Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The aetiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a chronic and severe debilitating disease with a complex phenotype, remains elusive. Associations with infectious diseases and autoimmune and neuropsychiatric disorders have been observed, without the identification of mechanisms. Previous studies suggest that genetic predisposition plays a role, but results are difficult to replicate, with Genome-Wide Association Studies of ME/CFS being challenging due to the relative rareness and heterogeneity of the disorder. We studied a well-defined Australian patient cohort diagnosed via the International Consensus Criteria, recruited by a specialist ME/CFS clinic. The whole-exome sequences of 77 patients were contrasted against genome variation in the 1000 Genome Project's genome-matched population. Significant associations with ME/CFS were harboured in genes that belong to the Neuroblastoma Breakpoint Family encoding Olduvai (DUF1220) domains, namely (rs3897177, -value = 3.15 × 10) (rs1553120233, -value = 9.262 × 10), and (rs200632836, -value = 1.04 × 10). Other significantly associated variants were detected in the , , , and genes, among others. Replication of these results was attempted via a GWAS on raw data from a US cohort, which confirmed shared significant associations with variation identified in the , , , , , , , and genes. These genes are involved in cortical neurogenesis, brain evolution, and neuroblastoma, and have been implicated by several studies in schizophrenia and autism. The sharing of these associations by the two cohorts supports their validity and grants the necessity of future studies to evaluate the implications for ME/CFS aetiology.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191824 | PMC |
| http://dx.doi.org/10.3390/diagnostics15121542 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Neurodevelopment Genes Encoding Olduvai Domains Link Myalgic Encephalomyelitis to Neuropsychiatric Disorders.
Diagnostics (Basel)
June 2025
National Centre for Epidemiology and Population Health (NCEPH), ANU College of Health and Medicine, The Australian National University, Canberra, ACT 2601, Australia.
The aetiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a chronic and severe debilitating disease with a complex phenotype, remains elusive. Associations with infectious diseases and autoimmune and neuropsychiatric disorders have been observed, without the identification of mechanisms. Previous studies suggest that genetic predisposition plays a role, but results are difficult to replicate, with Genome-Wide Association Studies of ME/CFS being challenging due to the relative rareness and heterogeneity of the disorder.
View Article and Find Full Text PDFOlduvai domain expression downregulates mitochondrial pathways: implications for human brain evolution and neoteny.
bioRxiv
October 2024
Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Article Synopsis
- Olduvai protein domains, linked to the NBPF gene family, show significant expansion in humans and correlate with brain size and neuron numbers in primates, as well as human brain variations like microcephaly and macrocephaly.
- Research indicates that overexpression of the Olduvai gene may lead to downregulation of mitochondrial functions, particularly affecting the electron transport chain and NADH dehydrogenase activity, based on transcriptome and proteome analyses.
- The findings suggest that this downregulation could slow development processes in primates, especially humans, potentially resulting in an extended neurogenic period that allows for the production of more neurons and a larger brain size.
Proteolytic activation of human-specific Olduvai domains by the furin protease.
Int J Biol Macromol
April 2023
Department of Biochemistry and Molecular Genetics, University of Colorado, Aurora, CO, USA. Electronic address:
Olduvai protein domains (formerly DUF1220) show the greatest human-specific increase in copy number of any coding region in the genome and are highly correlated with human brain evolution and cognitive disease. The majority of human copies are found within four NBPF genes organized in a variable number of a tandemly arranged three-domain blocks called Olduvai triplets. Here we show that these human-specific Olduvai domains are posttranslationally processed by the furin protease, with a cleavage site occurring once at each triplet.
View Article and Find Full Text PDFSolution NMR backbone assignments of disordered Olduvai protein domain CON1 employing Hα-detected experiments.
Biomol NMR Assign
April 2022
Department of Biochemistry & Molecular Genetics, School of Medicine, University of Colorado, 12801 E. 17th Avenue, Aurora, CO, 80045, USA.
Olduvai protein domains, encoded by the NBPF gene family, are responsible for the largest increase in copy number of any protein-coding region in the human genome. This has spawned various genetics studies which have linked these domains to human brain development and divergence from our primate ancestors, as well as currently relevant cognitive diseases such as schizophrenia and autism spectrum disorder (ASD). There are six separate Olduvai domains which together form the majority of the various protein products of the NBPF genes.
View Article and Find Full Text PDFMicrobial biomarkers reveal a hydrothermally active landscape at Olduvai Gorge at the dawn of the Acheulean, 1.7 Ma.
Proc Natl Acad Sci U S A
October 2020
Department of Earth, Atmospheric and Planetary Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139.
Landscape-scale reconstructions of ancient environments within the cradle of humanity may reveal insights into the relationship between early hominins and the changing resources around them. Many studies of Olduvai Gorge during Pliocene-Pleistocene times have revealed the presence of precession-driven wet-dry cycles atop a general aridification trend, though may underestimate the impact of local-scale conditions on early hominins, who likely experienced a varied and more dynamic landscape. Fossil lipid biomarkers from ancient plants and microbes encode information about their surroundings via their molecular structures and composition, and thus can shed light on past environments.
View Article and Find Full Text PDF