Skip to main content

Coding Mutations to Meningomyelocele

The contribution of de novo coding mutations to meningomyelocele



Meningomyelocele (also known as spina bifida) is considered to be a genetically complex disease resulting from a failure of the neural tube to close. Individuals with meningomyelocele display neuromotor disability and frequent hydrocephalus, requiring ventricular shunting.

A few genes have been proposed to contribute to disease susceptibility, but beyond that it remains unexplained. We postulated that de novo mutations under purifying selection contribute to the risk of developing meningomyelocele. Here we recruited a cohort of 851 meningomyelocele trios who required shunting at birth and 732 control trios, and found that de novo likely gene disruption or damaging missense mutations occurred in approximately 22.3% of subjects, with 28% of such variants estimated to contribute to disease risk.

The 187 genes with damaging de novo mutations collectively define networks including actin cytoskeleton and microtubule-based processes, Netrin-1 signalling and chromatin-modifying enzymes. Gene validation demonstrated partial or complete loss of function, impaired signalling and defective closure of the neural tube in Xenopus embryos. Our results indicate that de novo mutations make key contributions to meningomyelocele risk, and highlight critical pathways required for neural tube closure in human embryogenesis.

Mutations, Genetic Variability, DNA Alterations, Genomic Instability, Somatic Mutations, Germline Mutations, Point Mutation, Frameshift Mutation, Missense Mutation, Nonsense Mutation, Silent Mutation, Deletion Mutation, Insertion Mutation, Duplication Mutation, Chromosomal Aberrations, Single Nucleotide Polymorphism (SNP), Mutagenesis, Oncogenic Mutations, Hereditary Mutations, Evolutionary Adaptation

#Mutations #Genetics #DNAChanges #GenomicInstability #SomaticMutation #GermlineMutation #PointMutation #FrameshiftMutation #MissenseMutation #NonsenseMutation #SilentMutation #DeletionMutation #InsertionMutation #DuplicationMutation #ChromosomalMutation #SNP #Mutagenesis #OncogenicMutation #HereditaryMutation #Evolution

International Conference on Genetics and Genomics of Diseases

Visit: genetics-conferences.healthcarek.com

Award Nomination: genetics-conferences.healthcarek.com/award-nomination/?ecategory=Awards&rcategory=Awardee

Award registration: genetics-conferences.healthcarek.com/award-registration/

For Enquiries: contact@healthcarek.com

Get Connected Here
---------------------------------
---------------------------------
in.pinterest.com/Dorita0211
twitter.com/Dorita_02_11_
facebook.com/profile.php?id=61555903296992
instagram.com/p/C4ukfcOsK36
genetics-awards.blogspot.com/
youtube.com/@GeneticsHealthcare

Comments

Post a Comment

Popular posts from this blog

Chromosomal Abnormalities

  Chromosomal Abnormalities Chromosome abnormalities refer to structural or numerical changes in chromosomes that can disrupt normal genetic function, leading to developmental disorders, congenital abnormalities, and various genetic diseases. These abnormalities may arise from errors in cell division, such as nondisjunction or chromosomal breakage, resulting in conditions like Down syndrome , Turner syndrome, Klinefelter syndrome , and various deletion or duplication syndromes. Understanding chromosome abnormalities is essential for genetic counseling, prenatal diagnosis, disease risk assessment, and research in cytogenetics and molecular genetics. Chromosome abnormalities, chromosomal disorders, chromosomal mutations, aneuploidy, structural chromosome abnormalities, nondisjunction, deletion syndrome, duplication syndrome , translocation, inversion, cytogenetics, karyotyping, prenatal diagnosis , genetic testing, genomic instability, Down syndrome, Turner syndrome, Klinefelter syn...
Post a Comment
Read more

Multifactorial Genetic Conditions

Multifactorial Genetic Conditions Multifactorial genetic conditions are disorders caused by the combined effects of multiple genes and environmental factors , rather than a single gene mutation . These conditions do not follow classic Mendelian inheritance patterns and instead result from complex gene–environment interactions . Factors such as lifestyle, nutrition, infections, stress, and exposure to toxins can significantly influence disease onset and severity in genetically susceptible individuals. Common examples include diabetes, cardiovascular diseases , neural tube defects, asthma, and many neuropsychiatric disorders. Understanding multifactorial inheritance is essential for risk prediction, preventive medicine, and personalized healthcare strategies. Multifactorial inheritance, polygenic traits, gene–environment interaction, complex diseases, genetic susceptibility, environmental risk factors, non-Mendelian inheritance, disease predisposition, polygenic risk score, precision ...
Post a Comment
Read more

Human Brain Organoids

Human Brain Organoids Model Abnormal Prenatal Neural Development Induced by Thermal Stimulation The developing human foetal brain is sensitive to thermal stimulation during pregnancy. However, the mechanisms by which heat exposure affects human foetal brain development remain unclear, largely due to the lack of appropriate research models for studying thermal stimulation. To address this, we have developed a periodic heating model based on brain organoids derived from human pluripotent stem cells. The model recapitulated neurodevelopmental disruptions under prenatal heat exposure at the early stages, providing a paradigm for studying the altered neurodevelopment under environmental stimulation. Our study found that periodic heat exposure led to decreased size and impaired neural tube development in the brain organoids. Bulk RNA-seq analysis revealed that the abnormal WNT signalling pathway and the reduction of G2/M progenitor cells might be involved in heat stimulation. Further investi...
Post a Comment
Read more