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Background Preterm birth (PTB), defined as infant delivery before 37 weeks of completed gestation, results from the interaction of both genetic and environmental components and constitutes a complex multifactorial syndrome. Transcriptome analysis of PTB has proven challenging because of the multiple causes of PTB and the numerous maternal and fetal gestational tissues that must interact to facilitate parturition. The transcriptome of the chorioamnion membranes at the site of rupture in PTB and term fetuses may reflect the molecular pathways of preterm labor. Methods In this work, chorioamnion membranes from severe preterm and term fetuses were analyzed using RNA sequencing. Functional annotations and pathway analysis of differentially expressed genes were performed with the GAGE and GOSeq packages. A subset of differentially expressed genes in PTB was validated in a larger cohort using qRT-PCR and by comparing our results with genes and pathways previously reported in the literature. Results A total of 270 genes were differentially expressed (DE): 252 were upregulated and 18 were down-regulated in severe preterm births relative to term births. Inflammatory and immunological pathways were upregulated in PTB. Both types of pathways were previously suggested to lead to PTB. Pathways that were not previously reported in PTB, such as the hemopoietic pathway, appeared upregulated in preterm membranes. A group of 18 downregulated genes discriminated between term and severe preterm cases. These genes potentially characterize a severe preterm transcriptome pattern and therefore are candidate genes for understanding the syndrome. Some of the downregulated genes are involved in the nervous system, morphogenesis ( WNT1, DLX5, PAPPA2 ) and ion channel complexes ( KCNJ16, KCNB1 ), making them good candidates as biomarkers of PTB. Conclusions The identification of this DE gene pattern will help with the development of a multi-gene disease classifier. These markers were generated in an admixed South American population in which PTB has a high incidence. Since the genetic background may differentially impact different populations, it is necessary to include populations such as those from South America and Africa, which are usually excluded from high-throughput approaches. These classifiers should be compared to those in other populations to obtain a global landscape of PTB. Electronic supplementary material The online version of this article (10.1186/s12920-019-0498-3) contains supplementary material, which is available to authorized users.

The neotropical cichlid genus Gymnogeophagus is distributed in the Río de la Plata basin and in Dos Patos and Merín coastal lagoons on the border between Uruguay and southern Brazil. A phylogeographic approach based on mitochondrial cytochrome b analysis was performed to assess the patterns and processes of differentiation in this taxon. Gymnogeophagus gymnogenys showed high haplotype diversity (H = 0.992) and corrected mtDNA genetic distances ranged from 0 to 5.3%. Our analyses yielded robust support for the existence of four monophyletic groups within G. gymnogenys from the analyzed basins. No correlation between the aforementioned clades and geographic structure was found, since individuals belonging to different phylogenetic clades inhabit the same locality. The phylogeographic approach presented here showed that these four phylogroups (1, 2, 3 and 4) were sister groups. Our present findings would corroborate that G. gymnogenys could be integrated by different phylogenetic lineages, showing an explosive differentiation pattern and confirming the hypothesis that this taxon constitutes a species complex.

BackgroundComplex traits like cancer, diabetes, obesity or schizophrenia arise from an intricate interaction between genetic and environmental factors. Complex disorders often cluster in families without a clear-cut pattern of inheritance. Genomic wide association studies focus on the detection of tens or hundreds individual markers contributing to complex diseases. In order to test if a subset of single nucleotide polymorphisms (SNPs) from candidate genes are associated to a condition of interest in a particular individual or group of people, new techniques are needed. High-resolution melting (HRM) analysis is a new method in which polymerase chain reaction (PCR) and mutations scanning are carried out simultaneously in a closed tube, making the procedure fast, inexpensive and easy. Preterm birth (PTB) is considered a complex disease, where genetic and environmental factors interact to carry out the delivery of a newborn before 37 weeks of gestation. It is accepted that inflammation plays an important role in pregnancy and PTB.MethodsHere, we used real time-PCR followed by HRM analysis to simultaneously identify several gene variations involved in inflammatory pathways on preterm labor. SNPs from TLR4, IL6, IL1 beta and IL12RB genes were analyzed in a case-control study. The results were confirmed either by sequencing or by PCR followed by restriction fragment length polymorphism.ResultsWe were able to simultaneously recognize the variations of four genes with similar accuracy than other methods. In order to obtain non-overlapping melting temperatures, the key step in this strategy was primer design. Genotypic frequencies found for each SNP are in concordance with those previously described in similar populations. None of the studied SNPs were associated with PTB.ConclusionsSeveral gene variations related to the same inflammatory pathway were screened through a new flexible, fast and non expensive method with the purpose of analyzing their association to PTB. It can easily be used for simultaneously analyze any set of SNPs, either as the first choice for new association studies or as a complement to large-scale genotyping analysis. Given that inflammatory pathway is in the base of several diseases, it is potentially useful to analyze a broad range of disorders.

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15 16 Short title: Transcriptomic analysis of severe preterm birth 17 Key words: RNA-seq, preterm birth, gestational age, biomarkers 18 2 19Abstract 20 Preterm birth (PTB), defined as infant delivery before 37 weeks of completed gestation, results of 21 the interaction of both genetic and environmental components and constitutes a complex 22 multifactorial syndrome. Transcriptome analysis of PTB has proved challenging because of the 23 multiple causes of PTB and the numerous maternal and fetal gestational tissues that must interact 24 to facilitate parturition. A common pathway of labor and PTB may be the activation of fetal 25 membranes. In this work, chorioamnion membranes from severe preterm and term fetus were 26 analyzed using RNA sequencing. A total of 270 genes were differentially expressed (DE): 252 27 were up-regulated and 18 were down-regulated in the severe preterm compared to the term births. 28 We found great gene expression homogeneity in the control samples, and not in severe preterm 29 samples. In this work, we identified up-regulated pathways that were previously suggested as 30 leading to PTB like immunological and inflammatory paths. New pathways that were not 31 identified in preterm like the hemopoietic path appeared up-regulated in preterm membranes. A 32 group of 18 down-regulated genes discriminates between term and severe preterm cases. These 33 genes potentially characterize a severe preterm transcriptome pattern and therefore are candidate 34 genes for understanding the syndrome. Some of the down-regulated genes are involved in the 35 nervous system, morphogenesis (WNT-1, DLX5, PAPPA2) and ion channel complexes (KCNJ16, 36 KCNB1), making them good candidates as biomarkers of PTB.37 The identification of this DE gene pattern may help to develop a multi-gene disease classifier.38 These markers were generated in an admixtured South American population where PTB has a high 39 incidence. Since genetic background may impact differentially in different populations it is 40 mandatory to include populations like South American and African ones that are usually excluded 3 41 from high throughput approaches. These classifiers should be compared to those in other 42 populations to get a global landscape of PTB. 43 44 Introduction 45 Preterm birth (PTB), defined as the delivery of an infant before 37 weeks of completed gestation, 46 is a worldwide health problem and remains the leading cause of global perinatal morbidity and 47 mortality [1][2][3]. PTB is a complex, multifactorial syndrome comprised of multiple clinical 48 subtypes that can be defined as either 'spontaneous' or 'medically indicated' [4,5]. 70 % of PTB 49 cases are idiopathic; 5 % are due to the spontaneous onset of labor (sPTB) and the remaining 25 50 % are consequence of the preterm premature rupture of membranes (PPROM) [5,6]. PTB has also 51 been stratified according to gestational age (GA); neonates born between 24 and 33 weeks (severe 52 PTB) are at higher risk of death, and diseases later in life, than moderate PTB (GA betwee...

Population genetic analyses based on both mitochondrial cytochrome b and the internal transcribed spacer 2 of recombinant (r)DNA genes were implemented to examine hypotheses of population differentiation in the angular angel shark Squatina guggenheim, one of the four most-widespread endemic species inhabiting coastal ecosystems in the south-western Atlantic Ocean. A total of 82 individuals of S. guggenheim from 10 sampling sites throughout the Río de la Plata mouth, its maritime front, the outer shelf at the subtropical confluence and the coastal areas of the south-west Atlantic Ocean, were included. The analysis of molecular variance (AMOVA) based on the second internal transcribed spacer (its-2) region supports that the samples from the outer shelf represent an isolated group from other sites. Historical gene flow in a coalescent-based approach revealed significant immigration and emigration asymmetry between sampling sites. Based on the low level of genetic diversity, the existence of a long-term population decline or a past recent population expansion following a population bottleneck could be proposed in S. guggenheim. This demographic differentiation suggests a degree of vulnerability to overexploitation in this endemic and endangered south-west Atlantic Ocean shark, given its longevity and low reproductive potential.

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