Medical Perspectives: Recombination

Recombination is met both on the patient and pathogen sides. Homologous recombination during meiosis is responsible for generating much of human genetic diversity. In the future it will have a key role in gene therapy. It is also the foundation that permits positional cloning of disease-associated genes. In contrast, normally functioning homologous recombination can lead to gene conversion and loss of heterozygosity (LOH) - a process associated with tumor progression. Inborn errors in BRCA1 and BRCA2, components of the homologous recombination machinery lead to increased rates of some cancers, notably breast cancer and prostate cancer.

Mutations in RAG1 or RAG2 prevent Ig site-specific recombination and the generation of antibody diversity. Such people have an essentially non-functional adaptive immune system, making them profoundly susceptible to infection (the bubble boy). On the other side, the pathogen Salmonella uses site-specific recombination to change its surface appearance, thus evading recognition by the adaptive immune system.

Retrotransposons are one of the major mutagens acting on the human genome - and the damage cannot be fixed by any repair pathway! They are therefore one of the most active agents changing the content of the human genome. On the pathogen side, DNA transposons often carry antibiotic resistance genes and their ‘jumping’ frequently disperses antibiotic resistance genes among different bacterial strains.