Human Exome Sequencing and Prospects for Predictive Medicine: Analysis of International Data and Own Experience

Glotov, Oleg S.; Chernov, Alexander N.; Glotov, Andrey S.

doi:10.3390/jpm13081236

Cited by 7 publications

(5 citation statements)

References 91 publications

(142 reference statements)

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“…Additionally, genomic research can assist physicians in predicting a patient's functional status prior to disease onset, or before irreversible conditions emerge, and thus promoting and improving the health of the population. This enhances 3PM by enabling the prioritization of preventative measures and methods of treatment [ 25 ].…”

Section: Results and Data Interpretationmentioning

confidence: 99%

Promoting advanced medical services in the framework of 3PM—a proof-of-concept by the “Centro” Region of Portugal

Regateiro,

Silva,

Lemos

et al. 2024

EPMA Journal

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Multidisciplinary team from three universities based in the “Centro” Region of Portugal developed diverse approaches as parts of a project dedicated to enhancing and expanding Predictive, Preventive, and Personalized Medicine (3PM) in the Region. In a sense, outcomes acted as a proof-of-concept, in that they demonstrated the feasibility, but also the relevance of the approaches. The accomplishments comprise defining a new regional strategy for implementing 3PM within the Region, training of human resources in genomic sequencing, and generating good practices handbooks dedicated to diagnostic testing via next-generation sequencing, to legal and ethical concerns, and to knowledge transfer and entrepreneurship, aimed at increasing literacy on 3PM approaches. Further approaches also included support for entrepreneurship development and start-ups, and diverse and relevant initiatives aimed at increasing literacy relevant to 3PM. Efforts to enhance literacy encompassed citizens across the board, from patients and high school students to health professionals and health students. This focus on empowerment through literacy involved a variety of initiatives, including the creation of an illustrated book on genomics and the production of two theater plays centered on genetics. Additionally, authors stressed that genomic tools are relevant, but they are not the only resources 3PM is based on. Thus, they defend that other initiatives intended to enable citizens to take 3PM should include multi-omics and, having in mind the socio-economic burden of chronic diseases, suboptimal health status approaches in the 3PM framework should also be considered, in order to anticipate medical intervention in the subclinical phase.

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Section: Results and Data Interpretationmentioning

confidence: 99%

Promoting advanced medical services in the framework of 3PM—a proof-of-concept by the “Centro” Region of Portugal

Regateiro,

Silva,

Lemos

et al. 2024

EPMA Journal

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“…These findings are especially important given that more and more people in the world are getting their genome or exome sequenced. In light of these developments, researchers and clinicians will frequently face the question of interpreting the significance of genetic variants with incomplete penetrance (Glotov et al., 2023 ). Therefore, accumulation of data on the presence of presumably pathogenic variants in healthy individuals (especially in groups of highly skilled athletes, individuals involved in extreme activities, or elderly people) becomes crucial for the introduction of genomic medicine into clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Exome sequencing in extreme altitude mountaineers identifies pathogenic variants in RTEL1 and COL6A1 previously associated with respiratory failure

Maksiutenko,

Merkureva,

Barbitoff

et al. 2024

Physiological Reports

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Adaptation of humans to challenging environmental conditions, such as extreme temperature, malnutrition, or hypoxia, is an interesting phenomenon for both basic and applied research. Identification of the genetic factors contributing to human adaptation to these conditions enhances our understanding of the underlying molecular and physiological mechanisms. In our study, we analyzed the exomes of 22 high altitude mountaineers to uncover genetic variants contributing to hypoxic adaptation. To our surprise, we identified two putative loss‐of‐function variants, rs1385101139 in RTEL1 and rs1002726737 in COL6A1 in two extremely high altitude (personal record of more than 8500 m) professional climbers. Both variants can be interpreted as pathogenic according to medical geneticists' guidelines, and are linked to inherited conditions involving respiratory failure (late‐onset pulmonary fibrosis and severe Ullrich muscular dystrophy for rs1385101139 and rs1002726737, respectively). Our results suggest that a loss of gene function may act as an important factor of human adaptation, which is corroborated by previous reports in other human subjects.

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“…In connection with the above, it is preferable to perform whole-exome sequencing in patients with OI. Therefore, WES is the most relevant method of molecular genetics for OI [50]. Considering the variable approaches to OI classification, an integrated strategy is required for optimal patient management.…”

Section: Discussionmentioning

confidence: 99%

Exome Sequencing for the Diagnostics of Osteogenesis Imperfecta in Six Russian Patients

Koshevaya,

Turkunova,

Vechkasova

et al. 2024

CIMB

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Osteogenesis imperfecta (OI) is a group of inherited disorders of connective tissue that cause significant deformities and fragility in bones. Most cases of OI are associated with pathogenic variants in collagen type I genes and are characterized by pronounced polymorphisms in clinical manifestations and the absence of clear phenotype–genotype correlation. The objective of this study was to conduct a comprehensive molecular–genetic and clinical analysis to verify the diagnosis of OI in six Russian patients with genetic variants in the COL1A1 and COL1A2 genes. Clinical and laboratory data were obtained from six OI patients who were observed at the Medical Genetics Center in Saint Petersburg from 2016 to 2023. Next-generation sequencing on MGISEQ G400 (MGI, China) was used for DNA analysis. The GATK bioinformatic software (version 4.5.0.0) was used for variant calling and hard filtering. Genetic variants were verified by the direct automatic sequencing of PCR products using the ABI 3500X sequencer. We identified six genetic variants, as follows pathogenic c.3505G>A (p. Gly1169Ser), c.769G>A (p.Gly257Arg), VUS c.4123G>A (p.Ala1375Thr), and c.4114A>T (p.Asn1372Tyr) in COL1A1; and likely pathogenic c.2035G>A (p.Gly679Ser) and c.739-2A>T in COL1A2. In addition, clinical cases are presented due to the presence of the c.4114A>T variant in the COL1A2 gene. Molecular genetics is essential for determining different OI types due to the high similarity across various types of the disease and the failure of unambiguous diagnosis based on clinical manifestations alone. Considering the variable approaches to OI classification, an integrated strategy is required for optimal patient management.

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Human Exome Sequencing and Prospects for Predictive Medicine: Analysis of International Data and Own Experience

Cited by 7 publications

References 91 publications

Promoting advanced medical services in the framework of 3PM—a proof-of-concept by the “Centro” Region of Portugal

Promoting advanced medical services in the framework of 3PM—a proof-of-concept by the “Centro” Region of Portugal

Exome sequencing in extreme altitude mountaineers identifies pathogenic variants in RTEL1 and COL6A1 previously associated with respiratory failure

Exome Sequencing for the Diagnostics of Osteogenesis Imperfecta in Six Russian Patients

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