Determining the genome-wide kinship coefficient seems unhelpful in distinguishing consanguineous couples with a high versus low risk for adverse reproductive outcome

Background: Offspring of consanguineous couples are at increased risk of congenital disorders. The risk increases as parents are more closely related. Individuals that have the same degree of relatedness according to their pedigree, show variable genomic kinship coefficients. To investigate whether we can differentiate between couples with high- and low risk for offspring with congenital disorders, we have compared the genomic kinship coefficient of consanguineous parents with a child affected with an autosomal recessive disorder with that of consanguineous parents with only healthy children, corrected for the degree of pedigree relatedness. Methods: 151 consanguineous couples (73 cases and 78 controls) from 10 different ethnic backgrounds were genotyped on the Affymetrix platform and passed quality control checks. After pruning SNPs in linkage disequilibrium, 57,358 SNPs remained. Kinship coefficients were calculated using three different toolsets: PLINK, King and IBDelphi, yielding five different estimates (IBDelphi, PLINK (all), PLINK (by population), King robust (all) and King homo (by population)). We performed a one-sided Mann Whitney test to investigate whether the median relative difference regarding observed and expected kinship coefficients is bigger for cases than for controls. Furthermore, we fitted a mixed effects linear model to correct for a possible population effect. Results: Although the estimated degrees of genomic relatedness with the different toolsets show substantial variability, correlation measures between the different estimators demonstrated moderate to strong correlations. Controls have higher point estimates for genomic kinship coefficients. The one-sided Mann Whitney test did not show any evidence for a higher median relative difference for cases compared to controls. Neither did the regression analysis exhibit a positive association between case–control status and genomic kinship coefficient. Conclusions: In this case–control setting, in which we compared consanguineous couples corrected for degree of pedigree relatedness, a higher degree of genomic relatedness was not significantly associated with a higher likelihood of having an affected child. Further translational research should focus on which parts of the genome and which pathogenic mutations couples are sharing. Looking at relatedness coefficients by determining genome-wide SNPs does not seem to be an effective measure for prospective risk assessment in consanguineous parents

Dataorganization before learning Multi-Entity Bayesian Networks structure

Abstract―The objective of our work is to develop a new approach for discovering knowledge from a large mass of data, the result of applying this approach will be an expert system that will serve as diagnostic tools of a phenomenon related to a huge information system. We first recall the general problem of learning Bayesian network structure from data and suggest a solution for optimizing the complexity by using organizational and optimization methods of data. Afterward we proposed a new heuristic of learning a Multi-Entities Bayesian Networks structures. We have applied our approach to biological facts concerning hereditary complex illnesses where the literatures in biology identify the responsible variables for those diseases. Finally we conclude on the limits arched by this work. Keywords―Data-organization, data-optimization, automatic knowledge discovery, Multi-Entities Bayesian Networks, score mergin

Type-2 diabetes and carotid stenosis: a proposal for a screening strategy in asymptomatic patients.

International audienceThe objective of this prospective observational study was to establish the prevalence of carotid atherosclerosis in an asymptomatic diabetic population and to determine predictive factors for a screening optimization. A total of 300 consecutive type-2 diabetic subjects (166 males, 134 females) underwent a physical examination and duplex carotid scanning. Patients with a recent cerebrovascular event ( or = 60% or occlusion was 4.7%; the prevalence of carotid atherosclerosis was 68.3%. Risk factors for stenosis > or = 60% or occlusion were the presence of diabetic retinopathy (OR: 3.62; 95% CI: 1.12-11.73), ankle-brachial index (ABI) 60% stenosis is highest among men with a history of coronary heart disease or an ABI <0.85

Estimating the Total Pathogenic Allele Frequency of Autosomal Recessive Disorders in Case of Consanguinity

Objective: Estimating the total allele frequency of all pathogenic alleles of an autosomal recessive disease is not possible if only mutational data of a sample of affected individuals are available. However, if the affected individuals come from a population where consanguinity is not uncommon, this total allele frequency can be estimated by additionally using the positive individual inbreeding coefficients or an estimate of the population inbreeding coefficient. In this paper, we propose two estimators. Methods/Results: We propose to estimate the total allele frequency by a conditional maximum likelihood estimator if a part of the affected individuals in the sample comes from consanguineous marriages with known inbreeding coefficients. A simulation study shows that this estimator is unbiased and robust. We propose a second estimator which is based on an estimate of the population inbreeding coefficient. The method is applied to mutational data and individual inbreeding coefficients of Tunisian patients with congenital adrenal hyperplasia. Conclusion: Additionally using individual inbreeding coefficients or an estimate of the population inbreeding coefficient makes it possible to estimate the total allele frequency. Since consanguinity is commonly practiced in many parts of the world, the estimators proposed in the paper are of practical importance

An ABAQUS Implementation of a Solid-Shell Element: Application to Low Velocity Impact

International audienc