Iris Pattern

Inheritance

From a study of 100 monozygotic twin pairs, 99 dizygotic twin pairs, and 99 unrelated randomly paired age-matched German subjects, Larsson et al. (2003) concluded that variations in characteristic patterns of the human iris are under strong genetic influence.

Stellate pattern of the iris is characteristic of Williams syndrome (194050) and the Lester sign of nail-patella syndrome (161200). Neither of these is completely specific to the genetic syndrome, but both occur in low frequency in the general population.

Mapping

Larsson et al. (2011) performed genomewide association scans on 4 iris characteristics (crypt frequency, furrow contractions, presence of peripupillary pigmented ring, and number of nevi) in a total of 2,693 individuals in 3 Australian samples of European descent. They found evidence for association between crypt frequency and a SNP (rs10235789) in intron 6 of the axonal guidance gene SEMA3A on chromosome 7q21.11 (603961; combined p = 6.6 x 10(-11)); approximately 1.5% of the variance for crypts could be explained by the replicated SNP findings with rs10235789. They also found association between furrow contractions and a nonsynonymous coding SNP (rs3739070) within the cytoskeleton gene TRAF3IP1 on chromosome 2q37.3 (607380; combined p = 2.3 x 10(-12)); approximately 1.7% of variance in the discovery sample and 3% in the first replication sample were explained by rs3739070. In addition, association was found between the pigmented ring and a SNP (rs4900109) located in an intergenic region on chromosome 14q32.12 upstream of the pigmentation gene SLC24A4 (609840); rs4900109 is in high linkage disequilibrium with a SNP in SLC24A4, rs12896399 (609840.0001), that has been associated with multiple pigment-related phenotypes, including blue versus brown eye color and blue versus green eye color. Larsson et al. (2011) suggested that rs40900109 may influence where in the iris the pigment is placed, rather than overall eye color per se.