Figure 2.

Genetic variations causing disease

(A) Inherited genomic polymorphisms, which individually do not cause human illness, but when combined result in polygenic disease.

(B) The combination of rare, inherited, disease-causing variants together with common or rare polymorphisms, which by themselves do not cause disease. Jointly they induce a qualitatively different phenotype (phenotype conversion) as compared to the individual disorders themselves. Because the combination (disease 4) would be extremely infrequent it would qualify as hyper-rare disease.

(C) Three acquired chromosomal deletions of different lengths yielding different diseases with most abnormalities being infrequent and with some being extremely rare and belonging to the hyper-rare category. Boxes indicate changes resulting in disease. Letters correspond to different chromosomes. Blue color marks a common variation; red indicates a rare variation; red cross marks genetic abnormality causing disease.