<strong>Whole-Exome Data Analysis: Detection of Candidate Gene Mutations for Mitochondrial Encephalohepatopathy</strong>

Published: May 5, 2021

Mitochondrial Encephalohepatopathy (MEH) is an autosomal recessive neurodevelopmental disorder usually accompanied by microcephaly, white matter changes, cardiac and hepatic failure. Here, we applied the whole-exome sequencing (WES) framework on a trio family data with unaffected non-consanguineous parents proband (neonate girl) this inherited disorder. A total of 2,928,402 variants were observed 2,613,746 SNPs, 112,336 multiple nucleotide polymorphisms (MNPs), 72,610 insertions, 113,207 deletions 16,503 mixed variants. These variations are responsible for 82,813,631 effects various genomic regions. Our pipeline uncovered candidate gene mutations from these retained handful 5,277 harboring 3,598 genes, out which, 8 genes codes non-coding RNA while 178 those high impact severity. Among variants, 125 de-novo that not previously reported in ClinVar database. Consistent to previous studies, leftover severity involved encephalopathy, Leigh syndrome, Charcot&ndash;Marie&ndash;Tooth disease, global developmental disorder, seizures, spastic paraplegia, premature ovarian failure, mitochondrial myopathy-cerebellar, ataxia-pigmentary, retinopathy ocular retinal degeneration, deafness, intellectual disability, cardiofacioneurodevelopmental syndrome etc. All clinical features also patient studied. The current analysis highlights expands genetic architecture MEH phenotype. Furthermore, significantly broadens concept its usefulness as first-tier diagnostic method detection complex multisystem phenotypic disorders.

Language: Английский

De novo mutations in bipolar disorder implicate neurodevelopment, immunity, and synaptic signaling

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 5, 2023

Abstract Bipolar disorder (BD) is a debilitating affecting ~ 1% of the world’s population. Although many common and some rare alleles are associated with this complex disorder, little known about role de novo variation. For first time, study investigates mutations (DNMs) in families ascertained from genetically isolated populations. Exomes approximately 1200 individuals consisting 214 trios were quality controlled analyzed using Genome Analysis Toolkit (GATK). DNMs called HAIL, followed by stringent sample variant filters. Genes carrying deleterious (dDNMs) affected participants annotated for biological functions brain co-expression modules. A total 42 loss function or damaging missense genes, including NRXN1 , SHANK3 SPECC1 detected among BD related disorders. Additionally, five XKR6 MRC2 SUGP2 DICER1 PLEC showed recurrent dDNMs, which previously reported. These genes significantly enriched to learning, post-synaptic organization, nervous system development, calcium ion transport. also overlapped modules neurogenesis immunity expressed excitatory neurons, endothelial cells, microglia. findings support DNM shed light on its neurobiology. If replicated, significant burdens good candidates functional genomic studies.

Language: Английский