Diagnostic and Statistical Manual of Mental Disorders, 4th ed

https://repositorio.uca.edu.ar/bitstream/123456789/1653/1/melatonin-pleiotropic-orchestrating-regulator-molecule.pdf

Melatonin—A pleiotropic, orchestrating regulator molecule

Evidence is accumulating regarding the importance of circadian core oscillators, several associated factors, and melatonin signaling in the maintenance of health. Dysfunction of endogenous clocks, melatonin receptor polymorphisms, age- and disease-associated declines of melatonin likely contribute to numerous diseases including cancer, metabolic syndrome, diabetes type 2, hypertension, and several mood and cognitive disorders. Consequences of gene silencing, overexpression, gene polymorphisms, and deviant expression levels in diseases are summarized. The circadian system is a complex network of central and peripheral oscillators, some of them being relatively independent of the pacemaker, the suprachiasmatic nucleus. Actions of melatonin on peripheral oscillators are poorly understood. Various lines of evidence indicate that these clocks are also influenced or phase-reset by melatonin. This includes phase differences of core oscillator gene expression under impaired melatonin signaling, effects of melatonin and melatonin receptor knockouts on oscillator mRNAs or proteins. Cross-connections between melatonin signaling pathways and oscillator proteins, including associated factors, are discussed in this review. The high complexity of the multioscillator system comprises alternate or parallel oscillators based on orthologs and paralogs of the core components and a high number of associated factors with varying tissue-specific importance, which offers numerous possibilities for interactions with melatonin. It is an aim of this review to stimulate research on melatonin signaling in peripheral tissues. This should not be restricted to primary signal molecules but rather include various secondarily connected pathways and discriminate between direct effects of the pineal indoleamine at the target organ and others mediated by modulation of oscillators.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1600-079X.2011.00934.x

Melatonin, the circadian multioscillator system and health: the need for detailed analyses of peripheral melatonin signaling.

https://www.cysticfibrosisjournal.com/article/S1569-1993(11)60014-3/pdf

Recommendations for the classification of diseases as CFTR-related disorders

Heteroplasmy, the existence of multiple mtDNA types within an individual, has been previously detected by using mostly indirect methods and focusing largely on just the hypervariable segments of the control region. Next-generation sequencing technologies should enable studies of heteroplasmy across the entire mtDNA genome at much higher resolution, because many independent reads are generated for each position. However, the higher error rate associated with these technologies must be taken into consideration to avoid false detection of heteroplasmy. We used simulations and phiX174 sequence data to design criteria for accurate detection of heteroplasmy with the Illumina Genome Analyzer platform, and we used artificial mixtures and replicate data to test and refine the criteria. We then applied these criteria to mtDNA sequence reads for 131 individuals from five Eurasian populations that had been generated via a parallel tagged approach. We identified 37 heteroplasmies at 10% frequency or higher at 34 sites in 32 individuals. The mutational spectrum does not differ between heteroplasmic mutations and polymorphisms in the same individuals, but the relative mutation rate at heteroplasmic mutations is significantly higher than that estimated for all mutable sites in the human mtDNA genome. Moreover, there is also a significant excess of nonsynonymous mutations observed among heteroplasmies, compared to polymorphism data from the same individuals. Both mutation-drift and negative selection influence the fate of heteroplasmies to determine the polymorphism spectrum in humans. With appropriate criteria for avoiding false positives due to sequencing errors, next-generation technologies can provide novel insights into genome-wide aspects of mtDNA heteroplasmy.

Detecting heteroplasmy from high-throughput sequencing of complete human mitochondrial DNA genomes.

Differential Association of Circadian Genes with Mood Disorders: CRY1 and NPAS2 are Associated with Unipolar Major Depression and CLOCK and VIP with Bipolar Disorder

Genetics Unit, Pompeu Fabra University (UPF), Barcelona, Catalonia, SpainCommunicated by Garry R. CuttingMitochondrial DNA (mtDNA) mutations are an important cause of human disease. Most mtDNA mutationsare found in heteroplasmy, in which the proportion of mutant vs. wild-type species is believed to explain some ofthe observed high phenotypic heterogeneity. However, homoplasmic mutations also observe phenotypicheterogeneity, which may be in part due to undetected low levels of heteroplasmy. In the present report, we havedeveloped two assays, using DHPLC and Pyrosequencing (Biotage AB, Uppsala, Sweden), for reliably andaccurately detecting low-level mtDNA heteroplasmy. Using these assays we have identified a three-generationfamily segregating two mtDNA mutations in heteroplasmy: the deafness-related m.1555A4G mutation in the12S rRNA gene (MTRNR1) and a new variant (m.15287T4C) in the cytochrome b gene (MTCYB). Bothheteroplasmic mtDNA mutations are transmitted through generations in a random manner, thus showingdifferences in mutation load between siblings within the family. In addition, the developed assays were also usedto screen a group of deaf subjects of unknown etiology for the presence of heteroplasmy for both mtDNAvariants. Two additional heteroplasmic m.1555A4G samples, previously considered as homoplasmic, and twodeaf subjects carrying m.15287T4C variant were identified, thus confirming the high specificity and reliabilityof the approach. The development of assays for reliably detecting low-level heteroplasmy, together with thestudy of heteroplasmic mtDNAtransmission, are essential steps for a better knowledge and clinical managementof mtDNA diseases. Hum Mutat 29(2), 248–257, 2008.

/pdf/detection-of-unrecognized-low-level-mtdna-heteroplasmy-may-48kkh32zjz.pdf

Detection of unrecognized low-level mtDNA heteroplasmy may explain the variable phenotypic expressivity of apparently homoplasmic mtDNA mutations.

Objective:We have assessed whether CFTR gene has a major impact on chronic pancreatitis (CP) pathogenesis than that provided by the CFTR mutations. For this aim, we have evaluated clinical parameters, CFTR mutations, and 3 potential regulatory CFTR variants (coding single-nucleotide polymorphisms):

Cecilia García

Papers

Differential Association of Circadian Genes with Mood Disorders: CRY1 and NPAS2 are Associated with Unipolar Major Depression and CLOCK and VIP with Bipolar Disorder

Detection of unrecognized low-level mtDNA heteroplasmy may explain the variable phenotypic expressivity of apparently homoplasmic mtDNA mutations.

Independent contribution of common CFTR variants to chronic pancreatitis.

HLA-DQB105:02, 05:03, and *03:01 alleles as risk factors for myasthenia gravis in a Spanish cohort

Cecilia García

Papers

Differential Association of Circadian Genes with Mood Disorders: CRY1 and NPAS2 are Associated with Unipolar Major Depression and CLOCK and VIP with Bipolar Disorder

Detection of unrecognized low-level mtDNA heteroplasmy may explain the variable phenotypic expressivity of apparently homoplasmic mtDNA mutations.

Independent contribution of common CFTR variants to chronic pancreatitis.

HLA-DQB1*05:02, *05:03, and *03:01 alleles as risk factors for myasthenia gravis in a Spanish cohort

HLA-DQB105:02, 05:03, and *03:01 alleles as risk factors for myasthenia gravis in a Spanish cohort