Tracing a disease gene through a family tree

Family tree or pedigree showing the inheritance of the mutant gene causing arterial calcification due to deficiency of CD73 (ACDC). Squares are males, and circles are females. Horizontal lines connecting a male and female are matings. Vertical lines connect a mating pair to its offspring. Roman numerals designate generations; Arabic numerals designate individuals within generations. Half-filled squares or circles indicate an individual carrying one copy of the mutant gene. Filled squares or circles indicate an individual with two copies of the mutant gene and who have the ACDC disease. Either individual I-1 or I-2 must have carried the mutant gene, but which one carried it is uncertain as indicated by the “?”. Blue arrow indicates Louise Benge. Red arrows show the path of the mutant gene through the generations.

[Data from C. St. Hilaire et al., New England Journal of Medicine 364, 2011, 432-442]