Detecting Chromosome Condensation Defects in Gulf War Illness Patients

Abstract

Background: Gulf War Illness (GWI) impacts 25-30% of gulf war veterans. Due to its heterogeneity in both etiology and symptoms, it has been challenging to establish the commonly accepted case definition for GWI. Equally challenging are the understanding of the general mechanism of GWI and the development of biomarkers useful for its clinical diagnosis and treatment.Objective: We have observed that chromosome condensation defects can be detected in GWI patients. To document this phenomenon in GWI, we aim to describe and compare different types of chromosomal condensation defects in GWI patients, if possible. Since chromosomal condensation represents an important step of ensuring genome integrity, condensation defects could be used as a potential biomarker of GWI.Methods: Lymphocytes from GWI patients have been used for short term cell culture followed by chromosome slide preparation. Both Giemsa staining and multiple color spectral karyotyping (SKY) were applied to study chromosome aberrations, focusing on different types of condensation defects.Results: At least three subtypes of Defective Mitotic Figures (DMFs) were observed. Some individuals displayed elevated frequencies of DMFs. Another type of condensation defect identified as sticky chromosomes were also observed.Conclusion: Various types of condensation defects have been observed in GWI patients. It is rather surprising that some GWI patients exhibited a high level of chromosomal condensation defects. Previously, the elevated frequency of DMFs was only observed in cancer patients. Since chromosome condensation can be linked to other types of chromosome aberrations, as well as cellular stress conditions, the detailed mechanism and clinical impact should be further studied, especially with increased sample size.

Origins and Consequences of Chromosomal Instability: From Cellular Adaptation to Genome Chaos-Mediated System Survival

“…Of course, drastic environmental stresses can promote the heterogeneity of all bioprocesses, resulting in CIN. This explains why highly stressful environments (such as war conditions) and even lifestyles also impact the overall CIN [ 3 , 44 , 45 , 52 ].…”

FISH-Based Analysis of Mosaic Aneuploidy and Chromosome Instability for Investigating Molecular and Cellular Mechanisms of Disease

“…CIN cases have also exhibited 4-9 copy number variations (CNV) encompassing genes, involved in the pathways to genome instability and somatic mosaicism (genome stability, DNA reparation/replication, mitotic checkpoint, cell cycle regulation and programmed cell death) [35][36][37]. Using bioinformatics for processing molecular karyotypes and addressing previously published data [8,12,18,20,25,[38][39][40][41][42], we have concluded that a proportion of these cases of intellectual disability, autism, epilepsy and/or congenital malformations is likely to be associated with chromosomal instability, which is an element of the pathogenetic cascade and thereby, should be recognized as a contributor to the phenotypic manifestations. Interestingly, changes in the molecular pathways of cell cycle regulation and programmed cell death were mainly associated with aneuploidy.…”

“…Additionally, CIN is shown to mediate various changes in intellectual functioning influenced by a negative impact of the environment (i.e. stress) on the human body [18]. Finally, it is assumed that CIN-related variations of somatic cell genomes are able to cause tissue aging and cellular senescence [19].…”

A Postgenomic Perspective on Molecular Cytogenetics

“…We recently examined the genome instability of GWI patients by comparing the degree of stochastic chromosomal aberrations from short-term lymphocyte cultures. Various karyotypic abnormalities were observed, and we demonstrated that genome instability was significantly elevated in GWI patients compared to controls [ 37 , 97 , 127 ]. Similar analysis was also performed in a Chronic Fatigue Syndrome (CFS) study, where again the overall level of genome instability was significantly higher in CFS patients than controls [ 37 ], (Ye et al , manuscript in preparation).…”