Biology subjects

Scheinfeldt, L.

Publications and source records attributed to Scheinfeldt, L..

5 recordsLinked to original sources

bioRxiv2026

Community member, community liaison and researcher perspectives on the creation of HapMap and 1000 Genomes Project iPSCs

The National Human Genome Research Institute (NHGRI) Repository for Human Genetic Research (NHGRI Repository) distributes renewable lymphoblastoid cell lines (LCL) and cell line DNAs donated by members of 26 communities who have taken part in the International HapMap and 1000 Genomes Projects. The relatively recent introduction of induced pluripotent stem cell (iPSC) reprogramming technologies offers a new opportunity to create iPSCs from HapMap and 1000 Genomes Project biospecimens. However, since relevant iPSC technology did not exist when the HapMap and 1000 Genomes Projects began, it was not explicitly included in the consent process. To explore donor community and researcher perspectives on potential HapMap and 1000 Genomes Project iPSC creation, we conducted an online, semi-structured survey. The majority of community (86%) and research (86%) respondents agreed that creating iPSCs from HapMap and 1000 Genomes Project biospecimens could benefit the research community; however non-trivial concerns (36% community respondents and 16% researcher respondents) and doubts (21% community respondents and 11% researcher respondents) about HapMap and 1000 Genomes Project iPSC creation were also shared. Given these results, we will continue to explore opportunities to engage with HapMap and 1000 Genomes Project communities that include educational materials and detailed discussions regarding the potential for creating iPSCs from their community biospecimens. In parallel, we will continue to grow the existing NHGRI Repository iPSC collection with new donor submissions through the Human Pangenome Reference Consortium (HPRC) that explicitly consented to the creation of iPSCs.

genomics↗

bioRxiv2025

Complete genomes of a multi-generational pedigree to expand studies of genetic and epigenetic inheritance

Pedigree analysis remains the gold standard for rare disease diagnostics, yet whole genome sequencing studies typically omit critical regions like centromeres, telomeres, and acrocentric chromosome p-arms. Here, we present telomere-to-telomere (T2T) reference genomes for four self-identified African American individuals of admixed ancestry spanning three generations. Our parent-of-origin assigned, chromosome-level assemblies revealed precise meiotic recombination breakpoints in previously inaccessible regions, including recombination events across acrocentric and subtelomeric sequences. Centromeric regions were highly stable, with multi-megabase arrays inherited intact across three generations, while the position of kinetochore assembly sites remained consistent and predominantly associated with the p-arm proximal region. The relative lengths of telomeres on individual chromosomes were maintained across generations. Using a targeted rDNA assembly approach, we reconstructed a complete megabase-scale ribosomal DNA (rDNA) array corresponding to the paternal chromosome 14. This openly available pedigree provides a benchmark dataset for studying recombination and genetic and epigenetic variation across the complete genome.

genomics↗

bioRxiv2025

A new NHGRI Sample Repository for Human Genetic Research collection of induced pluripotent stem cell lines.

We describe here a new NHGRI Sample Repository for Human Genetic Research collection of induced pluripotent stem cell (iPSC) lines reprogrammed from whole blood derived peripheral blood mononuclear cells (PBMCs). PBMCs were reprogrammed using Sendai viral vectors carrying transcription factors OCT4, SOX2, KLF4, and c-MYC. All iPSC lines exhibit a normal karyotype, express common stemness and pluripotency markers, and demonstrate the ability to differentiate into cell types representing all three germ layers. This iPSC collection (n=7) will have accompanying public, near telomere to telomere genomic data through the Human Pangenome Reference Consortium, and provides an invaluable new in vitro resource for studying common genetic and genomic variation and its functional implications.

cell biology↗

bioRxiv2023

Star allele search: a pharmacogenetic annotation database and user-friendly search tool of publicly available 1000 Genomes Project biospecimens

Here we describe a new public pharmacogenetic (PGx) annotation database of a large (n=3202) and diverse biospecimen collection of 1000 Genomes Project cell lines and DNAs. The database is searchable with a user friendly, web-based tool (www.coriell.org/StarAllele/Search). This resource leverages existing whole genome sequencing data and PharmVar annotations to characterize *alleles for each biospecimen in the collection. This new tool is designed to facilitate in vitro functional characterization of *allele haplotypes and diplotypes as well as support clinical PGx assay development, validation, and implementation.

bioinformatics↗

bioRxiv2023

ursaPGx: a new R package to annotate pharmacogenetic star alleles using phased whole genome sequencing data

Long-read sequencing technologies offer new opportunities to generate high confidence phased whole genome sequencing data for robust pharmacogenetic annotation. Here we describe a new user-friendly R package, ursaPGx, designed to accept multi-sample phased whole genome sequencing data VCF input files and output star allele annotations for pharmacogenes annotated in PharmVar.

bioinformatics↗