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E J Louis

Publications and source records attributed to E J Louis.

50 records · Page 3Linked to original sources
PubMed1990

The subtelomeric Y' repeat family in Saccharomyces cerevisiae: an experimental system for repeated sequence evolution.

The subtelomeric Y' repeated sequence families in two divergent strains of the yeast Saccharomyces cerevisiae have been characterized in terms of copy number, location and restriction site differences. The strain YP1 has 26 to 30 Y's that fall into two previously described, long (6.7 kb) and short (5.2 kb), size classes. These Y's reside at 19 of the 32 chromosome ends and are concentrated in the higher molecular weight chromosomes. Five ends contain tandem arrays, each of which has only one size class of Y's. There is restriction site homogeneity among the Y's of YP1 even between size classes. The Y's of strain Y55 contrast sharply with the Y's of YP1 in terms of copy number, location and sequence differences. There are 14 to 16 Y's, both long and short, most of which are found at different chromosome ends than those of YP1. None of these are tandemly arrayed. Four to six of the Y's appear degenerate in that they have homology with a telomere distal end Y' probe but no homology with sequences at the telomere proximal end. The majority of the Y55 Y's have the same restriction sites as in YP1. Despite the conservation of restriction sites among Y's, a great deal of restriction fragment length heterogeneity between the strains is observed. The characterized Y' repeated sequence families provide an experimental system in which repeated sequence interactions and subsequent evolution can be studied.

Biological Evolution↗
PubMed1990

Mitotic recombination among subtelomeric Y' repeats in Saccharomyces cerevisiae.

Y's are a dispersed family of repeats that vary in copy number, location and restriction fragment lengths between strains but exhibit within-strain homogeneity. We have studied mitotic recombination between members of the subtelomeric Y' repeated sequence family of Saccharomyces cerevisiae. Individual copies of Y's were marked with SUP11 and URA3 which allowed for the selection of duplications and losses of the marked Y's. Duplications occurred by ectopic recombinational interactions between Y's at different chromosome ends as well as by unequal sister chromatid exchange. Several of the ectopic duplications resulted in an originally Y'-less chromosome end acquiring a marked Y'. Among losses, most resulted from ectopic exchange or conversion in which only the marker sequence was lost. In some losses, the chromosome end became Y'-less. Although the two subsets of Y's, Y'-longs (6.7 kb) and Y'-shorts (5.2 kb), share extensive sequence homology, a marked Y' recombines highly preferentially within its own subset. These mitotic interactions can in part explain the maintenance of Y's and their subsets, the homogeneity among Y's within a strain, as well as diversity between strains.

Biological Evolution↗
PubMed1989

Nonrecombinant meiosis I nondisjunction in Saccharomyces cerevisiae induced by tRNA ochre suppressors.

The presence of the tRNA ochre suppressors SUP11 and SUP5 is found to induce meiosis I nondisjunction in the yeast Saccharomyces cerevisiae. The induction increases with increasing dosage of the suppressor and decreases in the presence of an antisuppressor. The effect is independent of the chromosomal location of SUP11. Each of five different chromosomes monitored exhibited nondisjunction at frequencies of 0.1%-1.1% of random spores, which is a 16-160-fold increase over wild-type levels. Increased nondisjunction is reflected by a marked increase in tetrads with two and zero viable spores. In the case of chromosome III, for which a 50-cM map interval was monitored, the resulting disomes are all in the parental nonrecombinant configuration. Recombination along chromosome III appears normal both in meioses that have no nondisjunction and in meioses for which there was nondisjunction of another chromosome. We propose that a proportion of one or more proteins involved in chromosome pairing, recombination or segregation are aberrant due to translational read-through of the normal ochre stop codon. Hygromycin B, an antibiotic that can suppress nonsense mutations via translational read-through, also induces nonrecombinant meiosis I nondisjunction. Increases in mistranslation, therefore, increase the production of aneuploids during meiosis. There was no observable effect of SUP11 on mitotic chromosome nondisjunction; however some disomes caused SUP11 ade2-ochre strains to appear white or red, instead of pink.

Aneuploidy↗
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

An exact test for Hardy-Weinberg and multiple alleles.

Algorithms for generating the exact distribution of a finite sample drawn from a population in Hardy-Weinberg equilibrium are given for multiple alleles. The finite sampling distribution is derived analogously to Fisher's 2 X 2 exact distribution and is equivalent to Levene's conditional finite sampling distribution for Hardy-Weinberg populations. The algorithms presented are fast computationally and allow for quick alternatives to standard methods requiring corrections and approximations. Computation time is on the order of a few seconds for three-allele examples and up to 2 minutes for four-allele examples on an IBM 3081 machine.

Algorithms↗
PubMed1986

Three-allele synergistic mixed model for insulin-dependent diabetes mellitus.

Application of the method of antigen genotype frequencies among patients to HLA-DR data pertaining to insulin-dependent diabetes mellitus substantiates the results of Rotter et al. and Thomson that a single-predisposing-allele model is incompatible with the observed data. The method is also modified to take into account the possibility of blanks (untyped antigens) in the assumed homozygotes. The rejection of all intermediate single-allele models is still obtained. A minimum of two HLA-linked predisposing components are necessary to account for the data. The patterns observed are consistent with a three-allele model, in which the two predisposing alleles interact synergistically (negative complementation). Furthermore, a model in which the DR3-associated predisposition allele is recessive in the absence of the other allele and the DR4-associated predisposing allele is additive (dominant) in the absence of the other is more consistent with the data than a model in which both alleles are recessive or additive in the absence of the other.

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↗