Chromosome-wide linkage analysis found that moyamoya disease locus resides in chromosome 17q25.[6] Genome-wide linkage analysis of 15 Japanese families of autosomal dominant moyamoya disease narrowed down the locus to 17q25.3.[7] Direct sequencing of the region and whole-exome sequencing identified the p.Arg4810Lys mutation in RNF213 gene as a founder mutation of moyamoya disease.[8] A genome-wide association study also identified RNF213 as a disease causing gene for Moyamoya disease.[9] Comparative evolutionary genome sequencing analyses in humans and monkeys showed that the strongest evidence for acceleration along the branch leading to hominines was RNF213.[10] RNF213 has been shown to be associated with blood flow and oxygen consumption.[11][12][13] Given that oxygen and glucose consumption scales with total neuron number, RNF213 may have played a role in facilitating the evolution of larger brains in primates.[10]
