Herbert F. Polesky

Distribution of α1-Antitrypsin Variants in a US White Population

A white population from the State of Minnesota of primarily German and Scandinavian heritage was subtyped for alpha 1-antitrypsin variants using isoelectric focusing. The frequencies of the genes PI*M1 (0.724), PI*M2 (0.137) and PI*M3 (0.095) were consistent with those for white populations documented in the literature from Northern Europe. Other genes identified in the study were PI*F, PI*I, PI*P, PI*S and PI*Z.

Frequency of the ESD*5 allele in three ethnic groups in Minnesota

SummaryDetection of the ESD*5 gene products was simplified by the use of isoelectric focusing (IEF). Gene frequencies for ESD*5 in whites, blacks and Amerindians from the State of Minnesota were 0.019, 0.002 and 0.000, respectively. The gene frequencies observed in the white data set were similar to those reported for European whites.

Observations on the Gya and Hy Antigens and the Antibodies that Define Them

Two high frequency antigens, Hy (Holley) and Gya (Gregory), show an apparent association. All individuals lacking Gya are whites and these individuals are Hynegative. A second group of Hy‐negative individuals are blacks. All of these react weakly with anti‐Gya. Neither Gya nor Hy are well developed on cord cells, although antibodies to both factors have been stimulated by pregnancy. Anti‐Gya and anti‐Hy antibodies react best in the antihuman globulin test. These antibodies have low avidity, high titers, and have been implicated as causing transfusion reactions.

Isoelectric focusing of Gc (vitamin D binding globulin) in parentage testing

SummaryGc subtyping with isoelectric focusing (IEF) in paternity cases allowed us to increase the exclusion probability (P) of Gc in Whites to 31% from a (P) of 16% using agarose electrophoresis. Both IEF and agarose are necessary to identify certain rare variants, therefore it is recommended that both techniques be performed in cases of disputed parentage and population studies.

A FATAL HEMOLYTIC TRANSFUSION REACTION WITH ACUTE AUTOHEMOLYSIS.

A fatal hemolytic transfusion reaction due to anti‐Kidd (Jka) is described in a woman with aplastic anemia associated with acute leukemia. Radioactive chromium studies, which were in progress at the time, made it possible to demonstrate that a severe autohemolytic crisis was a part of the reaction. The relationship between a hemolytic transfusion reaction and the initiation or intensification of autohemolysis is discussed. The difficulties of serologic diagnosis and selection of blood for transfusion in patients with nonspecific antibodies are reviewed. This case again illustrates that nonspecific agglutinins can mask the presence of specific anti‐red cell antibodies.

A New Public Antigenic Determinant Gya (Gregory)

An antibody found in the sera of two sisters defines a new public antigenic determinant Gya (Gregory). The Gy(a—) individuals are the product of a consanguinous mating and are presumably homozygous for a rare gene, Gy, inherited from a common ancestor. Anti‐Gya is an IgG antibody that was stimulated by pregnancy.

Studies on the Distribution of the Blood Group Antigen Doa (Dombrock) and the Characteristics of Anti‐Doa

An antibody developing in Mrs. Dombrock following transfusion, defines a new blood group system. The antigen Doa, present in 64 per cent of Caucasians, has a lower frequency in Indians and Negroes. The immune characteristics of this antibody have been demonstrated by reactions in vitro and in vivo. It is to be expected that if Dombrock proves to be a two allele system, the antigen Dob will occur in 84 per cent of Caucasians.

The use and abuse of the full-sibling and half-sibling indices

Increasingly, parentage testing laboratories are called upon to provide documentation of genetic linkage between individuals applying for legal immigration to the United States. Many embassies require that the party who has already obtained legal immigrant status document that the person(s) he or she is trying to bring into the United States is a first-degree relative, for example, establishing that the parties are parent and child. As part of this process, several embassies have started to request not only parent-child calculations, but also statistical tests for other possible relatedness, such as uncle-child or possible sibling status. In that context, Wenk and Chiafari1 demonstrate both the ways in which these indices are used and the fact that paradoxical results are often observed. Specifically, with the use of three highly informative VNTR loci, 4 of 25 examples of proven full-sibling pairs yielded a ratio of greater than 2:1 against full-sibling status. Furthermore, 2 of 25 pairs proven beyond doubt to be half-siblings had ratios exceeding 5:1 in support of full-sibling status. Because of the stringent immigration requirements, we typically test at 5 to 7 pairs of VNTR loci, which yields greater power to distinguish possible relationships. Our concern is with the ways that these indices are used by various US embassies with regard to issues of immigration. Recently, we had a case in which a married couple had legally immigrated to the United States and were trying to bring in their son. We tested the man and the boy at five highly polymorphic VNTR alleles. They (father and son) shared both alleles at three systems, and so the full-sibling index exceeded the father-child index by over 40-fold. Because of this latter calculation, the embassy refused admission of the boy to the country, despite the observation that the man was almost 40 years older than the tested child and hence far more likely to be the boy’s father than a full sibling! We subsequently tested the woman’s blood; this showed that the boy’s results were consistent with the two adults’ being his parents. It is not uncommon for genetic heterogeneity to be less diverse within a small ethnic community than in the entire classification of the race, and this gives an overrated significance to the sharing of more than a single allele. When alleles are common within a tested population, the sharing of two alleles will be correspondingly more common. This occurs even more frequently when less polymorphic systems, such as serial tandem repeats (STRs), are used. For example, alleles are more broadly distributed among all Asians than within the Japanese population alone. Hence, finding parents that share both alleles with children is not a rare event in which certain alleles are common within the tested population. In short, while we appreciate the challenges faced by embassies to follow the rules limiting immigration sponsorship to direct family members, we urge greater dialog between testing centers and the individual embassies, to establish reasonable expectations for additional testing requirements when no exclusions are found. One year after the initial testing was performed, the child in the above example remains abroad and separated from his parents. As the current system stands, families that can ill afford it are required to pay for additional testing and legal and communications costs. Jed B. Gorlin, MD Herbert F. Polesky, MD Memorial Blood Centers of Minnesota 2304 Park Avenue Minneapolis, MN 55404-3789 e-mail: jed@mbcm.org

Post-perfusion syndrome due to Epstein-Barr virus: report of two cases and review of the literature

The post‐perfusion syndrome is rarely due to Epstein‐Barr virus (EBV), because most adult patients already carry protective neutralizing antibodies in their sera. Data are presented from two patients in whom heterophil‐antibody‐positive infectious mononucleosis developed 35 and 48 days after open‐heart surgery. The diagnoses of their predominantly febrile illnesses were delayed because of late appearance of atypical lymphocytes and heterophil antibodies. EBV‐specific antibody responses were also delayed, with peak titers appearing several weeks or months after onset. The differences in evolution of the present cases, compared to those of classic infectious mononucleosis, were presumably due to different portals of entry (blood stream versus oropharynx).

Review of isoelectric focusing for Gc, PGM1, Tf, and Pi subtypes: population distributions.

Isoelectric focusing (IEF) as a method for differentiating macromolecules with minor differences in isoelectric points has demonstrated an increase in the degree of genetic polymorphisms of the blood. Studies over the last 5 to 6 years have shown that genetic marker systems such as transferrin (TF), phosphoglucomutase (PGM1), the vitamin D-binding globulin (GC), and A1 antitrypsin (PI) are a great deal more polymorphic than observed using conventional electrophoresis. Additional genetic variants have been detected or further defined in such systems as esterase D (ESD) and hemoglobin (HB) to name a few. The increased heterozygosity levels of these genetic marker systems identified by IEF have added to their value in forensic medicine and resulted in further resolution of racial and population affinities. IEF should prove to be a valuable anthropological tool for measuring population structure and genetic distances.