An integrated personal and population-based Egyptian genome reference

AbstractThe human genome is composed of chromosomal DNA sequences consisting of bases A, C, G and T – the blueprint to implement the molecular functions that are the basis of every individual’s life. Deciphering the first human genome was a consortium effort that took more than a decade and considerable cost. With the latest technological advances, determining an individual’s entire personal genome with manageable cost and effort has come within reach. Although the benefits of the all-encompassing genetic information that entire genomes provide are manifold, only a small number of de novo assembled human genomes have been reported to date 1–3, and few have been complemented with population-based genetic variation 4, which is particularly important for North Africans who are not represented in current genome-wide data sets 5–7. Here, we combine long- and short-read whole-genome next-generation sequencing data with recent assembly approaches into the first de novo assembly of the genome of an Egyptian individual. The resulting assembly demonstrates well-balanced quality metrics and is complemented with high-quality variant phasing via linked reads into haploblocks, which we can associate with gene expression changes in blood. To construct an Egyptian genome reference, we further assayed genome-wide genetic variation occurring in the Egyptian population within a representative cohort of 110 Egyptian individuals. We show that differences in allele frequencies and linkage disequilibrium between Egyptians and Europeans may compromise the transferability of European ancestry-based genetic disease risk and polygenic scores, substantiating the need for multi-ethnic genetic studies and corresponding genome references. The Egyptian genome reference represents a comprehensive population data set based on a high-quality personal genome. It is a proof of concept to be considered by the many national and international genome initiatives underway. More importantly, we anticipate that the Egyptian genome reference will be a valuable resource for precision medicine targeting the Egyptian population and beyond.

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An integrated personal and population-based Egyptian genome reference

Nature Communications ◽

10.1038/s41467-020-17964-1 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Inken Wohlers ◽

Axel Künstner ◽

Matthias Munz ◽

Michael Olbrich ◽

Anke Fähnrich ◽

...

Keyword(s):

Genetic Variation ◽

De Novo ◽

Disease Risk ◽

Population Based ◽

European Ancestry ◽

Whole Genome Sequencing Data ◽

Sequencing Data ◽

Human Genomes ◽

Genome Wide ◽

Polygenic Scores

Abstract A small number of de novo assembled human genomes have been reported to date, and few have been complemented with population-based genetic variation, which is particularly important for North Africa, a region underrepresented in current genome-wide references. Here, we combine long- and short-read whole-genome sequencing data with recent assembly approaches into a de novo assembly of an Egyptian genome. The assembly demonstrates well-balanced quality metrics and is complemented with variant phasing via linked reads into haploblocks, which we associate with gene expression changes in blood. To construct an Egyptian genome reference, we identify genome-wide genetic variation within a cohort of 110 Egyptian individuals. We show that differences in allele frequencies and linkage disequilibrium between Egyptians and Europeans may compromise the transferability of European ancestry-based genetic disease risk and polygenic scores, substantiating the need for multi-ethnic genome references. Thus, the Egyptian genome reference will be a valuable resource for precision medicine.

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Genome-wide analyses reveal clustering in Cannabis cultivars: the ancient domestication trilogy of a panacea

10.7287/peerj.preprints.1553v2 ◽

2015 ◽

Cited By ~ 3

Author(s):

Philippe Henry

Keyword(s):

Genetic Variation ◽

Genetic Structure ◽

Open Access ◽

Nucleotide Polymorphisms ◽

Data Set ◽

Single Nucleotide ◽

Genome Wide ◽

Access Data ◽

Diagnostic Snps ◽

Shed Light

In the present research, I used an open access data set (Medicinal Genomics) consisting of nearly 200'000 genome-wide single nucleotide polymorphisms (SNPs) typed in 28 cannabis accessions to shed light on the plant's underlying genetic structure. Genome-wide loadings were used to sequentially cull less informative markers. The process involved reducing the number of SNPs to 100K, 10K, 1K, 100 until I identified a set of 42 highly informative SNPs that I present here. The two first principal components, encompass over 3/4 of the genetic variation present in the dataset (PCA1 = 48.6%, PCA2= 26.3%). This set of diagnostic SNPs is then used to identify clusters into which cannabis accession segregate. I identified three clear and consistent clusters; reflective of the ancient domestication trilogy of the genus Cannabis.

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Genome assembly of the JD17 soybean provides a new reference genome for Comparative genomics

10.1101/2021.11.23.469778 ◽

2021 ◽

Author(s):

Xinxin Yi ◽

Jing Liu ◽

Shengcai Chen ◽

Hao Wu ◽

Min Liu ◽

...

Keyword(s):

Nitrogen Fixation ◽

Genome Assembly ◽

Reference Genome ◽

De Novo ◽

Genomic Analysis ◽

Comparative Genomic ◽

High Quality ◽

Genome Wide ◽

A Genome ◽

Cultivated Soybean

Cultivated soybean (Glycine max) is an important source for protein and oil. Many elite cultivars with different traits have been developed for different conditions. Each soybean strain has its own genetic diversity, and the availability of more high-quality soybean genomes can enhance comparative genomic analysis for identifying genetic underpinnings for its unique traits. In this study, we constructed a high-quality de novo assembly of an elite soybean cultivar Jidou 17 (JD17) with chromsome contiguity and high accuracy. We annotated 52,840 gene models and reconstructed 74,054 high-quality full-length transcripts. We performed a genome-wide comparative analysis based on the reference genome of JD17 with three published soybeans (WM82, ZH13 and W05) , which identified five large inversions and two large translocations specific to JD17, 20,984 - 46,912 PAVs spanning 13.1 - 46.9 Mb in size, and 5 - 53 large PAV clusters larger than 500kb. 1,695,741 - 3,664,629 SNPs and 446,689 - 800,489 Indels were identified and annotated between JD17 and them. Symbiotic nitrogen fixation (SNF) genes were identified and the effects from these variants were further evaluated. It was found that the coding sequences of 9 nitrogen fixation-related genes were greatly affected. The high-quality genome assembly of JD17 can serve as a valuable reference for soybean functional genomics research.

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De Novo Assembly of a High-Quality Reference Genome for the Horned Lark (Eremophila alpestris)

G3 Genes|Genome|Genetics ◽

10.1534/g3.119.400846 ◽

2019 ◽

Vol 10 (2) ◽

pp. 475-478 ◽

Cited By ~ 3

Author(s):

Nicholas A. Mason ◽

Paulo Pulgarin ◽

Carlos Daniel Cadena ◽

Irby J. Lovette

Keyword(s):

Genome Assembly ◽

De Novo ◽

Single Copy ◽

Single Copy Gene ◽

High Quality ◽

Data Set ◽

Copy Gene ◽

Assembly Pipeline ◽

Horned Lark ◽

Gene Orthologs

The Horned Lark (Eremophila alpestris) is a small songbird that exhibits remarkable geographic variation in appearance and habitat across an expansive distribution. While E. alpestris has been the focus of many ecological and evolutionary studies, we still lack a highly contiguous genome assembly for the Horned Lark and related taxa (Alaudidae). Here, we present CLO_EAlp_1.0, a highly contiguous assembly for E. alpestris generated from a blood sample of a wild, male bird captured in the Altiplano Cundiboyacense of Colombia. By combining short-insert and mate-pair libraries with the ALLPATHS-LG genome assembly pipeline, we generated a 1.04 Gb assembly comprised of 2713 scaffolds, with a largest scaffold size of 31.81 Mb, a scaffold N50 of 9.42 Mb, and a scaffold L50 of 30. These scaffolds were assembled from 23685 contigs, with a largest contig size of 1.69 Mb, a contig N50 of 193.81 kb, and a contig L50 of 1429. Our assembly pipeline also produced a single mitochondrial DNA contig of 14.00 kb. After polishing the genome, we identified 94.5% of single-copy gene orthologs from an Aves data set and 97.7% of single-copy gene orthologs from a vertebrata data set, which further demonstrates the high quality of our assembly. We anticipate that this genomic resource will be useful to the broader ornithological community and those interested in studying the evolutionary history and ecological interactions of larks, which comprise a widespread, yet understudied lineage of songbirds.

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De novo mutations across 1,465 diverse genomes reveal novel mutational insights and reductions in the Amish founder population

10.1101/553214 ◽

2019 ◽

Author(s):

Michael D. Kessler ◽

Douglas P. Loesch ◽

James A. Perry ◽

Nancy L. Heard-Costa ◽

Brian E. Cade ◽

...

Keyword(s):

Genetic Variation ◽

Mutation Rate ◽

De Novo ◽

Population Level ◽

Mutation Rates ◽

Founder Population ◽

Single Nucleotide ◽

Genome Wide ◽

Nucleotide Mutation ◽

Rare Genetic Variation

Abstractde novo Mutations (DNMs), or mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease. Utilizing high-coverage whole genome sequencing data as part of the Trans-Omics for Precision Medicine (TOPMed) program, we directly estimate and analyze DNM counts, rates, and spectra from 1,465 trios across an array of diverse human populations. Using the resulting call set of 86,865 single nucleotide DNMs, we find a significant positive correlation between local recombination rate and local DNM rate, which together can explain up to 35.5% of the genome-wide variation in population level rare genetic variation from 41K unrelated TOPMed samples. While genome-wide heterozygosity does correlate weakly with DNM count, we do not find significant differences in DNM rate between individuals of European, African, and Latino ancestry, nor across ancestrally distinct segments within admixed individuals. However, interestingly, we do find significantly fewer DNMs in Amish individuals compared with other Europeans, even after accounting for parental age and sequencing center. Specifically, we find significant reductions in the number of T→C mutations in the Amish, which seems to underpin their overall reduction in DNMs. Finally, we calculate near-zero estimates of narrow sense heritability (h2), which suggest that variation in DNM rate is significantly shaped by non-additive genetic effects and/or the environment, and that a less mutagenic environment may be responsible for the reduced DNM rate in the Amish.SignificanceHere we provide one of the largest and most diverse human de novo mutation (DNM) call sets to date, and use it to quantify the genome-wide relationship between local mutation rate and population-level rare genetic variation. While we demonstrate that the human single nucleotide mutation rate is similar across numerous human ancestries and populations, we also discover a reduced mutation rate in the Amish founder population, which shows that mutation rates can shift rapidly. Finally, we find that variation in mutation rates is not heritable, which suggests that the environment may influence mutation rates more significantly than previously realized.

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Biodiversity genomics of small metazoans: high quality de novo genomes from single specimens of field-collected and ethanol-preserved springtails

10.1101/2020.08.10.244541 ◽

2020 ◽

Cited By ~ 2

Author(s):

Clément Schneider ◽

Christian Woehle ◽

Carola Greve ◽

Cyrille A. D’Haese ◽

Magnus Wolf ◽

...

Keyword(s):

Genome Sequencing ◽

De Novo ◽

Genetic Model ◽

Nuclear Genome ◽

High Quality ◽

Sequencing Technologies ◽

Natural Product Research ◽

Genome Wide ◽

Long Read ◽

Hmw Dna

ABSTRACTGenome sequencing of all known eukaryotes on Earth promises unprecedented advances in evolutionary sciences, ecology, systematics and in biodiversity-related applied fields such as environmental management and natural product research. Advances in DNA sequencing technologies make genome sequencing feasible for many non-genetic model species. However, genome sequencing today relies on large quantities of high quality, high molecular weight (HMW) DNA which is mostly obtained from fresh tissues. This is problematic for biodiversity genomics of Metazoa as most species are small and yield minute amounts of DNA. Furthermore, briging living specimens to the lab bench not realistic for the majority of species.Here we overcome those difficulties by sequencing two species of springtails (Collembola) from single specimens preserved in ethanol. We used a newly developed, genome-wide amplification-based protocol to generate PacBio libraries for HiFi long-read sequencing.The assembled genomes were highly continuous. They can be considered complete as we recovered over 95% of BUSCOs. Genome-wide amplification does not seem to bias genome recovery. Presence of almost complete copies of the mitochondrial genome in the nuclear genome were pitfalls for automatic assemblers. The genomes fit well into an existing phylogeny of springtails. A neotype is designated for one of the species, blending genome sequencing and creation of taxonomic references.Our study shows that it is possible to obtain high quality genomes from small, field-preserved sub-millimeter metazoans, thus making their vast diversity accessible to the fields of genomics.

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Measuring genetic variation in the multi-ethnic Million Veteran Program (MVP)

10.1101/2020.01.06.896613 ◽

2020 ◽

Author(s):

Haley Hunter-Zinck ◽

Yunling Shi ◽

Man Li ◽

Bryan R. Gorman ◽

Sun-Gou Ji ◽

...

Keyword(s):

Quality Control ◽

Association Studies ◽

Current Data ◽

Control Analysis ◽

Genome Wide Association Studies ◽

Genetic Associations ◽

High Quality ◽

Data Set ◽

Entire Cohort ◽

Genome Wide

AbstractThe Million Veteran Program (MVP), initiated by the Department of Veterans Affairs (VA), aims to collect consented biosamples from at least one million Veterans. Presently, blood samples have been collected from over 800,000 enrolled participants. The size and diversity of the MVP cohort, as well as the availability of extensive VA electronic health records make it a promising resource for precision medicine. MVP is conducting array-based genotyping to provide genome-wide scan of the entire cohort, in parallel with whole genome sequencing, methylation, and other omics assays. Here, we present the design and performance of MVP 1.0 custom Axiom® array, which was designed and developed as a single assay to be used across the multi-ethnic MVP cohort. A unified genetic quality control analysis was developed and conducted on an initial tranche of 485,856 individuals leading to a high-quality dataset of 459,777 unique individuals. 668,418 genetic markers passed quality control and showed high quality genotypes not only on common variants but also on rare variants. We confirmed the substantial ancestral diversity of MVP with nearly 30% non-European individuals, surpassing other large biobanks. We also demonstrated the quality of the MVP dataset by replicating established genetic associations with height in European Americans and African Americans ancestries. This current data set has been made available to approved MVP researchers for genome-wide association studies and other downstream analyses. Further data releases will be available for analysis as recruitment at the VA continues and the cohort expands both in size and diversity.

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Extensive sequencing of seven human genomes to characterize benchmark reference materials

10.1101/026468 ◽

2015 ◽

Cited By ~ 9

Author(s):

Justin M Zook ◽

David Catoe ◽

Jennifer McDaniel ◽

Lindsay Vang ◽

Noah Spies ◽

...

Keyword(s):

Human Genome ◽

Reference Materials ◽

De Novo ◽

Variant Calling ◽

Genome Project ◽

Genome Comparison ◽

Personal Genome ◽

Sequencing Data ◽

Sequencing Technologies ◽

Human Genomes

The Genome in a Bottle Consortium, hosted by the National Institute of Standards and Technology (NIST) is creating reference materials and data for human genome sequencing, as well as methods for genome comparison and benchmarking. Here, we describe a large, diverse set of sequencing data for seven human genomes; five are current or candidate NIST Reference Materials. The pilot genome, NA12878, has been released as NIST RM 8398. We also describe data from two Personal Genome Project trios, one of Ashkenazim Jewish ancestry and one of Chinese ancestry. The data come from 12 technologies: BioNano Genomics, Complete Genomics paired-end and LFR, Ion Proton exome, Oxford Nanopore, Pacific Biosciences, SOLiD, 10X Genomics GemCodeTM WGS, and Illumina exome and WGS paired-end, mate-pair, and synthetic long reads. Cell lines, DNA, and data from these individuals are publicly available. Therefore, we expect these data to be useful for revealing novel information about the human genome and improving sequencing technologies, SNP, indel, and structural variant calling, and de novo assembly.

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Genome-Wide Association Analyses Identify Variants in IRF4 Associated With Acute Myeloid Leukemia and Myelodysplastic Syndrome Susceptibility

Frontiers in Genetics ◽

10.3389/fgene.2021.554948 ◽

2021 ◽

Vol 12 ◽

Author(s):

Junke Wang ◽

Alyssa I. Clay-Gilmour ◽

Ezgi Karaesmen ◽

Abbas Rizvi ◽

Qianqian Zhu ◽

...

Keyword(s):

Gene Expression ◽

Acute Myeloid Leukemia ◽

Genetic Variation ◽

Myeloid Leukemia ◽

De Novo ◽

Genome Wide Association ◽

Genome Wide ◽

Increased Risk ◽

Acute Myeloid

The role of common genetic variation in susceptibility to acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS), a group of rare clonal hematologic disorders characterized by dysplastic hematopoiesis and high mortality, remains unclear. We performed AML and MDS genome-wide association studies (GWAS) in the DISCOVeRY-BMT cohorts (2,309 cases and 2,814 controls). Association analysis based on subsets (ASSET) was used to conduct a summary statistics SNP-based analysis of MDS and AML subtypes. For each AML and MDS case and control we used PrediXcan to estimate the component of gene expression determined by their genetic profile and correlate this imputed gene expression level with risk of developing disease in a transcriptome-wide association study (TWAS). ASSET identified an increased risk for de novo AML and MDS (OR = 1.38, 95% CI, 1.26-1.51, Pmeta = 2.8 × 10–12) in patients carrying the T allele at s12203592 in Interferon Regulatory Factor 4 (IRF4), a transcription factor which regulates myeloid and lymphoid hematopoietic differentiation. Our TWAS analyses showed increased IRF4 gene expression is associated with increased risk of de novo AML and MDS (OR = 3.90, 95% CI, 2.36-6.44, Pmeta = 1.0 × 10–7). The identification of IRF4 by both GWAS and TWAS contributes valuable insight on the role of genetic variation in AML and MDS susceptibility.

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