Search results for "Mendelian"
showing 10 items of 66 documents
Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
2021
Abstract Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci ass…
Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study.
2019
Key Points Question Is birth weight associated with type 2 diabetes and glycemic traits? Findings This mendelian randomization study found that a 1-SD decrease in birth weight due to the genetic risk score was associated with a higher risk of type 2 diabetes among European and East Asian populations. In addition, a 1-SD decrease in birth weight was associated with a 0.189-SD increase in fasting glucose concentration, but not with fasting insulin, 2-hour glucose, or hemoglobin A1c level. Meaning A genetic predisposition to lower birth weight was associated with an increased risk of type 2 diabetes and increased fasting glucose, suggesting potential mechanisms through which perturbation of th…
P5313The association between coffee and caffeine consumption and renal function: insight from individual-level data, Mendelian randomization, and met…
2019
Abstract Background The reported relationship between coffee intake and renal function is poorly understood. Purpose By applying on two-sample Mendelian randomization (MR) and systematic review and meta-analysis we investigated the association between caffeine and coffee intake with prevalent CKD and markers of renal function. Methods For the individual data analysis we analysed the NHANES data on renal function markers and caffeine intake. MR was implemented by using summary-level data from genome-wide association studies conducted on coffee intake (N=91,462) and kidney function (N=133,413). Inverse variance weighted method (IVW), weighted median-based method, MR-Egger, MR-RAPS, MR-PRESSO …
DNA methylation episignature testing improves molecular diagnosis of Mendelian chromatinopathies
2021
Abstract Purpose Chromatinopathies include more than 50 disorders caused by disease-causing variants of various components of chromatin structure and function. Many of these disorders exhibit unique genome-wide DNA methylation profiles, known as episignatures. In this study, the methylation profile of a large cohort of individuals with chromatinopathies was analyzed for episignature detection. Methods DNA methylation data was generated on extracted blood samples from 129 affected individuals with the Illumina Infinium EPIC arrays and analyzed using an established bioinformatic pipeline. Results The DNA methylation profiles matched and confirmed the sequence findings in both the discovery an…
A spontaneous mitonuclear epistasis converging on Rieske Fe-S protein exacerbates complex III deficiency in mice
2020
We previously observed an unexpected fivefold (35 vs. 200 days) difference in the survival of respiratory chain complex III (CIII) deficient Bcs1lp.S78G mice between two congenic backgrounds. Here, we identify a spontaneous homoplasmic mtDNA variant (m.G14904A, mt-Cybp.D254N), affecting the CIII subunit cytochrome b (MT-CYB), in the background with short survival. We utilize maternal inheritance of mtDNA to confirm this as the causative variant and show that it further decreases the low CIII activity in Bcs1lp.S78G tissues to below survival threshold by 35 days of age. Molecular dynamics simulations predict D254N to restrict the flexibility of MT-CYB ef loop, potentially affecting RISP dyna…
Understanding of Mendelian Inheritance Model after conventional teaching methods in Secondary Education students
2015
Mostrar que una nueva propuesta de enseñanza produce mejores actitudes y aprendizajes en los alumnos requiere disponer de un análisis de lo que se hace y se consigue con la enseñanza habitual. Para realizar dicho análisis se ha efectuado un estudio histórico y epistemológico de la evolución de las ideas en genética clásica, identificando los problemas que están en su origen, las ideas que permitieron avanzar y los obstáculos que hubo que superar. Como resultado de dicho estudio se han seleccionado un conjunto de indicadores de aprendizaje que deberían manifestarse en aquellas personas que hubieran comprendido los aspectos esenciales del modelo de herencia mendeliana, que se imparte en 4º de…
Molecular and patho-physiological basis of syndromes with developmental anomalies and intellectual disability
2013
Intellectual disability (ID) corresponds to abnormal intellectual performances and adaptive functions, beginning in childhood. It is estimated that 2-3% of individuals develop a ID, which represents a significant medical challenge since people with ID are frequently in situations of social dependence. Overall, a critical involvement of genetic factors in this disease is suspected. To date, several hundreds of genes are known to be responsible for ID. The ID is particularly characterized by extreme clinical and genetic heterogeneity, that made it resistant to conventional genetic studies. However, it is classicaly separated between syndromic ID, which may be clinically recognizable due to as…
Boris Ephrussi and the Synthesis of Genetics and Embryology
1991
The career of Boris Ephrussi (1901–1979) presents a series of fascinating perspectives on the intellectual and sociological difficulties that plagued those who wished to reconcile genetics and embryology during the middle of this century (2–8). Ephrussi was born in a suburb of Moscow, but spent much of his working career in France, with important periods in the United States. He made major contributions to the rapprochement between genetics and developmental biology. His work, which we believe has been undervalued both by historians of biology and by subsequent generations of biologists, is worth studying for at least three reasons: 1. Throughout his long career, he sought an adequate causa…
Confirmation of EP300 gene mutations as a rare cause of Rubinstein-Taybi syndrome.
2007
The Rubinstein-Taybi syndrome (RSTS, MIM 180849), a dominant Mendelian disorder with typical face, short stature, skeletal abnormalities, and mental retardation, is usually caused by heterozygous mutations of the CREBBP gene, but recently, EP300 gene mutations were reported in three individuals. Using quantitative PCR (for the CREBBP and EP300 genes) and genomic sequencing (for the EP300 gene), we studied here 13 patients who had shown no mutation after genomic sequencing of the CREBBP gene in a previous investigation. Two new disease-causing mutations were identified, including a partial deletion of CREBBP and a 1-bp deletion in EP300, c.7100delC (p.P2366fsX2401). The 1-bp deletion represe…