single nucleotide polymorphism
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Chronic wasting disease (CWD) is a deleterious brain proteinopathy caused by a pathogenic form of prion protein (PrPSc), which is converted from a benign form of prion protein (PrPC) encoded by the prion protein gene (PRNP). In elk, the M132L single nucleotide polymorphism (SNP) of the PRNP gene likely plays a pivotal role in susceptibility to CWD. However, the association of the M132L SNP with susceptibility to CWD has not been evaluated in Korean elk to date. To estimate the association of the M132L SNP with susceptibility to CWD in Korean elk, we investigated the genotype and allele frequencies of the M132L SNP by amplicon sequencing and performed association analysis between CWD-positive and CWD-negative elk. In addition, we performed a meta-analysis to evaluate the association between the M132L SNP and susceptibility to CWD in quantitatively synthesized elk populations. Furthermore, we estimated the effect of the M132L SNP on elk PrP using in silico programs, including PolyPhen-2, PROVEAN, AMYCO and Swiss-PdbViewer. We did not identify a significant association between the M132L SNP of PRNP and susceptibility to CWD in Korean elk. The meta-analysis also did not identify a strong association between the M132L SNP of PRNP and susceptibility to CWD in quantitatively synthesized elk populations. Furthermore, we did not observe significant changes in structure, amyloid propensity or electrostatic potential based on the M132L SNP in elk PrP. To the best of our knowledge, this was the first report of an association analysis and meta-analysis in Korean elk and quantitatively synthesized elk populations, respectively.

ABSTRACT Single-nucleotide polymorphism (SNPs) may cause the diverse functional impact on RNA or protein changing genotype and phenotype, which may lead to common or complex diseases like cancers. Accurate prediction of the functional impact of SNPs is crucial to discover the ‘influential’ (deleterious, pathogenic, disease-causing, and predisposing) variants from massive background polymorphisms in the human genome. Increasing computational methods have been developed to predict the functional impact of variants. However, predictive performances of these computational methods on massive genomic variants are still unclear. In this regard, we systematically evaluated 14 important computational methods including specific methods for one type of variant and general methods for multiple types of variants from several aspects; none of these methods achieved excellent (AUC ≥ 0.9) performance in both data sets. CADD and REVEL achieved excellent performance on multiple types of variants and missense variants, respectively. This comparison aims to assist researchers and clinicians to select appropriate methods or develop better predictive methods.

Abstract Background T and B cell receptor (TCR, BCR) repertoires constitute the foundation of adaptive immunity. Adaptive immune receptor repertoire sequencing (AIRR-seq) is a common approach to study immune system dynamics. Understanding the genetic factors influencing the composition and dynamics of these repertoires is of major scientific and clinical importance. The chromosomal loci encoding for the variable regions of TCRs and BCRs are challenging to decipher due to repetitive elements and undocumented structural variants. Methods To confront this challenge, AIRR-seq-based methods have recently been developed for B cells, enabling genotype and haplotype inference and discovery of undocumented alleles. However, this approach relies on complete coverage of the receptors’ variable regions, whereas most T cell studies sequence a small fraction of that region. Here, we adapted a B cell pipeline for undocumented alleles, genotype, and haplotype inference for full and partial AIRR-seq TCR data sets. The pipeline also deals with gene assignment ambiguities, which is especially important in the analysis of data sets of partial sequences. Results From the full and partial AIRR-seq TCR data sets, we identified 39 undocumented polymorphisms in T cell receptor Beta V (TRBV) and 31 undocumented 5 ′ UTR sequences. A subset of these inferences was also observed using independent genomic approaches. We found that a single nucleotide polymorphism differentiating between the two documented T cell receptor Beta D2 (TRBD2) alleles is strongly associated with dramatic changes in the expressed repertoire. Conclusions We reveal a rich picture of germline variability and demonstrate how a single nucleotide polymorphism dramatically affects the composition of the whole repertoire. Our findings provide a basis for annotation of TCR repertoires for future basic and clinical studies.

Ethiopia is the center of origin for sorghum [Sorghum bicolor (L.) Moench], where the distinct agro-ecological zones significantly contributed to the genetic diversity of the crops. A large number of sorghum landrace accessions have been conserved ex situ. Molecular characterization of this diverse germplasm can contribute to its efficient conservation and utilization in the breeding programs. This study aimed to investigate the genetic diversity of Ethiopian sorghum using gene-based single nucleotide polymorphism (SNP) markers. In total, 359 individuals representing 24 landrace accessions were genotyped using 3,001 SNP markers. The SNP markers had moderately high polymorphism information content (PIC = 0.24) and gene diversity (H = 0.29), on average. This study revealed 48 SNP loci that were significantly deviated from Hardy–Weinberg equilibrium with excess heterozygosity and 13 loci presumed to be under selection (P < 0.01). The analysis of molecular variance (AMOVA) determined that 35.5% of the total variation occurred within and 64.5% among the accessions. Similarly, significant differentiations were observed among geographic regions and peduncle shape-based groups. In the latter case, accessions with bent peduncles had higher genetic variation than those with erect peduncles. More alleles that are private were found in the eastern region than in the other regions of the country, suggesting a good in situ conservation status in the east. Cluster, principal coordinates (PCoA), and STRUCTURE analyses revealed distinct accession clusters. Hence, crossbreeding genotypes from different clusters and evaluating their progenies for desirable traits is advantageous. The exceptionally high heterozygosity observed in accession SB4 and SB21 from the western geographic region is an intriguing finding of this study, which merits further investigation.

Abstract Background To investigate whether the mitochondrial transcription factor A (TFAM) rs1937 single nucleotide polymorphism (SNP) is associated with longevity. Methods We conducted a case-control study among Chinese long-lived individuals (≥90 years). Data were obtained on 3294 participants who were able to voluntarily provided a saliva sample during 2008–2009 from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). In this study, 1387 young elderly (65–74 years) were allocated to the control group, and 1907 long-lived individuals were recruited as the case group. SNP rs1937 on TFAM were genotyped. Logistic regression models were applied to evaluate the association between rs1937 SNP and longevity. Results The genotype frequency of the SNP of rs1937 in the two groups had a significant difference (p = 0.003). Binary logistic regression analysis showed that compared to younger elderly, the long-lived individuals with “CC genotype” of rs1937 were more closely related to increased longevity than those with “GG genotype” (OR: 1.989, 95% CI: 1.160–3.411). The positive association between rs1937 SNP and longevity was robust in stratified analyses and sensitivity analyses. Conclusions We found the SNP of rs1937 may be a potential biomarker for longer human life span. Further studies are necessary to elucidate the biological mechanism of rs1937 on TFAM with promoting longevity.

Background: Molecular markers based approaches are essential to select fertile bulls for frozen semen production at an early age. The present investigation was undertaken to perform the molecular characterization and identify single nucleotide polymorphisms (SNP) in Y-chromosome specific DDX3Y gene in Murrah buffalo bulls. Methods: The genomic DNA isolated from the blood samples of 70 Murrah buffalo bulls, covering bulls with normal seminal traits and poor production performance (poor semen quality, freezability, libido), were subjected to PCR amplification. The sequences of DDX3Y gene were analyzed for single nucleotide polymorphism using the seqman module of DNASTAR LASERGENE software. The single nucleotide variations in the sequences with reference to the Bos taurus sequence were determined using Clustal W. The phylogenetic tree and genetic distance were constructed using the MegAlign module. Result: The analysis of sequences revealed that the exons and their adjacent intronic regions of the DDX3Y gene are monomorphic in nature without any variations indicating that the sequences are highly conserved in the studied population of Murrah buffalo bulls. However, a considerable number of single nucleotide variations were observed in the sequences of Murrah buffalo compared with Bos taurus sequences. Furthermore, the phylogenetic tree analysis revealed less divergence and close genetic association between the sequences of Murrah buffalo and other species in the bovinae family than the caprinea species. Further studies on DDX3Y gene in a more extensive and diverse population of Murrah buffalo bulls distributed in different regions could aid to discover substantial SNPs.