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Myriapods (e. g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history.
Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood(1). Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits(2). In an expanded genome-wide association metaanalysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.
The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia
(2019)
The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
The Cotentin Peninsula (Normandy, France) displays sequences of marine terraces and rasas, the latter being wide Late Cenozoic coastal erosion surfaces, that are typical of Western European coasts in Portugal, Spain, France and southern England. Remote sensing imagery and field mapping enabled reappraisal of the Cotentin coastal sequences. From bottom to top, the N Cotentin sequence includes four previously recognized Pleistocene marine terraces (T1 to T4) at elevations <40 m as well as four higher and older rasas (R1 to R4) reaching 200 +/- 5 m in elevation. Low-standing marine terraces are not observed in the central part of the Peninsula and a limited number of terraces are described to the south. The high-standing rasas are widespread all over the peninsula. Such strandline distributions reveal major changes during the Late Cenozoic. Progressive uplift of an irregular sea-floor led to subaerial exposure of bathymetric highs that were carved into rocky platforms, rasas and marine terraces. Eventually, five main islands coalesced and connected to the mainland to the south to form the Cotentin Peninsula. On the basis of previous dating of the last interglacial maximum terrace (i.e. Marine Isotopic Stage, MIS 5e), sequential morphostratigraphy and modelling, we have reappraised uplift rates and derived: (i) mean Upper Pleistocene (i.e. since MIS 5e similar to 122 +/- 6 ka, i.e. kilo annum) apparent uplift rates of 0.04 +/- 0.01 mm/yr, (ii) mean Middle Pleistocene eustasy-corrected uplift rates of 0.09 +/- 0.03 mm/yr, and (iii) low mean Pleistocene uplift rates of 0.01 mm/yr. Extrapolations of these slow rates combined with geological evidence implies that the formation of the sequences from the Cotentin Peninsula occurred between 3 Ma (Pliocene) and 15 Ma (Miocene), which cannot be narrowed down further without additional research. Along the coasts of Western Europe, sequences of marine terraces and rasas are widespread (169 preserve the MIS Se benchmark). In Spain, Portugal, S England and other parts of western France, the sequences morphostratigraphy is very similar to that of Cotentin. The onset of such Western European sequences occurred during the Miocene (e.g. Spain) or Pliocene (e.g. Portugal). We interpret this Neogene-Quaternary coastal uplift as a symptom of the increasing lithospheric compression that accompanies Cenozoic orogenies. (C) 2017 Elsevier B.V. All rights reserved.