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S Hasstedt

Publications and source records attributed to S Hasstedt.

10 recordsLinked to original sources
PubMed1997

Do non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) share genetic susceptibility loci? An analysis of putative IDDM susceptibility regions in familial NIDDM.

Non-insulin-dependent diabetes mellitus (NIDDM) has been viewed as genetically and physiologically distinct from insulin-dependent diabetes mellitus (IDDM), yet many of the recently suggested IDDM susceptibility loci are likely to increase the risk of diabetes through nonautoimmune mechanisms. To test the hypothesis that the IDDM susceptibility loci include important NIDDM susceptibility loci, we tested the linkage of 14 putative susceptibility regions with NIDDM among families and sibling pairs of Northern European descent. All regions were tested with highly informative microsatellite (simple tandem repeat) polymorphisms in up to 166 affected individuals from 42 families using both parametric and nonparametric methods (149 pairs for sibling pair analyses). We found no evidence for linkage to the majority of loci, including loci that appeared to be linked to IDDM in more than one study. We report some evidence for shared susceptibility for regions on chromosomes 1, 2, and 6. The best evidence based on multilocus affected pedigree member (APM) analysis of markers near D1S191 suggested linkage at P value .0001. This region has not yet been confirmed as an IDDM locus, and our analyses could represent a false-positive result. The role of these three regions will only be clarified by testing in additional families. In combination with other investigations in our laboratory for chromosome 11 susceptibility regions, our data generally do not provide convincing evidence that IDDM and NIDDM share common genetic factors among families of Northern European descent with ascertainment of two or more NIDDM siblings.

Adult↗
PubMed1996

Role of the beta 3-adrenergic receptor locus in obesity and noninsulin-dependent diabetes among members of Caucasian families with a diabetic sibling pair.

Obesity and insulin resistance are important risk factors for the development of noninsulin-dependent diabetes (NIDDM) and are prevalent among predisposed first degree relatives of diabetic individuals. Recent molecular screening and analysis of a common missense mutation of the beta 3-adrenergic receptor gene suggested this locus as a strong candidate for increased obesity, earlier age of diabetes onset, and insulin resistance. To test the hypothesis that the beta 3-adrenergic receptor locus affects diabetes susceptibility, obesity as measured by body mass index, and components of the insulin resistance syndrome, we examined the role of this region in families ascertained for two or more NIDDM siblings. Linkage analysis was conducted using both parametric and nonparametric analyses, including multipoint sibling pair analysis. We found no evidence for linkage to NIDDM as a dichotomous trait and no evidence for linkage to body mass index, waist/hip ratio, insulin levels, or glucose levels as quantitative traits or to reported age of onset among NIDDM individuals. The Trp64 Arg missense mutation was present in 11% of the population. The mutation was not associated with NIDDM, and Arg64 carriers did not have earlier NIDDM onset, higher body mass index, or higher waist/hip ratio than Trp64 homozygotes. Among relatives, Arg64 carriers had significantly lower fasting glucose levels and lower waist/hip ratios than Trp64 homozygotes, but no characteristics of the insulin resistance syndrome. We conclude that the beta 3-adrenergic receptor locus does not play an important role in NIDDM susceptibility or in the insulin resistance syndrome among members of families with a strong predisposition to NIDDM.

Adult↗
PubMed1988

Inference of a molecular defect of apolipoprotein B in hypobetalipoproteinemia by linkage analysis in a large kindred.

Heterozygous hypobetalipoproteinemia is characterized by reduced plasma concentrations of LDL cholesterol, total triglycerides, and apo B to less than 50% of normal values. The molecular basis of this disorder remains unknown. The phenotype cosegregates with a DNA haplotype of the apo B gene in an Idaho pedigree, with a maximum decimal logarithm of the ratio (LOD) score of 7.56 at a recombination rate of zero. Individuals carrying this haplotype had total cholesterol levels of 96 mg/dl, LDL cholesterol levels of 37 mg/dl, triglycerides levels of 51 mg/dl, and apo B levels of 38 mg/dl. This study strongly suggests that apo B mutations underlie hypobetalipoproteinemia, and demonstrates the power of the candidate gene approach in linkage analysis for unraveling genetic determinants in metabolic disorders of undefined etiology.

Adolescent↗
PubMed1986

Construction of a map of the short arm of human chromosome 6.

Four DNA sequences that reveal restriction fragment length polymorphisms (RFLPs) on the short arm of human chromosome 6 have been identified. Two of these sequences were isolated from recombinant DNA libraries enriched for DNA from human chromosome 6, one was isolated as a subclone from a human DNA segment having homology to an HLA class I sequence, and one was isolated by virtue of its homology to part of the insulin gene. Genetic linkage was determined among these four polymorphic sequences and several genes known to be on chromosome 6: glyoxylase I (GLO1), HLA-DR alpha, HLA-DQ alpha, and HLA-B. Additionally, two of the four RFLPs were regionally localized by using 53 deletion cell lines that had been typed for HLA-A, -B, and -DR, and for glyoxylase I. A genetic map of the short arm of chromosome 6 has been constructed on the basis of linkage studies with the eight markers. The map spans a minimum of 60 recombinational units and will be useful in the study of HLA-associated diseases.

Chromosome Mapping↗