Is shed hair the most effective non-invasive resource for estimating wild pedigrees?

AbstractWild pedigrees are critical for better understanding mating systems and inbreeding scenarios to inform conservation strategies for endangered species. To delineate pedigrees in wild populations, many identified individuals will have to be genotyped at thousands of loci, mostly from non-invasive samples. This requires us to quantify (a) the most common non-invasive sample available from identified individuals (b) the ability to acquire genome-wide data from such samples, and (c) the quality of such genome-wide data, and its ability to reconstruct relationships between animals within a population. We followed identified individuals from a wild endangered tiger population, and found that shed hair samples were most common compared to fecal samples, carcasses and opportunistic invasive samples. DNA extraction, library preparation and whole genome sequencing resulted in between 126,129 and 512,689 SNPs from across the genome for four such samples. Exploratory population genetic analyses revealed that these data were free of holistic biases, and could recover expected population structure and relatedness. Mitochondrial genomes recovered matrilineages as suggested by long-term monitoring data. Even with these few samples, we were able to uncover the matrilineage for an individual with unknown ancestry. In summary, we demonstrated that non-invasive shed hair samples yielded adequate quality/quantity DNA AND in conjunction with sensitive library preparation methods, provided reliable data from hundreds of thousands of SNPs across the genome. This makes shed hair are an effective resource for studying individual-based genetics of elusive endangered species.

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Genetic analysis of amyotrophic lateral sclerosis identifies contributing pathways and cell types

Science Advances ◽

10.1126/sciadv.abd9036 ◽

2021 ◽

Vol 7 (3) ◽

pp. eabd9036

Author(s):

Sara Saez-Atienzar ◽

Sara Bandres-Ciga ◽

Rebekah G. Langston ◽

Jonggeol J. Kim ◽

Shing Wan Choi ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Membrane Trafficking ◽

Molecular Mechanisms ◽

Cell Types ◽

Polygenic Risk Score ◽

Genome Wide ◽

Genome Wide Data ◽

Data Driven Approach ◽

Single Nucleus ◽

Lateral Sclerosis

Despite the considerable progress in unraveling the genetic causes of amyotrophic lateral sclerosis (ALS), we do not fully understand the molecular mechanisms underlying the disease. We analyzed genome-wide data involving 78,500 individuals using a polygenic risk score approach to identify the biological pathways and cell types involved in ALS. This data-driven approach identified multiple aspects of the biology underlying the disease that resolved into broader themes, namely, neuron projection morphogenesis, membrane trafficking, and signal transduction mediated by ribonucleotides. We also found that genomic risk in ALS maps consistently to GABAergic interneurons and oligodendrocytes, as confirmed in human single-nucleus RNA-seq data. Using two-sample Mendelian randomization, we nominated six differentially expressed genes (ATG16L2, ACSL5, MAP1LC3A, MAPKAPK3, PLXNB2, and SCFD1) within the significant pathways as relevant to ALS. We conclude that the disparate genetic etiologies of this fatal neurological disease converge on a smaller number of final common pathways and cell types.

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Genome-wide SNPs redefines species boundaries and conservation units in the freshwater mussel genus Cyprogenia of North America

Scientific Reports ◽

10.1038/s41598-021-90325-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kyung Seok Kim ◽

Kevin J. Roe

Keyword(s):

Phylogenetic Analyses ◽

Freshwater Mussel ◽

Conservation Strategies ◽

Nucleotide Polymorphisms ◽

Conservation Units ◽

Genetic Structuring ◽

The North ◽

Snp Data ◽

Genome Wide ◽

Significant Difference

AbstractDetailed information on species delineation and population genetic structure is a prerequisite for designing effective restoration and conservation strategies for imperiled organisms. Phylogenomic and population genomic analyses based on genome-wide double digest restriction-site associated DNA sequencing (ddRAD-Seq) data has identified three allopatric lineages in the North American freshwater mussel genus Cyprogenia. Cyprogenia stegaria is restricted to the Eastern Highlands and displays little genetic structuring within this region. However, two allopatric lineages of C. aberti in the Ozark and Ouachita highlands exhibit substantial levels (mean uncorrected FST = 0.368) of genetic differentiation and each warrants recognition as a distinct evolutionary lineage. Lineages of Cyprogenia in the Ouachita and Ozark highlands are further subdivided reflecting structuring at the level of river systems. Species tree inference and species delimitation in a Bayesian framework using single nucleotide polymorphisms (SNP) data supported results from phylogenetic analyses, and supports three species of Cyprogenia over the currently recognized two species. A comparison of SNPs generated from both destructively and non-destructively collected samples revealed no significant difference in the SNP error rate, quality and amount of ddRAD sequence reads, indicating that nondestructive or trace samples can be effectively utilized to generate SNP data for organisms for which destructive sampling is not permitted.

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Ancient genomic time transect from the Central Asian Steppe unravels the history of the Scythians

Science Advances ◽

10.1126/sciadv.abe4414 ◽

2021 ◽

Vol 7 (13) ◽

pp. eabe4414

Author(s):

Guido Alberto Gnecchi-Ruscone ◽

Elmira Khussainova ◽

Nurzhibek Kahbatkyzy ◽

Lyazzat Musralina ◽

Maria A. Spyrou ◽

...

Keyword(s):

Bronze Age ◽

Iron Age ◽

Gene Pools ◽

Social Rules ◽

Eurasian Steppe ◽

Central Asian ◽

Genome Wide ◽

Genome Wide Data ◽

History Of ◽

First Millennium

The Scythians were a multitude of horse-warrior nomad cultures dwelling in the Eurasian steppe during the first millennium BCE. Because of the lack of first-hand written records, little is known about the origins and relations among the different cultures. To address these questions, we produced genome-wide data for 111 ancient individuals retrieved from 39 archaeological sites from the first millennia BCE and CE across the Central Asian Steppe. We uncovered major admixture events in the Late Bronze Age forming the genetic substratum for two main Iron Age gene-pools emerging around the Altai and the Urals respectively. Their demise was mirrored by new genetic turnovers, linked to the spread of the eastern nomad empires in the first centuries CE. Compared to the high genetic heterogeneity of the past, the homogenization of the present-day Kazakhs gene pool is notable, likely a result of 400 years of strict exogamous social rules.

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Genome diversity in Ukraine

GigaScience ◽

10.1093/gigascience/giaa159 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Taras K Oleksyk ◽

Walter W Wolfsberger ◽

Alexandra M Weber ◽

Khrystyna Shchubelka ◽

Olga T Oleksyk ◽

...

Keyword(s):

Sequence Data ◽

Copy Number Variations ◽

Genomic Variation ◽

High Coverage ◽

Genome Data ◽

New Information ◽

Genome Wide ◽

Public Data ◽

Genome Wide Data ◽

Multiple Samples

Abstract Background The main goal of this collaborative effort is to provide genome-wide data for the previously underrepresented population in Eastern Europe, and to provide cross-validation of the data from genome sequences and genotypes of the same individuals acquired by different technologies. We collected 97 genome-grade DNA samples from consented individuals representing major regions of Ukraine that were consented for public data release. BGISEQ-500 sequence data and genotypes by an Illumina GWAS chip were cross-validated on multiple samples and additionally referenced to 1 sample that has been resequenced by Illumina NovaSeq6000 S4 at high coverage. Results The genome data have been searched for genomic variation represented in this population, and a number of variants have been reported: large structural variants, indels, copy number variations, single-nucletide polymorphisms, and microsatellites. To our knowledge, this study provides the largest to-date survey of genetic variation in Ukraine, creating a public reference resource aiming to provide data for medical research in a large understudied population. Conclusions Our results indicate that the genetic diversity of the Ukrainian population is uniquely shaped by evolutionary and demographic forces and cannot be ignored in future genetic and biomedical studies. These data will contribute a wealth of new information bringing forth a wealth of novel, endemic and medically related alleles.

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Initial Upper Palaeolithic humans in Europe had recent Neanderthal ancestry

Nature ◽

10.1038/s41586-021-03335-3 ◽

2021 ◽

Vol 592 (7853) ◽

pp. 253-257 ◽

Cited By ~ 3

Author(s):

Mateja Hajdinjak ◽

Fabrizio Mafessoni ◽

Laurits Skov ◽

Benjamin Vernot ◽

Alexander Hübner ◽

...

Keyword(s):

Family History ◽

East Asia ◽

Late Pleistocene ◽

Modern Human ◽

Human Migration ◽

Upper Palaeolithic ◽

Modern Humans ◽

Genome Wide ◽

Genome Wide Data

AbstractModern humans appeared in Europe by at least 45,000 years ago1–5, but the extent of their interactions with Neanderthals, who disappeared by about 40,000 years ago6, and their relationship to the broader expansion of modern humans outside Africa are poorly understood. Here we present genome-wide data from three individuals dated to between 45,930 and 42,580 years ago from Bacho Kiro Cave, Bulgaria1,2. They are the earliest Late Pleistocene modern humans known to have been recovered in Europe so far, and were found in association with an Initial Upper Palaeolithic artefact assemblage. Unlike two previously studied individuals of similar ages from Romania7 and Siberia8 who did not contribute detectably to later populations, these individuals are more closely related to present-day and ancient populations in East Asia and the Americas than to later west Eurasian populations. This indicates that they belonged to a modern human migration into Europe that was not previously known from the genetic record, and provides evidence that there was at least some continuity between the earliest modern humans in Europe and later people in Eurasia. Moreover, we find that all three individuals had Neanderthal ancestors a few generations back in their family history, confirming that the first European modern humans mixed with Neanderthals and suggesting that such mixing could have been common.

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Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma

npj Genomic Medicine ◽

10.1038/s41525-021-00179-8 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Brian C.-H. Chiu ◽

Chang Chen ◽

Qiancheng You ◽

Rudyard Chiu ◽

Girish Venkataraman ◽

...

Keyword(s):

B Cell Lymphoma ◽

Cell Free Dna ◽

Invasive Approach ◽

Non Invasive ◽

Signature Genes ◽

Non Hodgkin Lymphoma ◽

Free Dna ◽

Genome Wide ◽

Circulating Cell Free Dna

AbstractThe 5-methylcytosines (5mC) have been implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). However, the role of 5-hydroxymethylcytosines (5hmC) that are generated from 5mC through active demethylation, in lymphomagenesis is unknown. We profiled genome-wide 5hmC in circulating cell-free DNA (cfDNA) from 73 newly diagnosed patients with DLBCL and FL. We identified 294 differentially modified genes between DLBCL and FL. The differential 5hmC in the DLBCL/FL-differentiating genes co-localized with enhancer marks H3K4me1 and H3K27ac. A four-gene panel (CNN2, HMG20B, ACRBP, IZUMO1) robustly represented the overall 5hmC modification pattern that distinguished FL from DLBCL with an area under curve of 88.5% in the testing set. The median 5hmC modification levels in signature genes showed potential for separating patients for risk of all-cause mortality. This study provides evidence that genome-wide 5hmC profiles in cfDNA differ between DLBCL and FL and could be exploited as a non-invasive approach.

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A curated dataset of modern and ancient high-coverage shotgun human genomes

Scientific Data ◽

10.1038/s41597-021-00980-1 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Pierpaolo Maisano Delser ◽

Eppie R. Jones ◽

Anahit Hovhannisyan ◽

Lara Cassidy ◽

Ron Pinhasi ◽

...

Keyword(s):

Sequence Data ◽

Whole Genome ◽

Reference Dataset ◽

High Coverage ◽

Sample Distribution ◽

Human Samples ◽

Human Genomes ◽

Genome Wide ◽

Genome Wide Data ◽

Computationally Intensive

AbstractOver the last few years, genome-wide data for a large number of ancient human samples have been collected. Whilst datasets of captured SNPs have been collated, high coverage shotgun genomes (which are relatively few but allow certain types of analyses not possible with ascertained captured SNPs) have to be reprocessed by individual groups from raw reads. This task is computationally intensive. Here, we release a dataset including 35 whole-genome sequenced samples, previously published and distributed worldwide, together with the genetic pipeline used to process them. The dataset contains 72,041,355 sites called across 19 ancient and 16 modern individuals and includes sequence data from four previously published ancient samples which we sequenced to higher coverage (10–18x). Such a resource will allow researchers to analyse their new samples with the same genetic pipeline and directly compare them to the reference dataset without re-processing published samples. Moreover, this dataset can be easily expanded to increase the sample distribution both across time and space.

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Modeling cell-free DNA fragment size densities for non-invasive detection of cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.3058 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 3058-3058

Author(s):

Jacob Carey ◽

Bryan Chesnick ◽

Denise Butler ◽

Michael Rongione ◽

Giovanni Parmigiani ◽

...

Keyword(s):

Fragment Size ◽

Length Distribution ◽

Mixture Component ◽

Base Pairs ◽

Machine Model ◽

Cell Free Dna ◽

Non Invasive ◽

Free Dna ◽

Genome Wide ◽

Low Coverage

3058 Background: Circulating cell-free DNA (cfDNA) is largely nucleosomal in origin with typical fragment lengths of 167 base-pairs reflecting the length of DNA wrapped around-the histone and H1 linker. Given the nucleosomal origin of cfDNA, we have previously used low coverage whole genome sequencing to evaluate DNA fragmentation profiles to sensitively and specifically detect tumor-derived DNA with altered fragment lengths or coverage. Methods: Here we evaluate the use of Bayesian finite mixtures to model the fragment length distribution and demonstrate how the parameters from these models can be useful to distinguish between individuals with and without cancer. We examined the number of cfDNA fragments by size ranging from 100-220bp and approximated the mixture component location, scale, and weight using Markov Chain Monte Carlo. The performance of the method was determined using a ten-fold, ten repeat cross-validation of Gradient Boosted Machine model using 1) our previously described genome-wide fragmentation profile approach, 2) the parameters from the mixture model and 3) a combination of approaches 1) and 2) as features. Results: In this study of 215 cancer patients and 208 cancer-free individuals, we observed cross-validated AUCs of 1) 0.94, 2) 0.95, and 3) 0.97 among the three approaches. Conclusions: Our findings indicate that parsimonious mixture models may improve detection of cancer in conjunction with fragmentation profile analyses across the genome.

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Using non-invasive sampling methods to determine the prevalence and distribution of Chlamydia pecorum and koala retrovirus in a remnant koala population with conservation importance

Wildlife Research ◽

10.1071/wr17184 ◽

2018 ◽

Vol 45 (4) ◽

pp. 366 ◽

Cited By ~ 1

Author(s):

Faye Wedrowicz ◽

Jennifer Mosse ◽

Wendy Wright ◽

Fiona E. Hogan

Keyword(s):

Native Species ◽

Conservation Strategies ◽

The South ◽

Phascolarctos Cinereus ◽

Urogenital Infection ◽

Non Invasive ◽

Chlamydia Pecorum ◽

Genetic Sampling ◽

Pathogen Prevalence ◽

Koala Retrovirus

Context Pathogenic infections are an important consideration for the conservation of native species, but obtaining such data from wild populations can be expensive and difficult. Two pathogens have been implicated in the decline of some koala (Phascolarctos cinereus) populations: urogenital infection with Chlamydia pecorum and koala retrovirus subgroup A (KoRV-A). Pathogen data for a wild koala population of conservation importance in South Gippsland, Victoria are essentially absent. Aims This study uses non-invasive sampling of koala scats to provide prevalence and genotype data for C. pecorum and KoRV-A in the South Gippsland koala population, and compares pathogen prevalence between wild koalas and koalas in rescue shelters. Methods C. pecorum and KoRV-A provirus were detected by PCR of DNA isolated from scats collected in the field. Pathogen genetic variation was investigated using DNA sequencing of the C. pecorum ompA and KoRV-A env genes. Key results C. pecorum and KoRV-A were detected in 61% and 27% of wild South Gippsland individuals tested, respectively. KoRV-A infection tended to be higher in shelter koalas compared with wild koalas. In contrast with other Victorian koala populations sampled, greater pathogen diversity was present in South Gippsland. Conclusions In the South Gippsland koala population, C. pecorum is widespread and common whereas KoRV appears less prevalent than previously thought. Further work exploring the dynamics of these pathogens in South Gippsland koalas is warranted and may help inform future conservation strategies for this important population. Implications Non-invasive genetic sampling from scats is a powerful method for obtaining data regarding pathogen prevalence and diversity in wildlife. The use of non-invasive methods for the study of pathogens may help fill research gaps in a way that would be difficult or expensive to achieve using traditional methods.

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