Allele Research Articles

NON-TOXIGENIC VIBRIO CHOLERAE O1 STRAINS CAUSED GASTROENTEROCOLITIS IN THE ZAPORIZHIA AND KHERSON REGIONS: CASE REPORTS AND PATHOGEN MOLECULAR GENETIC CHARACTERISTICS

In 2023-2024, two cases of gastroenterocolitis caused by non-toxigenic Vibrio cholerae O1 were documented in Zaporizhzhya and Kherson regions. Previously, diseases of this etiology had not been detected in Russia over the last 18 years, although CTX- strains were isolated from water bodies. Aim of the study: molecular genetic characterization of clinical V.cholerae O1 strains isolated in Russia and comparative bioinformatics analysis of their whole genome sequences (WGSs). Materials and methods. The strains were identified in accordance with MUK 4.2.3745-22, sequencing was performed on the MiSeq Illumina platform, bioinformatics analysis – using BioEdit, Vector NTI, CARD and author’s software. Results. A patient from Zaporizhzhya region fell ill after consumption of market foods, and from the Kherson region – after bathing in the sea. Both were diagnosed with acute gastroenterocolitis, in the second case rotavirus was detected along with vibrio. The isolated cultures with identical PCR genotypes were identified as non-toxigenic V. cholerae O1. The first pathogen belonged to Ogawa serotype, the second to Inaba. The WGSs of both strains lacked prophages CTX, preCTX, islands VPI and VSP-II, genes of heat-stable and cholix toxins, proteins OmpT and OmpU, but shared RTX and msh clusters, genes of hemolysin, metallo- and serine proteases; cytotonic factor Cef, represented in two pathogens by different alleles. Significant differences included the presence in the 2024 pathogen of VSP-I island, T3SS cluster integrated into VPI-3, ompW and β-lactamase varG genes which were absent in the 2023 one. The latter contained an incomplete VPI-2 and significantly altered genes rtxA, as well as genes encoding proteases VesC and VchC . On the dendrogram, the isolates formed 2 distant clusters, which also included environmental waterborne strains isolated in other Russian territories in different years; in each cluster all genes had the same repertoires of genetic determinants and gene alleles. These data evidence an opportunity for their long-term preservation in water reservoirs and the absence of importations from abroad. Conclusion. Two new clonal complexes of CTX- V. cholerae O1 have been identified in the territory of Russian Federation. Non-toxigenic strains usually do not cause large-scale epidemiological complications, and the diseases caused by representatives of each complex could be associated with compromised immunity of patients.

Association of Alzheimer's Disease Polygenic Risk Score with Concussion Severity and Recovery Metrics.

Identification of genetic alleles associated with both Alzheimer's disease (AD) and concussion severity/recovery could help explain the association between concussion and elevated dementia risk. However, there has been little investigation into whether AD risk genes associate with concussion severity/recovery, and the limited findings are mixed. We used AD polygenic risk scores (PRS) and APOE genotypes to investigate any such associations in the NCAA-DoD Grand Alliance CARE Consortium (CARE) dataset. We assessed six concussion outcomes in 931 participants, including two recovery measures (number of days to asymptomatic and to return to play (RTP)) and four severity measures (scores on SAC and BESS, SCAT symptom severity and total number of symptoms). We calculated thePRS using a published score and performed multiple linear regression to assess the relationship of thePRS with outcomes. We also used ANOVAs, t-tests, and chi-square tests to examine outcomes by APOE genotype. Higher PRS was associated with longer injury to RTP time in the normal RTP (< 24days) subgroup (p = 0.024). A one standard deviation increase in the PRS resulted in a 9.89hour increase to RTP time. This result was no longer significant after inclusion of covariates. There were no other consistently significant effects. Our findings suggest high AD genetic risk is not associated with more severe concussions or poor recovery in young adults. Future studies should attempt to replicate these findings in larger samples with longer follow-up using PRS calculated from diverse populations.

MOLECULAR EPIDEMIOLOGY OF ALPHA THALASSEMIA MUTATIONS IN DUHOK CITY, KURDISTAN REGION OF IRAQ: A 9-YEAR RETROSPECTIVE STUDY

ABSTRACT Background: Alpha thalassemia demonstrates high prevalence in Iraq, particularly among consanguineous Kurdish subgroups. However, data remains limited regarding the molecular epidemiology of causative alpha globin mutations in this population. This study aimed to elucidate the mutational spectrum and temporal distribution of alpha thalassemia alleles among native inhabitants of Duhok City in northern Iraq. Methods: In this retrospective cross-sectional study, positive alpha globin genetic testing records of 1,295 Duhok natives at a specialized northern Iraqi laboratory from 2014-2022 were analyzed to determine mutant genotype and allele frequencies. Results: The five most common mutant genotypes detected were -α3.7/-α3.7 (5.5%), -α3.7/αα (19.1%), -αMED/αα (3.2%), -α3.7/-αMED (2.6%) and ααIVS1-5nt/αα (1.5%). The -α3.7 deletion was predominant affecting 43.8% of alleles. A steady 9-year upward annual detection trajectory was observed. Conclusions: Population-specific molecular analysis may provide seminal evidence to shape thalassemia screening and prevention policies targeting the high-risk marginalized Kurdish community in northern Iraq.

Systematic assessment of COVID-19 host genetics using whole genome sequencing data.

Courses of SARS-CoV-2 infections are highly variable, ranging from asymptomatic to lethal COVID-19. Though research has shown that host genetic factors contribute to this variability, cohort-based joint analyses of variants from the entire allelic spectrum in individuals with confirmed SARS-CoV-2 infections are still lacking. Here, we present the results of whole genome sequencing in 1,220 mainly vaccine-naïve individuals with confirmed SARS-CoV-2 infection, including 827 hospitalized COVID-19 cases. We observed the presence of autosomal-recessive or likely compound heterozygous monogenic disorders in six individuals, all of which were hospitalized and significantly younger than the rest of the cohort. We did not observe any suggestive causal variants in or around the established risk gene TLR7. Burden testing in the largest population subgroup (i.e., Europeans) suggested nominal enrichments of rare variants in coding and non-coding regions of interferon immune response genes in the overall analysis and male subgroup. Case-control analyses of more common variants confirmed associations with previously reported risk loci, with the key locus at 3p21 reaching genome-wide significance. Polygenic scores accurately captured risk in an age-dependent manner. By enabling joint analyses of different types of variation across the entire frequency spectrum, this data will continue to contribute to the elucidation of COVID-19 etiology.

Stratified Medicine Paediatrics: Cell free DNA and serial tumour sequencing identifies subtype specific cancer evolution and epigenetic states.

We profiled a large heterogenous cohort of matched diagnostic-relapse tumour tissue and paired plasma-derived cell free DNA (cfDNA) from patients with relapsed and progressive solid tumours of childhood. Tissue and cfDNA sequencing results were concordant, with a wider spectrum of mutant alleles and higher degree of intra-tumour heterogeneity captured by the latter, if sufficient circulating tumour-derived DNA (ctDNA) was present. Serial tumour sequencing identified putative drivers of relapse, with alterations in epigenetic drivers being a common feature. In keeping with epigenetic alterations being a common driver of many childhood cancers, fragmentomics analysis of cfDNA identified tumour-specific epigenetic states and transcription factor binding sites accessible in chromatin. This study leverages a large and well-annotated genomic dataset of aggressive childhood malignancies, identifies genomic and epigenetic drivers of childhood cancer relapse, and highlights the power and practicality of cfDNA analysis to capture both intra-tumoural heterogeneity and the epigenetic state of cancer cells.

Abstract 4115690: COL4A1-related Vascular Disease Displays Strikingly Different Penetrance, Onset, and Expressivity in Literature versus Biobank-Derived Cases

Monogenic cardiovascular diseases present throughout the human lifespan with varying symptoms. For most, our understanding of their penetrance, onset, and expressivity is derived from published case reports. The extent to which these literature-derived cases capture the full allelic and phenotypic spectrum is unknown, particularly since the literature is biased towards severe presentations. To illustrate, we investigated the penetrance (i.e. the presence of at least one symptom), onset, and phenotypic expressivity of a rare genetic disease linked to hemorrhagic stroke and other complications: COL4A1 -related vascular disease (COL4A1VD, or Gould Syndrome). We performed a systematic review of COL4A1VD cases reported in the biomedical literature ( N =459), normalizing their genetic variants and symptoms to controlled terminologies. We then investigated the phenotypic expression among COL4A1VD pathogenic variant carriers isolated from two population-scale biobanks (the UK Biobank and All of Us Research Program; combined N =714,246), identifying 178 subjects (prevalence: 0.025%) that should be at high risk for COL4A1VD-related symptoms. Based on the literature, the penetrance of COL4A1VD is approximately 92% (95% CI: 90%-95%), with each case expressing 4.3 symptoms on average. Neurologic complications were the most common finding, observed in 85% of symptomatic patients. Alternatively, the biobank-derived cohort displayed an overall enrichment for disease-related symptoms (COL4A1 pathogenic carriers are more likely to have increased symptom burden compared to non-carrier controls; P&lt;0.005), but the penetrance of the variants was substantially reduced (34%; 95% CI: 26%-41%). In addition, this cohort expressed fewer symptoms on average (0.8 per carrier), with renal complications being far more common (78% of symptomatic biobank patients vs 22% of literature-derived cases; P &lt; 0.001). Finally, the apparent age-of-onset was much later for the biobank-derived cohort (57-years vs 5-years for the literature cases). Most of these differences reflect the distinct ascertainment of these two COL4A1VD cohorts, but they also highlight our incomplete understanding of the true penetrance, expressivity, and onset for this rare disease. These results have important implications for COL4A1VD-related genetic counseling and surveillance, and they highlight a need for new methods that formally integrate the rare disease knowledge captured from these distinct data sources.

Genome-wide association analysis reveals insights into the molecular etiology of dilated cardiomyopathy

Abstract Introduction Dilated cardiomyopathy (DCM) is a primary heart muscle disease characterized by ventricular dilatation and impaired contractility. While considered a Mendelian disorder, recent evidence highlights the important role of common genetic variation. Better characterization of the genetic architecture will provide opportunities for improved diagnosis, risk stratification and biological understanding. Methods We performed a GWAS meta-analysis of 14,256 DCM cases and 1,185,671 controls of European ancestry from 16 studies (GWASDCM). To improve discovery power, we performed multi-trait analysis of GWAS (GWASMTAG) with three genetically correlated and clinically relevant cardiac imaging traits in 36,203 individuals. To identify effector genes at loci, we used a two-step approach: 1) the nearest gene and top 3 genes prioritized by PoPS or V2G were selected as candidates; and 2) totality of evidence including 5 additional methods (coding variant, co-localization with expression, TWAS, ABC-model, and known Mendelian cardiomyopathy genes) was summarized in a single score. We performed rare variant burden analysis (MAF&amp;lt;0.1%) for predicted truncating variants (PTV) in established DCM-causing genes to highlight DCM genetic architecture, and in prioritized GWAS genes, against DCM and quantitative CMR traits in UK Biobank (UKB) and 100,000 Genomes Project (GeL), implemented by REGENIE. A polygenic score (PGS) generated using a Bayesian framework (PRS-CS) was assessed for association with the same outcomes in UKB participants, including among PTV carriers in established DCM-causing genes. Results We identified 80 independent loci, of which 65 were novel (62 loci in GWASDCM, and 54 loci in GWASMTAG) (Figure 1A). High-confidence genes were prioritized at 62 loci, including in genes with established roles in Mendelian cardiomyopathies (TTN, BAG3, FLNC, MYBPC3, FHOD3, ALPK3), and were enriched in key biological processes (Figure 1B). We characterized DCM genetic architecture across the allelic spectrum (Figure 2A). Rare variant burden analysis highlighted novel associations with DCM and quantitative traits for PTVs in NEDD4L and MAP3K7 in UKB that were replicated in GeL (Figure 2B). PGS was associated with DCM and quantitative CMR traits (OR per PGS SD 1.8, P&amp;lt;1x10-16) (Figure 2C). Individuals in the top centile had 4-fold increased risk of having DCM compared with median risk. PGS stratified penetrance of rare variants in 1,546 carriers of pathogenic variants (top quintile 7.3%, bottom quintile 1.7%, P 0.005). Conclusion We have performed the largest DCM GWAS, resulting in 80 significant loci (65 novel), and prioritized genes using a systematic approach. We identify novel DCM-causing genes (NEDD4L and MAP3K7) and generate a PGS that associates with DCM and modulates penetrance in carriers of Mendelian disease-causing rare variants.Figure 1Figure 2

Voltage-Gated Ion Channel Compensatory Effect in DEE: Implications for Future Therapies.

Developmental and Epileptic Encephalopathies (DEEs) represent a clinically and genetically heterogeneous group of rare and severe epilepsies. DEEs commonly begin early in infancy with frequent seizures of various types associated with intellectual disability and leading to a neurodevelopmental delay or regression. Disease-causing genomic variants have been identified in numerous genes and are implicated in over 100 types of DEEs. In this context, genes encoding voltage-gated ion channels (VGCs) play a significant role, and part of the large phenotypic variability observed in DEE patients carrying VGC mutations could be explained by the presence of genetic modifier alleles that can compensate for these mutations. This review will focus on the current knowledge of the compensatory effect of DEE-associated voltage-gated ion channels and their therapeutic implications in DEE. We will enter into detailed considerations regarding the sodium channels SCN1A, SCN2A, and SCN8A; the potassium channels KCNA1, KCNQ2, and KCNT1; and the calcium channels CACNA1A and CACNA1G.

Does the Colonizing Population Exhibit a Reduced Genetic Diversity and Allele Surfing? A Case Study of the Midday Gerbil (Meriones meridianus Pallas) Expanding Its Range.

Colonizing populations at the leading edge of range expansion are expected to have a reduced genetic diversity and strong genetic structure caused by genetic drift and allele surfing. Until now, few studies have found the genetic signatures of allele surfing in expanding wild populations. Using mtDNA markers, we studied the genetic structure of the population of midday gerbils (Meriones meridianus) expanding their range to the west in Kalmykia (southern Russia) following the new cycle of desertification, re-colonizing areas abandoned in the mid-2010s. In the colonizing population, we found a reduced genetic diversity, the redistribution of haplotype frequencies-in particular, in favor of variants rare in the core population-and strong genetic structure combined with strong differentiation from the core population-patterns suggestive of allele surfing on the wave of expansion. In terms of genetic diversity and spatial structuration, the western edge population sampled in 2008 before its collapse in 2017 occupies the intermediate position between the current colonizing and core population. This suggests that reduced genetic diversity and increased genetic differentiation are general features of marginal populations, enhanced by the founder and allele-surfing effects at the leading edges of expanding ranges.

The Definition of Individual Biological Fitness

“Fitness” is one of the central concepts in biology. Despite this, the concept is still not clearly defined. Previous attempts at definition refer to what should be called an individual’s “potential fitness,” or, when mathematized, the relative fitness of genetic alleles. In contrast, the present work defines the actual fitness of an individual, exactly what is referred to in the expression “survival of the fittest.” This represents a new conceptualization, a mathematical definition that will extend across the entire set of ideas related to evolution.

The Spectrum of Disease-Associated Alleles in Countries with a Predominantly Slavic Population.

There are more than 260 million people of Slavic descent worldwide, who reside mainly in Eastern Europe but also represent a noticeable share of the population in the USA and Canada. Slavic populations, particularly Eastern Slavs and some Western Slavs, demonstrate a surprisingly high degree of genetic homogeneity, and, consequently, remarkable contribution of recurrent alleles associated with hereditary diseases. Along with pan-European pathogenic variants with clearly elevated occurrence in Slavic people (e.g., ATP7B c.3207C>A and PAH c.1222C>T), there are at least 52 pan-Slavic germ-line mutations (e.g., NBN c.657_661del and BRCA1 c.5266dupC) as well as several disease-predisposing alleles characteristic of the particular Slavic communities (e.g., Polish SDHD c.33C>A and Russian ARSB c.1562G>A variants). From a clinical standpoint, Slavs have some features of a huge founder population, thus providing a unique opportunity for efficient genetic studies.

The Role of B Lymphocytes in Type 1 Diabetes.

While autoreactive T cells are known to induce β-cell death in type 1 diabetes (T1D), self-reactive B cells also play an important role in the pathogenesis of T1D. Studies have shown that individuals living with T1D have an increased frequency of self-reactive B cells that escape from the bone marrow and populate peripheral organs, become activated, and participate in disease. These failed tolerance mechanisms may be attributed to genetic risk alleles that are associated with the development of T1D. Once in the periphery, these self-reactive B cells act as important antigen-presenting cells to autoreactive T cells and produce autoantibodies that are used to predict individuals at risk for or diagnosed with T1D. Here, we discuss the evidence that B cells are important in the pathogenesis of T1D, how these cells escape normal tolerance mechanisms, their role in disease progression, and how targeting these cells and/or monitoring them as biomarkers for response to therapy will be of clinical benefit.

Genetic complexity of killer-cell immunoglobulin-like receptor genes in human pangenome assemblies.

The killer-cell immunoglobulin-like receptor (KIR) gene complex, a highly polymorphic region of the human genome that encodes proteins involved in immune responses, poses strong challenges in genotyping owing to its remarkable genetic diversity and structural intricacy. Accurate analysis of KIR alleles, including their structural variations, is crucial for understanding their roles in various immune responses. Leveraging the high-quality genome assemblies from the Human Pangenome Reference Consortium (HPRC), we present a novel bioinformatic tool, the structural KIR annoTator (SKIRT), to investigate gene diversity and facilitate precise KIR allele analysis. In 47 HPRC-phased assemblies, SKIRT identifies a recurrent novel KIR2DS4/3DL1 fusion gene in the paternal haplotype of HG02630 and maternal haplotype of NA19240. Additionally, SKIRT accurately identifies eight structural variants and 15 novel nonsynonymous alleles, all of which are independently validated using short-read data or quantitative polymerase chain reaction. Our study has discovered a total of 570 novel alleles, among which eight haplotypes harbor at least one KIR gene duplication, six haplotypes have lost at least one framework gene, and 75 out of 94 haplotypes (79.8%) carry at least five novel alleles, thus confirming KIR genetic diversity. These findings are pivotal in providing insights into KIR gene diversity and serve as a solid foundation for understanding the functional consequences of KIR structural variations. High-resolution genome assemblies offer unprecedented opportunities to explore polymorphic regions that are challenging to investigate using short-read sequencing methods. The SKIRT pipeline emerges as a highly efficient tool, enabling the comprehensive detection of the complete spectrum of KIR alleles within human genome assemblies.

Association of Alzheimer's disease polygenic risk score with concussion severity and recovery metrics.

Identification of genetic alleles associated with both Alzheimer's disease (AD) and concussion severity/recovery could help explain the association between concussion and elevated dementia risk. However, there has been little investigation into whether AD risk genes associate with concussion severity/recovery, and the limited findings are mixed. We used AD polygenic risk scores (PRS) and APOE genotypes to investigate any such associations in the NCAA-DoD Grand Alliance CARE Consortium (CARE) dataset. We assessed six outcomes in 931 total participants. The outcomes were two concussion recovery measures (number of days to asymptomatic status, number of days to return to play (RTP)) and four concussion severity measures (scores on SAC and BESS, SCAT symptom severity, and total number of symptoms). We calculated PRS using a published score [1] and performed multiple linear regression (MLR) to assess the relationship of PRS with the outcomes. We also used t-tests and chi-square tests to examine outcomes by APOE genotype, and MLR to analyze outcomes in European and African genetic ancestry subgroups. Higher PRS was associated with longer injury to RTP in the normal RTP (<24 days) subgroup ( p = 0.024), and one standard deviation increase in PRS resulted in a 9.89 hour increase to the RTP interval. There were no other consistently significant effects, suggesting that high AD genetic risk is not strongly associated with more severe concussions or poor recovery in young adults. Future studies should attempt to replicate these findings in larger samples with longer follow-up using PRS calculated from diverse populations.

CYP21A2 Intron 2 Genetic Variants Might Be Associated with the Clinical Characteristics of Women with PCOS.

Pathogenic variants in the CYP21A2 gene are related to the classic and non-classic forms of congenital adrenal hyperplasia (CAH). However, the role of CAH carrier status in the clinical presentation of polycystic ovarian syndrome (PCOS) is still unclear. Moreover, the possible associations of different CYP21A2 gene polymorphisms with metabolic and reproductive abnormalities in PCOS have not been investigated. Therefore, the present study aims to examine the prevalence of the most common CYP21A2 pathogenic variant IVS2-13A/C>G (c.293-13A/C>G) in Eastern European women with PCOS and to evaluate the associations between common intron 2 genetic polymorphisms and the clinical symptoms of the patients. Sixty consecutively recruited women with PCOS were genotyped for the CYP21A2 intron 2 IVS2-13A/C>G genetic variant. Additionally, CYP21A2 intron 2 polymorphic variants rs6453 (c.293-44G>T), rs6451 (c.293-67C>A/G), rs369651496 (c.293-104del), and rs6474 (c.308G>A/p.R103L) were tested and described. The clinical and hormonal characteristics were compared in women with PCOS and with polymorphic and wild-type genotypes. The heterozygous CYP21A2 pathogenic variant IVS2-13A/C>G was found in one of the investigated PCOS patients (1.67%) with a non-hyperandrogenic type of PCOS. The presence of the rs6453 (c.293-44G>T) T-allele was associated with increased levels of DHEAS (15.18 vs. 9.14 µmol/L, p = 0.003) compared to the wild-type genotype in the investigated group. The rs6451 (c.293-67C>A/G) minor alleles were associated with an earlier age of menarche in the patients (12.0 vs. 13.0 years, p = 0.007). The polymorphic rs369651496 minor 6G allele was related to a better lipid profile in the women with PCOS, while the rs6474 variant modulated the blood pressure of the patients. The presence of CYP21A2 genetic minor alleles of rs6467 (IVS2-13A/C, c.293-13A/C), rs6453 (c.293-44G>T), rs6451 (c.293-67C>A/G), rs369651496 (c.293-104del), and rs6474 (c.308G>A/p.R103L) might modulate the adrenal androgens, age of menarche, and metabolic features in women with PCOS. Further studies on 21-hydroxylase genetic variants (pathogenic and polymorphisms) in different ethnic groups might help reveal the influence of adrenal steroidogenesis on PCOS development, clinical manifestations, and lifelong cardiovascular risks.

Genetic bias in repeated evolution of pigment loss in cave populations of the Asellus aquaticus species complex.

Similar phenotypes can evolve repeatedly under the same evolutionary pressures. A compelling example is the evolution of pigment loss and eye loss in cave-dwelling animals. While specific genomic regions or genes associated with these phenotypes have been identified in model species, it remains uncertain whether a bias towards particular genetic mechanisms exists. An isopod crustacean, Asellus aquaticus, is an ideal model organism to investigate this phenomenon. It inhabits surface freshwaters throughout Europe but has colonized groundwater on multiple independent occasions and evolved several cave populations with distinct ecomorphology. Previous studies have demonstrated that three different cave populations utilized common genetic regions, potentially the same genes, in the evolution of pigment and eye loss. Expanding on this, we conducted analysis on two additional cave populations, distinct either phylogenetically or biogeographically from those previously examined. We generated F2 hybrids from cave × surface crosses and tested phenotype-genotype associations, as well as conducted complementation tests by crossing individuals from different cave populations. Our findings revealed that pigment loss and orange eye pigment in additional cave populations were associated with the same genomic regions as observed in the three previously tested cave populations. Moreover, the lack of complementation across all cross combinations suggests that the same gene likely drives pigment loss. These results substantiate a genetic bias in the recurrent evolution of pigment loss in this model system. Future investigations should focus on the cause behind this bias, possibly arising from allele recruitment from ancestral surface populations' genetic variation or advantageous allele effects via pleiotropy.

Analysis of the Effects of the Vrn-1 and Ppd-1 Alleles on Adaptive and Agronomic Traits in Common Wheat (Triticum aestivum L.).

Wheat heading time is primarily governed by two loci: VRN-1 (response to vernalization) and PPD-1 (response to photoperiod). Five sets of near-isogenic lines (NILs) were studied with the aim of investigating the effect of the aforementioned genes on wheat vegetative period duration and 14 yield-related traits. Every NIL was sown in the hydroponic greenhouse of the Institute of Cytology and Genetics, SB RAS. To assess their allelic composition at the VRN-1 and PPD-1 loci, molecular markers were used. It was shown that HT in plants with the Vrn-A1vrn-B1vrn-D1 genotype was reduced by 29 and 21 days (p < 0.001) in comparison to HT in plants with the vrn-A1Vrn-B1vrn-D1 and the vrn-A1vrn-B1Vrn-D1 genotypes, respectively. In our study, we noticed a decrease in spike length as well as spikelet number per spike parameter for some NIL carriers of the Vrn-A1a allele in comparison to carriers of the Vrn-B1 allele. PCA revealed three first principal components (PC), together explaining more than 70% of the data variance. Among the studied genetic traits, the Vrn-A1a and Ppd-D1a alleles showed significant correlations with PCs. Regarding genetic components, significant correlations were calculated between PC3 and Ppd-B1a (-0.26, p < 0.05) and Vrn-B1 (0.57, p < 0.05) alleles. Thus, the presence of the Vrn-A1a allele affects heading time, while Ppd-D1a is associated with plant height reduction.

Omics-driven utilization of wild relatives for empowering pre-breeding in pearl millet.

Pearl millet wild relatives harbour novel alleles which could be utilized to broaden genetic base of cultivated species. Genomics-informed pre-breeding is needed to speed up introgression from wild to cultivated gene pool in pearl millet. Rising episodes of intense biotic and abiotic stresses challenge pearl millet production globally. Wild relatives provide a wide spectrum of novel alleles which could address challenges posed by climate change. Pre-breeding holds potential to introgress novel diversity in genetically narrow cultivated Pennisetum glaucum from diverse gene pool. Practical utilization of gene pool diversity remained elusive due to genetic intricacies. Harnessing promising traits from wild pennisetum is limited by lack of information on underlying candidate genes/QTLs. Next-Generation Omics provide vast scope to speed up pre-breeding in pearl millet. Genomic resources generated out of draft genome sequence and improved genome assemblies can be employed to utilize gene bank accessions effectively. The article highlights genetic richness in pearl millet and its utilization with a focus on harnessing next-generation Omics to empower pre-breeding.

Association between executive functions and COMT Val108/158Met polymorphism among healthy younger and older adults: A preliminary study.

Genetic variability in the dopaminergic system could contribute to age-related impairments in executive control. In this study, we examined whether genetic polymorphism for catechol-O-methyltransferase (COMT Val158Met) is related to performance on updating, shifting and inhibition tasks. We administered a battery of executive tasks assessing updating, shifting and inhibition functions to 45 older and 55 younger healthy participants, and created composite z-scores associated to each function. Six groups were created based on genetic alleles (Val/Val, Val/Met, Met/Met) derived from the COMT gene and age (younger, older). Age and genotype effects were assessed with t-test and ANOVA (p<0.05). A lower performance was observed in the older group for the three executive processes, and more particularly for inhibition. Moreover, older participants homozygous for the Val allele have a lower performance on the inhibition composite in comparison to younger Val/Val. These results confirm presence of executive performance decrease in healthy aging. With regard to genetic effect, older participants seem particularly disadvantaged when they have a lower baseline dopamine level (i.e., Val/Val homozygous) that is magnified by aging, and when the executive measure emphasize the need of stable representations (as in inhibition task requiring to maintain active the instruction to not perform an automated process).

Evaluating possible maternal effect lethality and genetic background effects in Naa10 knockout mice.

Amino-terminal (Nt-) acetylation (NTA) is a common protein modification, affecting approximately 80% of all human proteins. The human essential X-linked gene, NAA10, encodes for the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex. There is extensive genetic variation in humans with missense, splice-site, and C-terminal frameshift variants in NAA10. In mice, Naa10 is not an essential gene, as there exists a paralogous gene, Naa12, that substantially rescues Naa10 knockout mice from embryonic lethality, whereas double knockouts (Naa10-/Y Naa12-/-) are embryonic lethal. However, the phenotypic variability in the mice is nonetheless quite extensive, including piebaldism, skeletal defects, small size, hydrocephaly, hydronephrosis, and neonatal lethality. Here we replicate these phenotypes with new genetic alleles in mice, but we demonstrate their modulation by genetic background and environmental effects. We cannot replicate a prior report of "maternal effect lethality" for heterozygous Naa10-/X female mice, but we do observe a small amount of embryonic lethality in the Naa10-/y male mice on the inbred genetic background in this different animal facility.