MOLECULAR ANALYSIS OF THE HUNTINGTONS-DISEASE GENE IN NEW-ZEALAND

Aims. To establish and validate a polymerase chain reaction (PCR)-base d diagnostic test in New Zealand, which enables the number of CAG repe ats present in the Huntington's disease (HD) gene to be determined wit h speed and accuracy. To develop procedures for reporting and counsell ing probands and families. Methods. The analysis of the CAG repeat reg ion in Huntington's disease and normal chromosomes involved PCR amplif ication of genomic DNA using either the incorporation of radioactive d eoxynucleotides or fluorescent oligonucleotide primers. Results. The m olecular analysis of the CAG repeat sequence in the Huntington's disea se gene of over 100 New Zealand individuals has been performed. Huntin gton's disease chromosomes contained 37-70 (median 44) repeats whereas normal chromosomes contained 9-27 (median 18) repeats. Six individual s from three families had an allele in the intermediate range (30-36 r epeats). Instability of the CAG repeat upon transmission from generati on to generation was also observed. A comparison of the results obtain ed using radioactive and fluorescent assays indicates that while both methods are reliable, the latter method is more rapid and allows for a utomation to be incorporated in the scoring of allele sizes. Conclusio ns. Our analysis of Huntington's disease alleles has shown a profile o f CAG repeat lengths that is consistent with those reported internatio nally. In addition, reporting and counselling procedures have been est ablished for presymptomatic testing of Huntington's disease in New Zea land.