198 research outputs found
Discovery and genotyping of structural variation from long-read haploid genome sequence data
In an effort to more fully understand the full spectrum of human genetic variation, we generated deep single-molecule, real-time (SMRT) sequencing data from two haploid human genomes. By using an assembly-based approach (SMRT-SV), we systematically assessed each genome independently for structural variants (SVs) and indels resolving the sequence structure of 461,553 genetic variants from 2 bp to 28 kbp in length. We find that >89% of these variants have been missed as part of analysis of the 1000 Genomes Project even after adjusting for more common variants (MAF > 1%). We estimate that this theoretical human diploid differs by as much as ∼16 Mbp with respect to the human reference, with long-read sequencing data providing a fivefold increase in sensitivity for genetic variants ranging in size from 7 bp to 1 kbp compared with short-read sequence data. Although a large fraction of genetic variants were not detected by short-read approaches, once the alternate allele is sequence-resolved, we show that 61% of SVs can be genotyped in short-read sequence data sets with high accuracy. Uncoupling discovery from genotyping thus allows for the majority of this missed common variation to be genotyped in the human population. Interestingly, when we repeat SV detection on a pseudodiploid genome constructed in silico by merging the two haploids, we find that ∼59% of the heterozygous SVs are no longer detected by SMRT-SV. These results indicate that haploid resolution of long-read sequencing data will significantly increase sensitivity of SV detection.</jats:p
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The first molecular phylogeny of Chilodontidae (Teleostei: Ostariophysi: Characiformes) reveals cryptic biodiversity and taxonomic uncertainty
Chilodontidae is a small family of eight described characiform species popularly
known as headstanders. These small to moderately sized fishes are well known to
aquarists, who prize their striking spotted pigmentation and unusual behaviors, and to
systematists, who have revised both chilodontid genera in recent memory and studied
their phylogenetic relationships using a comprehensive morphological dataset.
However, no molecular phylogeny for the family has ever been proposed. Here, we
reconstruct phylogenetic relationships for all eight known chilodontid species using
three mitochondrial and two nuclear loci. Results largely agree with the previous
morphological hypothesis, and confirm the monophyly of the family as well as its
included genera, Caenotropus and Chilodus. The molecular topology differs slightly
from the morphological hypothesis by placing Caenotropus maculosus rather than C.
mestomorgmatos as the sister to the remaining three congeners, and by reconstructing
the Curimatidae as the closest outgroup family, rather than the Anostomidae. However,
the topologies supported by the morphological data were only slightly less likely and
could not be rejected via Shimodaira-Hasegawa tests. Within Chilodus, two described
species with distinctive pigmentation (C. fritillus and C. zunevei) appear embedded
within the broad distributed C. punctatus clade, suggesting the presence of cryptic taxa
with polymorphic pigmentation within the present concept of C. punctatus. Future work
should combine morphological and molecular data to revisit the taxonomy and
systematics of Chilodus and determine species limits within the C. punctatus-group
sensu lato.Keywords: Freshwater fishes, Headstanders, Multilocus analysis, AmazonKeywords: Freshwater fishes, Headstanders, Multilocus analysis, Amazo
In vivo biocompatibility assessment of (PTFE–PVDF–PP) terpolymer-based membrane with potential application for glaucoma treatment
The aim of the work was to evaluate the in vivo biological behaviour of polymeric membrane materials for glaucoma implants. The base material was biostable synthetic terpolymer (PTFE–PVDF–PP) with proved biocompability (PN-EN ISO 10993). The samples manufactured in the form a membrane were subjected to chemical and physical treatment to create an open pore system within the polymer matrix. As a porogenic phase biodegradable natrium alginate in a fibrous form was employed. The non-perforating deep sclerectomy technique was performed in a rabbit model. The clinical observations were made after 14 and 30 days. During the study clinical symptoms of a moderate degree were observed, and histopathological changes were typical for foreign body implantation. At the end stage of the study no significant difference in histopathological assessment was found between control and experimental group. Similarities observed in both groups and relatively mild histopathological changes in the tissue surrounding the implant indicate that the observed symptoms come from a deep scleral trauma caused by surgery, and not by the presence of the implant itself
A High-Quality Bonobo Genome Refines The Analysis Of Hominid Evolution
The divergence of chimpanzee and bonobo provides one of the few examples of recent hominid speciation(1,2). Here we describe a fully annotated, high-quality bonobo genome assembly, which was constructed without guidance from reference genomes by applying a multiplatform genomics approach. We generate a bonobo genome assembly in which more than 98% of genes are completely annotated and 99% of the gaps are closed, including the resolution of about half of the segmental duplications and almost all of the full-length mobile elements. We compare the bonobo genome to those of other great apes(1,3-5) and identify more than 5,569 fixed structural variants that specifically distinguish the bonobo and chimpanzee lineages. We focus on genes that have been lost, changed in structure or expanded in the last few million years of bonobo evolution. We produce a high-resolution map of incomplete lineage sorting and estimate that around 5.1% of the human genome is genetically closer to chimpanzee or bonobo and that more than 36.5% of the genome shows incomplete lineage sorting if we consider a deeper phylogeny including gorilla and orangutan. We also show that 26% of the segments of incomplete lineage sorting between human and chimpanzee or human and bonobo are non-randomly distributed and that genes within these clustered segments show significant excess of amino acid replacement compared to the rest of the genome
Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains
Genetics of disease, diagnosis and treatmen
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