individual is carrying at least 200 and possibly even 800 genetic defects that are considered as reasons for loss of function variants = broken genes.
- Many LOF (loss of function) genes are directly associated with severe genetic diseases.
- LOF variants have a strong association with a weakened immune system.
- Gain of function variants are also linked to genetic diseases.
- The number of harmful mutations in human genome is growing by rate of 1.5 every year.
- It's very difficult to discover random, fully beneficial DNA mutations.
- Human genome is rapidly deteriorating.
- Evolution is not happening.
