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Biomedical subjects

D F Roberts

Publications and source records attributed to D F Roberts.

At least 19 recordsLinked to original sources

Social class and diachronic trends in physique in young university women.

In a large sample of female students admitted to the University of Warwick in the period 1971-86, physique as measured by height, weight and ponderal index was examined in relation to family variables and socioeconomic class. Stature and weight both show a secular tendency to increase, and there is no indication of any slowing of rate. The different social classes do not participate equally in these trends, in a way that is difficult to reconcile with the attribution of the diachronic changes to simple improvement in environmental conditions. Maternal competence is suggested as a possible factor in the pattern of class difference.

Adolescent

P blood group phenotype, proteus antibody titres, and rheumatoid arthritis.

The interrelationships between P blood group phenotype, proteus antibodies and rheumatoid arthritis (RA) were investigated in 140 patients with RA and 114 of their siblings who did not have RA. In the group with RA P2 subjects had significantly higher titres of proteus antibodies than P1 patients. This was not observed in the group without RA, or for antibodies to Escherichia coli. Although C reactive protein was the best predictor of proteus antibodies in the group with RA, the P blood group had an independent and significant influence. These observations suggest a testable model in which asymptomatic carriage of proteus in the urinary tract may lead to antibody production, which in turn may be important in the pathogenesis of RA.

Acute Disease

Contribution of inherited factors to rheumatoid arthritis.

A total of 231 sibships of the same sex (186 female, 45 male), in which the proband had classical or definite rheumatoid arthritis (RA) have been selected from rheumatology clinics. Each sibship member was questioned about symptomatic joints, which were then examined. Hospital records, radiographs, and rheumatoid factor measurements allowed each sibling to be classified as having classical, definite, probable, or no RA. Each sibling was typed for HLA-A and B and was classified as sharing two, one, or zero HLA haplotypes with the proband. Concordance rates for classical and definite RA were three times greater in sibships of women than of men (9.3 v 3.0%). Concordance rates in HLA identical sibships were twice those in hemi- and non-identical sibships (15.5, 7.1, and 5.2%, respectively). Probable RA was more common in male and HLA hemi- and non-identical sibships. These results suggest that female sex and the two inherited HLA haplotypes are important for the presence and expression of RA. Although environmental factors may be shared more in twins than siblings, a concordance rate of 20.5% in seropositive HLA identical sibships of the same sex compared with 30% in monozygotic twins suggests that sex and HLA type account for about two thirds of the inherited risk of RA.

Arthritis, Rheumatoid

Effect of disease severity on rheumatoid arthritis concordance in same sexed siblings.

To assess the factors in a proband with rheumatoid arthritis (RA) that might predict the occurrence of the disease in siblings, 240 same sexed sibships (190 female, 50 male) in which the proband had classical or definite RA were clinically and immunologically documented. Sibship concordance rates were consistently higher for features of severe disease in the proband, reaching statistical significance for a clinical score of disease severity (the SS index). This trend for increasing disease severity to be associated with increasing sibship concordance rates could not be accounted for by age or disease duration of the proband. These results suggest that siblings of probands with severe RA are at greater risk of developing RA than those of probands with mild disease.

Age Factors

Population variation in molecular polymorphisms of the short arm of the human X chromosome.

Five DNA probes (RC8, 754, XJ 1-1, pert 87.8, and L1.28) from the short arm of the human X chromosome were investigated in samples from five populations (English, Nigerian, Chinese, Muslim, and Hindu from India). The variation in the allele frequencies of several probes between different groups was significant. The average heterozygosity in females of the five populations ranged from 32% to 51%. The genetic distance between the five groups was compatible with that using traditional polymorphic systems. There is an interesting suggestion of longitudinal cline for allele *2 (9 kb) detected with probe L1.28. The X-linked RFLPs are useful genetic markers for anthropological studies.

Alleles

Consanguinity and multiple sclerosis in Orkney.

For all patients with multiple sclerosis in Orkney who were alive in 1974 or who had died during 1958 to 1974, pedigree data were analysed. The relationship between their parents, expressed by kinship coefficients, was compared with that between parents of matched controls. The closer relationship between parents of patients suggests that it is the genes that are shared by a patient's parents, and that he inherits from both, that influence his susceptibility to multiple sclerosis.

Consanguinity

Genetic epidemiology of Down's syndrome in Shetland.

Pedigrees of all known cases, on Shetland, of Down's syndrome, cytogenetically confirmed as trisomy 21, and of a control for each patient matched by birth date, sex and birth place, were traced over a minimum of eight generations. Mean kinship coefficients in all pairs of Down's syndrome patients and in all pairs of controls were similar. The kinship between the father and mother of each case shows that the parents are more closely related than the general level of relationship in the population, suggesting some recessive element in the etiology. It is argued that the effect of the resulting increased homozygosity would be to prevent the loss of the conceptus that occurs in the majority of trisomy 21 conceptions.

Adult

Factor B (BF) allotypes and multiple sclerosis in north-east England.

A significant decrease in the frequency of BF*F allele and an increase of BF*F1 allele was found in 101 clinically definite multiple sclerosis patients compared to 270 normal controls from North-East England. In Dw2 types 41 patients and 60 controls, only the rare allele BF*F1 showed a significant increase in the patients group. For the common BF*S allele a significant increase was found in Dw2+ patients compared to the Dw2- patients, but a slight similar increase observed in Dw2+ controls did not attain significance. This increase in the patient group is attributed to a strong linkage disequilibrium between BF*S and Dw2 alleles. No such linkage disequilibrium exists in the normal controls. There is a suggestion that the BF*S and Dw2+ alleles are more prevalent in chronic progressive patients, implying that in Dw2+ patients BF may influence the progression of the disease.

Alleles

Autosomal dominant inheritance of autoantibodies to thyroid peroxidase and thyroglobulin--studies in families not selected for autoimmune thyroid disease.

Recently the tendency to produce autoantibodies to thyroid peroxidase (TPO Ab) and thyroglobulin (Tg Ab) was shown to be inherited as an autosomal dominant characteristic in women but not in men. Because of potential bias in this study which was carried out in families with autoimmune thyroid disease (AITD), the inheritance of thyroid autoantibodies has been evaluated in 49 families unselected for autoimmune thyroid disease. Among these families (24 with facioscapulohumeral disease, 10 with Friedreich's ataxia, and 15 with schizophrenia) the prevalences of TPO Ab and Tg Ab were 27.8% and 26.7%, respectively, in women and 9.2% and 11.7%, respectively, in men. In 40 families where one or more individual had TPO Ab and/or Tg Ab, segregation analysis showed that the tendency to make antibodies was consistent with a Mendelian dominant trait in women but not in men. In young women, however, the prevalence of both TPO Ab and Tg Ab increased with age, rising from 14% and 10%, respectively, at age 15-24 to 35% and 40% at age 35-44. As this is inconsistent with a simple dominant hypothesis, a further segregation analysis by age was carried out in the families unselected for thyroid disease together with 16 pedigrees with AITD previously studied and two additional large AITD families. The results of the combined analysis provided strong support for the hypothesis of dominant inheritance but also showed significant reduction in gene expression among women aged 15-24 yr.

Adolescent

Population structure of the Peljesac Peninsula, Yugoslavia.

We gathered serogenetic and parent-offspring migration data from 604 residents of 7 villages on the Peljesac peninsula in southern Yugoslavia. A variety of population genetics and multivariate statistics models and procedures give a concordant picture of the population structure of this region. Extensive migration is the dominant microevolutionary force patterning the variation seen today. Multiple population bottlenecks have also occurred over the past few centuries as a result of disease, famine, war, economic failure, and founder events, making it likely that genetic drift has been an important factor in the history of this population system.

Adult

Migration and genetic structure in Northumberland.

To understand the genetic variation that occurs among regions of northern England, we estimated migration from places of birth and residence in the last two generations for a sample of 1367 families in Northumberland. There has been an increase in kinship among regions, compatible with the increased mobility of recent decades, but the kinship patterns suggest that any regional gene frequency differences have remained relatively undiluted. Comparison of kinship and geographic distance between regions indicates that geographic location is an important determinant of genetic structure.

Blood Grouping and Crossmatching

Genetic polymorphisms in Transkei Bantu.

Data are presented on blood group, serum protein and red cell enzyme polymorphisms in a sample of Transkei Bantu. The gene frequencies, compared with those in other populations in Southern Africa, show general similarity to other Bantu from Transkei and neighbouring regions, and particularly to the southern Sotho and Nguni. Some admixture from San is suggested by the directions in which frequencies in a number of systems diverge.

Black People

The contribution of HLA to rheumatoid arthritis.

The contribution of genes within the major histocompatibility complex to rheumatoid arthritis has been calculated (Rotter & Landaw 1984). Separate data from hospital- and population-based studies of monozygotic twin concordance rates and sibling recurrence risks have been used, along with material from published haplotype-sharing studies. Using either source of information gives the same result, a contribution of 37%.

Arthritis, Rheumatoid

PHA-induced interferon in multiple sclerosis: association between gamma interferon and clinical and genetical variables.

Gamma interferon (INF-gamma) production, after PHA stimulation of peripheral blood mononuclear cells, from multiple sclerosis (MS) patients with the acute remitting and chronic progressive forms, in attack and remission phases, and from normal controls, was studied by immunoradiometric assay. MS patients in all these 4 clinical states of disease produced less INF-gamma (log value range from 2.55 to 2.65). MNC from the total MS patients produced significantly low levels of INF-gamma compared to the control group (log values 2.60 vs. 2.82; P = 0.001). No association between the interferon production and antigens at any HLA locus (A, B, C, Dw and Bf) was found. There was no correlation between IFN-gamma production and age, sex, duration of disease, or disability index. However there was a slight tendency to negative correlation with the progression index of the disease. The results suggest that this lower IFN-gamma production in MS may be secondary to the disease, and the primary defect may be a severe reduction of the essential lymphocyte populations required for an effective lymphokine cascade to produce the normal immune response against infection.

Adult

Population frequencies of three DNA alleles linked to the Duchenne muscular dystrophy gene.

To enquire whether the known X linked probes linked to the Duchenne muscular dystrophy gene vary in their RFLP frequencies, three probes, 754, XJ1.1, and pERT87.8, were tested in European, Indian Muslim, and West African samples. Though the average heterozygosity for the three together is fairly similar in the three populations, significant differences in allele frequencies were evident.

Alleles

HLA antigens in three populations of India.

In blood samples from a Hindu population of Uttar Pradesh (North India) and from two Muslim groups, one from Andhra Pradesh (South India) and the other from Gujurat (West India), frequencies of 38 HLA-A, -B and -C antigens were investigated. Eight antigens - A23, A25, A29, A32, Bw45, B21, Bw22 and Bw53 - were absent in the Hindu population, four different antigens - A29, Bw52, B14 and Bw42 - were absent in Hyderabad Muslims, two antigens - A31 and Bw45 - were lacking in Surat Muslims. The three populations showed considerable genetic heterogeneity. The genetic difference between the two Muslim groups was small, but the Hindu population showed pronounced differences from each of the Muslim groups.

Gene Frequency

Genetic markers in Sjögren's syndrome: the question of its genetic heterogeneity.

Genetic factors may be implicated in the causation of Sjögren's syndrome (SS) as shown by familial clustering of the disease and certain HLA associations. Non-HLA genetic markers in SS have not previously been studied in detail. In this study of 122 unrelated patients with various categories of SS and 104 control subjects, 29 genetic markers were studied (11 blood groups, 5 serum proteins and 13 red-cell enzymes). Almost all systems showed a considerable range of gene frequency among the various subgroups of patients with SS but only a few attained statistical significance (C3 and GPT). Multivariate (kinship) analysis, however, showed clear distinction between the subgroups of SS, suggesting that they are genetically distinct entities.

Alleles