In a departure from traditional gene-centric thinking with regard to cytogenetics and cytogenomics, the recently introduced genome theory calls upon a re-focusing of our attention on karyotype analyses of disease conditions. Karyotype heterogeneity has been demonstrated to be directly involved in the somatic cell evolution process which is the basis of many common and complex diseases such as cancer. To correctly use karyotype heterogeneity and apply it to monitor system instability, we need to include many seemingly unimportant non-specific chromosomal aberrations into our analysis. Traditionally, cytogenetic analysis has been focused on identifying recurrent types of abnormalities, particularly those that have been linked to specific diseases. In this perspective, drawing on the new framework of 4D-genomics, we will briefly review the importance of studying karyotype heterogeneity. We have also listed a number of overlooked chromosomal aberrations including defective mitotic figures, chromosome fragmentation as well as genome chaos. Finally, we call for the systematic discovery/characterization and classification of karyotype abnormalities in human diseases, as karyotype heterogeneity is the common factor that is essential for somatic cell evolution.

Cells are constantly exposed to various internal and external stresses. The importance of cellular stress and its implication to disease conditions have become popular research topics. Many ongoing investigations focus on the sources of stress, their specific molecular mechanisms and interactions, especially regarding their contributions to many common and complex diseases through defined molecular pathways. Numerous molecular mechanisms have been linked to endoplasmic reticulum stress along with many unexpected findings, drastically increasing the complexity of our molecular understanding and challenging how to apply individual mechanism-based knowledge in the clinic. A newly emergent genome theory searches for the synthesis of a general evolutionary mechanism that unifies different types of stress and functional relationships from a genome-defined system point of view. Herein, we discuss the evolutionary relationship between stress and somatic cell adaptation under physiological, pathological, and somatic cell survival conditions, the multiple meanings to achieve adaptation and its potential trade-off. In particular, we purposely defocus from specific stresses and mechanisms by redirecting attention toward studying underlying general mechanisms.

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.

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