Search results for "Mendelian inheritance"

Adaptive Evolution and Epigenetics

2023

Epigenetic changes, such as DNA methylation and certain histone modifications, can be inherited but in many cases they do not follow Mendelian inheritance patterns and their stability appears to be lower than for changes in DNA sequence. Adaptive evolution by natural selection requires that differences among individuals are heritable to some degree. Epigenetic changes can be incorporated into evolutionary theory, and given that properties of epigenetic variation are distinct from genetic variation, spontaneous epigenetic changes can affect evolutionary dynamics in interesting ways. In this chapter, I review the properties of epigenetic variation and how they relate to the main parameters of…

Maternal Inheritance of a Recessive RBP4 Defect in Canine Congenital Eye Disease

2018

SUMMARY Maternally skewed transmission of traits has been associated with genomic imprinting and oocyte-derived mRNA. We report canine congenital eye malformations, caused by an amino acid deletion (K12del) near the N terminus of retinol-binding protein (RBP4). The disease is only expressed when both dam and offspring are deletion homozygotes. RBP carries vitamin A (retinol) from hepatic stores to peripheral tissues, including the placenta and developing eye, where it is required to synthesize retinoic acid. Gestational vitamin A deficiency is a known risk factor for ocular birth defects. The K12del mutation disrupts RBP folding in vivo, decreasing its secretion from hepatocytes to serum. T…

Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders

2020

Contains fulltext : 218274.pdf (Publisher’s version ) (Closed access) Genetic syndromes frequently present with overlapping clinical features and inconclusive or ambiguous genetic findings which can confound accurate diagnosis and clinical management. An expanding number of genetic syndromes have been shown to have unique genomic DNA methylation patterns (called "episignatures"). Peripheral blood episignatures can be used for diagnostic testing as well as for the interpretation of ambiguous genetic test results. We present here an approach to episignature mapping in 42 genetic syndromes, which has allowed the identification of 34 robust disease-specific episignatures. We examine emerging pa…

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…

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…

The time to prevent mendelian genetic diseases from donated or own gametes has come

2015

The singular fate of Genetics in the History of French Biology, 1900-1940

1988

In this study we have examined the reception of Mendelism in France from 1900 to 1940, and the place of some of the extra-Mendelian traditions of research that contributed to the development of genetics in France after World War II. Our major findings are: (1) Mendelism was widely disseminated in France and thoroughly understood by many French biologists from 1900 on. With the notable exception of Lucien Cuenot, however, there were few fundamental contributions to the Mendelian tradition, and virtually none from about 1915 to the midthirties. Prior to 1900, Cuenot's work was already marked by a striking interest in physiological mechanisms; his physiological preoccupations played a consider…