Comparative Genomics Identifies Putative Interspecies Mechanisms Underlying Crbn-Sall4-Linked Thalidomide Embryopathy.

The identification of thalidomide-Cereblon-induced SALL4 degradation has brought new understanding for thalidomide embryopathy (TE) differences across species. Some questions, however, regarding species variability, still remain. The aim of this study was to detect sequence divergences between species, affected or not by TE, and to evaluate the regulated gene co-expression in a murine model.

Genetic variants in miRNAs differentially expressed during brain development and their relevance to psychiatric disorders susceptibility.

Objectives: MicroRNAs (miRNAs) play an important regulatory role in the expression of genes involved in brain functions during development. Genetic variants in miRNA genes may impact their regulatory function and lead to psychiatric disorders. To evaluate the role of genetic variants in genes of miRNAs differentially expressed during neurodevelopment on autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), schizophrenia (SCZ), and major depressive disorder (MDD).

Methylphenidate effects on mice odontogenesis and connections with human odontogenesis.

The purpose of this study is to evaluate the effects of Methylphenidate exposure on mice odontogenesis and connect them by bioinformatics with human odontogenesis. Thirty-two pregnant Swiss mice were divided into treated group and control group, which received, respectively, 5 mg/kg of Methylphenidate and saline solution from the 5th to the 17th day of pregnancy. The mouse embryos tooth germs were analyzed through optical microscopy, and the data collected were analyzed statistically by Fisher's exact test.

CRL4-Cereblon complex in Thalidomide Embryopathy: a translational investigation.

The Cereblon-CRL4 complex has been studied predominantly with regards to thalidomide treatment of multiple myeloma. Nevertheless, the role of Cereblon-CRL4 in Thalidomide Embryopathy (TE) is still not understood. Not all embryos exposed to thalidomide develop TE, hence here we evaluate the role of the CRL4-Cereblon complex in TE variability and susceptibility.

Analysis of a Protein Network Related to Copy Number Variations in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, with strong genetic influences as evidenced by its high heritability. Submicroscopic variations (ranging from one kilobase to several megabases) in DNA, called copy number variations (CNVs), have been associated with psychiatric diseases, including ASD. We aimed to identify CNVs in children diagnosed with idiopathic ASD.

Serotonin, behavior, and natural selection in New World monkeys.

Traits that undergo massive natural selection pressure, with multiple events of positive selection, are hard to find. Social behaviour, in social animals, is crucial for survival, and genetic networks involved in behaviour, such as those of serotonin (5-HT) and other neurotransmitters, must be the target of natural selection. Here, we used molecular analyses to search for signals of positive selection in the 5-HT system and found such signals in the M3-M4 intracellular domain of the 5-HT3A serotonin receptor subunit (HTR3A) in primates.

Clusters of genetic diseases in Brazil.

The aim of this paper is to present a database of isolated communities (CENISO) with high prevalence of genetic disorders or congenital anomalies in Brazil. We used two strategies to identify such communities: (1) a systematic literature review and (2) a "rumor strategy" based on anecdotal accounts. All rumors and reports were validated in a stepwise process.

Contrasting patterns of RUNX2 repeat variations are associated with palate shape in phyllostomid bats and New World primates.

Establishing the genetic basis that underlies craniofacial variability in natural populations is one of the main topics of evolutionary and developmental studies. One of the genes associated with mammal craniofacial variability is RUNX2, and in the present study we investigated the association between craniofacial length and width and RUNX2 across New World bats (Phyllostomidae) and primates (Catarrhini and Platyrrhini). Our results showed contrasting patterns of association between the glutamate/alanine ratios (Q/A ratio) and palate shape in these highly diverse groups.

Oxytocin and arginine vasopressin systems in the domestication process.

Domestication is of unquestionable importance to the technological revolution that has given rise to modern human societies. In this study, we analyzed the DNA and protein sequences of six genes of the oxytocin and arginine vasopressin systems (OXT-OXTR; AVP-AVPR1a, AVPR1b and AVPR2) in 40 placental mammals. These systems play an important role in the control of physiology and behavior.

Searching for ancient balanced polymorphisms shared between Neanderthals and Modern Humans.

Hominin evolution is characterized by adaptive solutions often rooted in behavioral and cognitive changes. If balancing selection had an important and long-lasting impact on the evolution of these traits, it can be hypothesized that genes associated with them should carry an excess of shared polymorphisms (trans- SNPs) across recent Homo species. In this study, we investigate the role of balancing selection in human evolution using available exomes from modern (Homo sapiens) and archaic humans (H.

Functional New World monkey oxytocin forms elicit an altered signaling profile and promotes parental care in rats.

The neurohormone oxytocin is a key player in the modulation of reproductive and social behavioral traits, such as parental care. Recently, a correlation between different forms of oxytocin and behavioral phenotypes has been described in the New World Monkeys (NWMs). Here, we demonstrate that, compared with the LeuOXT found in most placental mammals, the Cebidae ProOXT and ValProOXT taxon-specific variants act as equi-efficacious agonists for the G-dependent pathway but are weaker agonists for the β-arrestin engagement and subsequent endocytosis toward the oxytocin receptor (OXTR).

A tale of agriculturalists and hunter-gatherers: Exploring the thrifty genotype hypothesis in native South Americans.

Objectives: To determine genetic differences between agriculturalist and hunter-gatherer southern Native American populations for selected metabolism-related markers and to test whether Neel's thrifty genotype hypothesis (TGH) could explain the genetic patterns observed in these populations.

Materials And Methods: 375 Native South American individuals from 17 populations were genotyped using six markers (APOE rs429358 and rs7412; APOA2 rs5082; CD36 rs3211883; TCF7L2 rs11196205; and IGF2BP2 rs11705701). Additionally, APOE genotypes from 39 individuals were obtained from the literature.

FOXP in Tetrapoda: Intrinsically Disordered Regions, Short Linear Motifs and their evolutionary significance.

The FOXP subfamily is probably the most extensively characterized subfamily of the forkhead superfamily, playing important roles in development and homeostasis in vertebrates. Intrinsically disorder protein regions (IDRs) are protein segments that exhibit multiple physical interactions and play critical roles in various biological processes, including regulation and signaling. IDRs in proteins may play an important role in the evolvability of genetic systems.

Progesterone Response Element Variation in the OXTR Promoter Region and Paternal Care in New World Monkeys.

Paternal care is a complex social behavior common in primate species with socially monogamous mating systems and twin births. Evolutionary causes and consequences of such behavior are not well understood, nor are their neuroendocrine and genetic bases. However, the neuropeptide oxytocin (OXT) and its receptor (OXTR) are associated with parental care in mammalian lineages.

Oxytocin and arginine vasopressin receptor evolution: implications for adaptive novelties in placental mammals.

Oxytocin receptor (OXTR) and arginine vasopressin receptors (AVPR1a, AVPR1b, and AVPR2) are paralogous genes that emerged through duplication events; along the evolutionary timeline, owing to speciation, numerous orthologues emerged as well. In order to elucidate the evolutionary forces that shaped these four genes in placental mammals and to reveal specific aspects of their protein structures, 35 species were selected. Specifically, we investigated their molecular evolutionary history and intrinsic protein disorder content, and identified the presence of short linear interaction motifs.

The role of protein intrinsic disorder in major psychiatric disorders.

Although new candidate genes for Autism Spectrum Disorder (ASD), Schizophrenia (SCZ), Attention-Deficit/Hyperactivity Disorder (ADHD), and Bipolar Disorder (BD) emerged from genome-wide association studies (GWAS), their underlying molecular mechanisms remain poorly understood. Evidences of the involvement of intrinsically disordered proteins in diseases have grown in the last decade. These proteins lack tridimensional structure under physiological conditions and are involved in important cellular functions such as signaling, recognition and regulation.

The contribution of protein intrinsic disorder to understand the role of genetic variants uncovered by autism spectrum disorders exome studies.

Several autism spectrum disorders (ASD) exome studies suggest that coding single nucleotide variants (SNVs) play an important role on ASD etiology. Usually, the pathogenic effect of missense mutations is estimated through predictors that lose accuracy for those SNVs placed in intrinsically disordered regions of protein. Here, we used bioinformatics tools to investigate the effect of mutations described in ASD published exome studies (549 mutations) in protein disorder, considering post-translational modification, PEST and Molecular Recognition Features (MoRFs) motifs.

Origins and evolvability of the PAX family.

The paired box (PAX) family of transcription/developmental genes plays a key role in numerous stages of embryonic development, as well as in adult organogenesis. There is evidence linking the acquisition of a paired-like DNA binding domain (PD) to domestication of a Tc1/mariner transposon. Further duplication/deletion processes led to at least five paralogous metazoan protein groups, which can be classified into two supergroups, PAXB-like or PAXD-like, using ancestral defining structures; the PD plus an octapeptide motif (OP) and a paired-type homeobox DNA binding domain (PTHD), producing the PD-OP-PTHD structure characteristic of the PAXB-like group, whereas an additional domain, the paired-type homeodomain tail (PHT), is present in the PAXD-like group, producing a PD-OP-PTHD-PHT structure.

Evolutionary pattern in the OXT-OXTR system in primates: coevolution and positive selection footprints.

Oxytocin is a nonapeptide involved in a wide range of physiologic and behavioral functions. Until recently, it was believed that an unmodified oxytocin sequence was present in all placental mammals. This study analyzed oxytocin (OXT) in 29 primate species and the oxytocin receptor (OXTR) in 21 of these species.

MSX1 and PAX9 investigation in monozygotic twins with variable expression of tooth agenesis.

Non-syndromic agenesis of permanent teeth is one of the most common anomalies in human development, a multifactorial characteristic caused by genetic and environmental factors. We describe a pair of monozygotic twins who showed second premolar and third molar agenesis, albeit with different expressions. We studied the DNA of two genes, paired domain box gene 9 (PAX9) and muscle segment homeodomain-homeobox1 (MSX1), encoding transcription factors that earlier studies found were involved in the manifestation of this condition.

Evolutionary history of chordate PAX genes: dynamics of change in a complex gene family.

Paired box (PAX) genes are transcription factors that play important roles in embryonic development. Although the PAX gene family occurs in animals only, it is widely distributed. Among the vertebrates, its 9 genes appear to be the product of complete duplication of an original set of 4 genes, followed by an additional partial duplication.

The cognitive ability of extinct hominins: bringing down the hierarchy using genomic evidences.

Background: The availability of the full genomes of Homo sapiens, Homo neanderthalensis, and Denisovans, as well as modern bioinformatic tools, are opening new possibilities for the understanding of the differences and similarities present in these taxa.

Methods: We searched for cognitive genes, examined their status in the genomes of these three entities. All substitutions present among them were retrieved.