Genetic heterogeneity in Sardinia: 15 polymorphisms examined in 11 isolates.

Blood group systems ABO, RH, MNS, KEL, FY, LU and P, red cell enzymes ACP1, PGM1, PGM2, ADA, DIA and PHI, serum markers GC, HP, IGHG1, IGHG3 and IGK were examined in about 900 individuals sampled in 11 Sardinian isolates. The genetic differentiation turned out to be relatively high and the relevance of selected and neutral genes has been evaluated.

Uncommon Gm* haplotypes in the Tunisian population: further contribution to the genetics of the IgG immunoglobulins.

In this work, eight family studies were conducted to establish the suspected unusual Gm* haplotypes in 13 persons (among 418) showing uncommon Gm phenotypes. Usually, the Gm (21 and 28)--or Gm (g1 and g5)--allotypes are both present or absent. Exceptions to this rule were observed: on the one hand, only the Gm (28) allotype was present in 12 persons, and on the other hand, only the Gm (21) allotype was found in 1 person.

Further contribution of common Gm*-Am* haplotypes and Km* alleles in the characterization of the Tunisian population.

The Gm, Am and Km allotypes have been investigated in 405 sera from unrelated students and blood donors coming from the different areas of Tunisia. Thirty Gm and fourty-seven Gm-A2m common phenotypes have been observed. Eleven Gm* and seventeen Gm*-A2m* common haplotypes have been deduced from these phenotypes.

Lymphoid chimerism after allogeneic bone marrow transplantation. Y-chromatin staining of peripheral T and B lymphocytes and allotyping of serum immunoglobulins.

Lymphoid cell engraftment was monitored for several years after bone marrow transplantation by Y-chromatin staining of T and B lymphocytes in the peripheral blood and/or by immunoglobulin allotyping in the serum of 20 of 52 pediatric patients grafted successively between October 1973 and October 1983. Data on 2 patients with severe combined immunodeficiency, grafted earlier in December 1968 and April 1971, are also included. These children received an allogeneic bone marrow graft for leukemia (n = 7), severe aplastic anemia (n = 11), or severe combined immunodeficiency (n = 4) and were informative for this study, because they differed from their donor by sex (n = 16) and/or by immunoglobulin phenotype (n = 13).

Gene conversion in human immunoglobulin gamma locus shown by unusual location of IgG allotypes.

The constant region of the gamma 1, gamma 2 and gamma 3 heavy chains of the human IgG1, IgG2 and IgG3 immunoglobulins carries antigenic determinants or G1m, G2m and G3m allotypes, which are genetic markers of these subclasses. The exceptional presence on gamma 1 and gamma 2 chains of Gm allotypes usually located on the CH3 domain of gamma 3 shows an unexpected clustering of base changes and subsequent identity of short DNA sequences in the CH3 exon of the non-allelic gamma 1, gamma 2 and gamma 3 genes. Such clusters of substitutions are not easily explained on the classical basis of point mutations.

Molecular analysis of a case of IgA2 deficiency.

A family with two members with selective IgA2 deficiency was analysed by direct gene analysis with different probes for the IgCH region. No gross gene deletions or rearrangements were detected. Genetic analysis based on serological and molecular markers did not rule out linkage with the IgCH region.

Immunoglobulin allotypes in Hungarian Gypsies. Relationship to populations from India.

The allotypic markers of immunoglobulin heavy chains (Gm, Am and Em allotypes) provide important contributions to the differentiation between populations, and they are informative for tracing racial origin, migration and admixture of isolates and stray groups. The combined G1m; G2m; G3m; A2m; Em haplotypes are a highly polymorphic system that is a powerful tool in population genetics because of the existence of haplotypes that are unique for a particular race. In this paper, data on Gypsies living in Hungary are compared with those obtained in other populations, in particular Hindus and non-Hindus from India.

Correlation between G2m(n) immunoglobulin allotype and human antibody response and susceptibility to polysaccharide encapsulated bacteria.

To determine whether genetic factors influence the human antibody response to polysaccharides, we correlated Ig allotypes with the concentrations of antibody to 14 bacterial capsular antigens in 130 actively immunized Caucasian adults. The 88 individuals possessing G2m(n), an allotype antigen of IgG2 subclass heavy chains, had significantly higher postimmunization antibody levels to Haemophilus influenzae type b (Hib) and 8 of 11 pneumococcal types (P less than 0.05) than the 42 lacking this antigen.

Linkage studies in autosomal dominant facioscapulohumeral muscular dystrophy.

Linkage studies were undertaken in 120 individuals from 10 kindreds with autosomal dominant facioscapulohumeral muscular dystrophy using 35 different marker genes. No linkage was found. The highest lod score was 1.

HLA and GM in insulin-dependent diabetes in the Netherlands: report on a combined multiplex family and population study.

This report deals with the genetic factors involved in insulin-dependent diabetes mellitus (IDD) in The Netherlands. Twenty-two Dutch multiplex families with IDD were typed for HLA-A, -B, -C, and -DR antigens, for BF, C2, C4, and GLO polymorphisms, as well as for GM allotypes of immunoglobulins. In addition, 53 unrelated IDD children and 31 unrelated patients with adult onset IDD were typed for HLA-A, -B, -C, and -DR antigens.

Genetic study of Tunisian Berbers. I. Gm, Am and Km immunoglobulin allotypes and ABO blood groups.

The Gm, Am and Km immunoglobulin allotypes and ABO blood groups were studied in three groups of Tunisian Berbers . The results showed that the actual Berbers of Tunisia present certain heterogeneity and their ancestors were probably the first inhabitants of North Africa. Indeed, although their Gm-Am haplotypes are mainly Caucasoid, some of them are typically African.

Immunoglobulin heavy chain haplotypes in caucasian New Zealanders.

In the course of studies on the genetic basis of autoimmune disease, immunoglobulin allotypes were measured in New Zealand people of caucasian origin. We report the observed frequencies of the various allotypes of the gamma heavy chains, together with the frequencies of the combinations observed to occur in individuals (phenotypes) and the nature and frequency of the combinations on individual chromosomes (haplotypes), as calculated by application of Kurczynski and Steinberg's computer programme MAXIM.

A solution to the genetic and environmental puzzles of insulin-dependent diabetes mellitus.

Studies of the segregation of heterozygous immunoglobulin allotypes in families with several cases of insulin-dependent diabetes mellitus (IDDM) show that germline heavy-chain V (variable region) genes are not major genetic determinants for IDDM, but data for IDDM and Graves' disease together suggest involvement of kappa light-chain V genes. Absence of IDDM at birth, the semi-random age of onset, and the 50% discordance of identical twins suggest that somatic mutation of germline V genes is involved in the development of the pathogenetic anti-beta-cell clones. The effect of histocompatibility and other alloantigens on the prevalence of IDDM is readily accounted for by the effect of the "holes" they induce, by natural tolerance, in the immune response repertoire; these alterations apparently affect the chance of emergence of anti-beta-cell clones by the somatic mutations and network of interclonal deletions that constantly change the fringes of the repertoire.

Monoclonal antibodies to an immunoglobulin allotype marker G1m(f).

The properties of a group of mouse monoclonal antibodies (McAbs) specific for the human G1m(f) allotype marker on immunoglobulin G are described. The specificity of all 5 McAbs was anti-Gm(f) in haemagglutination assays detecting the G1m(f) determinant on 6 ng of purified G1m(f) paraproteins. A high dilution (greater than or equal to 1/10(4)) could be used for the majority of McAbs in this assay.

Genetic linkage between erythrokeratodermia variabilis and Rh locus.

A genetic linkage study was performed in a large Dutch kindred with erythrokeratodermia variabilis (EKV, McKusick no. 13320). The autosomal-dominant trait appeared to segregate rather consistently with the cde (r) gene complex of the Rh system.

A new case of gamma-heavy chain disease (LIA protein) with deletion of the hinge region.

An IgG1K monoclonal component with abnormal covalent H and L chains structure (LIA protein) was identified during a systematic screening of myeloma proteins by means of non-reducing/reducing SDS-polyacrylamide gel electrophoresis. Using immunochemical and immunogenetic analysis the mutation was characterized as a hinge region deletion, with loss of L-H and H-H disulphide bridges and direct L-L bonds. Moreover, non-expression of the G1m(z) allotype suggested that the deletion might start at residue 216, a preferential site previously observed in other HCD proteins.

A genetic marker of human IgE heavy chains, Em(1).

A monoclonal anti-IgE antibody was obtained that reacted with some IgE myeloma proteins and with all but a few normal sera. Family studies proved that a genetic marker of IgE had been detected. This allotype, called Em(1), segregates in association with certain Gm-Am haplotypes.

Selective deficiency of immunoglobulin A2.

A case of familial selective IgA2 deficiency is described. The mother had no detectable IgA2, but a low level of IgA1. She had anti-alpha 2 antibodies of the IgG class.

Instability of the human immunoglobulin heavy chain constant region locus indicated by different inherited chromosomal deletions.

Previously we reported a gross genetic polymorphism of the human immunoglobulin heavy chain locus manifest by a large internal deletion within the constant region gene segment. We now describe a detailed serological and molecular genetic study of a Tunisian family in which members appear to carry two chromosomes 14 with different DNA deletions. The first is similar to that previously described encompassing three gamma subclass genes, a pseudo-epsilon gene and the alpha 1 subclass gene; the second deletion is less complex involving only the pseudo-epsilon gene and the alpha 1 gene.

Allotypic and isotypic aspects of human immunoglobulin A.

The location of isotypic, isoallotypic and allotypic determinants is reviewed in the light of data obtained when specific antisera are tested with proteolytic fragments of IgA molecules or mutants of IgA obtained from patients with alpha-heavy chain disease. Isotypic determinants are distributed throughout the alpha chain constant regions although when intact IgA proteins are used as immunogens the CH3 domain is immunodominant. Alpha 1 subclass specific isotypic determinants are present in both Fab and Fc fragments.

IgG and IgA heavy chain allotypes in Type 1 diabetes.

IgG and IgA heavy chain allotypes were determined in the sera of 483 Caucasian Type 1 diabetes patients and 503 Caucasian healthy controls. There was no significant difference between patients and controls neither on the level of Gm phenotype frequencies nor on the level of Gm three-locus and two-locus haplotype frequencies. A selective IgA deficiency was found in 14 patients (2.

Simultaneous absence of the human IgG1, IgG2, IgG4 and IgA1 subclasses: immunological and immunogenetical considerations.

Simultaneous absence of the IgG1, IgG2, IgG4 and IgA1 immunoglobulins has been unambiguously demonstrated in a healthy 75-year-old woman by testing for allotypes, isoallotypes and for isotypes of these four subclasses. Only IgM, IgD, IgG3, IgA2 and IgE were present. The IgG3 levels were significantly increased.