ABSTRACT
Systems that have yet to stand the test of time carry imperfections that need to be skillfully addressed with the least amount of authoritarianism as possible. The communication and transmission of knowledge that we hold dear are essential pillars to social progress. As such, it is necessary to analyze with the greatest scientific objectivity the applications arising from the deep revolution rooted in the total sequencing of the human genome which affects all aspects of our societies. This extraordinary advance in human knowledge and the resulting technological achievements should not lend themselves to the fears or fantasies often fueled by those who criticize all scientific progress calling into question the most established dogmas. Certain supposedly scholarly analyses of the health situation with which we are currently confronted worldwide are a perfect illustration of this unfortunate trend. It is undeniable that the progress of molecular genetics has opened up a wide range of applications in many fields, affecting the well-being of humans, their mental and physical health. The apparent universal and individual interest for the most advanced genetic profile analyzing technologies is a testimony to this strong common desire to better understand one's genetic heritage and to control their usage. Despite this movement, little attention is given to the recent advances in genetics applied to essential aspects of the social life of individuals through their inter-personal interactions. It is particularly distressing that the contributions of molecular biology and genetics to the daily well-being of individuals have not yet allowed open-access non-medical genetic testing to gain the recognition it deserves and are still viewed as recreational applications. Through an analysis of the cross influences that genetic biotechnologies have had since the beginning of the century in the fields of nutrition and cosmetics, we have tried to project ourselves into the near future which should witness major behavioral and social upheavals.
ABSTRACT
BACKGROUND: Mitochondrial genome copy number (MT-CN) varies among humans and across tissues and is highly heritable, but its causes and consequences are not well understood. When measured by bulk DNA sequencing in blood, MT-CN may reflect a combination of the number of mitochondria per cell and cell-type composition. Here, we studied MT-CN variation in blood-derived DNA from 19184 Finnish individuals using a combination of genome (N = 4163) and exome sequencing (N = 19034) data as well as imputed genotypes (N = 17718). RESULTS: We identified two loci significantly associated with MT-CN variation: a common variant at the MYB-HBS1L locus (P = 1.6 × 10-8), which has previously been associated with numerous hematological parameters; and a burden of rare variants in the TMBIM1 gene (P = 3.0 × 10-8), which has been reported to protect against non-alcoholic fatty liver disease. We also found that MT-CN is strongly associated with insulin levels (P = 2.0 × 10-21) and other metabolic syndrome (metS)-related traits. Using a Mendelian randomization framework, we show evidence that MT-CN measured in blood is causally related to insulin levels. We then applied an MT-CN polygenic risk score (PRS) derived from Finnish data to the UK Biobank, where the association between the PRS and metS traits was replicated. Adjusting for cell counts largely eliminated these signals, suggesting that MT-CN affects metS via cell-type composition. CONCLUSION: These results suggest that measurements of MT-CN in blood-derived DNA partially reflect differences in cell-type composition and that these differences are causally linked to insulin and related traits.
Subject(s)
Apoptosis Regulatory Proteins/genetics , DNA Copy Number Variations/genetics , DNA, Mitochondrial/blood , GTP-Binding Proteins/genetics , Membrane Proteins/genetics , Proto-Oncogene Proteins c-myb/genetics , Adult , Aged , Cell Lineage/genetics , DNA, Mitochondrial/genetics , Female , Genetic Predisposition to Disease , Genome, Mitochondrial/genetics , Genome-Wide Association Study , Humans , Male , Mendelian Randomization Analysis , Middle Aged , Phenotype , Polymorphism, Single Nucleotide/genetics , Sequence Analysis, DNA , Exome SequencingABSTRACT
The 22 Arab nations have a unique genetic structure, which reflects both conserved and diverse gene pools due to the prevalent endogamous and consanguineous marriage culture and the long history of admixture among different ethnic subcultures descended from the Asian, European, and African continents. Human genome sequencing has enabled large-scale genomic studies of different populations and has become a powerful tool for studying disease predictions and diagnosis. Despite the importance of the Arab genome for better understanding the dynamics of the human genome, discovering rare genetic variations, and studying early human migration out of Africa, it is poorly represented in human genome databases, such as HapMap and the 1000 Genomes Project. In this review, I demonstrate the significance of sequencing the Arab genome and setting an Arab genome reference(s) for better understanding the molecular pathogenesis of genetic diseases, discovering novel/rare variants, and identifying a meaningful genotype-phenotype correlation for complex diseases.