A molecular framework for enhancing quality control and sample integrity in forensic genome sequencing.

DNA typing is essential for identifying crime scene evidence and missing and unknown persons. Molecular tags historically have been incorporated into DNA typing reactions to improve result interpretation. Molecular tags like barcodes and unique identifiers are integral to MPS, aiding in sample tracking and error detection.

Dense SNP-based analyses complement forensic anthropology biogeographical ancestry assessments.

Identification of unidentified human remains (UHRs) is crucial yet challenging, especially with traditional forensic techniques. Forensic anthropological examinations can yield ancestry estimations; however, the utility of these estimates is limited by the data points that can be collected from partial remains, complexities of admixture, and variation of phenotypic expression due to environmental effects. While it is generally known that anthropological estimates can be imprecise, the performance of these methods has not been studied at scale.

Prioritizing privacy and presentation of supportable hypothesis testing in forensic genetic genealogy investigations.

Investigative leads are not generated by traditional forensic DNA testing, if the source of the forensic evidence or a 1st degree relative of unidentified human remains is not in the DNA database. In such cases, forensic genetic genealogy (FGG) can provide valuable leads. However, FGG generated genetic data contain private and sensitive information.

Dense single nucleotide polymorphism testing revolutionizes scope and degree of certainty for source attribution in forensic investigations.

The field of forensic DNA analysis has experienced significant advancements over the years, such as the advent of DNA fingerprinting, the introduction of the polymerase chain reaction for increased sensitivity, the shift to a primary genetic marker system based on short tandem repeats, and implementation of national DNA databases. Now, the forensics field is poised for another revolution with the advent of dense single nucleotide polymorphisms (SNPs) testing. SNP testing holds the potential to significantly enhance source attribution in forensic cases, particularly those involving low-quantity or low-quality samples.

FEVR findings in patients with Loeys-Dietz syndrome type II.

Background: Loeys-Dietz syndrome (LDS) is a connective tissue disorder that has phenotypic overlap with Marfan syndrome. In LDS, the aortic root dissections can be more aggressive and occur at a younger age than Marfan syndrome.

Materials And Methods: Review of two cases.

Consumer genomics will change your life, whether you get tested or not.

With more than 10 million genotyped customers, the consumer genomics industry is maturing and becoming a mainstream phenomenon. At last, innovations and applications, some unforeseen, are being brought to the masses.

Whole genome sequencing of one complex pedigree illustrates challenges with genomic medicine.

Background: Human Phenotype Ontology (HPO) has risen as a useful tool for precision medicine by providing a standardized vocabulary of phenotypic abnormalities to describe presentations of human pathologies; however, there have been relatively few reports combining whole genome sequencing (WGS) and HPO, especially in the context of structural variants.

Methods: We illustrate an integrative analysis of WGS and HPO using an extended pedigree, which involves Prader-Willi Syndrome (PWS), hereditary hemochromatosis (HH), and dysautonomia-like symptoms. A comprehensive WGS pipeline was used to ensure reliable detection of genomic variants.

Punctuated bursts in human male demography inferred from 1,244 worldwide Y-chromosome sequences.

We report the sequences of 1,244 human Y chromosomes randomly ascertained from 26 worldwide populations by the 1000 Genomes Project. We discovered more than 65,000 variants, including single-nucleotide variants, multiple-nucleotide variants, insertions and deletions, short tandem repeats, and copy number variants. Of these, copy number variants contribute the greatest predicted functional impact.

Polymorphic tandem repeats within gene promoters act as modifiers of gene expression and DNA methylation in humans.

Despite representing an important source of genetic variation, tandem repeats (TRs) remain poorly studied due to technical difficulties. We hypothesized that TRs can operate as expression (eQTLs) and methylation (mQTLs) quantitative trait loci. To test this we analyzed the effect of variation at 4849 promoter-associated TRs, genotyped in 120 individuals, on neighboring gene expression and DNA methylation.

TAF1 Variants Are Associated with Dysmorphic Features, Intellectual Disability, and Neurological Manifestations.

We describe an X-linked genetic syndrome associated with mutations in TAF1 and manifesting with global developmental delay, intellectual disability (ID), characteristic facial dysmorphology, generalized hypotonia, and variable neurologic features, all in male individuals. Simultaneous studies using diverse strategies led to the identification of nine families with overlapping clinical presentations and affected by de novo or maternally inherited single-nucleotide changes. Two additional families harboring large duplications involving TAF1 were also found to share phenotypic overlap with the probands harboring single-nucleotide changes, but they also demonstrated a severe neurodegeneration phenotype.

Tandem repeat variation in human and great ape populations and its impact on gene expression divergence.

Tandem repeats (TRs) are stretches of DNA that are highly variable in length and mutate rapidly. They are thus an important source of genetic variation. This variation is highly informative for population and conservation genetics.

Focusing of mammalian cells under an ultrahigh pH gradient created by unidirectional electropulsation in a confined microchamber†Electronic supplementary information (ESI) available: Figures S1-S5 and videos S1-S2. See DOI: 10.1039/c4sc00319eClick here for additional data file.Click here for additional data file.Click here for additional data file.

The transport and manipulation of cells in microfluidic structures are often critically required in cellular analysis. Cells typically make consistent movement in a dc electric field in a single direction, due to their electrophoretic mobility or electroosmotic flow or the combination of the two. Here we demonstrate that mammalian cells focus to the middle of a closed microfluidic chamber under the application of unidirectional direct current pulses.

An analytical framework for optimizing variant discovery from personal genomes.

The standardization and performance testing of analysis tools is a prerequisite to widespread adoption of genome-wide sequencing, particularly in the clinic. However, performance testing is currently complicated by the paucity of standards and comparison metrics, as well as by the heterogeneity in sequencing platforms, applications and protocols. Here we present the genome comparison and analytic testing (GCAT) platform to facilitate development of performance metrics and comparisons of analysis tools across these metrics.

Dragging scientific publishing into the 21st century.

Scientific publishers must shake off three centuries of publishing on paper and embrace 21st century technology to make scientific communication more intelligible, reproducible, engaging and rapidly available.

GFP-based fluorescence assay for CAG repeat instability in cultured human cells.

Trinucleotide repeats can be highly unstable, mutating far more frequently than point mutations. Repeats typically mutate by addition or loss of units of the repeat. CAG repeat expansions in humans trigger neurological diseases that include myotonic dystrophy, Huntington disease, and several spinocerebellar ataxias.

The landscape of human STR variation.

Short tandem repeats are among the most polymorphic loci in the human genome. These loci play a role in the etiology of a range of genetic diseases and have been frequently utilized in forensics, population genetics, and genetic genealogy. Despite this plethora of applications, little is known about the variation of most STRs in the human population.

Lentiviral and targeted cellular barcoding reveals ongoing clonal dynamics of cell lines in vitro and in vivo.

Background: Cell lines are often regarded as clonal, even though this simplifies what is known about mutagenesis, transformation and other processes that destabilize them over time. Monitoring these clonal dynamics is important for multiple areas of biomedical research, including stem cell and cancer biology. Tracking the contributions of individual cells to large populations, however, has been constrained by limitations in sensitivity and complexity.

Natural variation in genome architecture among 205 Drosophila melanogaster Genetic Reference Panel lines.

The Drosophila melanogaster Genetic Reference Panel (DGRP) is a community resource of 205 sequenced inbred lines, derived to improve our understanding of the effects of naturally occurring genetic variation on molecular and organismal phenotypes. We used an integrated genotyping strategy to identify 4,853,802 single nucleotide polymorphisms (SNPs) and 1,296,080 non-SNP variants. Our molecular population genomic analyses show higher deletion than insertion mutation rates and stronger purifying selection on deletions.

Integrating human sequence data sets provides a resource of benchmark SNP and indel genotype calls.

Clinical adoption of human genome sequencing requires methods that output genotypes with known accuracy at millions or billions of positions across a genome. Because of substantial discordance among calls made by existing sequencing methods and algorithms, there is a need for a highly accurate set of genotypes across a genome that can be used as a benchmark. Here we present methods to make high-confidence, single-nucleotide polymorphism (SNP), indel and homozygous reference genotype calls for NA12878, the pilot genome for the Genome in a Bottle Consortium.

The fractured genome of HeLa cells.

Whole-genome sequencing of the widely used HeLa cell line provides a nucleotide-resolution view of a greatly mutated and in some places shattered genome.

Personal genomes and precision medicine.

A report of the fifth annual Personal Genomes and Medical Genomics meeting, held at Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA, November 14-17, 2012.

Accurate human microsatellite genotypes from high-throughput resequencing data using informed error profiles.

Repetitive sequences are biologically and clinically important because they can influence traits and disease, but repeats are challenging to analyse using short-read sequencing technology. We present a tool for genotyping microsatellite repeats called RepeatSeq, which uses Bayesian model selection guided by an empirically derived error model that incorporates sequence and read properties. Next, we apply RepeatSeq to high-coverage genomes from the 1000 Genomes Project to evaluate performance and accuracy.