67 research outputs found
Sur l'hyperbolicit\'e de graphes associ\'es au groupe de Cremona
No full textTo reinforce the analogy between the mapping class group and the Cremonagroup of rank over an algebraic closed field, we look for a graphanaloguous to the curve graph and such that the Cremona group acts on itnon-trivially. A candidate is a graph introduced by D. Wright. However, wedemonstrate that it is not Gromov-hyperbolic. This answers a question of A.Minasyan and D. Osin. Then, we construct two graphs associated to a Vorono\"itesselation of the Cremona group introduced in a previous work of the autor. Weshow that one is quasi-isometric to the Wright graph. We prove that the secondone is Gromov-hyperbolic.Comment: 29 pages, en Fran\c{c}ai
Genetic epidemiology of single-nucleotide polymorphisms
No full textOn the causal hypothesis, most genetic determinants of disease are single-nucleotide polymorphisms (SNPs) that are likely to be selected as markers for positional cloning. On the proximity hypothesis, most disease determinants will not be included among markers but may be detected through linkage disequilibrium with other SNPs. In that event, allelic association among SNPs is an essential factor in positional cloning. Recent simulation based on monotonic population expansion suggests that useful association does not usually extend beyond 3 kb. This is contradicted by significant disequilibrium at much greater distances, with corresponding reduction in the number of SNPs required for a cost-effective genome scan. A plausible explanation is that cyclical expansions follow population bottlenecks that establish new disequilibria. Data on more than 1,000 locus pairs indicate that most disequilibria trace to the Neolithic, with no apparent difference between haplotypes that are random or selected through a major disease gene. Short duration may be characteristic of alleles contributing to disease susceptibility and haplotypes characteristic of particular ethnic groups. Alleles that are highly polymorphic in all ethnic groups may be older, neutral, or advantageous, in weak disequilibrium with nearby markers, and therefore less useful for positional cloning of disease genes. Significant disequilibrium at large distance makes the number of suitably chosen SNPs required for genome screening as small as 30,000, or 1 per 100 kb, with greater density (including less common SNPs) reserved for candidate regions
Searching for candidate genes for asthma using combined linkage and segregation analysis
No full textAllelic association between marker loci
No full textAllelic association has proven useful to refine the location of major genes prior to positional cloning, but it is of uncertain value for genome scans in complex inheritance. We have extended kinship theory to give information content for linkage and allelic association. Application to pairs of closely linked markers as a surrogate for marker x oligogene pairs indicates that association is largely determined by regional founders, with little effect of subsequent demography. Sub-Saharan Africa has the least allelic association, consistent with settlement of other regions by small numbers of founders. Recent speculation about substantial advantages of isolates over large populations, of constant size over expansion, and of F1 hybrids over incrosses is not supported by theory or data. On the contrary, fewer affected cases, less opportunity for replication, and more stochastic variation tend to make isolates less informative for allelic association, as they are for linkage.</p
A linkage tournament: affection status, parametric analysis, multivariate traits, and enhancements to variance components and relative pairs
No full textLinkage tests to localize oligogenes have been extended during the past year. Using simulated data and multiplex selection we find that several tests on affected sib pairs have comparable power and type I error. Three variants of SIBPAL2 are favoured when substantial numbers of normal sibs are included, but performance relative to the BETA benchmark degrades rapidly as normal sibs are depleted by selective sampling or typing. Neglect of this fact may explain recent failure of retrospective collaboration to confirm asthma candidates in the 5q cytokine region that are supported by other studies. A fully quantitative trait favours variance components under complete ascertainment and two options in SIBPAL2 under multiplex selection, with substantial gain in power from covariance analysis if the covariate is independent of the candidate locus. A dichotomy and liability threshold give virtually identical results in the SOLAR variance components program. Comparison with single-marker parametric analysis suggests that extension to multiple markers would be competitive with nonparametric methods in power, and superior in depth of genetic analysis. The simulated examples illustrate common problems encountered with linkage scans for oligogenes. They show that nonparametric methods provide no panacea for analytical problems posed by different phenotypes and methods of ascertainment
Méthodologie des exercices juridiques : C. Laronde-Clérac, A. de Luget, M. Flores-Lonjou
No full textLes examens commencent cette semaine à Nancy. Il est sans doute trop tard pour acquérir les bases de la méthodologie juridique, mais il est encore temps pour signaler la parution d'un ouvrage intéressant les étudiants en droit : Méthodologie des exercices juridiques, par Céline Laronde-Clérac, Agnès de Luget et Magalie Florès-Lonjou, avec la participation de Arnaud Jaulin. Prenant place parmi de très nombreux ouvrages dédiés à la méthodologie juridique, l'ouvrage se distingue par son approche..
Limb girdle muscular dystrophy type 2A (CAPN3): Mapping using allelic association
No full textRecently a graphical study of linkage disequilibrium around the CAPN3 locus failed to refine the 1.3-Mb interval suggested by haplotype sharing. On the contrary, the Malecot model as implemented in the ALLASS program maps CAPN3 within 3 kb of its true location (23 kb from the locus midpoint), overcoming identified problems with small samples, interrelated sibships, and short duration.</p
Hardy-Weinberg quality control
No full textAn efficient test of deviation from Hardy-Weinberg frequencies with one degree of freedom was applied to 44 marker loci in a genome scan, and 7 loci had a significant excess of apparent homozygotes (χ2((1)) > 6) suggestive of typing error. In this example evidence for linkage did not increase when outliers were censored. Statistical quality control is an essential part of genotyping, and the effect of mistyping and map error should be considered in evaluating any genome scan.</p
Meta-analysis and retrospective collaboration: two methods to map oligogenes for atopy and asthma
No full textCombination of evidence over samples, each of which is too small to be conclusive, is the central problem in complex inheritance. There are three approaches: meta-analysis, prospective collaboration, and retrospective collaboration. Our experience with the first and last, which are the most cost-effective, is discussed
A retrospective collaboration on chromosome 5 by the International Consortium on Asthma Genetics (COAG)
No full textAsthma is the most common chronic childhood disease in developed nations [ 1], affecting more than 155 million individuals. The cost of treating the disease in the USA alone approximates 6 billion dollars per annum [ 2]. Asthma is a complex disease that has proven extremely difficult to dissect genetically [ 3]. Considerable effort is currently being expended in attempts to detect genetic loci contributing to asthma susceptibility [ 4–7], with the ultimate goal of improving preventive strategies, diagnostic tools and therapies. However, no specific major gene exhibiting functional effects has been mapped to date. <br/
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