scholarly journals Sweeps in time: leveraging the joint distribution of branch lengths

2021 ◽  
Author(s):  
Gertjan Bisschop ◽  
Konrad Lohse ◽  
Derek Setter

AbstractCurrent methods of identifying positively selected regions of the genome are limited by their underlying model in two key ways: the model cannot account for the timing of the adaptive event and the analytic predictions are limited to single nucleotide polymorphisms. Here we develop a tractable method of describing the effect of positive selection on the genealogical histories in the surrounding genome, explicitly modeling both the timing and context of the adaptive event. In addition, our framework allows us to go beyond simple polymorphism data. We are able to leverage information contained in patterns of linked variants, and even with very small sample sizes, our analytic framework has high power to identify historically adaptive regions of the genome and to correctly infer both the time and strength of selection. Finally, we derived the marginal distribution of genealogical branch lengths at a locus affected by selection acting at a linked site. This provides a much-needed link between current theoretical models to recent advances in simulation procedures that have allowed researchers both to examine the evolution of genealogical histories at the level of full chromosomes and build methods that attempt to reconstruct full ancestries from genome sequence data.

Genetics ◽  
2021 ◽  
Author(s):  
Gertjan Bisschop ◽  
Konrad Lohse ◽  
Derek Setter

Abstract Current methods of identifying positively selected regions in the genome are limited in two key ways: the underlying models cannot account for the timing of adaptive events and the comparison between models of selective sweeps and sequence data is generally made via simple summaries of genetic diversity. Here we develop a tractable method of describing the effect of positive selection on the genealogical histories in the surrounding genome, explicitly modeling both the timing and context of an adaptive event. In addition, our framework allows us to go beyond analyzing polymorphism data via the site frequency spectrum or summaries thereof and instead leverage information contained in patterns of linked variants. Tests on both simulations and a human data example, as well as a comparison to SweepFinder2, show that even with very small sample sizes, our analytic framework has higher power to identify old selective sweeps and to correctly infer both the time and strength of selection. Finally, we derived the marginal distribution of genealogical branch lengths at a locus affected by selection acting at a linked site. This provides a much-needed link between our analytic understanding of the effects of sweeps on sequence variation and recent advances in simulation and heuristic inference procedures that allow researchers to examine the sequence of genealogical histories along the genome.


2020 ◽  
Vol 21 (5) ◽  
pp. 1604 ◽  
Author(s):  
Regina F. Nasyrova ◽  
Polina V. Moskaleva ◽  
Elena E. Vaiman ◽  
Natalya A. Shnayder ◽  
Nataliya L. Blatt ◽  
...  

According to the recent data, nitric oxide (NO) is a chemical messenger that mediates functions such as vasodilation and neurotransmission, as well as displaying antimicrobial and antitumoral activities. NO has been implicated in the neurotoxicity associated with stroke and neurodegenerative diseases; neural regulation of smooth muscle, including peristalsis; and penile erections. We searched for full-text English publications from the past 15 years in Pubmed and SNPedia databases using keywords and combined word searches (nitric oxide, single nucleotide variants, single nucleotide polymorphisms, genes). In addition, earlier publications of historical interest were included in the review. In our review, we have summarized information regarding all NOS1, NOS2, NOS3, and NOS1AP single nucleotide variants (SNVs) involved in the development of mental disorders and neurological diseases/conditions. The results of the studies we have discussed in this review are contradictory, which might be due to different designs of the studies, small sample sizes in some of them, and different social and geographical characteristics. However, the contribution of genetic and environmental factors has been understudied, which makes this issue increasingly important for researchers as the understanding of these mechanisms can support a search for new approaches to pathogenetic and disease-modifying treatment.


Blood ◽  
2011 ◽  
Vol 117 (24) ◽  
pp. 6681-6684 ◽  
Author(s):  
Jonathan M. Flanagan ◽  
Denise M. Frohlich ◽  
Thad A. Howard ◽  
William H. Schultz ◽  
Catherine Driscoll ◽  
...  

Abstract Stroke is a devastating complication of sickle cell anemia (SCA), affecting 5% to 10% of patients before adulthood. Several candidate genetic polymorphisms have been proposed to affect stroke risk, but few have been validated, mainly because previous studies were hampered by relatively small sample sizes and the absence of additional patient cohorts for validation testing. To verify the accuracy of proposed genetic modifiers influencing stroke risk in SCA, we performed genotyping for 38 published single nucleotide polymorphisms (SNPs), as well as α-thalassemia, G6PD A− variant deficiency, and β-globin haplotype in 2 cohorts of children with well-defined stroke phenotypes (130 stroke, 103 nonstroke). Five polymorphisms had significant influence (P < .05): SNPs in the ANXA2, TGFBR3, and TEK genes were associated with increased stroke risk, whereas α-thalassemia and a SNP in the ADCY9 gene were linked with decreased stroke risk. Further investigation at these genetic regions may help define mutations that confer stroke risk or protection in children with SCA.


Author(s):  
Regina F. Nasyrova ◽  
Polina V. Moskaleva ◽  
Elene E. Vaiman ◽  
Natalya A. Shnayder ◽  
Nataliya L. Blatt ◽  
...  

According to the recent data, nitric oxide (NO) is a chemical messenger that mediates functions such as vasodilation and neurotransmission, it also possesses antimicrobial and antitumoral activities. Nitric oxide has been implicated in neurotoxicity associated with stroke and neurodegenerative diseases, neural regulation of smooth muscle, including peristalsis, and penile erection. We searched for full-text English publications in Pubmed and SNPedia databases using keywords and combined word searches (nitric oxide, single nucleotide variants, single nucleotide polymorphisms, genes) over the past 15 years. In addition, earlier publications of historical interest were included in the review. In our review, we have sum up all NOS1, NOS2, NOS3, and NOS1AP single nucleotide variants (SNVs) involved in the development of mental disorders and neurological diseases/conditions. The results of studies we have discussed in this review are contradictory, that might be due to different designs of the studies, small sample sizes in some of them, as well as different social and geographical characteristics. However, the contribution of genetic and environmental factors has been understudied, that makes this issue increasing for researchers as the understanding of these mechanisms can support a search for new approaches to pathogenetic and disease-modifying treatment.


2017 ◽  
Author(s):  
Najla Saad Elhezzani

AbstractLinear mixed models (LMM) are widely used to estimate narrow sense heritability explained by tagged single-nucleotide polymorphisms (SNPs). However, those estimates are valid only if large sample sizes are used. We propose a Bayesian matrix-variate model that takes into account the genetic correlation among phenotypes and genetic correlation among individuals. The use of multivariate Bayesian methods allows us to circumvent some issues related to small sample sizes, mainly overfitting and boundary estimates. Using gene expression pathways, we demonstrate a significant improvement in SNP-based heritability estimates over univariate and likelihood-based methods, thus explaining why recent progress in eQTL identification has been limited.


2020 ◽  
Author(s):  
Zhong-Yin Zhou ◽  
Hang Liu ◽  
Yue-Dong Zhang ◽  
Yin-Qiao Wu ◽  
Min-Sheng Peng ◽  
...  

AbstractUnderstanding the mutational and evolutionary dynamics of SARS-CoV-2 is essential for treating COVID-19 and the development of a vaccine. Here, we analyzed publicly available 15,818 assembled SARS-CoV-2 genome sequences, along with 2,350 raw sequence datasets sampled worldwide. We investigated the distribution of inter-host single nucleotide polymorphisms (inter-host SNPs) and intra-host single nucleotide variations (iSNVs). Mutations have been observed at 35.6% (10,649/29,903) of the bases in the genome. The substitution rate in some protein coding regions is higher than the average in SARS-CoV-2 viruses, and the high substitution rate in some regions might be driven to escape immune recognition by diversifying selection. Both recurrent mutations and human-to-human transmission are mechanisms that generate fitness advantageous mutations. Furthermore, the frequency of three mutations (S protein, F400L; ORF3a protein, T164I; and ORF1a protein, Q6383H) has gradual increased over time on lineages, which provides new clues for the early detection of fitness advantageous mutations. Our study provides theoretical support for vaccine development and the optimization of treatment for COVID-19. We call researchers to submit raw sequence data to public databases.


2013 ◽  
Vol 11 (3) ◽  
pp. 221-224
Author(s):  
Masaru Takeya ◽  
Fukuhiro Yamasaki ◽  
Sachiko Hattori ◽  
Kaworu Ebana

The NIASGBsnp system manages data on single nucleotide polymorphisms (SNPs) of rice (Oryzasativa L.) genetic resources in the National Institute of Agrobiological Science (NIAS) Genebank. NIASGBsnp currently holds data on 768 SNP markers for 301 rice accessions and plans to add the SNP data of active rice accessions in the NIAS Genebank. It can show differences between accessions by graphical genotyping. Passport, characteristics and evaluation data of accessions can be retrieved to allow phenotype to be associated with genotype. NIASGBsnp will support various research purposes such as genomic selection and plant pathology research.


2020 ◽  
Author(s):  
Evert den Drijver ◽  
Joep J.J.M. Stohr ◽  
Jaco J. Verweij ◽  
Carlo Verhulst ◽  
Francisca C. Velkers ◽  
...  

AbstractDistinguishing epidemiologically related and unrelated plasmids is essential to confirm plasmid transmission. We compared IncI1-pST12 plasmids from both human and livestock origin and explored the degree of sequence similarity between plasmids from Enterobacteriaceae with different epidemiological links. Short-read sequence data of Enterobacteriaceae cultured from humans and broilers were screened for the presence of both a blaCMY-2 gene and an IncI1-pST12 replicon. Isolates were long-read sequenced on a MinION sequencer (OxfordNanopore Technologies). After plasmid reconstruction using hybrid assembly, pairwise single nucleotide polymorphisms (SNP) were determined. The plasmids were annotated, and a pan-genome was constructed to compare genes variably present between the different plasmids. Nine Escherichia coli sequences of broiler origin, four Escherichia coli sequences and one Salmonella enterica sequence of human origin were selected for the current analysis. A circular contig with the IncI1-pST12 replicon and blaCMY-2 gene was extracted from the assembly graph of all fourteen isolates. Analysis of the IncI1-pST12 plasmids revealed a low number of SNP differences (range of 0-9 SNPs). The range of SNP differences overlapped in isolates with different epidemiological links. One-hundred and twelve from a total of 113 genes of the pan-genome were present in all plasmid constructs. NGS-analysis of blaCMY--2-containing IncI1-pST12 plasmids isolated from Enterobacteriaceae with different epidemiological links show a high degree of sequence similarity in terms of SNP differences and the number of shared genes. Therefore, statements on the horizontal transfer of these plasmids based on genetic identity should be made with caution.


2017 ◽  
Author(s):  
Kelly J Vining ◽  
Natalia Salinas ◽  
Jacob A Tennessen ◽  
Jason D Zurn ◽  
Daniel James Sargent ◽  
...  

With the goal of evaluating genotyping-by-sequencing (GBS) in a species with a complex octoploid genome, GBS was used to survey genome-wide single-nucleotide polymorphisms (SNPs) in three biparental strawberry (Fragaria ×ananassa) populations. GBS sequence data were aligned to the F. vesca ‘Fvb’ reference genome in order to call SNPs. Numbers of polymorphic SNPs per population ranged from 1,163 to 3,190. Linkage maps consisting of 30-65 linkage groups were produced from the SNP sets derived from each parent. The linkage groups covered 99% of the Fvb reference genome, with three to seven linkage groups from a given parent aligned to any particular chromosome. A phylogenetic analysis performed using the POLiMAPS pipeline revealed linkage groups that were most similar to ancestral species F. vesca for each chromosome. Linkage groups that were most similar to a second ancestral species, F. iinumae, were only resolved for Fvb 4. The quantity of missing data and heterogeneity in genome coverage inherent in GBS complicated the analysis, but POLiMAPS resolved F. ×ananassa chromosomal regions derived from diploid ancestor F. vesca.


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