The CMT1A-REP repeat consists of two copies of a 24-kb sequence on human ch
romosome 17p11.2-12 that flank a 1.5-Mb region containing a dosage-sensitiv
e gene, peripheral nerve protein-22 (PMP22). Unequal meiotic cross over med
iated by misalignment of proximal and distal copies of the CMT1A-REP in hum
ans leads to a 1.5-Mb duplication or deletion associated with two common pe
ripheral nerve diseases, Charcot-Marie-Tooth disease type 1A (CMT1A) and he
reditary neuropathy with liability to pressure palsies (HNPP). Previous mol
ecular hybridization studies with CMT1A-REP sequences suggested that two co
pies of the repeat are also found in the chimpanzee, raising the possibilit
y that this unique repeat arose during primate evolution. To further charac
terize the structure and evolutionary synthesis of the CMT1A-REP repeat, fl
uorescent in situ hybridization (FISH) analysis and heterologous PCR-based
assays were carried out for a series of primates. Genomic DNA was analyzed
with primers selected to differentially amplify the centromeric and telomer
ic ends of the human proximal and distal CMT1A-REP elements and an associat
ed mariner (MLE) sequence. All primate species examined (common chimpanzee,
pygmy chimpanzee, gorilla, orangutan, gibbon, baboon, rhesus monkey, green
monkey, owl monkey, and galago) tested positive for a copy of the distal e
lement. In addition to humans, only the chimpanzee was found to have a copy
of the proximal CMT1A-REP element. All but one primate species (galago) te
sted positive for the MLE located within the CMT1A-REP sequence. These obse
rvations confirm the hypothesis that the distal CMT1A-REP element is the an
cestral sequence which was duplicated during primate evolution, provide sup
port for a human-chimpanzee clade, and suggest that insertion of the MLE in
to the CMT1A-REP sequence occurred in the ancestor of anthropoid primates.