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Biomedical subjects

D Goldgar

Publications and source records attributed to D Goldgar.

43 records · Page 3Linked to original sources
PubMed1988

Prevalence of hemochromatosis among 11,065 presumably healthy blood donors.

There is evidence that iron loading and organ damage can be prevented in patients with hemochromatosis if prophylactic phlebotomy is employed early in the disease--findings emphasizing the importance of early detection before clinical signs occur. This study was designed to determine the efficacy of transferrin saturation as a screening tool for hemochromatosis and to assess the frequency of homozygosity for the HLA-linked hemochromatosis gene in a healthy population. We screened 11,065 presumably healthy blood donors (5840 men and 5225 women). Donors with transferrin saturations of 62 percent or more after an overnight fast were considered potential homozygotes and were asked to undergo liver biopsy and pedigree analysis. The frequency of values for transferrin saturation of 62 or higher in men was 0.008 and in women 0.003. Thirty-eight persons with values higher than 62 were studied in detail; 35 underwent liver biopsy. Liver iron stores ranged from normal to markedly increased. Twelve siblings with an identical HLA match to a proband underwent liver biopsy, and 11 had increased liver iron stores. According to likelihood analysis of the pedigrees, 26 of the 38 probands were homozygotes, and 12 were heterozygotes. The estimated frequency of homozygosity was based on the data in men, because the threshold value of 62 for the transferrin saturation identified only half as many female homozygotes as expected. The frequency of homozygosity was 0.0045, corresponding to a gene frequency of 0.067. The value of population screening is demonstrated in these studies by the detection of homozygotes before clinical manifestations of hemochromatosis occur.

Adolescent↗
PubMed1988

Insulin gene in familial NIDDM. Lack of linkage in Utah Mormon pedigrees.

Although non-insulin-dependent diabetes mellitus (NIDDM) is well recognized to be an inherited disease, the genetic lesion responsible remains to be determined. Several pedigrees have been reported in which defects of the insulin gene result in glucose intolerance or diabetes in affected members, but the role of insulin gene mutations in NIDDM is unknown. To evaluate this role, we ascertained 23 Caucasian pedigrees for a diabetic individual with at least one diabetic family member, sampled the unaffected individuals by a 75-g glucose tolerance test, and prepared leukocyte DNA on all family members. Included in the pedigrees ascertained were those with both predominantly lean and predominantly obese diabetic members and four pedigrees included as insulin-dependent diabetic individual. Insulin gene involvement was evaluated via previously described restriction-fragment-length polymorphisms (RFLPs) for the insulin gene and the nearby c-Ha-Ras oncogene (HRAS). Combination of these RFLPs resulted in the ability to trace the insulin alleles in all pedigrees studied. Analysis of individual pedigrees for sharing of insulin alleles was possible in 12 pedigrees, and lack of linkage was demonstrated in 6 of them. Neither linkage nor lack of linkage could be proved in the remaining pedigrees. Analysis of the pooled pedigree data failed to demonstrate linkage under several models, including autosomal-dominant and -recessive inheritance with different sporadic frequencies of diabetes and different prevalence figures. These results show that mutations of the insulin gene and the immediately surrounding area, including regulatory regions of the insulin gene, are unlikely to account for a significant subset of NIDDM in Caucasian individuals.

Diabetes Mellitus, Type 2↗
PubMed1987

Gene for von Recklinghausen neurofibromatosis is in the pericentromeric region of chromosome 17.

Linkage analysis of 15 Utah kindreds demonstrated that a gene responsible for von Recklinghausen neurofibromatosis (NF) is located near the centromere on chromosome 17. The families also gave no evidence for heterogeneity, indicating that a significant proportion of NF cases are due to mutations at a single locus. Further genetic analysis can now refine this localization and may lead to the eventual identification and cloning of the defective gene responsible for this disorder.

Centromere↗
PubMed1987

Total bone calcium in normal women: effect of age and menopause status.

Bone density in different regions of the skeleton was measured in 392 normal women aged 20-80 years by dual photon absorpiometry. In premenopausal women, aged 25-50 years, multiple regression analysis of regional bone density on age, height, and weight showed a small significant decrease in total bone density (less than 0.01) but no significant change in other regions of the skeleton. In postmenopausal women there were highly significant decreases in all regions of the skeleton (p less than 0.001), and bone density in these areas decreased as a logarithmic function of years since menopause. Based on multiple regression analyses, the decrease in spine density and total bone calcium was 2.5-3.0 times greater in the 25 years after menopause than the 25 years before menopause. The largest change, however, occurred in the first five years after menopause. During this time the estimated annual change in spine density and total bone calcium was about 10 times greater than that in the premenopausal period. These results demonstrate the important effect of the menopause in determining bone mass in later life.

Adult↗
PubMed1987

Tightly linked markers for the neurofibromatosis type 1 gene.

Relationships among genetic markers in the region of the neurofibromatosis type 1 (NF1) gene on chromosome 17 were investigated by linkage studies in a large sample set of affected families and in a panel of 58 normal families. A new marker, pHHH202 (D17S33), was included along with two markers known to be closely linked to NF. The maximum likelihood estimate of the recombination rate between the pHHH202 and NF1 loci was found to be O. Multilocus analysis suggested the following marker order: pA10-41-(p3-6, pHHH202); the NF1 gene fell with equal likelihood between either pA10-41-p3-6 or p3-6-pHHH202. The odds against NF1 being outside this cluster of tightly linked markers were greater than 15:1.

Chromosome Mapping↗
PubMed1987

A genomic search for linkage of neurofibromatosis to RFLPs.

Our initial attempt to map NF was directed towards chromosomes 4 and 19, both of which had provided positive evidence for linkage in previous reports. This analysis showed no evidence in support of either hypothesis. Our second attempt at mapping NF was a general search of the genome, analysing a set of markers selected according to their degree of polymorphism, chromosomal location, ease of use, and availability. Data for linkage analysis were obtained from 17 multiplex families which are segregating a gene for NF. Linkage analyses were performed using PAP. Of note is the lod score of +1.17 at a recombination fraction of 0.1 between NF and the centromere of chromosome 17.

Chromosome Mapping↗