Repeat Expansion Detection (RED) is an efficient and simple method for detecting repeat expansions in the human genome, including expansion mutations resulting in disease. Here we report the first population survey of CTG/CAG repeat lengths in humans using the RED method; we have determined maximum CTG/CAG repeat length in 244 individuals from six human populations: Danes, Chinese, Japanese, Rondonian Surui, Maya and Mbuti/Biaka Pygmies. We have also sampled a number of non-human primates including eight orang-utans (Pongo pygmaeus), seven gorillas (Gorilla gorilla), seven pygmy chimpanzees (Pan paniscus), 13 common chimpanzees (Pan troglodytes) and three Hylobatidae (one Hylobates lar, one H. klossii, and one H. syndactylus). Our results demonstrate the existence of significant variation in the sizes and frequencies of the longest CTG/CAG repeat length seen per individual both within and between human populations. The population differences argue that overall mutation rates at CTG/CAG repeat loci are sufficiently low that mutation does not obliterate the effect of random genetic drift and clearly indicate that population stratification could occur in disease association studies using the RED method. No significant differences were detected among the non-human primates sampled. Our results also show that both common chimpanzees and pygmy chimpanzees (bonobos) are polymorphic for maximum length of any CTG/CAG repeats while no variation was found for gorillas and orang-utans.
Bibliographical noteFunding Information:
G.S. dedicates this paper to the memory of Elisabetta Sirugo.We thank Drs Francesc Calafell and Wayne Fenton and Matthew Hawley for helpful discussions and advice. This work was supported by research grants MH-30929, MH-39239, MH-50390 (to K.K.K.), NSF Grant SBR 9408934 (to J.R.K.) and by grants of the Leakey Foundation and Wenner-Gren Foundation for Anthropological Research (to A.S.D.).