Journal of medical genetics
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Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV) is a lethal disorder of lung development. ACDMPV is associated with haploinsufficiency of the transcription factor FOXF1, which plays an important role in the development of the lung and intestine. CNVs upstream of the FOXF1 gene have also been associated with an ACDMPV phenotype, but mechanism(s) by which these deletions disrupt lung development are not well understood. The objective of our study is to gain insights into the mechanisms by which CNVs contribute to an ACDMPV phenotype. ⋯ Together, these data suggest that the deletion disrupts an enhancer responsible for directing FOXF1 expression in the developing lung and provide novel insights into the mechanisms underlying a fatal developmental lung disorder.
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Between 0.02% and 0.04% of articles are retracted. We aim to: (a) describe the reasons for retraction of genetics articles and the time elapsed between the publication of an article and that of the retraction notice because of research misconduct (ie, fabrication, falsification, plagiarism); and (b) compare all these variables between retracted medical genetics (MG) and non-medical genetics (NMG) articles. ⋯ Genetics is a discipline with a high article retraction rate (estimated retraction rate 0.15%). Fabrication/falsification and plagiarism were almost mutually exclusive reasons for article retraction. Retracted MG articles were more frequently subject to investigation than NMG articles. Retracted articles due to fabrication/falsification required 2.0-2.8 times longer to retract than when plagiarism was involved.
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Meta Analysis
Genome-wide meta-analysis identifies genetic locus on chromosome 9 associated with Modic changes.
Low back pain (LBP) is a common disabling condition. Lumbar disc degeneration (LDD) may be a contributing factor for LBP. Modic change (MC), a distinct phenotype of LDD, is presented as a pathological bone marrow signal change adjacent to vertebral endplate on MRI. It is strongly associated with LBP and has heritability around 30%. Our objective was to identify genetic loci associated with MC using a genome-wide meta-analysis. ⋯ PTPRD is a novel candidate gene for MC that may act via the development of cartilage or nervous system; further work is needed to define the mechanisms underlying the pathways leading to development of MC. This is the first genome-wide meta-analysis of MC, and the results pave the way for further studies on the genetic factors underlying the various features of spine degeneration and LBP.
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Heart failure, coronary artery disease and myocardial infarction are the most prominent cardiovascular diseases contributing significantly to death worldwide. In the majority of situations, except for surgical interventions and transplantation, there are no reliable therapeutic approaches available to address these health problem. Despite several advances that led to the development of biomarkers and therapies based on the renin-angiotensin system, adrenergic pathways, etc, more definitive and consistent biomarkers and specific target based molecular therapies are still being sought. ⋯ Approximately 32 000 human exonic circular RNAs have been catalogued and their functions are still being ascertained. In the heart, circular RNAs were shown to bind micro RNAs in a specific manner and regulate the expression of transcription factors and stress response genes, and expression of these non-coding RNAs were found to change in conditions such as cardiac hypertrophy, heart failure and cardiac remodelling, reflecting their significance as diagnostic and prognostic biomarkers. In this review, we address the present state of understanding on the biogenesis, regulation and pathophysiological roles of micro and circular RNAs in cardiovascular diseases, and on the potential future perspectives on their use as biomarkers and therapeutic agents.
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The 11p15 region contains two clusters of imprinted genes. Opposite genetic and epigenetic anomalies of this region result in two distinct growth disturbance syndromes: Beckwith-Wiedemann (BWS) and Silver-Russell syndromes (SRS). Cytogenetic rearrangements within this region represent less than 3% of SRS and BWS cases. Among these, 11p15 duplications were infrequently reported and interpretation of their pathogenic effects is complex. ⋯ The phenotype associated with 11p15 duplications depends on the size, genetic content, parental inheritance and imprinting status. Identification of these rare duplications is crucial for genetic counselling.