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L R Weitkamp

Publications and source records attributed to L R Weitkamp.

At least 37 records · Page 2Linked to original sources
PubMed1988

Further studies of the plasma alpha 1 B-glycoprotein polymorphism: two new alleles and allele frequencies in Caucasians and in American blacks.

Two new alleles (A1 B*3 and A1 B*4) of human plasma alpha 1 B-glycoprotein (alpha 1 B) were reported. alpha 1 B phenotyping was done by using either a simple method of two-dimensional (2-D) agarose gel-horizontal polyacrylamide gel electrophoresis (PAGE) followed by protein staining or by one-dimensional horizontal PAGE and immunoblotting. Seven different alpha 1 B phenotypes (1-1, 1-2, 1-3, 1-4, 2-2, 2-3 and 3-3) were observed; phenotypes 1-3 and 1-4 were differentiated from each other only by the 2-D method. The respective frequencies Af A1 B*1, A1 B*2, A1 B*3 and A1 B*4 alleles in the studied populations were estimated as follows: American Blacks (New York) 0.732, 0.204, 0.064, 0; American Whites (New York) 0.947, 0.053; Czechs (Mĕlník) 0.964, 0.034, 0, 0.002; Slovaks (Bratislava and Trencin) 0.977, 0.023, 0, 0. The population of American Blacks showed a much higher degree of alpha 1 B polymorphism (polymorphism information content = 0.37) than the Caucasian populations that have been studied.

Alleles↗
PubMed1987

Genetic differentiation associated with gait within American standardbred horses.

American Standardbred horses are divided into two groups based upon gait: the trot and the pace. The tendency to trot (diagonally opposite legs moving forward together) or pace (the two legs on the same side of the body moving forward together) appears to be genetically determined, although no formal genetic analysis has been undertaken. There is nearly complete assortative mating for gait; however, about 20% of the offspring sired by trotters are registered as pacers, while fewer than 1% of those sired by pacers are registered as trotters. Electrophoretically detectable genic variation at 13 protein loci has been analysed for 371 trotters and 856 pacers, and 10 blood group loci have been examined for 600 trotters and 1227 pacers. Trotters and pacers shared common alleles at 20 of the 23 loci; however, there were significant differences in allele frequencies at 21 of the 23 loci. Highly significant fixation indices (FSTS) were observed for 17 of the loci. The extent of genetic difference between Standardbred trotters and pacers was as great as or greater than that seen between some distinct horse breeds.

Alleles↗
PubMed1987

The relationship of HLA to depression and manic depression. I. The Newfoundland follow-up.

This report constitutes the Newfoundland component of a large scale replication study to assess the relationship of HLA to affective disorders; the Ontario component will be published subsequently. In a collaborative study between the University of Toronto, Memorial University and the University of Rochester, first degree family members of Probands with major affective disorder in Newfoundland were assessed for the lifetime presence of psychiatric disorder; their blood was also typed for Human Leucocyte Antigens (HLA). Because of the high rate of refusal to participate, only 10 Newfoundland families could be assessed completely. While this number of families is too small to evaluate the role of HLA as a marker of susceptibility to affective disorder, the results will be added to those of the larger Ontario component. Some problems of conducting research in communities similar to those found in Newfoundland are briefly discussed in the context of characteristics of the Probands in the study group as compared with those of subjects who refused entry into the study.

Adult↗
PubMed1986

Gm, Km, and HLA in insulin-dependent type I diabetes mellitus. A log-linear analysis of association.

Two hundred sixty families, in which at least one family member had insulin-dependent (type I) diabetes mellitus (IDDM), were typed for HLA antigens and the Gm and Km allotypes. Frequencies of Gm and Km allotypes in the diabetic subjects were compared with family controls (oldest nondiabetic sibling within a family). There were no significant differences between patients and controls for either Gm or Km allotype frequencies considered individually. When the log-linear model was used to analyze subjects and sibling controls, three significant findings emerged. First, there was a significant HLA-Gm interaction, indicating nonrandom segregation of HLA antigens with Gm allotypes, regardless of disease status. Second, there was, as expected, a significant HLA-IDDM interaction, indicating that HLA type is nonrandom with respect to IDDM status. Third, there was a significant HLA-sex-Gm-IDDM interaction, indicating that combinations of HLA antigens, Gm allotypes, and sex may play an important role in defining risk for IDDM. Thus, Gm and sex interacting with HLA may reflect the influence of an unlinked modifier previously hypothesized for IDDM pathogenesis.

Adolescent↗
PubMed1986

An autosomal-dominant form of juvenile periodontitis: its localization to chromosome 4 and linkage to dentinogenesis imperfecta and Gc.

Study of a large five-generation kindred from southern Maryland revealed that type III dentinogenesis imperfecta (DGI-III) and a localized form of juvenile periodontitis (JP) were both segregating as autosomal-dominant traits. Linkage analyses demonstrated that these were two distinct clinical entities, making this family the first documented instance of an autosomal-dominant form of JP. Since the locus for the more common form of dentinogenesis imperfecta (DGI-II) is on chromosome 4q [Ball et al, 1982], a linkage analysis of genetic and chromosomal markers on chromosome 4 was undertaken. The results suggested that the locus for the DGI-III subtype is located a similar distance from the Gc locus (theta = 0.12) as the distance previously observed between Gc and DGI-II loci (theta = 0.11) [Ball et al, 1982; Conneally et al, 1984]. Most likely the two DGI subtypes are determined by genes at closely linked loci, by allelic genes, or by the same gene with the variable expression in different families. In addition, close linkage between the Gc locus and that determining the autosomal-dominant form of JP was observed in this family (theta = 0.05). The known map of chromosome 4q and our analysis of the markers tested suggested the gene order to be 4cen----JP----Gc----DGI----MNS----qter with a large distance (at least 15 cM) between 4cen and JP.

Aggressive Periodontitis↗
PubMed1985

Transferrin and HLA: spontaneous abortion, neural tube defects, and natural selection.

We report evidence that transferrin C3, a gene present in 9 to 10 per cent of whites, is associated with recurrent spontaneous abortion (P = 0.001) and that maternal transferrin genotype has an effect on the transmission ratio of the common transferrin genes (C1, C2, and C3) from heterozygous fathers to normal offspring (P less than 0.002). The effect of maternal genotype on paternal gene transmission is an unusual example of the operation of selection in the human reproductive process. This effect, together with the separate evidence for association of the transferrin C3 allele with spontaneous abortion, indicates that transferrin is a second marker (in addition to HLA) of genes important in reproduction. On the basis of comparison of the frequencies of transferrin (chromosome 3) and HLA (chromosome 6) mating types in 348 control couples and in 81 couples who had had a child with a neural tube defect, we hypothesize that some combinations of maternal and fetal genes on these two chromosomes may be associated with neural tube defects.

Abortion, Habitual↗
PubMed1985

Tourette syndrome and HLA.

Five kindreds with multiple individuals manifesting Tourette syndrome (TS) or related abnormal movements were evaluated for linkage between TS and HLA-A, B, C and DR antigens. Families were selected to have a constellation of affected individuals which gave the appearance of transmission of a major susceptibility gene. All kindreds had at least two clearly affected first or second degree relatives. Although developmental neurobehavioral disorders are candidates for showing a relationship to specific tissue antigens, we found no evidence for a close linkage between a gene locus determining susceptibility to TS and the HLA loci.

Adolescent↗
PubMed1984

Spinocerebellar ataxia in a large kindred: age at onset, reproduction, and genetic linkage studies.

We studied a large kindred with autosomal dominant spinocerebellar ataxia (SCA) to assess reproductive performance, the impact of genetic counseling, and linkage relationships of the SCA locus. Reproduction was not lower in those with SCA than in unaffected sibs or first cousins. Genetic counseling reduced reproduction during the risk period for development of SCA. Given autosomal dominant transmission of a single gene, we found strong evidence that the locus for SCA in this kindred is linked to the HLA loci.

Adolescent↗
PubMed1984

Genetic heterogeneity of insulin-dependent (type I) diabetes mellitus: evidence from a study of extended haplotypes.

Two hundred subjects with insulin-dependent (type I) diabetes mellitus (IDDM) were typed for HLA-B, HLA-DR, and properdin factor B (Bf). HLA and Bf antigen and haplotype frequencies in subjects were compared with control frequencies derived from the 8th HLA Workshop. Frequencies of extended haplotypes (defined by B-Bf-DR alleles on a chromosome) were also contrasted with control frequencies. Significant positive associations between IDDM and HLA-B8, DR3, DR4, BfS, and BfF1 were confirmed, as were significant negative associations between IDDM and HLA-B7, DR2, DR5, DR7, and BfF. One haplotype (B7-BfS-DR2) exhibited significant negative association, while five haplotypes (B8-BfS-DR3, B8-BfS-DR4, B15-BfS-DR4, B18-BfF1-DR3, and B40-BfS-DR4) exhibited significant positive associations with IDDM. In this sample, 64% of all probands carried at least one of the high-risk haplotypes. In conclusion, the occurrence of five "high-risk" haplotypes associated with IDDM provides evidence for previously undocumented genetic heterogeneity and suggests that possibly more than two HLA-region genes may be involved in IDDM susceptibility.

Adolescent↗
PubMed1984

Parental HLA compatibility, fetal wastage and neural tube defects: evidence for a T/t-like locus in humans.

To test the hypothesis that a locus in or near the human major histocompatibility complex (HLA) contributes to both involuntary fetal loss and neural tube defects (NTD), we evaluated sharing of antigens of the HLA-A, HLA-B, or HLA-DR loci of couples who had three or more first-trimester spontaneous abortions or who had a child with an NTD (myelomeningocele or anencephaly). HLA-A antigen sharing was increased in couples with three or more spontaneous abortions and in couples who had an anencephalic fetus, when compared with couples who had three or more pregnancies and no fetal loss. Increased sharing of antigens at the HLA-A and B loci was not seen in the entire group of couples with children with myelomeningocele, but was found in the subgroup of 36 couples whose child had a lumbar myelomeningocele. An increase in HLA-DR sharing was not seen in any group or subgroup when compared with the control couples. Among the aborting couples, increased sharing was not restricted to the couples who had no term pregnancies, but was also found in the couples whose fetal losses occurred after one or more normal term pregnancies. These results are consistent with the hypothesis that a locus on the HLA-A side of the HLA-DR locus contributes to some fetal loss and susceptibility to NTD. This model is proposed as an alternative to the hypothesis that the maternal immune response to paternal major histocompatibility complex (MHC) antigens is the basis for increased HLA sharing in couples with fetal wastage.

Abortion, Spontaneous↗
PubMed1983

Multiple sclerosis susceptibility. Interaction between sex and HLA.

The sex of patients with multiple sclerosis (MS) in relation to the sex, number, and relationship of affected relatives indicates an interaction between sex and autosomal genes in determining susceptibility to MS in some persons. This conclusion is confirmed by the observation that the proportion of laterally-related affected female pairs (siblings or cousins) who share the maximum possible number of HLA haplotypes is greater than that proportion in corresponding unlike-sex pairs.

Female↗
PubMed1983

Equine marker genes: polymorphism for plasminogen.

Polymorphism for two autosomal alleles of equine plasminogen, PLG1 and PLG2, was demonstrated in plasma by isoelectric focusing and immunofixation, with a goat anti-human plasminogen antibody. The frequency of PLG2 was 0.16 in 150 Standardbreds, 0.20 in 96 Thoroughbreds, and 0.39 in 32 Shetland ponies. No evidence for linkage of PLG with any of 13 marker loci was found.

Alleles↗
PubMed1983

Genetics of HLA-associated disease; rheumatoid arthritis.

An association between rheumatoid arthritis (RA) and the HLA antigen DR4 supports the view that genes in the HLA region are important in susceptibility to this disease. To further define the basis for genetic susceptibility to RA, we analyzed HLA haplotype sharing among affected and unaffected individuals in 29 multiple-case families with definite or classic RA. We have observed a non-random distribution of HLA haplotypes to unaffected as compared with affected offspring in sibships containing two or more affected individuals having 3 of 4 parental haplotypes. These data support the view that susceptibility to RA is determined, at least in part, by genes in the HLA region of chromosome 6.

Arthritis, Rheumatoid↗
PubMed1983

Alzheimer disease: evidence for susceptibility loci on chromosomes 6 and 14.

We report the transmission of HLA haplotypes and Gm allotypes in 97 members of a single kindred containing 257 individuals, 45 of whom were determined by clinical examination, autopsy, or historical data to have had Alzheimer disease (AD). Extensive inbreeding suggests that more than one gene may contribute to susceptibility to AD in this family, despite the apparent vertical transmission of illness. The distribution of HLA haplotypes and of Gm allotypes to affected and unaffected siblings is consistent with the possibility that genes in the HLA region of chromosome 6 and perhaps also in the Gm region of chromosome 14 are determinants of susceptibility. Further studies are needed to investigate whether susceptibility to AD may result from an interaction between (immune response?) genes on these two chromosomes.

Adult↗