Search results for "Human genetics"

Testing for goodness rather than lack of fit of an X–chromosomal SNP to the Hardy-Weinberg model

2019

The problem of checking the genotype distribution obtained for some diallelic marker for compatibility with the Hardy-Weinberg equilibrium (HWE) condition arises also for loci on the X chromosome. The possible genotypes depend on the sex of the individual in this case: for females, the genotype distribution is trinomial, as in the case of an autosomal locus, whereas a binomial proportion is observed for males. Like in genetic association studies with autosomal SNPs, interest is typically in establishing approximate compatibility of the observed genotype frequencies with HWE. This requires to replace traditional methods tailored for detecting lack of fit to the model with an equivalence test…

Palaeogenomics of Upper Palaeolithic to Neolithic European hunter-gatherers

2023

Acknowledgements: The authors thank G. Marciani and O. Jöris for comments on archaeology; C. Jeong, M. Spyrou and K. Prüfer for comments on genetics; M. O’Reilly for graphical support for Fig. 5 and Extended Data Fig. 9; the entire IT and laboratory teams at the Department of Archaeogenetics of MPI-SHH for technical assistance; M. Meyer and S. Nagel for support with single-stranded library preparation; K. Post, P. van Es, J. Glimmerveen, M. Medendorp, M. Sier, S. Dikstra, M. Dikstra, R. van Eerden, D. Duineveld and A. Hoekman for providing access to human specimens from the North Sea (The Netherlands); M. D. Garralda and A. Estalrrich for providing access to human specimens from La Riera (S…

Aerobic Fitness Does Not Modify the Effect of FTO Variation on Body Composition Traits

2012

Purpose Poor physical fitness and obesity are risk factors for all cause morbidity and mortality. We aimed to clarify whether common genetic variants of key energy intake determinants in leptin (LEP), leptin receptor (LEPR), and fat mass and obesity-associated (FTO) are associated with aerobic and neuromuscular performance, and whether aerobic fitness can alter the effect of these genotypes on body composition. Methods 846 healthy Finnish males of Caucasian origin were genotyped for FTO (rs8050136), LEP (rs7799039) and LEPR (rs8179183 and rs1137101) single nucleotide polymorphisms (SNPs), and studied for associations with maximal oxygen consumption, body fat percent, serum leptin levels, wa…

Untersuchungen zur Frage von leberregenerationsf�rdernden Substanzen im Serum teilhepatektomierter Ratten

1961

De Novo Mutations in SLC25A24 Cause a Disorder Characterized by Early Aging, Bone Dysplasia, Characteristic Face, and Early Demise

2017

International audience; A series of simplex cases have been reported under various diagnoses sharing early aging, especially evident in congenitally decreased subcutaneous fat tissue and sparse hair, bone dysplasia of the skull and fingers, a distinctive facial gestalt, and prenatal and postnatal growth retardation. For historical reasons, we suggest naming the entity Fontaine syndrome. Exome sequencing of four unrelated affected individuals showed that all carried the de novo missense variant c.649C>T (p.Arg217Cys) or c.650G>A (p.Arg217His) in SLC25A24, a solute carrier 25 family member coding for calcium-binding mitochondrial carrier protein (SCaMC-1, also known as SLC25A24). SLC25A24 all…

WNT Signaling Perturbations Underlie the Genetic Heterogeneity of Robinow Syndrome

2018

International audience; Locus heterogeneity characterizes a variety of skeletal dysplasias often due to interacting or overlapping signaling pathways. Robinow syndrome is a skeletal disorder historically refractory to molecular diagnosis, potentially stemming from substantial genetic heterogeneity. All current known pathogenic variants reside in genes within the noncanonical Wnt signaling pathway including ROR2, WNT5A, and more recently, DVL1 and DVL3. However, ∼70% of autosomal-dominant Robinow syndrome cases remain molecularly unsolved. To investigate this missing heritability, we recruited 21 families with at least one family member clinically diagnosed with Robinow or Robinow-like pheno…

NBEA : developmental disease gene with early generalized epilepsy phenotypes

2018

Abstract: NBEA is a candidate gene for autism, and de novo variants have been reported in neurodevelopmental disease (NDD) cohorts. However, NBEA has not been rigorously evaluated as a disease gene, and associated phenotypes have not been delineated. We identified 24 de novo NBEA variants in patients with NDD, establishing NBEA as an NDD gene. Most patients had epilepsy with onset in the first few years of life, often characterized by generalized seizure types, including myoclonic and atonic seizures. Our data show a broader phenotypic spectrum than previously described, including a myoclonic-astatic epilepsy-like phenotype in a subset of patients. Ann Neurol 2018;84:796-803

Gender as a Modifying Factor Influencing Myotonic Dystrophy Type 1 Phenotype Severity and Mortality: A Nationwide Multiple Databases Cross-Sectional …

2016

International audience; BACKGROUND: Myotonic Dystrophy type 1 (DM1) is one of the most heterogeneous hereditary disease in terms of age of onset, clinical manifestations, and severity, challenging both medical management and clinical trials. The CTG expansion size is the main factor determining the age of onset although no factor can finely predict phenotype and prognosis. Differences between males and females have not been specifically reported. Our aim is to study gender impact on DM1 phenotype and severity.METHODS: We first performed cross-sectional analysis of main multiorgan clinical parameters in 1409 adult DM1 patients (\textgreater18y) from the DM-Scope nationwide registry and obser…

Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium

2016

Background Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. Methods We performed a two-stage GWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898 MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5×10−6 in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with total mortality in individuals who experienced MI during follow-up. Res…

Diagnostic strategy in segmentation defect of the vertebrae: a retrospective study of 73 patients

2018

BackgroundSegmentation defects of the vertebrae (SDV) are non-specific features found in various syndromes. The molecular bases of SDV are not fully elucidated due to the wide range of phenotypes and classification issues. The genes involved are in the Notch signalling pathway, which is a key system in somitogenesis. Here we report on mutations identified in a diagnosis cohort of SDV. We focused on spondylocostal dysostosis (SCD) and the phenotype of these patients in order to establish a diagnostic strategy when confronted with SDV.Patients and methodsWe used DNA samples from a cohort of 73 patients and performed targeted sequencing of the five known SCD-causing genes (DLL3,MESP2,LFNG,HES7…