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H Payami

Publications and source records attributed to H Payami.

45 records · Page 3Linked to original sources
PubMed1987

The affected sib method. V. Testing the assumptions.

The affected sib methods, which are used to make inferences about the genetic components of HLA associated diseases, have many underlying assumptions which may not always be realistic. These include no selective disadvantage of affected individuals, little or no recombination between the marker loci and the 'disease' locus, a single panmictic population, Mendelian segregation of the disease locus alleles and random distribution of individuals over environments. The effects of breaking these assumptions have been investigated. We have explicitly derived the haplotype sharing identity by descent (IBD) expectations for the cases of selection against affected individuals and recombination between the HLA marker loci and the 'disease' predisposing locus for affected sib trios (as was previously done for affected sib pairs). We have also derived, for both affected sib pairs and trios, the haplotype sharing expectations for non-random mating (positive assortative), admixture, meiotic drive (of disease allele carrying haplotypes), and a random versus shared environmental component for sibs. In order to assess the sensitivity of the affected sib methods to perturbations in the assumptions, the expectation spaces of haplotype sharing in affected sib pairs and sib trios under the single diallelic locus model with varying penetrances and allele frequencies are fully described. The effects on haplotype sharing and subsequent disease parameter estimation are different for each of the factors we have considered. The affected sib methods are found to be robust in many situations.

Alleles↗
PubMed1987

Analysis of genetic interrelationship among HLA-associated diseases.

We have developed a method to study the genetic relationship between any two HLA-associated diseases. We have considered the following hypotheses: (1) both diseases are caused by a common allele; (2) different alleles at the same locus predispose to the two diseases; (3) one disease is predisposed by two alleles, one of which can also lead to the second disease; and (4) different HLA-linked loci are involved in the etiology of each disease. For each hypothesis, we have derived the expected HLA haplotype-sharing distribution in sib pairs who are affected with two diseases. The comparison of the expectations indicate that, in many cases, the alternate hypotheses can be distinguished, if the sample size is appropriately large. The knowledge of the mode of inheritance of each disease is not usually necessary; however, it can greatly increase the power of the test. Analyses of data on pairwise combinations of rheumatoid arthritis (RA), autoimmune thyroid disease (ATD), and insulin-dependent (type I) diabetes mellitus (IDDM) suggest that (a) IDDM is predisposed by two HLA-linked alleles, one of which also predisposes to ATD, (b) one of the IDDM alleles also confers susceptibility to RA, and (c) although the HLA-linked susceptibilities to RA and ATD appear to be primarily due to distinct alleles, the ATD allele may also have a minor role in predisposition to RA.

Alleles↗
PubMed1986

Genetics of rheumatoid arthritis.

The haplotype sharing distribution in affected sib pairs are used to demonstrate the linkage of a susceptibility gene for rheumatoid arthritis (RA) to the HLA region. Family and population studies suggest heterogeneity in the etiology of RA.

Alleles↗
PubMed1985

The affected sib method. IV. Sib trios.

The classical sib pair method uses the expected and observed HLA (human leukocyte antigen) haplotype sharing distribution in sib pairs, who are affected with an HLA associated disease, to make inferences about the inheritance of the disease. In this paper we present the expected HLA haplotype sharing distributions in affected sib trios, and sib pairs, from families with three or more affected sibs. The underlying model for both distributions, as for the classical sib pair method, is that disease predisposition is determined by a single allele at an HLA-linked locus. The sib trio tests of hypotheses (additive and recessive), and disease parameter estimates (additive, recessive and intermediate), can be compared with those obtained from the classical sib pair analysis. In addition, the sib trio data allow parameter estimation for a general disease model to be made, if the data fall within the bounds of the expectation. This study forms the basis of later investigations which show that haplotype sharing of affected sib trios for two susceptibility alleles (negative complementation) model, which appears appropriate for insulin dependent diabetes mellitus (IDDM), moves outside the bound of the single susceptibility expectations outlined here, whereas haplotype sharing values for sib pairs are bound by the single susceptibility allele expectations. Available Caucasian IDDM data have been analysed. The results support genetic heterogeneity of IDDM.

Diabetes Mellitus, Type 1↗
PubMed1984

The affected sib method. III. Selection and recombination.

The affected sib-pair method has been used to investigate the mode of inheritance, and to estimate the "disease" allele frequency, for a number of HLA-associated diseases. One of the assumptions of the original sib-pair method is that the disease confers no selective disadvantage on affected individuals. This is obviously not the situation for most diseases. We have determined the expected HLA haplotype-sharing distribution among affected sib-pairs when selection against individuals with the disease is taken into account. We have shown that if the mode of inheritance of the selectively disadvantageous disease is recessive or additive, the original affected sib-pair analysis, ignoring selection, still estimates the true mode of inheritance, but usually yields an underestimate of the "disease" allele frequency. For intermediate and dominant models of disease predisposition, both the estimates of the degree of penetrance of the "disease" genotypes, and the "disease" allele frequency, are altered if selection is ignored in the analysis. Similarly, allowing for recombination between the "disease" locus and the HLA region does not affect the determination of the mode of inheritance of the disease if it is recessive or additive; in other cases, however, the estimate of the mode of inheritance is affected. The "disease" allele frequency is overestimated when nonzero recombination is ignored for all the modes of inheritance that have been studied.

Alleles↗
PubMed1983

The affected sib method. II. The intermediate model.

An iteration procedure is outlined which uses HLA haplotype sharing data from sib pairs in which both sibs have the disease of interest. The procedure allows estimation of the degree of dominance of the HLA linked 'disease' allele, and its frequency in the population, for intermediate models where it is assumed that individuals who do not have at least one copy of the 'disease' allele do not contract the disease. Parameter estimates from sib-pair data on multiple sclerosis, insulin dependent diabetes mellitus, haemochromatosis, coeliac disease juvenile rheumatoid arthritis, and Graves' and Hashimoto's diseases are given.

Alleles↗
PubMedDate not supplied

Apolipoprotein E epsilon4 is associated with neuronal loss in the substantia nigra in Alzheimer's disease.

Apolipoprotein E epsilon4 (ApoE epsilon4) is associated with an earlier age at onset of Alzheimer's (AD) and possibly Parkinson's disease, suggesting a general role for ApoE epsilon4 in neuronal plasticity. Among 31 prospectively assessed subjects with pathologically confirmed AD (without Lewy bodies), epsilon4+ subjects had a longer duration of disease (by 2.8 years, p = 0.04). Only cell loss in the substantia nigra (p = 0.002) was associated with epsilon4. Neither neurofibrillary tangles nor plaque counts were associated with epsilon4. Cell counts of pigmented neurons in single midbrain sections in epsilon4+ specimens were 72% of those in epsilon4- substantia nigra (p = 0.04). These findings confirm that cell loss in the substantia nigra is associated with epsilon4 in AD. Copyrightz1999S.KargerAG,Basel

Age of Onset↗