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J H Edwards

Publications and source records attributed to J H Edwards.

At least 55 records · Page 3Linked to original sources
PubMed1989

Familiarity, recessivity and germline mosaicism.

In man evidence of autosomal recessive disease is usually based on a high sib risk, absence of parent-child transmission and increased consanguinity. Discrimination from what are sometimes termed multifactorial disorders and their associated environmental effects is usually based on the latter having a lower recurrence risk, an increased recurrence risk after a second affected child and no increase in consanguinity. Another cause of familial disorders with recurrence restricted to sibs which has received little attention is germline mosaicism for a mutation expressed as a dominant. If, for example, an embryonic mutation resulted in half the precursors of the germ cells carrying a mutation with dominant expression, then the proportion of haploid nuclei conveying the mutation, which is the recurrence risk, would be a quarter. If severity precluded reproduction the disorder would tend to be classified as a recessive. While germline mosaicism will rarely be expressed with such a high recurrence risk, the estimation of this risk in rare disorders is difficult due to extreme and unpredictable bias in ascertainment.

Consanguinity↗
PubMed1989

Chromosome maps of man and mouse. IV.

Current knowledge of man-mouse genetic homology is presented in the form of chromosomal displays, tables and a grid, which show locations of the 322 loci now assigned to chromosomes in both species, as well as 12 DNA segments not yet associated with gene loci. At least 50 conserved autosomal segments with two or more loci have been identified, twelve of which are over 20 cM long in the mouse, as well as five conserved segments on the X chromosome. All human and mouse chromosomes now have conserved regions; human 17 still shows the least evidence of rearrangement, with a single long conserved segment which apparently spans the centromere. The loci include 102 which are known to be associated with human hereditary disease; these are listed separately. Human parental effects which may well be the result of genomic imprinting are reviewed and the location of the factors concerned displayed in relation to mouse chromosomal regions which have been implicated in imprinting phenomena.

Animals↗
PubMed1989

The locus positioning problem.

The likelihood method of optimizing the position of loci within a given order using data from pairs of loci is discussed in relation to Fisher's paper of 1922 and to recent data on chromosome 22 in man.

Animals↗
PubMed1989

Immunoregulatory proteins in bronchoalveolar lavage fluid. A comparative analysis of pigeon breeders' disease, sarcoidosis and idiopathic pulmonary fibrosis.

Bronchoalveolar lavage fluid (BALF) cell profiles, interleukins 1 and 2, (IL-1 and IL-2) and soluble interleukin 2 receptor (IL-2R) levels from patients with pigeon breeders' disease (PBD) (n = 24) and asymptomatic pigeon breeders (n = 10) were compared with those from patients with active sarcoidosis (n = 11), inactive sarcoidosis (n = 10), idiopathic pulmonary fibrosis (n = 25) and normal subjects (n = 10). BALF total cells, lymphocytes and OKT4 receptor-bearing lymphocytes/ml were higher in PBD and active sarcoidosis compared with normals (P less than 0.02 all comparisons). In the asymptomatic pigeon breeders bronchoalveolar (BA) lymphocyte numbers/ml were higher than controls (P less than 0.01) producing a subclinical lymphocytic "alveolitis" in 80% of subjects, although compared with symptomatics, % OKT4 (helper) cell numbers were lower (P less than 0.05). OKT4/OKT8 ratios in both groups were normal, whereas in active sarcoidosis ratios were higher (P less than 0.05) but with considerable overlap. Mean levels of IL-1 and IL-2 were raised in the BALF from all groups compared with normals (P less than 0.01 all comparisons), IL-2 being higher in active sarcoidosis and IPF compared with PBD (P less than 0.01). There was no significant difference in detectable BALF soluble IL-2R between patient groups, although its levels correlated positively with IL-1 (22 paired samples from all groups (rs = 0.8, P less than 0.02) and negatively with % and T-lymphocytes/ml in PBD (rs = 0.75, P less than 0.02, rs less than 0.8, P less than 0.01). However, when BALF soluble IL-2R is expressed in terms of T lymphocytes/ml of epithelial lining fluid (ELF), asymptomatic pigeon breeders had significantly higher levels than their symptomatic counterparts (P less than 0.01). It is concluded that percentage lymphocytes [corrected] are similar in both groups of pigeon breeders, although those with PBD had increased numbers of OKT4 (helper) cells. Patients with active sarcoidosis could not be reliably differentiated from those with acute PBD on the basis of BAL cell profiles. Our results suggest that IL-1 leads to soluble IL-2R formation and that continued antigenic stimulation, as with inhaled pigeon allergens, results in a down regulation of BALF IL-2. Excess BALF soluble IL-2R on a cellular basis suggests a mechanism by which some pigeon breeders remain asymptomatic.

Adolescent↗
PubMed1988

Neurofibromatosis.

Explore the source record for details and available documents.

Achondroplasia↗
PubMed1988

The importance of genetic disease and the need for prevention.

Until recently the effects of disease could only be reduced by prevention and treatment. It is now possible to interrupt development after fetal diagnosis. This prevents birth, but not the cause of the disease, and is usefully termed 'avoidance'. Genetic disorders are the consequence of mutational events in the past, including the remote and the immediate past, and prevention, in its true sense, can only be applied to preventing further mutations. This requires a knowledge both of the mechanism of mutation and of the mutagens to which populations and individuals are exposed, and the maintenance of public health requires the collection of data relevant to mutational disease.

Genetic Diseases, Inborn↗
PubMed1988

The analysis of close linkage in large families.

In large families, if two closely linked loci both have rare alleles and several distant members are ascertained through one having rare alleles at both loci, simple estimates of their recombination fraction are possible. This information is free from errors due to both reduced penetrance and erratic paternity. Simple estimates based on counting will often have high efficiency and limited bias. Some problems of linkage analysis between loci with codominant expression in complete three generation families are also considered. The omission of individuals of uncertain genotype at the test locus will be more efficient than their inclusion.

Female↗
PubMed1987

Heterogeneity of human C4 gene size. A large intron (6.5 kb) is present in all C4A genes and some C4B genes.

In this article we present a study showing that the human C4 genes differ in length because of the presence or absence of a 6.5 kb intron near the 5' end of the gene. DNA from individuals of known HLA, factor B, and C4 haplotypes was analyzed for restriction fragment length polymorphism (RFLP) by Southern blot analysis with C4-specific cDNA probes. The RFLP patterns obtained showed that the C4 genes are either 22.5 kb or 16 kb in length. They are referred to as long and short C4 genes, respectively. A population study was carried out to examine the distribution of the gene size according to C4 allotypes and haplotypes. Long C4 genes included all C4A genes studied and also some C4B allotypes, e.g., B1 on most C4 A3B1 haplotypes. Similarly, C4B null genes were found to be of the long form. Other C4B allotypes tested were found to be coded for by short C4 genes, including B2, B1 in C4 A6B1 and C4 AQOB1 (with a single C4B gene haplotype).

Complement C4↗
PubMed1987

Chromosome maps of man and mouse, III.

Data on loci whose positions are known in both man and mouse are presented in the form of chromosomal displays, a table, and autosomal and X-chromosomal grids. At least 40 conserved autosomal segments with two or more loci, as well as 17 homologous X-linked loci, are now known in the two species, in which mitochondrial DNA is also highly conserved. Apart from the Y, the only chromosome now lacking a conserved group is human 13. Human 17 has a single conserved group which includes both short and long arms, and so may have remained largely intact in mammalian evolution. Human and mouse chromosomal maps show the approximate locations of homologous genes while the mouse map also shows the positions of translocations used in gene location.

Animals↗
PubMed1987

Antibodies to bird serum proteins in confectionery workers exposed to egg spray.

In an extended study of group of confectionery workers sensitized by exposure to egg spray, it was found that their blood serum contained antibodies to avian serum proteins. Comparison of the ratio of IgG antibodies determined by ELISA to egg yolk 'livetins' and pigeon serum in these patients and in pigeon breeders showed that the phenomenon is entirely due to immunological cross-reactivity among avian blood serum proteins. These avian serum proteins in hens' eggs, not ovalbumin, were identified as the major sensitizing antigens.

Egg Proteins↗
PubMed1987

The locus ordering problem.

Studies of phenotypes defined by codominant alleles at two or more loci in three-generation families allow haplotypes to be deduced. These data are easily summarized by the Mendelian convention of upper and lower case, with case defining phase rather than nature. In two-generation families haplotypes may be inferred with high precision for closely linked loci even if an allele at one locus is recessive. Coding procedures are discussed and a simple solution to inferring the most likely order of three or more loci, and defining its likelihood compared with other orders, is presented.

Chromosome Mapping↗
PubMed1987

An exclusion map for Von Recklinghausen neurofibromatosis.

By using all the genetic linkage data available between Von Recklinghausen neurofibromatosis (VRNF) and various loci on the autosomes, a graphical display of all the non-excluded areas is presented. The probability of VRNF being on any of the 22 autosomes is also shown. The exclusion map presented is for 90 markers that have been localised relatively accurately. Data are also presented for a further 24 markers that have not yet been adequately localised. This exclusion map shows that most of the genome has been excluded as a likely location of any locus responsible for this disorder in the majority of families. Chromosomes 5, 10, 17, and 18 remain largely unexcluded. Concentration on these parts of the genome should help in the identification of the site of the VRNF gene.

Chromosome Mapping↗