Structural polymorphism and diversity of human segmental duplications

Nature Genetics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 8, 2025

Abstract Segmental duplications (SDs) contribute significantly to human disease, evolution and diversity but have been difficult resolve at the sequence level. We present a population genetics survey of SDs by analyzing 170 genome assemblies (from 85 samples representing 38 Africans 47 non-Africans) in which majority autosomal are fully resolved using long-read assembly. Excluding acrocentric short arms sex chromosomes, we identify 173.2 Mb duplicated (47.4 not telomere-to-telomere reference) distinguishing fixed from structurally polymorphic events. find that intrachromosomal among most variable, with rare events mapping near their progenitor sequences. African genomes harbor more likely recently gene families higher copy numbers than non-African samples. Comparison resource 563 million full-length isoform sequencing reads identifies 201 novel, potentially protein-coding genes corresponding these number SDs.

Язык: Английский

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Advancing genetic improvement in the omics era: status and priorities for United States aquaculture

BMC Genomics, Год журнала: 2025, Номер 26(1)

Опубликована: Фев. 17, 2025

The innovations of the "Omics Era" have ushered in significant advancements genetic improvement agriculturally important animal species through transforming genetics, genomics and breeding strategies. These were often coordinated, part, by support provided over 30 years 1993-2023 National Research Support Project 8 (NRSP8, Animal Genome Program, NAGRP) affiliate projects focused on enabling genomic discoveries livestock, poultry, aquaculture species. parallel advances demand strategic planning future research priorities. This paper, as an output from May 2023 Aquaculture Genomics, Genetics, Breeding Workshop, provides updated status resources for United States species, highlighting major achievements emerging Finfish shellfish genome omics enhance our understanding architecture heritability performance production traits. Workshop identified present aims genomics/omics to build this progress: (1) advancing reference assembly quality; (2) integrating multi-omics data analysis traits; (3) developing collection integration phenomics data; (4) creating pathways applying information across industries; (5) providing training, extension, outreach application phenome. focuses should emphasize collection, artificial intelligence, identifying causative relationships between genotypes phenotypes, establishing apply tools industries, expansion training programs next-generation workforce facilitate sciences into operations productivity, competitiveness, sustainability. collective vision with focus highlighted priorities is intended continued advancement genomics, genetics community industries. Critical challenges ahead include practical analytical frameworks beyond academic communities that require collaborative partnerships academia, government, industry. scope review encompasses use applications study aquatic animals cultivated human consumption settings throughout their life-cycle.

Язык: Английский

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A familial, telomere-to-telomere reference for humande novomutation and recombination from a four-generation pedigree

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

Опубликована: Авг. 5, 2024

ABSTRACT Using five complementary short- and long-read sequencing technologies, we phased assembled >95% of each diploid human genome in a four-generation, 28-member family (CEPH 1463) allowing us to systematically assess de novo mutations (DNMs) recombination. From this family, estimate an average 192 DNMs per generation, including 75.5 single-nucleotide variants (SNVs), 7.4 non-tandem repeat indels, 79.6 indels or structural (SVs) originating from tandem repeats, 7.7 centromeric SVs SNVs, 12.4 Y chromosome events generation. STRs VNTRs are the most mutable with 32 loci exhibiting recurrent mutation through generations. We accurately assemble 288 centromeres six chromosomes across generations, documenting SVs, demonstrate that DNM rate varies by order magnitude depending on content, length, sequence identity. show strong paternal bias (75-81%) for all forms germline DNM, yet 17% SNVs postzygotic origin no bias. place variation context high-resolution recombination map (∼3.5 kbp breakpoint resolution). observe maternal (1.36 maternal:paternal ratio) consistent reduction number crossovers increasing (r=0.85) (r=0.65) age. However, correlation between meiotic crossover locations arguing against non-allelic homologous as predominant mechanism. The use multiple orthogonal near-telomere-to-telomere assemblies, multi-generation transmission has created comprehensive, publicly available “truth set” classes genomic variants. resource can be used test benchmark new algorithms technologies understand fundamental processes underlying genetic variation.

Язык: Английский

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Structural polymorphism and diversity of human segmental duplications

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

Опубликована: Июнь 6, 2024

Segmental duplications (SDs) contribute significantly to human disease, evolution, and diversity yet have been difficult resolve at the sequence level. We present a population genetics survey of SDs by analyzing 170 genome assemblies where majority are fully resolved using long-read assembly. Excluding acrocentric short arms, we identify 173.2 Mbp duplicated (47.4 not in telomere-to-telomere reference) distinguishing fixed from structurally polymorphic events. find that intrachromosomal among most variable with rare events mapping near their progenitor sequences. African genomes harbor more likely recently gene families higher copy number when compared non-African samples. A comparison resource 563 million full-length Iso-Seq reads identifies 201 novel, potentially protein-coding genes corresponding these SDs.

Язык: Английский

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Human de novo mutation rates from a four-generation pedigree reference

Nature, Год журнала: 2025, Номер unknown

Опубликована: Апрель 23, 2025

Язык: Английский

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The value of hybrid genomes: Building two highly contiguous reference genome assemblies to advance Canis genomic studies

Journal of Heredity, Год журнала: 2024, Номер 115(4), С. 480 - 486

Опубликована: Фев. 28, 2024

Abstract Previous studies of canid population and evolutionary genetics have relied on high-quality domestic dog reference genomes that been produced primarily for biomedical trait mapping in breeds. However, the absence highly contiguous from other Canis species like gray wolf coyote, represent additional distinct demographic histories, may bias inferences regarding interspecific genetic diversity phylogenetic relationships. Here, we present single haplotype de novo genome assemblies generated by applying trio-binning approach to long sequence reads a female first-generation hybrid coyote mating. The were contiguous, with contig N50 sizes 44.6 42.0 Mb respectively. Genome scaffolding alignments between two published showed near complete collinearity, one exception: coyote-specific chromosome fission 13 fusion proximal portion 8, retaining Canis-typical haploid number 2n = 78. We evaluated quality previous RADseq data 334 canids found nearly identical patterns among regional populations regardless used alignment (dog, or wolf). These novel will be important resources proper accurate inference demography, taxonomic evaluation, conservation genetics.

Язык: Английский

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Integrating evolutionary genomics of forest trees to inform future tree breeding amidst rapid climate change

Plant Communications, Год журнала: 2024, Номер 5(10), С. 101044 - 101044

Опубликована: Авг. 7, 2024

Global climate change is leading to rapid and drastic shifts in environmental conditions, posing threats biodiversity nearly all life forms worldwide. Forest trees serve as foundational components of terrestrial ecosystems play a crucial role combating mitigating the adverse effects extreme events, despite their own vulnerability these threats. Therefore, understanding monitoring how natural forests respond key priority for conservation. Recent progress evolutionary genomics, driven primarily by cutting-edge multi-omics technologies, offers powerful new tools address several issues. These include precise delineation species units, inference past histories demographic fluctuations, identification environmentally adaptive variants, measurement genetic load levels. As urgency deal with more stresses grows, genomics history, local adaptation, future responses change, conservation restoration forest will be critical research at nexus global population biology. In this review, we explore application assess using approaches discuss outlook breeding climate-adapted trees.

Язык: Английский

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Emerging trends in pharmacogenomics: from common variant associations toward comprehensive genomic profiling

Human Genomics, Год журнала: 2023, Номер 17(1)

Опубликована: Ноя. 24, 2023

Язык: Английский

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The Next, Next-Generation of Sequencing, Promising to Boost Research and Clinical Practice

Seminars in Thrombosis and Hemostasis, Год журнала: 2024, Номер 50(07), С. 1039 - 1046

Опубликована: Май 11, 2024

Five years on from our award-winning review Next-generation sequencing and emerging technologies,[1] a rapid pace of fundamental advances has markedly altered the landscape capability. Technological, methodological, analytical innovations are driving practice in both research clinical spaces, often at breakneck speeds. Some current challenges to keep with technology, implement update standardized validated practices timely manner, perform representative diverse population-scale studies, rapidly translate advanced understanding pathological drivers provide optimal policy, practice, provision, care, outcomes.

Язык: Английский

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Rare disease genomic testing in the UK and Ireland: promoting timely and equitable access

Journal of Medical Genetics, Год журнала: 2024, Номер 61(12), С. 1103 - 1112

Опубликована: Сен. 26, 2024

Purpose and scope The aim of this position statement is to provide recommendations regarding the delivery genomic testing patients with rare disease in UK Ireland. has been developed facilitate timely equitable access reporting results within commissioned turnaround times. Methods development A 1-day workshop was convened by Association for Clinical Genomic Science attended key stakeholders NHS Medicine Service, including clinical scientists, geneticists patient support group representatives. identify best practice innovations streamlined, geographically consistent services delivering results. Attendees senior responsible officers nations Ireland were invited contribute. Results conclusions We identified eight fundamental requirements describe these together enablers form specific recommendations. These relate laboratory (proportionate variant analysis, bioinformatics pipelines, multidisciplinary team working model test request monitoring), compliance national guidance (variant classification, incidental findings, reanalysis), service improvement (multimodal innovation through research, informed experience), demand, capacity management, workforce (recruitment, retention development), education training users. This specialist genomics but relevant any publicly funded healthcare system seeking deliver context high demand limited resources.

Язык: Английский

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