Since its discovery, human plasminogen (PLG) polymorphism has received widespread acceptance in population genetics and forensic haematology. Due to the large number of variant alleles described, a PLG reference typing and Plasminogen Symposium was held, at which a nomenclature proposal was inaugurated. The technology of comparing PLG variants was based on isoelectric focusing and subsequent detection by caseinolytic overlay and ‘Western’ blotting. Typing results permitted comparison of so far described variant designations and resulted in a new nomenclature proposal for PLG polymorphism. It is recommended that the two most common alleles found in all investigated races be called: PLG*A (previously also PLG*1) and PLG*B (previously also PLG*2), the known variants with acidic pi: PLG*A1 to *A3, intermediate variants: PLG*M1 to *M5, PLG*M5 being functionally inactive, and basic variants: PLG*B1 to *B3. For future classification of newly discovered variants, samples should be compared at any of the laboratories participating in the reference typing.

Plasminogen polymorphism (PLG) has attained considerable importance in forensic hemogenetics. PLG comprises two common, codominant autosomal alleles, PLG*A and PLG*B, more than 18 variants, and the silent allele PLG*Q0. Isoelectric focusing followed by functional or immunochemical detection seems to be the optimal method for the determination of phenotypes. PLG*A is the most common allele in all populations, having its highest frequency in Mongoloids, Amerindians and Eskimos, the lowest in Caucasoids. The functionally inactive plasminogen M5 so far has been seen exclusively in Japanese individuals. Silent PLG alleles were only observed in the heterozygous state. No clear differences in functional activity or plasma level could be ascertained for any of the other allotypes. PLG polymorphism is now widely used for many haemogenetic investigations. From the allele distribution in European Caucasoids a single exclusion chance of 17.2% for non-fathers in paternity testing may be calculated. The major prerequisites of a new genetic marker in the parentage expertise, established Mendelian inheritance, favorable distribution of common alleles, low frequency of silent alleles, and simple reproducible typing technology, are fulfilled.

Since its discovery, human plasminogen (PLG) polymorphism has received widespread acceptance in population genetics and forensic haematology. Due to the large number of variant alleles described, a PLG reference typing and Plasminogen Symposium was held, at which a nomenclature proposal was inaugurated. The technology of comparing PLG variants was based on isoelectric focusing and subsequent detection by caseinolytic overlay and 'Western' blotting. Typing results permitted comparison of so far described variant designations and resulted in a new nomenclature proposal for PLG polymorphism. It is recommended that the two most common alleles found in all investigated races be called: PLG*A (previously also PLG*1) and PLG*B (previously also PLG*2), the known variants with acidic pI: PLG*A1 to *A3, intermediate variants: PLG*M1 to *M5, PLG*M5 being functionally inactive, and basic variants: PLG*B1 to *B3. For future classification of newly discovered variants, samples should be compared at any of the laboratories participating in the reference typing.

The subtypes of transferrin (TF) and alpha 1-antitrypsin (PI), first discovered using isoelectric focusing, are now mostly determined in immobilized pH gradient gels. We report on our experience in the parentage expertise with both polymorphisms over a period of three years. The complexity of the technology was compensated by the fact that most subtypes of TF and PI could be more reliably recognized. The PI alleles PI*M1, M2, M3, S, F, T, and Z and TF alleles TF*C1, C2 and C3, and in addition four further rare TF alleles were observed. The allele frequencies from non-related individuals did not deviate from the Hardy-Weinberg equilibria and corresponded well to known frequencies from West Germany and other Caucasoid populations. With the TF system 36 accused men, and with the PI system 54 were excluded from paternity from a total of 344 (TF) respectively 347 (PI) cases. From the data presented here isoelectric focusing in immobilized pH gradient gels appears to be a major improvement over carrier ampholyte generated pH gradients in the distinction of TF and PI phenotypes.

Genetic polymorphism of human plasminogen (PLG) was investigated in 1252 unrelated individuals from eight South African Bantu-speaking Negro tribes. PLG phenotypes were determined by isoelectric focusing (pH 3.5-9.5 and 5-8 gradients) of neuraminidase-treated samples and subsequent detection by caseinolytic overlay or immunoblotting with specific antibody. No significant difference in the distribution of PLG alleles among the eight ethnic groups was observed. The combined allele frequencies of the common alleles in South African Negroes were 0.6977 for PLG*A, 0.2736 for PLG*B. In addition, six rare alleles were seen: PLG*A3, *A1, *M2, *B1, *B2, *B3. The rare variant PLG*B2 was proven to segregate by autosomal Mendelian inheritance in a family. The combined frequency for the rare alleles was 0.0287. The distribution of phenotypes in the total population sample was found to be in Hardy-Weinberg equilibrium. A striking difference in PLG allele distribution between Negroes from South Africa and published Negroid frequencies from North America could be observed. This difference was also seen in comparison with Mongoloid populations; in contrast, PLG frequencies for South African Negroes were similar or almost identical to known Caucasoid distributions.

The accumulation of the homozygous plasminogen (PLG) variant A3 in 4 siblings of a family led to the detection of 5 cases of apparent inverse homozygosity of PLG phenotypes which seemed to exclude paternity. Determination of 22 blood group markers and HLA typing, but under exclusion of PLG phenotypes, confirmed paternity in all cases (biostatistical probability of paternity greater than 99.9985%). Comparing the results of 'Western blots' with functional-caseinolytic phenotyping, the existence of inactive plasmin, as described earlier, could be excluded. Besides inverse homozygosity the assumption of a silent allele was confirmed by reduction of PLG antigenic levels and functional activities to approximately 50% of normal range. The PLG phenotype A in 1 individual with anamnestic thrombosis, reduced values of PLG antigen, and reduced functional activity, although in accordance with Mendelian inheritance, was also considered as indicative for PLG hemizygosity.

The accumulation of the homozygous plasminogen (PLG) variant A3 in 4 siblings of a family led to the detection of 5 cases of apparent inverse homozygosity of PLG phenotypes which seemed to exclude paternity. Determination of 22 blood group markers and HLA typing, but under exclusion of PLG phenotypes, confirmed paternity in all cases (biostatistical probability of paternity >99.9985%). Comparing the results of‘Western blots’ with functional-caseinolytic phenotyping, the existence of inactive plasmin, as described earlier, could be excluded. Besides inverse homozygosity the assumption of a silent allele was confirmed by reduction of PLG antigenic levels and functional activities to approximately 50% of normal range. The PLG phenotype A in 1 individual with anamnestic thrombosis, reduced values of PLG antigen, and reduced functional activity, although in accordance with Mendelian inheritance, was also considered as indicative for PLG hemizygosity.