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J I Rotter

Publications and source records attributed to J I Rotter.

At least 163 records · Page 9Linked to original sources
PubMed1982

Genetic heterogeneity in common disease.

It is not apparent that diabetes mellitus and peptic ulcer disease are not single polygenic diseases, but are each genetically heterogeneous, consisting of numerous distinct entities. The delineation of genetic heterogeneity has important implications for genetic counseling, treatment, and prognosis, and is essential in determining the pathophysiology and etiology of a disorder. Unless each of the distinct component diseases of a symptom complex has been identified and separated, the basic pathophysiological abnormalities cannot be identified, and a common biochemical abnormality will not be found in all affected individuals. In approaching the genetics of any common disease disorder in man, heterogeneity must first be unmasked, and genetic and pathogenetic studies must be separately performed in each of the component, etiologically distinct disorders producing the aberrant phenotype.

Carbohydrate Metabolism, Inborn Errors↗
PubMed1982

Minor chromosomal variants and major chromosomal anomalies in couples with recurrent abortion.

One hundred three women with prior histories of recurrent spontaneous abortion and 81 of their mates were karyotyped with Q-banding during 1976-1980. Recurrent abortion was defined as two or more spontaneous pregnancy losses; no couple with a previous malformed fetus or child was included. These cases were reviewed in order to examine the possible contributions of minor polymorphic chromosomal variants and major chromosomal abnormalities to recurrent spontaneous pregnancy loss. Balanced translocations were detected in four women and two men in the study; mosaic X aneuploidy was noted in one woman. Quantitative (1 qh, 9qh, 16qh, Yqh) and qualitative (3c, 4c, 13p, 13s, 14p, 14s, 15p, 15s, 21p, 21s, 22p, 22s) heterochromatic polymorphisms were blindly assessed and compared with a control group. Cases and controls did not differ in the frequency of any qualitative polymorphisms or in the length of any quantitative polymorphism. Thus, while major parental cytogenetic aberrations are significantly associated with fetal wastage, these data suggest that minor polymorphic chromosomal variants do not play an important role in the etiology of recurrent spontaneous abortion.

Abortion, Habitual↗
PubMed1981

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.

Blood Group Antigens↗
PubMed1981

Two locus models for gluten sensitive enteropathy: population genetic considerations.

Familial occurrence of coeliac disease (gluten-sensitive enteropathy, GSE) is well known, but the mode of inheritance remains unclear. Pena et al proposed that the genetic basis for GSE was due to disease-predisposing alleles at two loci: DRw3 at the HLA-D locus and a GSE-associated B-cell alloantigen at another, unlinked locus. They concluded that clinical disease required one DRw3 (dominant inheritance) and two B-cell alloantigen alleles (recessive inheritance), but the observed gene frequencies were not consistent with the observed disease prevalence. Here we examine the gene frequencies allowed, assuming a 2-locus model, under the constraints of known disease prevalence limits and the segregation ratio calculated from 42 published families. The gene frequencies found by Pena et al predict the segregation ratio observed in the published pedigrees and the best estimates of disease prevalence of GSE, provided 1) a 2-locus model is assumed and 2) both loci exhibit recessive inheritance. The segregation ratio appears incompatible with a 2-locus dominant-recessive model without assuming reduced penetrance.

Celiac Disease↗
PubMed1981

Gastric and duodenal ulcer are each many different diseases.

It is becoming increasingly apparent that peptic ulcer is not one disease, but a genetically, etiologically, and pathogenetically heterogeneous group of diseases that share a common endpoint, an ulcer crater in those parts of the gastrointestinal tract exposed to acid and pepsin. The evidence that both gastric and duodenal ulcer are each many different diseases is reviewed and a classification of the peptic diseases is proposed. The implication of this extensive heterogeneity is that each of the disorders leading to peptic ulcer may have a distinct etiology, pathophysiology, genetics, and natural history, and thus may be amenable to different modes of therapy and prevention. Only through the complete delineation of each of the disorders leading to peptic ulcer will specific diagnosis, prognosis, and treatment be possible for peptic ulcer patients and their families.

Duodenal Ulcer↗
PubMed1981

The genetics of the glucose intolerance disorders.

Genetic heterogeneity, the concept that diabetes can have many different causes, was first suggested by the existence of rare genetic syndromes with diabetes, ethnic differences in clinical features and genetic heterogeneity of animal models. Genetic heterogeneity is now considered to be firmly established by family, twin, metabolic, immunologic and HLA disease association studies that separate idiopathic diabetes into insulin-dependent types (juvenile-onset type) and noninsulin-dependent types (maturity-onset type). Further heterogeneity is being demonstrated within each of these broad groups of disorders--within insulin-dependent diabetes using the HLA antigens and immunologic studies, and within noninsulin-dependent diabetes using such criteria as obesity, insulin response, age of onset and chlorpropamide-primed alcohol-induced flushing. This heterogeneity has major implications for the research and care of our diabetic patients since the precise etiology, risk of complications and genetic counseling are likely to vary among these different disorders that result in diabetes.

Animals↗
PubMed1981

Family studies of hypergastrinemic, hyperpepsinogenemic I duodenal ulcer.

Antral G-cell hyperfunction is a rare cause of hypergastrinemia, hyperchlorhydria, and duodenal ulcer disease. We found evidence for a familial basis for this disorder. The probands were two young men with aggressive duodenal ulcer who had basal and postprandial hypergastrinemia, hyperpepsinogenemia I, and basal and pentagastrin-stimulated hyperchlorhydria. All characteristics returned to normal after antrectomy and vagotomy. Antral gastrin concentrations and quantitative G-cell counts were normal, indicating hyperfunction of G-cells rather than hyperplasia. Four of 10 first-degree relatives of the two patients shared with them the combination of postprandial hypergastrinemia and hyperpepsinogenemia I. The aggregation of these abnormalities in tow families, each identified by a proband with hypergastrinemic, hyperpepsinogenemic l duodenal ulcer, suggests that antral G-cell hyperfunction may have a genetic basis.

Adolescent↗
PubMed1981

Peptic ulcer: new therapies, new diseases.

Although hospitalizations and deaths attributable to peptic ulcer have decreased notably during the past decade, it is not certain whether this decrease is because of reduced incidence of new cases or changes in other factors, such as the severity of the disease. Several genetic traits associated with peptic ulcer have been recognized. Hyperpepsinogenemia I is the most prevalent. Peptic ulcer is a heterogeneous group of disorders with multiple genetic and environmental causes. One manifestation of the diversity of ulcer disease is the variety of physiologic abnormalities seen in patients. The use of endoscopy has enabled more reliable evaluation of new treatments. Histamine H2-receptor antagonists are the dominant mode of treatment, but increasing attention is being given to agents that enhance the resistance of the mucosa to injury, such as prostaglandins. Because of the lower frequency of side effects, proximal gastric vagotomy is gradually replacing truncal vagotomy with drainage. The possibility that endoscopic treatments, such as laser coagulation, may reduce mortality from bleeding ulcers is being investigated.

Duodenal Ulcer↗
PubMed1981

Genetic heterogeneity in diabetes mellitus and diabetic microangiopathy.

Diabetes mellitus is a heterogeneous group of disorders associated with glucose intolerance. It appears that the prevalence and severity of diabetic microangiopathy differs between the different diabetic syndromes, but the extent of this heterogeneity and the cause and degree of the angiopathic differences is still unknown. Since glucose intolerance can be produced by a large number of different etiologic factors and pathogenetic mechanisms, it is not inconceivable that diabetic microangiopathy could also be due to a number of different factors. Delineation of the extent of the genetic heterogeneity in diabetes, the relationship between the pathogenesis of the glucose intolerance and the microangiopathy, and the prevalence and severity of the microangiopathy in each of the diabetic syndromes will have profound implications on the prognosis and therapy of each individual diabetic patient.

Blood Glucose↗
PubMed1981

The genetics of gastritis and peptic ulcer.

Genetic studies help to explain the pathogenesis, natural history, and nosology of the spectrum of gastroduodenal disorders encompassed by atrophic gastritis-pernicious anemia, gastric cancer, and peptic ulcer. All these disorders aggregate within families, and twin and disease-association studies have demonstrated that this aggregation has a genetic basis. Modern genetic studies are demonstrating that each of these disorders comprises several different diseases, and that many of the biochemical, physiologic, or immunologic abnormalities in such patients have a genetic basis. Thus, family members at risk can be identified. The optimum therapy and prevention of these diseases should ultimately depend on the specific genetic predisposition of the individual patient and family, and the recognition of individual susceptibilities to specific environmental influences.

Adenocarcinoma↗
PubMed1981

The modes of inheritance of insulin-dependent diabetes mellitus or the genetics of IDDM, no longer a nightmare but still a headache.

The discovery of HLA antigen associations with juvenile-type insulin-dependent diabetes mellitus (IDDM) provided strong evidence separating this disorder, or group of disorders, from maturity-type noninsulin-dependent diabetes, as well as adding to the evidence for an immunologic pathogenesis. In addition, it was hoped that the use of these disease-marker associations in appropriate studies might clarify the genetics of IDDM. While these associations have provided a useful tool to further investigate the genetics and pathogenesis of IDDM, the mode or modes of inheritance of this group of disorders remain an area of great controversy. Susceptibility to IDDM is currently being proposed as being inherited as a single autosomal dominant, as a single autosomal recessive, as recessive and some dominant forms, in an intermediate gene dosage model, in a heterogeneous three-allele or two HLA loci model, and as a two-locus disorder. The arguments for each of these proposals is presented, as well as the problems of each. We surmise that the weight of evidence supports the heterogeneity hypothesis but that the modes of inheritance of IDDM will be fully resolved only when we can more reliably identify the diabetogenic genotype, rather than being limited in our investigations to the study of only full-blown clinical disease.

Chromosome Mapping↗
PubMed1980

A three-allele model for heterogeneity of juvenile onset insulin-dependent diabetes.

A three-allele model is presented for the inheritance of 'juvenile' insulin-dependent diabetes mellitus (IDDM). The model postulates a susceptibility locus S tightly linked to the HLA complex. The model incorporates relative-risk and HLA-association data from the literature which suggest genetic heterogeneity within IDDM, together with population prevalence, twin and sib concordance rates, and distortions in HLA-haplotype concordance values for affected sib pairs. The model appears to provide a reasonable fit to existing data. It predicts low penetrances for some, but not all, genotypes and a strong association between HLA B8 and one of the S alleles. The model makes additional specific predictions about how different forms of IDDM are distributed in sporadic and familial cases. These predictions can be tested in future genetic-epidemiologic studies.

Alleles↗
PubMed1980

Racial differences in juvenile-type diabetes are consistent with more than one mode of inheritance.

The ratio of the prevalences of insulin-dependent type (juvenile) diabetes (IDDM) in blacks and Caucasians is examined. It has been argued that this ratio is of the same order as the estimated proportion of Caucasian genes in the American black population. It has been further argued that this observation, together with an assumption of equal penetrances in the two races, is consistent with autosomal dominant inheritance for IDDM. The present paper shows that the ratio is equally compatible with a three-allele model which, moreover, incorporates observed immunogenetic heterogeneity within IDDM. This three-allele heterogeneity model exhibits some features of both dominant and recessive inheritance. The model predicts that, compared with Caucasians, there will be less pancreatic autoimmunity in the black IDDM population and lower recurrence risks to relatives of black diabetics. These predictions can be tested in future studies.

Alleles↗
PubMed1980

Second-order approximations of ascertainment probabilities.

A second-order correction is derived for the usual first-order order approximation to the probability of ascertaining a pedigree. Both the first- and second-order approximations are compared to the exact ascertainment probability for selected examples of monogenic and polygenic traits. The second-order approximation is shown to be accurate within 10% when the individual ascertainment probability is less than 0.2, for most cases examined. In all cases, the first- and second-order approximations provide upper and lower bounds, respectively, for the exact ascertainment probability.

Humans↗