Alpha-1-Antitrypsin (AAT) deficiency is the most common inherited risk factor for COPD. While most individuals with AAT deficiency are either PI*ZZ or PI*SZ, there appear to be a number of rare AAT alleles which may be associated with AAT deficiency. One new approach to the identification of novel AAT mutations is high resolution DNA melt curve analysis. The technique involves PCR amplification of the entire coding region of AAT gene including the intron-exon junctions, using thirteen sets of overlapping primers. The amplified products are transferred to a capillary tube and allowed to melt in the presence of a double stranded DNA binding fluorescent dye in a high resolution DNA melter. The melting data obtained is then analyzed to detect known or unknown mutations in the AAT gene. We have used this approach to characterize single nucleotide polymorphisms (SNPs) and other DNA mutations in DNA samples obtained from individuals with rare PI types or unknown null alleles identified by AAT Deficiency Detection Program at University of Florida.