Interaction between M. tuberculosis Lineage and Human Genetic Variants Reveals Novel Pathway Associations with Severity of TB

Tuberculosis (TB) remains a major public health threat globally, especially in sub-Saharan Africa. Both human and Mycobacterium tuberculosis (MTBC) genetic variation affect TB outcomes, but few studies have examined if and how the two genomes interact to affect disease. We hypothesize that long-term coexistence between human genomes and MTBC lineages modulates disease to affect its severity. We examined this hypothesis in our TB household contact study in Kampala, Uganda, in which we identified three MTBC lineages, of which one, L4.6-Uganda, is clearly derived and hence recent. We quantified TB severity using the Bandim TBscore and examined the interaction between MTBC lineage and human single-nucleotide polymorphisms (SNPs) genome-wide, in two independent cohorts of TB cases (n = 149 and n = 127). We found a significant interaction between an SNP in PPIAP2 and the Uganda lineage (combined p = 4 × 10−8). PPIAP2 is a pseudogene that is highly expressed in immune cells. Pathway and eQTL analyses indicated potential roles between coevolving SNPs and cellular replication and metabolism as well as platelet aggregation and coagulation. This finding provides further evidence that host–pathogen interactions affect clinical presentation differently than host and pathogen genetic variation independently, and that human–MTBC coevolution is likely to explain patterns of disease severity.

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Interaction between M. tuberculosis Lineage and Human Genetic Variants Reveals Novel Pathway Associations With Severity of TB

10.20944/preprints202110.0045.v1 ◽

2021 ◽

Author(s):

Michael McHenry ◽

Eddie Wampande ◽

Moses Joloba ◽

LaShaunda Malone ◽

Harriet Mayanja-Kizza ◽

...

Keyword(s):

Genetic Variation ◽

Clinical Presentation ◽

Sub Saharan Africa ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Human Genomes ◽

Genome Wide ◽

Sub Saharan ◽

Cellular Replication

Tuberculosis (TB) remains a major public health threat globally, especially in sub-Saharan Africa. Both human and Mycobacterium tuberculosis (MTBC) genetic variation affect TB outcomes, but few studies have examined if and how the two genomes interact to affect disease. We hypothesize that long-term coexistence between human genomes and MTBC lineages modulate disease to affect its severity. We examined this hypothesis in our TB household contact study in Kampala, Uganda, in which we identified 3 MTBC lineages of which one, L4.6-Uganda, is clearly derived and hence recent. We quantified TB severity using the Bandim TBscore and examined the interaction between MTBC lineage and human single nucleotide polymorphisms (SNPs) genome-wide, in two independent cohorts of TB cases (N=149 and N=127). We found a significant interaction between a SNP in PPIAP2 and the Uganda lineage (combined p=4x10-8). PPIAP2 is a pseudogene that is highly expressed in immune cells. Pathway and eQTL analyses indicated potential roles between coevolving SNPs and cellular replication and metabolism as well as platelet aggregation and coagulation. This finding provides further evidence that host-pathogen interactions affect clinical presentation differently than host and pathogen genetic variation independently, and that human-MTBC coevolution is likely to explain patterns of disease severity.

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Genomic Analyses of Globodera pallida, A Quarantine Agricultural Pathogen in Idaho

Pathogens ◽

10.3390/pathogens10030363 ◽

2021 ◽

Vol 10 (3) ◽

pp. 363

Author(s):

Sulochana K. Wasala ◽

Dana K. Howe ◽

Louise-Marie Dandurand ◽

Inga A. Zasada ◽

Dee R. Denver

Keyword(s):

Genetic Variation ◽

Potato Production ◽

Globodera Pallida ◽

Fixation Index ◽

Parasitic Nematodes ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Genome Wide ◽

Field Samples ◽

Multiple Introduction

Globodera pallida is among the most significant plant-parasitic nematodes worldwide, causing major damage to potato production. Since it was discovered in Idaho in 2006, eradication efforts have aimed to contain and eradicate G. pallida through phytosanitary action and soil fumigation. In this study, we investigated genome-wide patterns of G. pallida genetic variation across Idaho fields to evaluate whether the infestation resulted from a single or multiple introduction(s) and to investigate potential evolutionary responses since the time of infestation. A total of 53 G. pallida samples (~1,042,000 individuals) were collected and analyzed, representing five different fields in Idaho, a greenhouse population, and a field in Scotland that was used for external comparison. According to genome-wide allele frequency and fixation index (Fst) analyses, most of the genetic variation was shared among the G. pallida populations in Idaho fields pre-fumigation, indicating that the infestation likely resulted from a single introduction. Temporal patterns of genome-wide polymorphisms involving (1) pre-fumigation field samples collected in 2007 and 2014 and (2) pre- and post-fumigation samples revealed nucleotide variants (SNPs, single-nucleotide polymorphisms) with significantly differentiated allele frequencies indicating genetic differentiation. This study provides insights into the genetic origins and adaptive potential of G. pallida invading new environments.

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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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Mitochondrial genomes of Anopheles arabiensis, An. gambiae and An. coluzzii show no clear species division

F1000Research ◽

10.12688/f1000research.13807.2 ◽

2019 ◽

Vol 7 ◽

pp. 347 ◽

Cited By ~ 2

Author(s):

Mark J. Hanemaaijer ◽

Parker D. Houston ◽

Travis C. Collier ◽

Laura C. Norris ◽

Abdrahamane Fofana ◽

...

Keyword(s):

Sub Saharan Africa ◽

Mitochondrial Genomes ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Chromosomal Form ◽

Operational Taxonomic Units ◽

Mitogenome Sequence ◽

Mitochondrial Sequences ◽

Sub Saharan ◽

Species Specific

Here we report the complete mitochondrial sequences of 70 individual field collected mosquito specimens from throughout Sub-Saharan Africa. We generated this dataset to identify species specific markers for the following Anopheles species and chromosomal forms: An. arabiensis, An. coluzzii (The Forest and Mopti chromosomal forms) and An. gambiae (The Bamako and Savannah chromosomal forms). The raw Illumina sequencing reads were mapped to the NC_002084 reference mitogenome sequence. A total of 783 single nucleotide polymorphisms (SNPs) were detected on the mitochondrial genome, of which 460 are singletons (58.7%). None of these SNPs are suitable as molecular markers to distinguish among An. arabiensis, An. coluzzii and An. gambiae or any of the chromosomal forms. The lack of species or chromosomal form specific markers is also reflected in the constructed phylogenetic tree, which shows no clear division among the operational taxonomic units considered here.

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

10.7287/peerj.preprints.1553 ◽

2015 ◽

Cited By ~ 1

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

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Cannabis labelling is associated with genetic variation in terpene synthase genes

Nature Plants ◽

10.1038/s41477-021-01003-y ◽

2021 ◽

Vol 7 (10) ◽

pp. 1330-1334

Author(s):

Sophie Watts ◽

Michel McElroy ◽

Zoë Migicovsky ◽

Hugo Maassen ◽

Robin van Velzen ◽

...

Keyword(s):

Genetic Variation ◽

Single Nucleotide Polymorphisms ◽

Terpene Synthase ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Genome Wide ◽

A Genome ◽

Wide Scale ◽

Tandem Arrays

AbstractAnalysis of over 100 Cannabis samples quantified for terpene and cannabinoid content and genotyped for over 100,000 single nucleotide polymorphisms indicated that Sativa- and Indica-labelled samples were genetically indistinct on a genome-wide scale. Instead, we found that Cannabis labelling was associated with variation in a small number of terpenes whose concentrations are controlled by genetic variation at tandem arrays of terpene synthase genes.

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