Oligonucleotide ligation assay: applications to molecular diagnosis of inherited disorders

Oligonucleotide ligation assay combined with polymerase chain reaction (PCR -OLA) is a technique which can be used for the detection of characterized s equence variations. In the present study, new PCR-OLA methods were develope d for the detection of the major mutations causing infantile neuronal ceroi d lipofuscinosis (INCLFin), congenital nephrotic syndrome of Finnish type ( NPHS1 Fin(Major) and Fin(Minor)) and medium chain acyl-CoA dehydrogenase de ficiency (MCAD A985G). The prevalence of these mutations in the Finnish pop ulation was studied by analyzing blood samples collected in eastern Finland . The throughput of PCR-OLA was further enhanced by optimizing the direct u se of dried blood spot (DBS) specimens for PCR. This study demonstrated tha t PCR-OLA is an accurate method for the detection of gene defects causing i nherited disorders. With automation, PCR-OLA can be applied for routine dia gnosis and for carrier screening from a large number of specimens.