Haploinsufficency in Human Diseases: A Mini-Review

Haploinsufficency (HI) results due to single functional copy of a gene. Heterozygosity may be deleterious in since it can disrupt a balance between various components within a complex or network in critical cellular processes which are sensitive to the dosage of their effectors. Human disease studies have identified several hundred haploinsufficient genes affecting a range of phenotypes such as cancer, asthma, anemia and schizophrenia. They are also implicated as cause of several diseases of organs such as skin, kidney, skeletal and muscular. Their involvement in multi-organ disorders implicates their importance during development. The mechanism affects several key cell signaling pathways. With rapid advancements in sequencing, computational and knock-out methods several HI are now annotated and catalogued in several eukaryotes suggesting their conservation and evolutionary significance. In this mini-review we review the topic of HI with reference to historical aspects of dosage effects, the causes and mechanisms. Further, animal models and laboratory detection methods are briefly reviewed. We elaborate on the genetic, clinical, and pathological implications of the mechanism using few examples. Finally, the potential clinical applications with few future areas of importance are discussed. In summary, the study of HI therefore assumes significance since its spectrum extends to the realm of biophysics, gene expression, chromosome biology, quantitative traits, and evolutionary biology.