Figure 4.

Clan Genomics, Rare Variants, and Medical Actionability

Above shows the types of conditions that can be influenced by genetic variation and human genome variation. These include chromosomal syndromes as analogized in Figure 1 and genomic disorders delineated and defined in Figure 2. Mendelian disease traits are due to single locus variation while some of complex diseases and multi-factorial traits may result from digenic and oligogenic inheritance or multi-locus pathogenic variation. Below analogizes the concept of a clan genomics whereby rare variants that have arisen recently in the patient, family, or clan are more likely to be the medically actionable variants and provide insight into the genetic influences on disease phenotypes as this variation is tied to disease biology and disease trait manifestation. Figure modified from Lupski et al.¹⁰⁹