Rachel A. Ungar

Recommendations for the ethical and accurate use of population descriptors: a trainee-led survey of early-career researchers

Jayati Sharma, Betzaida Maldonado, Rachel A. Ungar, Alvina Adimoelja et autres

Despite the importance of population descriptors in human genomics research, many scientists struggle to translate evolving ethical guidelines into their computational workflows. To characterize this gap between recommendations and implementation, we conducted a mixed-methods survey of early-career researchers to assess how they …

us (code pays fourni par la source)

Building an Interoperable Rare Disease Multi-omic Resource: The GREGoR Data Model and Dataset

Ben Heavner, Marsha M. Wheeler, Jesse D. Bengtsson, Claudia M B Carvalho et autres

Rare disease research and diagnosis rely on the integration of genomic and phenotypic data generated across diverse clinical sites; however, the absence of widely adopted standards for representing genomic data and associated metadata has limited data interoperability, reuse, and cross-study analysis. The …

us (code pays fourni par la source)

Bi-allelic RNU6ATAC variants cause a minor spliceopathy characterized by transcriptome-wide minor intron retention and multisystem manifestations

Rodrigo Mendez, Taylor M. Arriaga, Jialan Ma, Devon Bonner et autres

We report three individuals with bi-allelic variants in RNU6ATAC, which encodes the U6atac minor spliceosomal small nuclear RNA (snRNA), causing a multisystem minor spliceopathy. Through RNA sequencing analysis, we identified a distinctive excess of minor intron retention (MIR) in two unrelated individuals, …

us, sa (code pays fourni par la source)

GREGoR: accelerating genomics for rare diseases

Moez Dawood, Ben Heavner, Marsha M. Wheeler, Rachel A. Ungar et autres

us, tr, kw, jp (code pays fourni par la source)

An optimized variant prioritization process for rare disease diagnostics: recommendations for Exomiser and Genomiser

Isabelle Cooperstein, Shruti Marwaha, Alistair Ward, Shilpa N. Kobren et autres

BACKGROUND: Exome sequencing (ES) and genome sequencing (GS) are increasingly used as standard genetic tests to identify diagnostic variants in rare disease cases. However, prioritizing these variants to reduce the time and burden of manual interpretation by clinical teams remains a significant …

us, gb (code pays fourni par la source)

Transcriptome-wide outlier approach identifies individuals with minor spliceopathies

Rodrigo Mendez, Rachel A. Ungar, Devon Bonner, Dena R. Matalon et autres

RNA sequencing has improved the diagnostic yield of individuals with rare diseases. Current analyses predominantly focus on identifying outliers in single genes that can be attributed to cis-acting variants within the gene locus. This approach overlooks causal variants with trans-acting effects on …

us (code pays fourni par la source)

Joint, multifaceted genomic analysis enables diagnosis of diverse, ultra-rare monogenic presentations

Shilpa N. Kobren, Mikhail A. Moldovan, Rebecca Reimers, Daniel Traviglia et autres

Genomics for rare disease diagnosis has advanced at a rapid pace due to our ability to perform in-depth analyses on individual patients with ultra-rare diseases. The increasing sizes of ultra-rare disease cohorts internationally newly enables cohort-wide analyses for new discoveries, but well-calibrated …

us, nl, es (code pays fourni par la source)

Transcriptomic signatures of rare variant impacts across sex and the X chromosome

Rachel A. Ungar, Taibo Li, Nikolai G. Vetr, Nicole Ersaro et autres

The human X chromosome contains hundreds of genes and has well-established impacts on sex differences and traits. However, the X chromosome is often excluded from many genetic analyses, limiting broader understanding of variant effects. In particular, the functional impact of rare variants …

us (code pays fourni par la source)

Integration of transcriptomics and long-read genomics prioritizes structural variants in rare disease

Tanner Jensen, Bohan Ni, Chloe M. Reuter, John E. Gorzynski et autres

Rare structural variants (SVs)—insertions, deletions, and complex rearrangements—can cause Mendelian disease, yet they remain difficult to accurately detect and interpret. We sequenced and analyzed Oxford Nanopore Technologies long-read genomes of 68 individuals from the undiagnosed disease network (UDN) with no previously identified …

us (code pays fourni par la source)

Functional impact of rare variants and sex across the X-chromosome and autosomes

Rachel A. Ungar, Taibo Li, Nikolai G. Vetr, Nicole M. Ferraro et autres

Abstract The human X-chromosome contains hundreds of genes and has well-established impacts on sex differences and traits. However, the X-chromosome is often excluded from many genetic analyses, limiting broader understanding of variant effects. In particular, the functional impact of rare variants on …

us (code pays fourni par la source)

Enriched phenotypes in rare variant carriers suggest pathogenic mechanisms in rare disease patients

Lane Fitzsimmons, Maria T. Acosta, David R. Adams, Ben Afzali et autres

BACKGROUND: The mechanistic pathways that give rise to the extreme symptoms exhibited by rare disease patients are complex, heterogeneous, and difficult to discern. Understanding these mechanisms is critical for developing treatments that address the underlying causes of diseases rather than merely the …

us (code pays fourni par la source)

Transcriptome-wide outlier approach identifies individuals with minor spliceopathies

Rodrigo Mendez, Rachel A. Ungar, Devon Bonner, Dena R. Matalon et autres

RNA-sequencing has improved the diagnostic yield of individuals with rare diseases. Current analyses predominantly focus on identifying outliers in single genes that can be attributed to cis-acting variants within or near that gene. This approach overlooks causal variants with trans-acting effects on …

us (code pays fourni par la source)