Michol Crist

CLOSE GENETIC LINKAGE BETWEEN DIABETES MELLITUS AND KIDD BLOOD GROUP

27 polymorphic genetic markers were analysed for possible linkage with insulin-dependent diabetes mellitus (IDDM). The data set contained 71 families with at least one affected member each. Under three different genetic models for IDDM, evidence was found for linkage between the disease and two distinct sets of marker loci: three markers on chromosome 6 (HLA, properdin factor B, and glyoxalase-1), and the Kidd blood group locus. The families apparently do not fall into two groups, one exhibiting linkage to the HLA complex and the other to the Kidd locus. Thus, two distinct disease-susceptibility loci may be involved in the inheritance of IDDM.

Evidence for a null allele at the esterase D (EC 3.1.1.1) locus.

SummaryElectrophoretic and quantitative assays of esterase D in a Caucasian family demonstrate the inheritance of a null allele, which was observed in the heterozygous state in six individuals.

Gene markers in human bone marrow transplantation.

Abstract. One or more differences between donors and recipients were found in polymorphic red blood cell antigens and enzymes in each of 56 bone marrow transplant sibling pairs. These results identify those polymorphic traits which are potentially most informative for detection of donor cells in a recipient following transplantation.

Improved technique for electrophoresis of human galactose-1-p uridyl transferase (EC 2.7.7.12).

SummaryA newly developed electrophoretic technique for human galactose-1-phosphate uridyl transferase confirms the multiple band patterns for the Duarte and Los Angeles variants. This represents the first confirmation for the Los Angeles variant. The observed frequencies of N, D, and LA types are similar to earlier reports for these variants.

Genetic linkage studies of transferrin, pseudocholinesterase, and chromosome 1 loci

Genetic linkage analysis of a pedigree with four different alleles for pseudocholinesterase (CHE1) gives a positive lod score of 0.37 at theta = 0.16 for linkage with transferrin (TF), a finding which supports previous reports of linkage between CHE1 and TF. Evaluation of linkage relations of CHE1 and TF using unreported families from our data bank fails to establish linkage with chromosome 1 loci (6-PGD, Rh, PGM1, AMY2 and FY). These results are consistent with recent studies which suggest that TF is on human chromosome 3.

Possible Assignment of a Dominant Retinitis pigmentosa Gene to Chromosome 1

A genetic linkage study, performed on a large family with autosomal dominant retinitis pigmentosa (RP), demonstrated that the RP gene may be linked to the Rh locus, known to be on the short arm of human chromosome 1. Linkage studies on RP along with other studies, can help to more accurately classify these disease entities. Localizing the RP gene locus has the potential for allowing the early diagnosis of individuals at risk.

Association studies between Type 1 (insulin-dependent) diabetes and 27 genetic markers: lack of association between Type 1 diabetes and Kidd blood group.

SummaryOne hundred and three unrelated patients with Type 1 (insulin-dependent) diabetes were typed for HLA, properdin factor B (BF), glyoxalase1 (GLO), Kidd blood group, and 24 other genetic markers. Observed distributions of marker phenotypes among these patients were compared with those expected according to population frequencies, in an attempt to detect associations between Type 1 diabetes and the markers. Strong associations between Type 1 diabetes and both HLA and properdin factor B were confirmed, as was a lack of association between Type 1 diabetes and glyoxalase (GLO). There was an apparent deviation from Hardy-Weinberg equilibrium at the GLO locus, and statistically significant distortions in the distributions of pancreatic amylase (AMY2), galactose-1-phosphate uridyl transferase (GALT), and groupspecific component (GC) among Type 1 diabetes patients, but these results are not significant when corrected for performance of multiple tests. An increase in the Lewis-negative phenotype reported elsewhere was observed here but was not statistically significant. A distortion in the distribution of Kidd types reported elsewhere was not confirmed.

Genetic linkage analysis of the carpal tunnel syndrome

Two generations of a family with autosomal dominant carpal tunnel syndrome were studied for genetic linkage to 20 informative polymorphic blood markers. No linkage was demonstrated between the syndrome and the markers tested; exclusion of close linkage (lod score less than -2.0) was found for MNSs, ACP, GALT, GPT, GLO, Hp, Gc, and Pi.

Linkage analyses of multiple endocrine neoplasia, type 2 (MEN-2) with 23 classical genetic polymorphisms

Linkage analyses were performed in a single large family with multiple endocrine neoplasia, type 2 (MEN-2) between 23 classical genetic polymorphisms and MEN-2. We exclude close linkage of the locus for MEN-2 with ABO, ACP1, BF, ESD, Fy, GALT, GLO1, Jk, MNSs, P, PGM1, Rh and TF, as well as absolute linkage with GPT. These results raise to about 6% the proportion of the genome that has been excluded in this one family. Somewhat positive lod scores were obtained for GC (0.92 at theta = 0), GPT (0.73 at theta = 0.1) and HP (1.49 at theta = 0.05); although not statistically significant, these findings suggest regions of the genome that warrant additional study.

Expression of esterase D and other gene markers in trisomy 13.

SummaryA gene dosage effect was observed for esterase D in a patient with trisomy 13. Isoelectric focusing of hemoglobin from the same patient showed three unidentified bands. A gene dosage effect for several other enzymes was not observed in two other patients with trisomy 13.