Closing the gap: Solving complex medically relevant genes at scale

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 18, 2024

Comprehending the mechanism behind human diseases with an established heritable component represents forefront of personalized medicine. Nevertheless, numerous medically important genes are inaccurately represented in short-read sequencing data analysis due to their complexity and repetitiveness or so-called 'dark regions' genome. The advent PacBio as a long-read platform has provided new insights, yet HiFi whole-genome (WGS) cost remains frequently prohibitive. We introduce targeted framework, Twist Alliance Dark Genes Panel (TADGP), designed offer phased variants across 389 complex autosomal genes. highlight TADGP accuracy eleven control samples compare it WGS. This demonstrates that achieves variant calling comparable HiFi-WGS data, but at fraction cost. Thus, enabling scalability broad applicability for studying rare complementing previously sequenced gain insights into these revealed several candidate all cases insight

Язык: Английский

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Graph-based pan-genomes: increased opportunities in plant genomics

Journal of Experimental Botany, Год журнала: 2022, Номер 74(1), С. 24 - 39

Опубликована: Окт. 17, 2022

Abstract Due to the development of sequencing technology and great reduction in costs, an increasing number plant genomes have been assembled, numerous revealed large amounts variations. However, a single reference genome does not allow exploration species diversity, therefore concept pan-genome was developed. A is collection all sequences available for species, including consensus sequences, structural variations, small variations nucleotide polymorphisms insertions/deletions. simple linear these be intuitively characterized, so graph-based pan-genomes These store sequence variation information form nodes paths display more intuitive manner. The key role expand coordinate system accommodate regions genetic diversity. Here, we review origin pan-genomes, explore their application research, further highlight future breeding.

Язык: Английский

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Genome-wide structural variant analysis identifies risk loci for non-Alzheimer’s dementias

Cell Genomics, Год журнала: 2023, Номер 3(6), С. 100316 - 100316

Опубликована: Май 4, 2023

We characterized the role of structural variants, a largely unexplored type genetic variation, in two non-Alzheimer's dementias, namely Lewy body dementia (LBD) and frontotemporal (FTD)/amyotrophic lateral sclerosis (ALS). To do this, we applied an advanced variant calling pipeline (GATK-SV) to short-read whole-genome sequence data from 5,213 European-ancestry cases 4,132 controls. discovered, replicated, validated deletion

Язык: Английский

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Best Practices in Microbial Experimental Evolution: Using Reporters and Long-Read Sequencing to Identify Copy Number Variation in Experimental Evolution

Journal of Molecular Evolution, Год журнала: 2023, Номер 91(3), С. 356 - 368

Опубликована: Апрель 3, 2023

Abstract Copy number variants (CNVs), comprising gene amplifications and deletions, are a pervasive class of heritable variation. CNVs play key role in rapid adaptation both natural, experimental, evolution. However, despite the advent new DNA sequencing technologies, detection quantification heterogeneous populations has remained challenging. Here, we summarize recent advances use CNV reporters that provide facile means quantifying de novo at specific locus genome, nanopore sequencing, for resolving often complex structures CNVs. We guidance engineering analysis practical guidelines single-cell using flow cytometry. discuss utility this technology, bioinformatic these data to define molecular structure The combination reporter systems tracking isolating lineages long-read characterizing enables unprecedented resolution mechanisms by which generated their evolutionary dynamics.

Язык: Английский

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Single-haplotype comparative genomics provides insights into lineage-specific structural variation during cat evolution

Nature Genetics, Год журнала: 2023, Номер 55(11), С. 1953 - 1963

Опубликована: Ноя. 1, 2023

Язык: Английский

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