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Biomedical subjects

A P Read

Publications and source records attributed to A P Read.

At least 73 records · Page 4Linked to original sources
PubMed1990

Linkage analysis of two cloned DNA sequences, DXS197 and DXS207, in hypophosphatemic rickets families.

The human X-linked hypophosphatemic rickets gene locus (HYP, formerly HPDR) has been previously localized by linkage analysis to Xp22.31-Xp21.3 and the locus order Xpter-DXS43-HYP-DXS41-Xcen established. Recombination between HYP and these flanking markers is frequently observed and additional markers have been sought. The polymorphic loci DXS197 and DXS207 have been localized to Xpter-Xp11 and Xp22-Xp21, respectively. We have further localized DXS197 to Xpter-Xp21.3 by using a panel of rodent-human hybrid cells and have established the map positions of DXS197 and DXS207 in relation to HYP by linkage studies of hypophosphatemic rickets families. Linkage between DXS197 and the loci DXS43, DXS85, and DXS207 was established with peak lod score values of 6.19, 0 = 0.032; 4.14, 0 = 0.000; and 3.01, 0 = 0.000, respectively. Multilocus linkage analysis mapped the DXS197 and DXS207 loci distal to HYP and demonstrated the locus order Xpter-DXS85-(DXS207, DXS43, DXS197)-HYP-DXS41-Xcen. These additional genetic markers DXS197 and DXS207 will be useful as alternative markers in the genetic counseling of some families.

Animals↗
PubMed1990

Recombination or heterogeneity: is there a second locus for adult polycystic kidney disease?

Twenty-four families with adult onset polycystic kidney disease were typed for markers flanking the PKD1 locus on chromosome 16. The aggregated results gave a significant lod score in favour of linkage to PKD1. Within this group of families two showed unusual features: recombinations, including double recombinations, and, in one family, an unexpectedly high proportion of affected people. We consider the evidence that in these families the disease might result from a mutation at a different locus, PKD2, not linked to PKD1. We suggest that a useful test is to compare the relative numbers of meioses apparently non-recombinant and doubly recombinant for markers flanking the normal disease locus, ignoring meioses recombinant for only a single marker. Using this test, neither our two families nor the data published so far on other families provide compelling evidence for the existence of a second locus for adult polycystic kidney disease. For genetic counselling in families too small to give internal evidence for or against linkage, the extra uncertainty can be handled by using a higher recombination rate.

Adolescent↗
PubMed1990

Assignment of the locus for Waardenburg syndrome type I to human chromosome 2q37 and possible homology to the Splotch mouse.

We have demonstrated close linkage between the locus for the autosomal dominant Waardenburg syndrome type I and the placental alkaline phosphatase locus on chromosome 2q37. In five families the peak lod score was 4.76 at a recombination fraction of .023. In the mouse the Splotch locus maps to near the homologous position. Splotch mice have white spotting and hearing defects, suggesting that Splotch may be the murine homologue of Waardenburg syndrome type I.

Abnormalities, Multiple↗
PubMed1989

X linked or autosomal recessive? A new approach to an old problem.

Families in which a single male is affected with a disease which might be either X linked recessive or autosomal recessive present problems in counselling. Before female relatives can be counselled, the probabilities of each mode of inheritance must be assessed, taking into account the prior probabilities, the pedigree structure, any DNA probe data, and any carrier testing data. The widely used linkage analysis package LINKAGE can be used to do the calculation, which is much simpler than the conventional Bayesian method.

Bayes Theorem↗
PubMed1989

Neural tube defect recurrence after 'partial' vitamin supplementation.

A total of 227 mothers enrolled for periconceptional multivitamin supplementation because of previous neural tube defect (NTD) births took vitamins for less than the recommended minimum period (at least 28 days before conception until two menstrual periods have been missed). Of 213 examined infants/fetuses born to these partially supplemented mothers, two had NTD, one of whom followed four previous NTDs. The observed NTD recurrence rate is similar to that observed in fully supplemented mothers. A further 14 mothers started supplements before the second missed period but after the normal time of neural tube closure. Three of their offspring had NTD. The significance of this apparently high recurrence rate is discussed.

Ascorbic Acid↗
PubMed1989

Testing for cystic fibrosis using allelic association.

A particular haplotype defined by probes XV2c, KM19, and CS.7 at the D7S23 locus was found on 90% of chromosomes which carry cystic fibrosis (CF), but on only 11% of normal chromosomes in a UK sample of CF carriers. We show how such data can be used to calculate carrier risks for people with and without a family history of CF, and give examples of clinical applications. For parents or sibs of dead CF patients, phase and genotypes can often be assigned with only 1 to 2% error. However, this method is not suitable for prenatal testing where there is no history of CF; for couples with no family history, no fetus can be shown to be at more than 2% risk of being affected.

Adult↗
PubMed1988

Patterns of exon deletions in Duchenne and Becker muscular dystrophy.

A panel of patients with Duchenne and Becker muscular dystrophy (DMD and BMD) has been screened with the cDNA probes Cf56a and Cf23a, which detect exons in the central part of the DMD gene. One or more exons were deleted in 60% of patients. The deletions were mapped and prove to be heterogeneous in size and extent, particularly in DMD. Deletions specific to DMD and to BMD are described. Half of all BMD patients have a deletion of one particular small group of exons; smaller deletions within this same group produce the more severe DMD.

Chromosome Deletion↗
PubMed1988

What a rheumatologist should know about genetics.

Rheumatic diseases are generally non-mendelian, depending on an interaction between genetic susceptibility and environmental factors. The overall role of genetic factors can be estimated from family resemblances and twin studies, while the role of individual susceptibility genes is studied by lod score analysis, haplotype sharing and population associations. Linkage analysis allows a long-range search of chromosomes for susceptibility loci, while population associations depend on much shorter-range effects. It is often very hard to tell whether an association of a disease with a marker is because the marker confers susceptibility or because it is in linkage disequilibrium with a separate susceptibility gene. When searching for individual susceptibility genes, it is important to avoid postulating models which would require an unrealistically high degree of genetic determination of the disease.

Disease Susceptibility↗
PubMed1988

A survey of neural tube defect pregnancies in north-west England.

The preliminary results are reported of the first eighteen months of a three year survey of NTD affected pregnancies in the North Western Region of England. The results are consistent with a general decline in the incidence of NTD. Prenatal screening has been available for 10 years but babies continue to be born with NTD. Supportive services are often lacking for parents having had an affected pregnancy and methods of imparting advice regarding recurrence risks have been shown to be variable and not always efficient.

Cross-Sectional Studies↗
PubMed1988

Mild and severe muscular dystrophy associated with deletions in Xp21 of the human X chromosome.

We have analysed over 300 patients suffering from Duchenne or Becker muscular dystrophy (DMD or BMD). Deletions have been characterised which encompass either the pERT87 (DXS164) locus only, the XJ1.1 (DXS206) and HIP25 loci only, or all three loci. These loci have been shown to lie within the DMD region covering several hundred kilobases (kb) of DNA. One mildly affected BMD patient possesses a deletion of at least 110 kb including exons of the DMD gene. Other patients with similar exon deletions, or smaller deletions, show the more severe phenotype typical of DMD. We conclude from these studies that the severity of the clinical phenotype cannot be explained on the basis of the size of the deletion. We discuss this in the context of candidate gene sequences.

Chromosome Deletion↗
PubMed1988

Hypomelanosis of Ito: a manifestation of mosaicism or chimerism.

We describe three patients with the cutaneous manifestations of hypomelanosis of Ito. Two, with unusual abnormalities of their toes, had a mixture of diploid and triploid cells in cultured skin fibroblasts. The published clinical descriptions of hypomelanosis of Ito and diploid-triploid mosaicism are reviewed. Chromosome heteromorphisms, HLA types, and DNA fingerprints were studied in an attempt to elucidate the origin of the disease in our patients. We conclude that hypomelanosis of Ito is a manifestation of a heterogeneous group of disorders, the common factor being the presence of two genetically different cell lines. It can result from chromosomal mosaicism or chimerism, from a postzygotic mutation, or from X inactivation. The risk of recurrence is negligible if the proband is a male; if the proband is female the risk is also low but an X linked mutation must be considered.

Chimera↗
PubMed1988

Norrie disease resulting from a gene deletion: clinical features and DNA studies.

We describe a family in which two boys with Norrie disease have a deletion of the DXS7 locus. The deletion does not extend as far distally as the OTC or DXS84 loci. A full clinical description of the patients is given to help establish the range of manifestations of Norrie disease. There is no evidence of any other X linked disease in our patients.

Abnormalities, Multiple↗
PubMed1987

Effective strategy for prenatal prediction of Duchenne and Becker muscular dystrophy.

Deletions in the gene sequence for Duchenne (DMD) and Becker (BMD) muscular dystrophy were detected in affected males with four cDNA probes, Cf56a, Cf23a, Ca1A, and Cf27. Most of the deletions were seen with only one of the probes. Cf23a detected all BMD deletions seen with Cf56a and some that were not. The same markers also detected restriction fragment length polymorphisms for those cases where deletions were not evident. The probes were also used successfully for prenatal diagnosis in two families each with two DMD affected males. In DMD families successive application of probes Cf56a, Ca1A, and Cf27 will give a 70% chance of detecting the mutation. BMD families should first be screened with the Cf23a probe.

Chromosome Deletion↗
PubMed1987

Clinic experience of prenatal diagnosis of cystic fibrosis by use of linked DNA probes.

96 families at risk of having a child with cystic fibrosis have been counselled about prenatal diagnosis by the use of linked DNA probes. Of the first 30 pregnancies 9 children have been born and confirmed to be free from CF, as predicted; 8 pregnancies were terminated (1 of these was found to be miscarrying at time of termination); 12 pregnancies, in which the fetuses are predicted to be unaffected, are in progress; and 1 has miscarried. No couple with a prenatal prediction of CF decided to continue with the pregnancy. 1 pregnancy was terminated because of a 50:50 chance of an affected fetus. In 1 twin pregnancy the affected fetus was selectively aborted, and the other baby was confirmed after birth to be unaffected, as predicted. In the other twin pregnancy the two chorionic plates could not be samples separately; the pregnancy was continued on the basis of normal findings for the lower plate, and both twins have turned out to be normal. Many couples at risk see early prenatal diagnosis as a way to help them have an unaffected child.

Abortion, Induced↗