A5091909433- Prenatal Screening and Diagnostics
- Cystic Fibrosis Research Advances
- Genomic variations and chromosomal abnormalities
- Fetal and Pediatric Neurological Disorders
- Genomics and Rare Diseases
- Cancer Genomics and Diagnostics
- Fungal and yeast genetics research
- BRCA gene mutations in cancer
- Genetic Syndromes and Imprinting
- Gene Regulatory Network Analysis
- RNA and protein synthesis mechanisms
- Microbial Metabolic Engineering and Bioproduction
- Congenital Heart Disease Studies
- RNA Research and Splicing
- Tracheal and airway disorders
- Assisted Reproductive Technology and Twin Pregnancy
- Congenital heart defects research
- Nutrition, Genetics, and Disease
- Parvovirus B19 Infection Studies
- Hemoglobinopathies and Related Disorders
- Iron Metabolism and Disorders
- Genetic factors in colorectal cancer
- Single-cell and spatial transcriptomics
- CRISPR and Genetic Engineering
- Pregnancy and preeclampsia studies
Myriad Genetics
2018-2024
Myriad (Germany)
2019-2024
University of California, San Francisco
2014-2018
Mayo Clinic
2017
Freenome (United States)
2017
QB3
2014
Howard Hughes Medical Institute
2013-2014
Massachusetts Institute of Technology
2006-2009
Harvard University
2006-2009
Harvard Bioscience (United States)
2006-2009
The propagation of information through signaling cascades spans a wide range time scales, including the rapid ligand-receptor interaction and much slower response downstream gene expression. To determine which dynamic dominates response, we used periodic stimuli to measure frequency dependence signal transduction in osmo-adaptation pathway Saccharomyces cerevisiae. We applied system identification methods infer concise predictive model. found that dynamics are dominated by fast-acting...
Fluctuations in protein numbers (noise) due to inherent stochastic effects single cells can have large on the dynamic behavior of gene regulatory networks. Although deterministic models predict average network behavior, they fail incorporate stochasticity characteristic expression, thereby limiting their relevance when cell behaviors deviate from population average. Recently, been used distributions steady-state levels within a but not dynamic, presteady-state distributions. In present work,...
Abstract Background Candida albicans is a ubiquitous opportunistic fungal pathogen that afflicts immunocompromised human hosts. With rare and transient exceptions the yeast diploid, yet despite its clinical relevance respective sequences of two homologous chromosomes have not been completely resolved. Results We construct phased diploid genome assembly by deep sequencing standard laboratory wild-type strain panel strains homozygous for particular chromosomes. The has 700-fold coverage on...
Expanded carrier screening (ECS) informs couples of their risk having offspring affected by certain genetic conditions. Limited data exists assessing the actions and reproductive outcomes at-risk (ARCs). We describe impact ECS on planned actual pregnancy management in largest sample ARCs studied to date.Couples who elected were found be at high a least one 176 conditions invited complete survey about management.Three hundred ninety-one completed survey. Among those screened before becoming...
Heritable differences in gene expression between individuals are an important source of phenotypic variation. The question how closely the effects genetic variation on protein levels mirror those mRNA remains open. Here, we addressed this by using ribosome profiling to examine two strains yeast S. cerevisiae affect translation. Strain translation were observed for hundreds genes. Allele specific measurements diploid hybrid revealed roughly half as many cis-acting levels. In both parents and...
Abstract BACKGROUND By identifying pathogenic variants across hundreds of genes, expanded carrier screening (ECS) enables prospective parents to assess the risk transmitting an autosomal recessive or X-linked condition. Detection at-risk couples depends on number conditions tested, prevalence respective diseases, and screen's analytical sensitivity for disease-causing variants. Disease-level is often <100% in ECS tests because copy (CNVs) are typically not interrogated their technical...
Carrier screening identifies couples at high risk for conceiving offspring affected with serious heritable conditions. Minimal guidelines recommend offering testing cystic fibrosis and spinal muscular atrophy, but expanded carrier (ECS) assesses hundreds of conditions simultaneously. Although medical societies consider ECS an acceptable practice, the health economics remain incompletely characterized.Preconception was modeled using a decision tree comparing minimal 176-condition panel. rates...
Carrier status associates strongly with genetic ancestry, yet current carrier screening guidelines recommend testing for a limited set of conditions based on patient's self-reported ethnicity. Ethnicity, which can reflect both ancestry and cultural factors (e.g., religion), may be imperfectly known or communicated by patients. We sought to quantitatively assess the efficacy equity ethnicity-based captures recessive disease risk.For 93,419 individuals undergoing 96-gene expanded screen (ECS),...
PurposeThe recent growth in pan-ethnic expanded carrier screening (ECS) has raised questions about how such panels might be designed and evaluated systematically. Design principles for ECS improve clinical detection of at-risk couples facilitate objective discussions panel choice.MethodsGuided by medical-society statements, we propose a method the design that aims to maximize aggregate per-disease sensitivity specificity across range Mendelian disorders considered serious systematic...
Though sequence differences between alleles are often limited to a few polymorphisms, these can cause large and widespread allelic variation at the expression level. Such allele-specific (ASE) has been extensively explored level of transcription but not translation. Here we measured ASE in diploid yeast Candida albicans both transcriptional translational levels using RNA-seq ribosome profiling, respectively. Since C. is an obligate diploid, our analysis isolates arising from cis elements...
The American College of Obstetricians and Gynecologists (ACOG) proposed seven criteria for expanded carrier screening (ECS) panel design. To ensure that a condition is sufficiently sensitive to identify carriers reduce residual risk noncarriers, one criterion requires per-condition rate greater than 1 in 100. However, it unestablished whether this threshold corresponds with loss clinical detection. impact the design on at-risk couple detection warrants data-driven evaluation.
The percentage of a maternal cell-free DNA (cfDNA) sample that is fetal-derived (the fetal fraction; FF) key driver the sensitivity and specificity noninvasive prenatal screening (NIPS). On certain NIPS platforms, >20% women with high body mass index (and >5% overall) receive test failure due to low FF (<4%).A scalable fraction amplification (FFA) technology was analytically validated on 1264 samples undergoing whole-genome sequencing (WGS)-based NIPS. All were tested without FFA.Zero had <...
Objective Performance of noninvasive prenatal screening (NIPS) methodologies when applied to low fetal fraction samples is not well established. The single-nucleotide polymorphism (SNP) method fails below a predetermined threshold, whereas some laboratories employing the whole-genome sequencing (WGS) report aneuploidy calls for all samples. Here, performance two methods was compared determine which approach actually detects more aneuploidies. Methods Computational models were parameterized...
Medical society guidelines recommend offering genotyping-based cystic fibrosis (CF) carrier screening to pregnant women or considering pregnancy. We assessed the performance of sequencing-based CF relative genotyping, in terms analytical validity, clinical impact, and utility.Analytical validity was using orthogonal confirmation reference samples. Clinical evaluated CFTR2 database. impact ~100,000 screened patients. Three strategies were compared: genotyping 23 guideline-recommended variants...
22q11.2 deletion syndrome (DS) is a serious condition with range of features. The small microdeletion causing 22q11.2DS makes it technically challenging to detect using standard prenatal cfDNA screening. Here, we assess clinical performance by screen that incorporates fetal fraction (FF) amplification.
ABSTRACT Objective To describe our clinical experience across the entire range of fetal‐fraction (FF) measurements a non‐invasive prenatal screen (NIPS) that uses whole‐ genome sequencing (WGS). Methods We analyzed retrospectively results from 58 105 singleton pregnancies underwent NIPS on customized WGS platform during an 8‐month period and assessed test performance for trisomy 21, 18 13. Pregnancy outcomes were sought all screen‐positive patients 18% screen‐negative patients. As...
Hereditary cancer screening (HCS) for germline variants in the 3′ exons of PMS2, a mismatch repair gene implicated Lynch syndrome, is technically challenging due to homology with its pseudogene PMS2CL. Sequences PMS2 and PMS2CL are so similar that next-generation sequencing (NGS) short fragments—common practice multigene HCS panels—may identify presence variant but fail disambiguate whether origin or pseudogene. Molecular approaches utilizing longer DNA fragments, such as long-range PCR...
Abstract Background Pathogenic variants in HEXA that impair β‐hexosaminidase A (Hex A) enzyme activity cause Tay‐Sachs Disease (TSD), a severe autosomal‐recessive neurodegenerative disorder. Hex analysis demonstrates near‐zero patients affected with TSD and can also identify carriers, whose single functional copy of results reduced relative to noncarriers. Although testing has been optimized widely used for carrier screening Ashkenazi Jewish (AJ) individuals, it unproven sensitivity...