Reduced meiotic recombination in rhesus macaques and the origin of the human recombination landscape.

Characterizing meiotic recombination rates across the genomes of nonhuman primates is important for understanding the genetics of primate populations, performing genetic analyses of phenotypic variation and reconstructing the evolution of human recombination. Rhesus macaques (Macaca mulatta) are the most widely used nonhuman primates in biomedical research. We constructed a high-resolution genetic map of the rhesus genome based on whole genome sequence data from Indian-origin rhesus macaques.

CD56 Expression Marks Human Group 2 Innate Lymphoid Cell Divergence from a Shared NK Cell and Group 3 Innate Lymphoid Cell Developmental Pathway.

According to the established model of murine innate lymphoid cell (ILC) development, helper ILCs develop separately from natural killer (NK) cells. However, it is unclear how helper ILCs and NK cells develop in humans. Here we elucidated key steps of NK cell, ILC2, and ILC3 development within human tonsils using ex vivo molecular and functional profiling and lineage differentiation assays.

Whole-Exome Sequencing Reveals Uncaptured Variation and Distinct Ancestry in the Southern African Population of Botswana.

Large-scale, population-based genomic studies have provided a context for modern medical genetics. Among such studies, however, African populations have remained relatively underrepresented. The breadth of genetic diversity across the African continent argues for an exploration of local genomic context to facilitate burgeoning disease mapping studies in Africa.

Extremely low-coverage whole genome sequencing in South Asians captures population genomics information.

Background: The cost of Whole Genome Sequencing (WGS) has decreased tremendously in recent years due to advances in next-generation sequencing technologies. Nevertheless, the cost of carrying out large-scale cohort studies using WGS is still daunting. Past simulation studies with coverage at ~2x have shown promise for using low coverage WGS in studies focused on variant discovery, association study replications, and population genomics characterization.

Practical Approaches for Whole-Genome Sequence Analysis of Heart- and Blood-Related Traits.

Whole-genome sequencing (WGS) allows for a comprehensive view of the sequence of the human genome. We present and apply integrated methodologic steps for interrogating WGS data to characterize the genetic architecture of 10 heart- and blood-related traits in a sample of 1,860 African Americans. In order to evaluate the contribution of regulatory and non-protein coding regions of the genome, we conducted aggregate tests of rare variation across the entire genomic landscape using a sliding window, complemented by an annotation-based assessment of the genome using predefined regulatory elements and within the first intron of all genes.

A hybrid computational strategy to address WGS variant analysis in >5000 samples.

Background: The decreasing costs of sequencing are driving the need for cost effective and real time variant calling of whole genome sequencing data. The scale of these projects are far beyond the capacity of typical computing resources available with most research labs. Other infrastructures like the cloud AWS environment and supercomputers also have limitations due to which large scale joint variant calling becomes infeasible, and infrastructure specific variant calling strategies either fail to scale up to large datasets or abandon joint calling strategies.

ITD assembler: an algorithm for internal tandem duplication discovery from short-read sequencing data.

Background: Detection of tandem duplication within coding exons, referred to as internal tandem duplication (ITD), remains challenging due to inefficiencies in alignment of ITD-containing reads to the reference genome. There is a critical need to develop efficient methods to recover these important mutational events.

Results: In this paper we introduce ITD Assembler, a novel approach that rapidly evaluates all unmapped and partially mapped reads from whole exome NGS data using a De Bruijn graphs approach to select reads that harbor cycles of appropriate length, followed by assembly using overlap-layout-consensus.

Genomic Profiling of Pediatric Acute Myeloid Leukemia Reveals a Changing Mutational Landscape from Disease Diagnosis to Relapse.

The genomic and clinical information used to develop and implement therapeutic approaches for acute myelogenous leukemia (AML) originated primarily from adult patients and has been generalized to patients with pediatric AML. However, age-specific molecular alterations are becoming more evident and may signify the need to age-stratify treatment regimens. The NCI/COG TARGET-AML initiative used whole exome capture sequencing (WXS) to interrogate the genomic landscape of matched trios representing specimens collected upon diagnosis, remission, and relapse from 20 cases of de novo childhood AML.