LINKAGE DISEQUILIBRIUM BETWEEN THE EXPANDED (GAG)(N) REPEAT AND AN ALLELE OF THE ADJACENT (CCG)(N) REPEAT IN HUNTINGTONS-DISEASE PATIENTS OF GREEK ORIGIN
C. Yapijakis et al., LINKAGE DISEQUILIBRIUM BETWEEN THE EXPANDED (GAG)(N) REPEAT AND AN ALLELE OF THE ADJACENT (CCG)(N) REPEAT IN HUNTINGTONS-DISEASE PATIENTS OF GREEK ORIGIN, European journal of human genetics, 3(4), 1995, pp. 228-234
Huntington's disease (HD) is associated with an expanded unstable (GAG
)(n) repeat in the IT15 gene. This repeat was investigated in 44 HD pa
tients and 59 of their relatives at risk who were members of 29 unrela
ted families from various parts of Greece. Abnormal elongation of the
(GAG)(n) repeat ranging from 39 to 95 trinucleotide units was found in
all but one of the 44 HD patients tested with 70% of these patients s
howing 42-47 repeats. The size of the expanded sequence correlated inv
ersely with the age at disease onset (r = 0.77, p < 0.00001, n = 43).
In a single sporadic case, de novo expansion of the (GAG)(n) repeat wa
s detected. Twenty-four of 59 asymptomatic family members at risk show
ed expansion of the (GAG)(n) repeat in the HD range (39-56 trinucleoti
de units) while three had intermediate alleles (36-37 repeats). Evalua
tion of the adjacent polymorphic (CCG)(n) repeat showed a strong linka
ge disequilibrium between the 7-unit (CCG), repeat allele and the HD m
utation, with 51% of normal and 93% of HD chromosomes showing this all
ele (chi(2) = 15.55, p < 0.0001, n = 260). These data on HD patients o
f creek origin are consistent with the thesis that the (GAG)(n) expans
ion is the primary gene defect of the disease and that this mutation o
ccurred primarily on chromosomes with the (CCG)(7) repeat haplotype.