Moses S. Schanfield

The Central Siberian Origin for Native American Y Chromosomes

Y chromosomal DNA polymorphisms were used to investigate Pleistocene male migrations to the American continent. In a worldwide sample of 306 men, we obtained 32 haplotypes constructed with the variation found in 30 distinct polymorphic sites. The major Y haplotype present in most Native Americans was traced back to recent ancestors common with Siberians, namely, the Kets and Altaians from the Yenissey River Basin and Altai Mountains, respectively. Going further back, the next common ancestor gave rise also to Caucasoid Y chromosomes, probably from the central Eurasian region. This study, therefore, suggests a predominantly central Siberian origin for Native American paternal lineages for those who could have migrated to the Americas during the Upper Pleistocene.

Identification of War Victims from Mass Graves in Croatia, Bosnia, and Herzegovina by the Use of Standard Forensic Methods and DNA Typing

The postmortem remains of sixty-one war victims were excavated from 6 mass graves in Bosnia and Herzegovina one and a half years after interment Using standard identification methods, including the matching of medical and dental records, the recognition of distinguishing characteristics such as the use of clothing and belongings, and video superimposition, 35 persons were identified. For the remaining 26 persons identification efforts continue. DNA typing was performed at the HLA DQA1 locus and five PM system loci. Results from DNA typing were confirmed by other methods. DNA profiles of family members of 150 missing persons are now being developed using the 6 loci. These DNA profiles will then be compared with those generated from the bone and teeth remains of the unidentified victims.

Gluten-sensitive enteropathy. Immunoglobulin G heavy-chain (Gm) allotypes and the immune response to wheat gliadin.

Anti-gliadin antibody was measured by radioimmunoassay in 30 Caucasians with gluten-sensitive enteropathy (GSE). 22 GSE patients maintained on a gluten-free diet for 1.5 to 20 yr (mean duration 76 mo) had elevated serum concentrations of IgG antigliadin antibody. Among GSE patients on a gluten-free diet, antigliadin antibody was seen only in those having the chromosome 14-encoded IgG immunoglobulin heavy chain allotype marker G2m(n). IgG antigliadin antibody was found in GSE patients with G2m(n) regardless of whether the HLA-B8 and/or -DR3 major histocompatibility complex antigens that occur frequently in GSE were present. No patient lacking G2m(n) had significant levels of antigliadin antibody. The association between antigliadin antibody and the immunoglobulin heavy chain allotype marker G2m(n) in GSE patients likely reflects the presence of Gmn-linked variable region genes or Gmn-linked genes that regulate variable region gene expression.

Anaphylactic reactions to plasma infusions in patients with hypogammaglobulinemia and anti-IgA antibodies☆

Abstract Two patients with common variable hypogammaglobulinemia developed anaphylactic reactions when given very small infusions of normal human plasma containing IgA. Their sera were examined for antibodies to human IgA by passive hemagglutination against human erythrocytes coated by the chromic chloride method with a panel of purified IgA myeloma and normal proteins, and specificity was determined by inhibition of agglutination. Both patients were found to have IgG anti-IgA antibodies of multiple specificity. Differential absorption studies in the second case showed antibodies to IgA 1 and IgA 2 and to A2m(1) and A2m(2). To our knowledge, this is the first report of anti-IgA antibodies with multiple specificities in a single patient. These two cases illustrate the possibility of sensitization to human IgA in patients with severe humoral antibody deficiency syndromes, who might not be expected to form antibodies to new antigens. Presumably and kind of anti-IgA, regardless of specificity, can cause severe anaphylactic reaction.

IMMUNOGLOBULIN ALLOTYPE MARKERS IN GLUTEN-SENSITIVE ENTEROPATHY

Immunoglobulin allotype markers and HLA-A, HLA-B, and HLA-DR locus antigens were determined in 30 White patients with gluten-sensitive enteropathy and 30 controls matched for age, ethnic background, and geographic origin. All patients lacking HLA-B8 and HLA-DR3 had the IgG (Gm) immunoglobulin heavy-chain phenotype Gm (f;n;b). Thus, in addition to major histocompatibility locus genes, it appears that genes linked to the immunoglobulin heavy-chain allotype locus on chromosome 14 may influence susceptibility in gluten-sensitive enteropathy.

A 50-SNP assay for biogeographic ancestry and phenotype prediction in the U.S. population

When an STR DNA profile obtained from crime scene evidence does not match identified suspects or profiles from available databases, further DNA analyses targeted at inferring the possible ancestral origin and phenotypic characteristics of the perpetrator could yield valuable information. Single Nucleotide Polymorphisms (SNPs), the most common form of genetic polymorphisms, have alleles associated with specific populations and/or correlated to physical characteristics. We have used single base primer extension (SBE) technology to develop a 50 SNP assay (composed of three multiplexes) designed to predict ancestry among the primary U.S. populations (African American, East Asian, European American, and Hispanic American/Native American), as well as pigmentation phenotype (eye, hair, and skin color) among European American. We have optimized this assay to a sensitivity level comparable to current forensic DNA analyses, and shown robust performance on forensic-type samples. In addition, we developed a prediction model for ancestry in the U.S. population, based on the random match probability and likelihood ratio formulas already used in forensic laboratories. Lastly, we evaluated the biogeographic ancestry prediction model using a test set, and we evaluated an existing model for eye color with our U.S. sample set. Using these models with recommended thresholds, the 50 SNP assay provided accurate ancestry information in 98.6% of the test set samples, and provided accurate eye color information in 61% of the European samples tested (25% were inconclusive and 14% were incorrect). This method, which uses equipment already available in forensic DNA laboratories, is recommended for use in U.S. forensic casework to provide additional information about the donor of a DNA sample when the STR profile has not been linked to an individual.

Immunoglobulin Allotypes of European Populations

The distribution of G1m(f, z, a, and x), G2m(n), G3m(b0, b1, b3, b5, c3, c5, g, s, t, and v), A2m(1 and 2) and Km(1) (formerly Inv[1]) allotypic determinants has been examined in a series of Czechoslovakian blood donors. The results indicate that Gmza;–;gv A2m1, Gmzax;-;gvA2m1Gmf;n;bvA2m1 and Gmf;–;bvA2m1 are present in polymorphic frequencies. Further, 9 idiomorphic phenotypes were observed; however, without family data it was not possible to exactly define the majority of these. The observed frequencies of Gmza;–g, Gmzax;–g and Gmf;b and Km1are similar to those observed previously in Czechoslovakians and similar to those observed in adjacent populations, though different from those observed in Western Europeans, primarily due to a higher frequency of Gmf;b in Czechoslovakians.

Association Between Crohn's Disease and Immunoglobulin Heavy Chain (Gm) Allotypes

Immunoglobulin allotype markers on immunoglobulin G (Gm markers), immunoglobulin A (A2m markers), and kappa light chains (Km markers) were determined in 68 Crohns disease patients, 39 ulcerative colitis patients, and 1027 healthy controls. Patients and controls were all Caucasians of Northern European origin and not Jewish. The distribution of immunoglobulin heavy-chain (Gm) allotypes differed markedly between Crohns disease patients and controls. Crohns disease patients had a significant increase in the frequency of the phenotype Gm(a,x,f;b,g) and the haplotype Gma,x;g. The frequency of Gm phenotypes and haplotypes did not differ significantly between ulcerative colitis patients and controls. Further, there was no significant association between Km markers or A2m markers and inflammatory bowel disease.

Automated determination of ABO/Rh in microplates.

Abstract. A semi‐automated system for determining the ABO group and Rh type of blood samples has been developed using a commercially available automated microplate (ELISA) reader and a microcomputer. Optimization of serologic, measurement and interpretation parameters was accomplished without significantly changing an existing manual procedure. The first pass noninterpretation rate of this system in the laboratory prior to field trials is 7.1%. A commercial system of this type should be cost‐effective as a primary instrument for small to medium sized blood centers and transfusion services.

Association of CSF IgG concentration and immunoglobulin allotype in multiple sclerosis and optic neuritis

The cerebrospinal fluid (CSF) and serum from 64 patients with multiple sclerosis (MS) and 47 patients with monosymptomatic optic neuritis (ON) were analyzed for the distribution of allotypic determinants on IgG and compared to similar samples from 51 patients with other neurological diseases (OND) as well as to serum samples from 97 healthy controls. The results indicate a significantly increased frequency of the haplotypes Gm a;g and Gm a,x;g among MS patients (P = 0.024) with an associated increase in relative risk for MS among individuals with the Gm a,(x);g haplotypes compared to those individuals without them (P = 0.014). Among MS patients, those with the Gm a,(x);g haplotypes had significantly higher CSF levels of IgG than those without (P = 0.016); levels of serum IgG did not covary with Gm haplotype. Two-way analysis of variance indicates that familial cases have significantly higher levels of CSF IgG than nonfamilial cases (P less than 0.001) and that familial cases with the Gm a,(x);g haplotypes have the highest CSF IgG levels (P less than 0.005). There was no correlation between Gm haplotype and CSF or serum IgG levels in patients with ON or OND. The allotype effects were independent of age at onset and duration of disease. In all patients, regardless of disease classification, the phenotypes found in serum samples were identical to those found in CSF samples. The data presented support the hypothesis that the etiology of MS has as one of its parameters an immunoregulatory/immunogenetic factor. The successful analysis of these various parameters will provide useful information not only about MS but also about general principles of human immune responsiveness.