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Biomedical subjects

M A Spence

Publications and source records attributed to M A Spence.

At least 91 records · Page 5Linked to original sources
PubMed1986

Genetic linkage studies in Alzheimer's disease.

We studied 18 families with Alzheimer's disease in family members, under the assumption that the disease is due to a single gene with an autosomal dominant form of inheritance. There was no evidence of linkage of Alzheimer's disease with any of 27 phenotypic gene markers analyzed, but close linkage for the Rh and MNS blood group loci was excluded.

Alzheimer Disease↗
PubMed1986

Cowden disease: gene marker studies and measurements of epidermal growth factor.

Cowden disease (CD) is a familial syndrome characterized by tumors of the skin, oral mucosa, breast, thyroid, and intestinal epithelium. Since the syndrome is inherited as an autosomal dominant, we examined a battery of gene markers in a family with CD to detect linkage between the CD gene and known marker genes. There was no positive evidence for linkage of a CD locus with any of the markers; other investigators can add to our data to confirm and extend these findings. Additionally, we measured epidermal growth factor (EGF) in body fluids from CD patients and controls to determine if elevated EGF levels might be responsible for the widespread epithelial proliferation in CD. EGF levels in saliva, serum, plasma, and urine were similar in CD patients and control subjects. Although alterations in growth factors or their receptors may play a role in CD, excess circulating EGF is not responsible for the manifestations of the syndrome.

Adult↗
PubMed1986

Major gene determination of liability to cleft lip with or without cleft palate: a multiracial view.

Despite nearly half a century of intensive investigation, the etiology of non-syndromic cleft lip with or without cleft palate (CL +/- P) remains unknown because most studies have been descriptive rather than analytic. This study summarizes rigorous analyses of CL +/- P in the families of non-syndromic, CL +/- P surgical probands from three populations: Denmark, London, England, and Shanghai, China. Three main conclusions could be drawn from the results. The data provide no support for the multifactorial threshold model summarized by Carter (1976) and most often proposed to explain the etiology of CL +/- P. Each dataset provides evidence that there may be a major gene for liability to CL +/- P in at least a portion of cases. The data are consistent with possible genetic heterogeneity in CL +/- P.

China↗
PubMed1986

HLA-dependent GM effects in insulin-dependent diabetes: evidence from pairs of affected siblings.

In a recent study of GM allotype frequencies in HLA-defined subsets of patients with insulin-dependent diabetes mellitus (IDDM) and similarly defined healthy sibling controls, we found evidence for an HLA-dependent GM effect on IDDM susceptibility. To circumvent problems inherent in such patient-control studies of complex diseases, we have now examined sharing of genes in the HLA and GM regions in 26 informative pairs of siblings who were both affected with IDDM. We found that: (1) in the total sample of affected sib-pairs, sharing of two HLA haplotypes was increased compared to Mendelian expectations, in agreement with many previous studies; (2) in the total sample, sharing of GM region genes (as measured by GM phenotype concordance) was not different from Mendelian expectations, given the distribution of parental mating types; and (3) affected sib-pairs who shared two HLA haplotypes showed significantly increased sharing of GM region genes compared to affected sib-pairs who shared one or zero HLA haplotypes (P = .018). These results provide new evidence for HLA-dependent effects of a locus at or near GM on susceptibility to IDDM.

Diabetes Mellitus, Type 1↗
PubMed1985

Glutamate pyruvate transaminase null allele (GPT0) in the Navajo.

During genetic linkage studies of retinitis pigmentosa in a Navajo Amerindian family, an apparent null allele of erythrocyte GPT (GPT0) was observed in a man and 2 of his daughters. This is the fourth description of a (GPT0) allele, the first outside of Europe and the first in the Navajo.

Alanine Transaminase↗
PubMed1985

Genetic linkage analysis of the carpal tunnel syndrome.

Two generations of a family with autosomal dominant carpal tunnel syndrome were studied for genetic linkage to 20 informative polymorphic blood markers. No linkage was demonstrated between the syndrome and the markers tested; exclusion of close linkage (lod score less than -2.0) was found for MNSs, ACP, GALT, GPT, GLO, Hp, Gc, and Pi.

Carpal Tunnel Syndrome↗
PubMed1985

Evidence for autosomal recessive inheritance in 46 families with multiple incidences of autism.

The authors ascertained 46 families with multiple incidences of autism (41 with two and five with three autistic probands). Classical segregation analyses revealed a maximum likelihood estimate of the segregation ratio of p = 0.19 +/- 0.07. This is not significantly less than 0.25, the expected value for autosomal recessive inheritance. However, it is significantly less than 0.50, the expected value for autosomal dominant inheritance. The polygenic threshold model was tested and rejected over a full range of values of heritability and ascertainment probability for these families. These results are most consistent with the hypothesis of autosomal recessive inheritance in this subset of 46 families with multiple incidences of autism.

Adolescent↗
PubMed1984

Genetic analysis of cleft lip with or without cleft palate in Danish kindreds.

The present study population consists of 2,532 families ascertained through non-syndromic cleft lip with or without cleft palate (CL +/- P) surgical probands born in Denmark between 1941 and 1971. Three samples were derived for analyses of the trait "clefted (CL +/- P) or not." Sample 1 consists of the 26 largest multigenerational families with four or more affected members. Both samples 2-MG and 2-N consist of nuclear families with at least two children and at least one proband among the children. Sample 2-MG contains 846 nuclear families derived from the kindreds with three or more generations. Sample 2-N contains a further 1,181 kindreds with only two generations, nuclear family information available. Four methods of analysis were used: 1) Pedigree analysis was performed on each of the multigenerational kindreds of Sample 1. Results were consistent with autosomal recessive inheritance in eight families and codominant inheritance in three families. These simple genetic hypotheses could not be distinguished in the remaining 15 families. 2) The goodness-of-fit of the multifactorial threshold (MF/T) model was tested in Samples 2-MG and 2-N. The MF/T model was rejected in both samples. 3) Classical segregation analysis was performed on Samples 2-MG and 2-N. Results were consistent with a possible recessive major gene for CL +/- P in Sample 2-MG, but not in Sample 2-N, and with significant admixture of sporadic cases in both samples. 4) Complex segregation analysis under the mixed model was performed on Samples 2-MG and 2-N. In Sample 2-MG, results were consistent with either the general mixed model or with an hypothesis of no major gene. In Sample 2-N, four hypotheses were equally likely: the mixed model with no polygenic component, the mixed model with the major gene component, the mixed model with no sib environmental correlation, and major gene alone. Three conclusions may be drawn: 1) The data provide no support for the MF/T model. 2) The data are consistent with the possibility of a major gene in a portion of the kindreds. 3) The data provide evidence for genetic heterogeneity for CL +/- P.

Child↗
PubMed1984

No evidence for linkage between an insulin-dependent diabetes mellitus-susceptibility locus and immunoglobulin loci KM or GM.

We studied 52 families having more than one member affected with insulin-dependent diabetes mellitus (IDDM) for linkage of an IDDM-susceptibility locus to the immunoglobulin loci KM and GM. Linkage was analyzed by the LOD score method using single-locus recessive and dominant models of IDDM inheritance, with penetrances of the disease-susceptible genotypes being dependent on age and reaching a maximum of 20% by age 40. We found no evidence for linkage of IDDM to KM or GM. Close linkage (recombination fraction less than 5%) was rejected for KM under the recessive model and for GM under both models. These results suggest either that there are no IDDM-susceptibility loci closely linked to KM or GM or that use of a single-locus model of IDDM (which ignores the effects of the susceptibility locus in the HLA region) is inadequate for their detection.

Adult↗
PubMed1984

Interaction of HLA and immunoglobulin antigens in type 1 (insulin-dependent) diabetes.

We analyzed 88 unrelated subjects with Type 1 (insulin-dependent) diabetes and 64 sibling controls (maximum one per diabetic) for associations between immunoglobulin allotype antigens (GM and KM) and Type 1 diabetes. None were found. However, we did find interactions between GM, HLA-DR, and Type 1 diabetes (significant or of borderline significance after considering the effect of multiple tests): possession of Glm(2) appeared to increase susceptibility to diabetes in individuals who had HLA-DR3 but not HLA-DR4, while possession of G3m(5) appeared to increase susceptibility in individuals who had HLA-DR4 but not HLA-DR3. These results suggest that genetic predisposition to Type 1 diabetes is partially determined by alleles at the GM locus (or a locus in linkage disequilibrium with GM) interacting with alleles at the HLA-DR locus (or a locus in linkage disequilibrium with HLA-DR).

Adult↗
PubMed1984

Genetic linkage studies of transferrin, pseudocholinesterase, and chromosome 1 loci.

Genetic linkage analysis of a pedigree with four different alleles for pseudocholinesterase (CHE1) gives a positive lod score of 0.37 at theta = 0.16 for linkage with transferrin (TF), a finding which supports previous reports of linkage between CHE1 and TF. Evaluation of linkage relations of CHE1 and TF using unreported families from our data bank fails to establish linkage with chromosome 1 loci (6-PGD, Rh, PGM1, AMY2 and FY). These results are consistent with recent studies which suggest that TF is on human chromosome 3.

Alleles↗