Dear Anjani

Disease expression variability may be explained by the effect of genes other than the primary one involved in the disease, and it is these that are usually referred to as modifier genes. Their effect on disease expression may vary from strong effects under a “monogenic-like” model to much milder effects under a “multifactorial-like” model.

Under the monogenic-like model, a single modifier gene exhibits rare fully or almost fully penetrant mutations that explain all or a very important part of the variability in disease expression.

Under the multifactorial-like model, disease expression depends on the effects of several genetic variants located in different modifier genes that, by themselves, only explain a small proportion of the variability but interact both with one another and with environmental factors. These genetic modifiers are in fact very similar to the genetic risk factors involved in complex diseases.

Best Regards

Thank you for the explanation. I understood that genes are secondary factors. Are these genes related only to severity or/ and progression of disease ?