Human core duplicon gene families: game changers or game players?

Bekpen, Cemalettin; Tautz, Diethard

The LRRC37 proteins contain six leucine-rich repeat motifs (LRR), which consist of repeating 20-30 amino acid stretches. Wellknown LRR domain-containing proteins include those of the innate immune system, especially in mammals and plants. For example, Toll-like receptors are single-membrane-spanning proteins, and their extracellular domains are composed of LRRs, which recognize pathogen-associated molecular patterns such as LPS, single-stranded RNA and flagellin. LRR-containing proteins may also be involved in neuron-specific functions, such as axonal guidance and neuronal migration [71, 72] . However, it is not known whether LRRC37 genes play a role in any of these functions. On the other hand, the LRRC37 gene family in humans is located at the boundary of a common inversion polymorphism of approximately 970 kb at 17q21.31 [69, 73, 74] . This has been shown to be a significant risk factor locus for the tangle diseases, including progressive supranuclear palsy [75] , corticobasal degeneration [76, 77] , Parkinson's disease [78, 79] and Alzheimer's disease [80] , and it is associated with microdeletion syndromes [81] [82] [83] . LRRC37B, a member of the LRRC37 gene family is also a breakpoint for NF1 microdeletion syndrome [84] .