Genomic analyses reveal moderate levels of ploidy, high heterozygosity and structural variations in a Colombian isolate of Leishmania (Leishmania) amazonensis
The availability of high-quality genome sequences of great ape species provides unprecedented opportunities for genomic analyses. Herein, we reviewed the recent progress in evolutionary comparative genomic studies of the existing great ape species, including human, chimpanzee, bonobo, gorilla, and orangutan. We elaborate discovery on evolutionary history, natural selection, structural variations, and new genes of these species, which is informative for understanding the origin of human-specific phenotypes.
AbstractThe human reference genome serves as the foundation for genomics by providing a scaffold for alignment of sequencing reads, but currently only reflects a single consensus haplotype, which impairs read alignment and downstream analysis accuracy. Reference genome structures incorporating known genetic variation have been shown to improve the accuracy of genomic analyses, but have so far remained computationally prohibitive for routine large-scale use. Here we present a graph genome implementation that enables read alignment across 2,800 diploid genomes encompassing 12.6 million SNPs and 4.0 million indels. Our Graph Genome Pipeline requires 6.5 hours to process a 30x coverage WGS sample on a system with 36 CPU cores compared with 11 hours required by the GATK Best Practices pipeline. Using complementary benchmarking experiments based on real and simulated data, we show that using a graph genome reference improves read mapping sensitivity and produces a 0.5% increase in variant calling recall, or about 20,000 additional variants being detected per sample, while variant calling specificity is unaffected. Structural variations (SVs) incorporated into a graph genome can be genotyped accurately under a unified framework. Finally, we show that iterative augmentation of graph genomes yields incremental gains in variant calling accuracy. Our implementation is a significant advance towards fulfilling the promise of graph genomes to radically enhance the scalability and accuracy of genomic analyses.
Mitochondrial alterations were studied in 25 liver biopsies from patients with alcoholic liver disease. Of special interest were the morphologic resemblance of certain fine structural variations in mitochondria and crystalloid inclusions. Four types of alterations within mitochondria were found that seemed to relate to cytoplasmic crystalloids.Type 1 alteration consisted of localized groups of cristae, usually oriented in the long direction of the organelle (Fig. 1A). In this plane they appeared serrated at the periphery with blind endings in the matrix. Other sections revealed a system of equally-spaced diagonal lines lengthwise in the mitochondrion with cristae protruding from both ends (Fig. 1B). Profiles of this inclusion were not unlike tangential cuts of a crystalloid structure frequently seen in enlarged mitochondria described below.
DNA lesion such as
metholcytosine(<sup>m</sup>C), 8-OXO-guanine(<sup>O</sup>G), inosine(I) <i>etc</i>
could cause the genetic diseases. Identification of the varieties of lesion
bases are usually beyond the capability of conventional DNA sequencing which is
mainly designed to discriminate four bases only. Therefore, lesion detection
remain challenge due to the massive varieties and less distinguishable readouts
for minor structural variations. Moreover, standard amplification and labelling
hardly works in DNA lesions detection. Herein, we designed a single molecule
interface from the mutant K238Q Aerolysin, whose confined sensing region shows
the high compatible to capture and then directly convert each base lesion into
distinguishable current readouts. Compared with previous single molecule
sensing interface, the resolution of the K238Q Aerolysin nanopore is enhanced
by 2-order. The novel K238Q could direct discriminate at least 3 types (<sup>m</sup>C,
<sup>O</sup>G, I) lesions without lableing and quantify modification sites
under mixed hetero-composition condition of oligonucleotide. Such nanopore
could be further applied to diagnose genetic diseases at high sensitivity.
Current Progress in Evolutionary Comparative Genomics of Great Apes
