Ultra-rapid metagenotyping of the human gut microbiome

AbstractSequence variation is used to quantify population structure and identify genetic determinants of phenotypes that vary within species. In the human microbiome and other environments, single nucleotide polymorphisms (SNPs) are frequently detected by aligning metagenomic sequencing reads to catalogs of genes or genomes. But this requires high-performance computing and enough read coverage to distinguish SNPs from sequencing errors. We solved these problems by developing the GenoTyper for Prokaytotes (GT-Pro), a suite of novel methods to catalog SNPs from genomes and use exact k-mer matches to perform ultra-fast reference-based SNP calling from metagenomes. Compared to read alignment, GT-Pro is more accurate and two orders of magnitude faster. We discovered 104 million SNPs in 909 human gut species, characterized their global population structure, and tracked pathogenic strains. GT-Pro democratizes strain-level microbiome analysis by making it possible to genotype hundreds of metagenomes on a personal computer.Software availabilityGT-Pro is available at https://github.com/zjshi/gt-pro.

Download Full-text

Genome-Wide Single Nucleotide Polymorphisms are Robust in Resolving Fine-Scale Population Genetic Structure of the Small Brown Planthopper, Laodelphax striatellus (Fallén) (Hemiptera: Delphacidae)

Journal of Economic Entomology ◽

10.1093/jee/toz145 ◽

2019 ◽

Vol 112 (5) ◽

pp. 2362-2368

Author(s):

Yan Liu ◽

Lei Chen ◽

Xing-Zhi Duan ◽

Dian-Shu Zhao ◽

Jing-Tao Sun ◽

...

Keyword(s):

Population Structure ◽

Discriminant Analysis ◽

Genetic Structure ◽

Population Genetic ◽

Brown Planthopper ◽

Fine Scale ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Small Brown Planthopper ◽

Scale Population

Abstract Deciphering genetic structure and inferring migration routes of insects with high migratory ability have been challenging, due to weak genetic differentiation and limited resolution offered by traditional genotyping methods. Here, we tested the ability of double digest restriction-site associated DNA sequencing (ddRADseq)-based single nucleotide polymorphisms (SNPs) in revealing the population structure relative to 13 microsatellite markers by using four small brown planthopper populations as subjects. Using ddRADseq, we identified 230,000 RAD loci and 5,535 SNP sites, which were present in at least 80% of individuals across the four populations with a minimum sequencing depth of 10. Our results show that this large SNP panel is more powerful than traditional microsatellite markers in revealing fine-scale population structure among the small brown planthopper populations. In contrast to the mixed population structure suggested by microsatellites, discriminant analysis of principal components (DAPC) of the SNP dataset clearly separated the individuals into four geographic populations. Our results also suggest the DAPC analysis is more powerful than the principal component analysis (PCA) in resolving population genetic structure of high migratory taxa, probably due to the advantages of DAPC in using more genetic variation and the discriminant analysis function. Together, these results point to ddRADseq being a promising approach for population genetic and migration studies of small brown planthopper.

Download Full-text

Genetic Determinants of Neurobehavioral Responses to Caffeine Administration during Sleep Deprivation: A Randomized, Cross Over Study (NCT03859882)

Genes ◽

10.3390/genes12040555 ◽

2021 ◽

Vol 12 (4) ◽

pp. 555

Author(s):

Mégane Erblang ◽

Fabien Sauvet ◽

Catherine Drogou ◽

Michaël Quiquempoix ◽

Pascal Van Beers ◽

...

Keyword(s):

Sleep Deprivation ◽

Nucleotide Polymorphisms ◽

Genetic Determinants ◽

Placebo Condition ◽

Double Blind ◽

Single Nucleotide ◽

Psychomotor Vigilance Test ◽

Tnf Α ◽

And Performance ◽

Psychomotor Vigilance

This study investigated whether four single nucleotide polymorphisms (SNPs) moderated caffeine effects on vigilance and performance in a double-blind and crossover total sleep deprivation (TSD) protocol in 37 subjects. In caffeine (2 × 2.5 mg/kg/24 h) or placebo-controlled condition, subjects performed a psychomotor vigilance test (PVT) and reported sleepiness every six hours (Karolinska sleepiness scale (KSS)) during TSD. EEG was also analyzed during the 09:15 PVT. Carriers of the TNF-α SNP A allele appear to be more sensitive than homozygote G/G genotype to an attenuating effect of caffeine on PVT lapses during sleep deprivation only because they seem more degraded, but they do not perform better as a result. The A allele carriers of COMT were also more degraded and sensitive to caffeine than G/G genotype after 20 h of sleep deprivation, but not after 26 and 32 h. Regarding PVT reaction time, ADORA2A influences the TSD effect but not caffeine, and PER3 modulates only the caffeine effect. Higher EEG theta activity related to sleep deprivation was observed in mutated TNF-α, PER3, and COMT carriers, in the placebo condition particularly. In conclusion, there are genetic influences on neurobehavioral impairments related to TSD that appear to be attenuated by caffeine administration. (NCT03859882).

Download Full-text

Nonsynonymous single nucleotide polymorphisms of NHE3 differentially decrease NHE3 transporter activity

AJP Cell Physiology ◽

10.1152/ajpcell.00421.2014 ◽

2015 ◽

Vol 308 (9) ◽

pp. C758-C766 ◽

Cited By ~ 7

Author(s):

Xinjun Cindy Zhu ◽

Rafiquel Sarker ◽

John R. Horton ◽

Molee Chakraborty ◽

Tian-E Chen ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Large Fraction ◽

Regulatory Protein ◽

Nucleotide Polymorphisms ◽

Genetic Determinants ◽

Single Nucleotide ◽

Mutant Proteins ◽

Homologous Protein ◽

Genetic Abnormalities ◽

The Impact

Genetic determinants appear to play a role in susceptibility to chronic diarrhea, but the genetic abnormalities involved have only been identified in a few conditions. The Na+/H+ exchanger 3 (NHE3) accounts for a large fraction of physiologic intestinal Na+ absorption. It is highly regulated through effects on its intracellular COOH-terminal regulatory domain. The impact of genetic variation in the NHE3 gene, such as single nucleotide polymorphisms (SNPs), on transporter activity remains unexplored. From a total of 458 SNPs identified in the entire NHE3 gene, we identified three nonsynonymous mutations (R474Q, V567M, and R799C), which were all in the protein's intracellular COOH-terminal domain. Here we evaluated whether these SNPs affect NHE3 activity by expressing them in a mammalian cell line that is null for all plasma membrane NHEs. These variants significantly reduced basal NHE3 transporter activity through a reduction in intrinsic NHE3 function in variant R474Q, abnormal trafficking in variant V567M, or defects in both intrinsic NHE3 function and trafficking in variant R799C. In addition, variants NHE3 R474Q and R799C failed to respond to acute dexamethasone stimulation, suggesting cells with these mutant proteins might be defective in NHE3 function during postprandial stimulation and perhaps under stressful conditions. Finally, variant R474Q was shown to exhibit an aberrant interaction with calcineurin B homologous protein (CHP), an NHE3 regulatory protein required for basal NHE3 activity. Taken together, these results demonstrate decreased transport activity in three SNPs of NHE3 and provide mechanistic insight into how these SNPs impact NHE3 function.

Download Full-text

Effect of P450 Oxidoreductase Polymorphisms on the Metabolic Activities of Ten Cytochrome P450s Varied by Polymorphic CYP Genotypes in Human Liver Microsomes

Cellular Physiology and Biochemistry ◽

10.1159/000490934 ◽

2018 ◽

Vol 47 (4) ◽

pp. 1604-1616 ◽

Cited By ~ 8

Author(s):

Yan Fang ◽

Na Gao ◽

Xin Tian ◽

Jun Zhou ◽

Hai-Feng Zhang ◽

...

Keyword(s):

Gene Polymorphisms ◽

High Performance ◽

Liver Microsomes ◽

Nucleotide Polymorphisms ◽

Liquid Chromatograph ◽

Single Nucleotide ◽

P450 Oxidoreductase ◽

Human Livers ◽

Metabolic Activities ◽

The Impact

Background/ Aims: Little is known about the effect of P450 oxidoreductase (POR) gene polymorphisms on the activities of CYPs with multiple genotypes. Methods: We genotyped 102 human livers for 18 known POR single nucleotide polymorphisms (SNPs) with allelic frequencies greater than 1% as well as for 27 known SNPs in 10 CYPs. CYP enzyme activities in microsomes prepared from these livers were determined by measuring probe substrate metabolism by high performance liquid chromatograph. Results: We found that the effects of the 18 POR SNPs on 10 CYP activities were CYP genotype-dependent. The POR mutations were significantly associated with decreased overall Km for CYP2B6 and 2E1, and specific genotypes within CYP1A2, 2A6, 2B6, 2C8, 2D6 and 2E1 were identified as being affected by these POR SNPs. Notably, the effect of a specific POR mutation on the activity of a CYP genotype could not be predicted from other CYP genotypes of even the same CYP. When combining one POR SNP with other POR SNPs, a hitherto unrecognized effect of multiple-site POR gene polymorphisms (MSGP) on CYP activity was uncovered, which was not necessarily consistent with the effect of either single POR SNP. Conclusions: The effects of POR SNPs on CYP activities were not only CYP-dependent, but more importantly, CYP genotype-dependent. Moreover, the effect of a POR SNP alone and in combination with other POR SNPs (MSGP) was not always consistent, nor predictable. Understanding the impact of POR gene polymorphisms on drug metabolism necessitates knowing the complete SNP complement of POR and the genotype of the relevant CYPs.

Download Full-text

INFLUENCE ON HOMEOSTASIS AS THE CRITERION FOR SELECTING SINGLE NUCLEOTIDE POLYMORPHISMS FOR THE STUDY OF METABOLIC SYNDROM IN THE KAZAKH POPULATION

REPORTS ◽

10.32014/2020.2518-1483.123 ◽

2020 ◽

Vol 5 (333) ◽

pp. 86-93

Author(s):

V.V. Benberin ◽

◽

T.A. Voshchenkova ◽

A.A. Nagymtayeva ◽

A.S. Sibagatova ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Traditional Approach ◽

Population Based ◽

Malignant Neoplasms ◽

Nucleotide Polymorphisms ◽

Genetic Determinants ◽

Single Nucleotide ◽

Sequence Of Events ◽

Kazakh Population ◽

Symptom Complex

Metabolic syndrome (MS) is increasingly cited as the world's leading health risk. The sequence of events toward multimorbidity in most cases passes through MS. According to the research, MS heritability ranges from 23 to 27% in Europeans, and 51 to 60% in Asians. The purpose of the review: to form a strategy for the selection of single nucleotide polymorphisms (SNPs) for the study of MS in the Kazakh population based on the effect of SNPs on homeostasis indicators The stable symptom complex of MS is a complicated dynamic system of successive accumulations of dysmetabolic disorders of homeostasis. This system starts the development of subsequent age-associated diseases), such as cardiometabolic, neurodegenerative, and malignant neoplasms. The system for selecting SNPs for the MS study, proposed on the basis of the concept of homeostasis dysfunction, assumes, in conditions of limited resources, to see the greatest level of their influence within the conditional framework of three genetic models of homeostasis dysregulation: insulin resistance , oxidative stress, and chronic inflammation. This approach is fundamentally different from the traditional approach involving candidate genes. It is expected that scientific research in this direction will contribute not only to the understanding of general biological processes, but also to the targeted search for genetic determinants and for new opportunities for personalized interventions.

Download Full-text

Population Structure and Genetic Diversity in Korean Cowpea Germplasm Based on SNP Markers

Plants ◽

10.3390/plants9091190 ◽

2020 ◽

Vol 9 (9) ◽

pp. 1190 ◽

Cited By ~ 1

Author(s):

Eunju Seo ◽

Kipoong Kim ◽

Tae-Hwan Jun ◽

Jinsil Choi ◽

Seong-Hoon Kim ◽

...

Keyword(s):

Genetic Diversity ◽

Population Structure ◽

Principal Component ◽

Snp Markers ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Useful Knowledge ◽

Population Structure Analysis ◽

Group 3 ◽

Genetic Diversity Study

Cowpea is one of the most essential legume crops providing inexpensive dietary protein and nutrients. The aim of this study was to understand the genetic diversity and population structure of global and Korean cowpea germplasms. A total of 384 cowpea accessions from 21 countries were genotyped with the Cowpea iSelect Consortium Array containing 51,128 single-nucleotide polymorphisms (SNPs). After SNP filtering, a genetic diversity study was carried out using 35,116 SNPs within 376 cowpea accessions, including 229 Korean accessions. Based on structure and principal component analysis, a total of 376 global accessions were divided into four major populations. Accessions in group 1 were from Asia and Europe, those in groups 2 and 4 were from Korea, and those in group 3 were from West Africa. In addition, 229 Korean accessions were divided into three major populations (Q1, Jeonra province; Q2, Gangwon province; Q3, a mixture of provinces). Additionally, the neighbor-joining tree indicated similar results. Further genetic diversity analysis within the global and Korean population groups indicated low heterozygosity, a low polymorphism information content, and a high inbreeding coefficient in the Korean cowpea accessions. The population structure analysis will provide useful knowledge to support the genetic potential of the cowpea breeding program, especially in Korea.

Download Full-text

High‐Performance Sieving Electrophoresis for Single‐Nucleotide Polymorphisms with a Structuring Hydrogel Network

Macromolecular Chemistry and Physics ◽

10.1002/macp.201900385 ◽

2019 ◽

Vol 221 (2) ◽

pp. 1900385

Author(s):

Qingxiang You ◽

Ping Wang ◽

Dawei Zhang ◽

Zhenqing Li ◽

Yoshinori Yamaguchi

Keyword(s):

Single Nucleotide Polymorphisms ◽

High Performance ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Hydrogel Network

Download Full-text

Single nucleotide polymorphisms in piRNA-pathway genes: an insight into genetic determinants of human diseases

Molecular Genetics and Genomics ◽

10.1007/s00438-019-01612-5 ◽

2019 ◽

Vol 295 (1) ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Jyoti Roy ◽

Kalyani Anand ◽

Swati Mohapatra ◽

Rojalin Nayak ◽

Trisha Chattopadhyay ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Human Diseases ◽

Nucleotide Polymorphisms ◽

Genetic Determinants ◽

Single Nucleotide ◽

Pirna Pathway ◽

Insight Into

Download Full-text

Human genetic determinants of the gut microbiome and their associations with health and disease: a phenome-wide association study

Scientific Reports ◽

10.1038/s41598-020-70724-5 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Hilde E. Groot ◽

Yordi J. van de Vegte ◽

Niek Verweij ◽

Erik Lipsic ◽

Jacco C. Karper ◽

...

Keyword(s):

Gut Microbiome ◽

Healthy Aging ◽

Total Sample ◽

Causal Link ◽

Small Scale ◽

Nucleotide Polymorphisms ◽

Genetic Determinants ◽

Human Gut ◽

Human Gut Microbiome ◽

Health And Disease

Abstract Small-scale studies have suggested a link between the human gut microbiome and highly prevalent diseases. However, the extent to which the human gut microbiome can be considered a determinant of disease and healthy aging remains unknown. We aimed to determine the spectrum of diseases that are linked to the human gut microbiome through the utilization of its genetic determinants as a proxy for its composition. 180 single nucleotide polymorphisms (SNPs) known to influence the human gut microbiome were used to assess the association with health and disease outcomes in 422,417 UK Biobank participants. Potential causal estimates were obtained using a Mendelian randomization (MR) approach. From the total sample analysed (mean age was 57 ± 8 years), 194,567 (46%) subjects were male. Median exposure was 66-person years (interquartile range 59–72). Eleven SNPs were significantly associated with 28 outcomes (Bonferroni corrected P value < 4.63·10−6) including food intake, hypertension, atopy, COPD, BMI, and lipids. Multiple SNP MR pointed to a possible causal link between Ruminococcus flavefaciens and hypertension, and Clostridium and platelet count. Microbiota and their metabolites might be of importance in the interplay between overlapping pathophysiological processes, although challenges remain in establishing causal relationships.

Download Full-text