Identification of Structural Variation in Chimpanzees Using Optical Mapping and Nanopore Sequencing

Recent efforts to comprehensively characterize great ape genetic diversity using short-read sequencing and single-nucleotide variants have led to important discoveries related to selection within species, demographic history, and lineage-specific traits. Structural variants (SVs), including deletions and inversions, comprise a larger proportion of genetic differences between and within species, making them an important yet understudied source of trait divergence. Here, we used a combination of long-read and -range sequencing approaches to characterize the structural variant landscape of two additional Pan troglodytes verus individuals, one of whom carries 13% admixture from Pan troglodytes troglodytes. We performed optical mapping of both individuals followed by nanopore sequencing of one individual. Filtering for larger variants (>10 kbp) and combined with genotyping of SVs using short-read data from the Great Ape Genome Project, we identified 425 deletions and 59 inversions, of which 88 and 36, respectively, were novel. Compared with gene expression in humans, we found a significant enrichment of chimpanzee genes with differential expression in lymphoblastoid cell lines and induced pluripotent stem cells, both within deletions and near inversion breakpoints. We examined chromatin-conformation maps from human and chimpanzee using these same cell types and observed alterations in genomic interactions at SV breakpoints. Finally, we focused on 56 genes impacted by SVs in >90% of chimpanzees and absent in humans and gorillas, which may contribute to chimpanzee-specific features. Sequencing a greater set of individuals from diverse subspecies will be critical to establish the complete landscape of genetic variation in chimpanzees.

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Intercommunity interactions and killings in central chimpanzees (Pan troglodytes troglodytes) from Loango National Park, Gabon

Primates ◽

10.1007/s10329-021-00921-x ◽

2021 ◽

Author(s):

Laura Martínez-Íñigo ◽

Pauline Baas ◽

Harmonie Klein ◽

Simone Pika ◽

Tobias Deschner

Keyword(s):

Pan Troglodytes ◽

National Park ◽

Camera Traps ◽

Encounter Rate ◽

Visual Contact ◽

Intergroup Interactions ◽

Killing Rate ◽

The Core ◽

Pan Troglodytes Troglodytes

AbstractIntercommunity competition in chimpanzees (Pan troglodytes) has been widely studied in eastern (P. t. schweinfurthii) and western (P. t. verus) communities. Both subspecies show hostility towards neighboring communities but differ in rates of lethal attacks and female involvement. However, relatively little is known about the territorial behavior of the two other subspecies, central (P. t. troglodytes) and Nigeria-Cameroon chimpanzees (P. t. ellioti). Here, we present the first insights into intercommunity interactions of individuals of a community of central chimpanzees living in the Loango National Park in Gabon. The presence of individuals of neighboring communities in the Rekambo home range was assessed using 27 camera traps. Information was compiled on intergroup interactions recorded before (2005–2016) and after (January 2017–June 2019) the habituation of the community. Individuals from neighboring communities entered the core area, where nine out of 16 recorded intercommunity encounters occurred. Males were the main participants in territorial patrols and intercommunity aggressions. Females were part of all six territorial patrols recorded and dependent offspring participated in five patrols. Females were involved in intercommunity aggression in five out of twelve recorded encounters in which there was visual contact between communities. While the intercommunity encounter rate was lower than that reported across most other long-term chimpanzee sites, the annual intercommunity killing rate was among the highest. These results suggest that the frequency of lethal attacks at Loango is comparable to that reported for the eastern subspecies. In contrast, female involvement in intercommunity interactions mirrors that of the western subspecies.

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High resolution copy number inference in cancer using short-molecule nanopore sequencing

10.1101/2020.12.28.424602 ◽

2020 ◽

Author(s):

Timour Baslan ◽

Sam Kovaka ◽

Fritz J. Sedlazeck ◽

Yanming Zhang ◽

Robert Wappel ◽

...

Keyword(s):

Copy Number ◽

Cost Effective ◽

Chromosome Analysis ◽

Ease Of Use ◽

Precision Oncology ◽

Nanopore Sequencing ◽

Dna Molecules ◽

Sequencing Data ◽

Short Read ◽

Short Read Sequencing

ABSTRACTGenome copy number is an important source of genetic variation in health and disease. In cancer, clinically actionable Copy Number Alterations (CNAs) can be inferred from short-read sequencing data, enabling genomics-based precision oncology. Emerging Nanopore sequencing technologies offer the potential for broader clinical utility, for example in smaller hospitals, due to lower instrument cost, higher portability, and ease of use. Nonetheless, Nanopore sequencing devices are limited in terms of the number of retrievable sequencing reads/molecules compared to short-read sequencing platforms. This represents a challenge for applications that require high read counts such as CNA inference. To address this limitation, we targeted the sequencing of short-length DNA molecules loaded at optimized concentration in an effort to increase sequence read/molecule yield from a single nanopore run. We show that sequencing short DNA molecules reproducibly returns high read counts and allows high quality CNA inference. We demonstrate the clinical relevance of this approach by accurately inferring CNAs in acute myeloid leukemia samples. The data shows that, compared to traditional approaches such as chromosome analysis/cytogenetics, short molecule nanopore sequencing returns more sensitive, accurate copy number information in a cost effective and expeditious manner, including for multiplex samples. Our results provide a framework for the sequencing of relatively short DNA molecules on nanopore devices with applications in research and medicine, that include but are not limited to, CNAs.

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Korean Genome Project: 1094 Korean personal genomes with clinical information

Science Advances ◽

10.1126/sciadv.aaz7835 ◽

2020 ◽

Vol 6 (22) ◽

pp. eaaz7835 ◽

Cited By ~ 2

Author(s):

Sungwon Jeon ◽

Youngjune Bhak ◽

Yeonsong Choi ◽

Yeonsu Jeon ◽

Seunghoon Kim ◽

...

Keyword(s):

Genome Wide Association Study ◽

Imputation Accuracy ◽

Clinical Information ◽

Genome Project ◽

Single Nucleotide Variants ◽

Single Nucleotide ◽

Genome Wide ◽

A Genome ◽

Whole Genomes ◽

Personal Genomes

We present the initial phase of the Korean Genome Project (Korea1K), including 1094 whole genomes (sequenced at an average depth of 31×), along with data of 79 quantitative clinical traits. We identified 39 million single-nucleotide variants and indels of which half were singleton or doubleton and detected Korean-specific patterns based on several types of genomic variations. A genome-wide association study illustrated the power of whole-genome sequences for analyzing clinical traits, identifying nine more significant candidate alleles than previously reported from the same linkage disequilibrium blocks. Also, Korea1K, as a reference, showed better imputation accuracy for Koreans than the 1KGP panel. As proof of utility, germline variants in cancer samples could be filtered out more effectively when the Korea1K variome was used as a panel of normals compared to non-Korean variome sets. Overall, this study shows that Korea1K can be a useful genotypic and phenotypic resource for clinical and ethnogenetic studies.

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Closed Genome Sequence of Salmonella enterica Serovar Richmond Strain CFSAN000191, Obtained with Nanopore Sequencing

Microbiology Resource Announcements ◽

10.1128/mra.01472-18 ◽

2018 ◽

Vol 7 (23) ◽

Cited By ~ 3

Author(s):

Narjol González-Escalona ◽

Kuan Yao ◽

Maria Hoffmann

Keyword(s):

Genome Sequence ◽

Salmonella Enterica ◽

Nanopore Sequencing ◽

Short Read ◽

Content Type ◽

Short Read Sequencing ◽

Long Read

Here we report the genome sequence of Salmonella enterica serovar Richmond strain CFSAN000191, isolated from tilapia from Thailand in 2005. The genome was determined by a combination of long-read and short-read sequencing.

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Survey of gorillas ( Gorilla gorilla gorilla ) and chimpanzees ( Pan troglodytes troglodytes ) in Southwestern Cameroon

Primates ◽

10.1007/s10329-003-0058-4 ◽

2004 ◽

Vol 45 (1) ◽

pp. 15-24 ◽

Cited By ~ 40

Author(s):

Adele Matthews ◽

Andreas Matthews

Keyword(s):

Pan Troglodytes ◽

Gorilla Gorilla ◽

Gorilla Gorilla Gorilla ◽

Pan Troglodytes Troglodytes

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Untraditional methods for targeting the kidney in transgenic mice

AJP Renal Physiology ◽

10.1152/ajprenal.00207.2003 ◽

2003 ◽

Vol 285 (6) ◽

pp. F1027-F1033 ◽

Cited By ~ 10

Author(s):

Robert A. Bianco ◽

Henry L. Keen ◽

Julie L. Lavoie ◽

Curt D. Sigmund

Keyword(s):

Gene Expression ◽

Human Genome Project ◽

Target Gene ◽

Cell Types ◽

Experimental Models ◽

Genome Project ◽

Renal Physiology ◽

Physiological Relevance ◽

The Human Genome Project

With the completion of the human genome project and the sequencing of many genomes of experimental models, there is a pressing need to determine the physiological relevance of newly identified genes. Gene-targeting approaches have become an important tool in our arsenal to dissect the significance of genes expressed in many tissues. A wealth of experimental models has been made to assess the role of gene expression in renal function and development. The development of new and informative models is presently limited by the anatomic complexity of the kidney and the lack of cell-specific promoters to target the numerous diverse cell types in that organ. Because of this, new approaches may have to be developed. In this review, we will discuss several untraditional methods to target gene expression to the kidney. These approaches should provide some additional tricks and tools to help in developing additional informative models for studying renal physiology.

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Identification of a likely pathogenic structural variation in the LAMA1 gene by Bionano optical mapping

npj Genomic Medicine ◽

10.1038/s41525-020-0138-z ◽

2020 ◽

Vol 5 (1) ◽

Author(s):

Min Chen ◽

Min Zhang ◽

Yeqing Qian ◽

Yanmei Yang ◽

Yixi Sun ◽

...

Keyword(s):

Optical Mapping ◽

Pathogenic Variant ◽

Screening Methods ◽

Single Nucleotide Variants ◽

Single Nucleotide ◽

Real Time Quantitative Pcr ◽

Pathogenic Variants ◽

Whole Exome ◽

Great Insight

Abstract Recent advances in Bionano optical mapping (BOM) provide a great insight into the determination of structural variants (SVs), but its utility in identification of clinical likely pathogenic variants needs to be further demonstrated and proved. In a family with two consecutive pregnancies affected with ventriculomegaly, a splicing likely pathogenic variant at the LAMA1 locus (NM_005559: c. 4663 + 1 G > C) inherited from the father was identified in the proband by whole-exome sequencing, and no other pathogenic variant associated with the clinical phenotypes was detected. SV analysis by BOM revealed an ~48 kb duplication at the LAMA1 locus in the maternal sample. Real-time quantitative PCR and Sanger sequencing further confirmed the duplication as c.859-153_4806 + 910dup. Based on these variants, we hypothesize that the fetuses have Poretti-Boltshauser syndrome (PBS) presenting with ventriculomegaly. With the ability to determine single nucleotide variants and SVs, the strategy adopted here might be useful to detect cases missed by current routine screening methods. In addition, our study may broaden the phenotypic spectrum of fetuses with PBS.

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