SNP associated genomics

Recent advances in the study of alcoholism have thrown
light on the involvement of various neurotransmitters in the
phenomenon of alcohol addiction. Various neurotransmitters
have been implicated in alcohol addiction due to their
imbalance in the brain, which could be either due to their
excess activity or inhibition. This review paper aims to
consolidate and to summarize some of the recent papers
which have been published in this regard. The review
paper will give an overview of the neurobiology of alcohol
addiction, followed by detailed reviews of some of the recent
papers published in the context of the genetics of alcohol
addiction. Furthermore, the author hopes that the present
text will be found useful to novices and experts alike in the
field of neurotransmitters in alcoholism.

Human settlement and migrations along sides of Bay-of-Bengal have played a vital role in shaping the genetic landscape of
Bangladesh, Eastern India and Southeast Asia. Bangladesh and Northeast India form the vital land bridge between the South
and Southeast Asia. To reconstruct the population history of this region and to see whether this diverse region
geographically acted as a corridor or barrier for human interaction between South Asia and Southeast Asia, we, for the first
time analyzed high resolution uniparental (mtDNA and Y chromosome) and biparental autosomal genetic markers among
aboriginal Bangladesh tribes currently speaking Tibeto-Burman language. All the three studied populations; Chakma,
Marma and Tripura from Bangladesh showed strikingly high homogeneity among themselves and strong affinities to
Northeast Indian Tibeto-Burman groups. However, they show substantially higher molecular diversity than Northeast Indian
populations. Unlike Austroasiatic (Munda) speakers of India, we observed equal role of both males and females in shaping
the Tibeto-Burman expansion in Southern Asia. Moreover, it is noteworthy that in admixture proportion, TB populations of
Bangladesh carry substantially higher mainland Indian ancestry component than Northeast Indian Tibeto-Burmans. Largely
similar expansion ages of two major paternal haplogroups (O2a and O3a3c), suggested that they arose before the
differentiation of any language group and approximately at the same time. Contrary to the scenario proposed for
colonization of Northeast India as male founder effect that occurred within the past 4,000 years, we suggest a significantly
deep colonization of this region. Overall, our extensive analysis revealed that the population history of South Asian Tibeto-
Burman speakers is more complex than it was suggested before.

Identification of single nucleotide polymorphisms (SNPs) for specific genes involved in reproduction might improve reliability of genomic estimates for these low-heritability traits. Semen from 550 Holstein bulls of high (≥ 1.7; n = 288) or low (≤ −2; n = 262) daughter pregnancy rate (DPR) was genotyped for 434 candidate SNPs using the Sequenom MassARRAY® system. Three types of SNPs were evaluated: SNPs previously reported to be associated with reproductive traits or physically close to genetic markers for reproduction, SNPs in genes that are well known to be involved in reproductive processes, and SNPs in genes that are differentially expressed between physiological conditions in a variety of tissues associated in reproductive function. Eleven reproduction and production traits were analyzed.

Proteogenomics provide opportunities for proteomic validation of gene structures, genomic alterations and functional relevance of novel findings obtained from genomic data analysis. However, for effective proteogenomic data integration, an extensive proteome profiling, approaching the gene coverage of genomics data, is critical. Here we developed a multi-stage database search method for comprehensive proteomics data analysis to complement whole transcriptome sequencing data. The method utilizes two complementary database search engines, MS-GF+ and MODa/MODi, in tandem. The MS/MS data were first subjected to MS-GF+ database search (1st stage search) and the unidentified MS/MS data from the 1st stage search were subsequently analyzed with the combined use of MODa and MODi (2nd stage search), tools for blind and unrestrictive modification search, respectively. When combined with mPE-MMR, a tool for accurate and extensive precursor masses assignments to MS/MS data, the multi-stage method exhibited a significant increase in identified peptides, modified peptides, mutated peptides, identified proteins and coding genes, compared to a conventional single-stage method. With the increased coverage of proteome profile, the genomics and proteomics data obtained from the same gastric tumor tissue were effectively integrated as evidenced by proBAMsuite analysis results, which showed abundant examples of peptides uniquely mapped to genomic locations as well as increased coverages of exon-exon junctions and coding regions with the multi-stage search method.

To characterize the genetic basis of facial features in Latin Americans, we performed a genome-wide association study (GWAS) of more than 6000 individuals using 59 landmark-based measurements from two-dimensional profile photographs and ~9,000,000 genotyped or imputed single-nucleotide polymorphisms. We detected significant association of 32 traits with at least 1 (and up to 6) of 32 different genomic regions, more than doubling the number of robustly associated face morphology loci reported until now (from 11 to 23). These GWAS hits are strongly enriched in regulatory sequences active specifically during craniofacial development. The associated region in 1p12 includes a tract of archaic adaptive introgression, with a Denisovan haplotype common in Native Americans affecting particularly lip thickness. Among the nine previously unidentified face morphology loci we identified is the VPS13B gene region, and we show that variants in this region also affect midfacial morphology in mice.

닭을 포함하여 많은 동 물 들의 모집 단 구조를 결정
하는 데 있어서 연관 불 균 형은 매우 중요하다. 본 연
구는 상업용 닭, 한국 개 량 토종닭 등 한국에서 사
육 되는 14개의 닭 품종에 대한 연관 불 균 형의 확 인
한 결과이다. 본 연구를 위하여 187 마 리의 DNA
샘플 들이 고 밀 도 600K SNP chip을 이용하여
genotyping되었다. 그 결과 LD(linkage
disequilibrium)의 100 kb 지점 길 이가 0.20에서
0.55로 측 정되었다. 집 단간 LD 값 의 차이는 유전적
변 동이나 집 단구조를 바꾸 는 집 단에서 나타나는 선
발 강 도의 증거가 되기 때문 에 작 은 규 모 의 집 단을
가 진 한국 개 량 토종닭은 LD 값 이 높게 나타내어지
는 데 이러한 점에서, 이 집 단은 작 은 규 모 집 단에
의한 높은 육 종가를 갖 게 될 것으로 예측 할 수 있
다.

Life-history theory assumes that animal life histories are a consequence of trade-offs between current activities and future reproductive performance or survival, because resource supply is limited. Empirical evidence for such trade-offs in the wild are common, yet investigations of the underlying mechanisms are rare. Life-history trade-offs may have both physiological and ecological mediated costs. One hypothesized physiological mechanism is that elevated energy metabolism may increase reactive oxygen species production, leading to somatic damage and thus compromising future survival. We investigated the impact of experimentally elevated energy expenditure on oxidative damage, protection and lifespan in short-tailed field voles (Microtus agrestis) maintained in captivity to remove any confounding ecological factor effects. Energy expenditure was elevated via lifelong cold exposure (7G28C), relative to siblings in the warm (22G28C). No treatment effect on cumulative mortality risk was observed, with negligible effects on oxidative stress and antioxidant protection. These data suggest that in captive animals physiologically mediated costs on life history do not result from increased energy expenditure and consequent elevations in oxidative stress and reduced survival.

The IGF1 gene (insulin-like growth factor 1) is a candidate gene for marker-assisted selection strategies. A single nucleotide polymorphism in the promoter region (IGF1/SnaBI) has been reported to be associated with production traits in several cattle breeds. Here, we report its allelic frequencies in Charolais and Beefmaster breeds; we confirm its association with three growth traits: weaning weight, weaning weight adjusted to 210 days and preweaning weight gain in the Charolais breed. In addition, we designed a strategy to search these breeds for new polymorphisms in four coding regions of the gene. A C/A transversion was detected in intron 4, but it was not associated with the growth traits. A single nucleotide polymorphism (IGF1/SnaBI) is proposed as a selection marker for Mexican Charolais cattle; validation of its association with weaning weight, weaning weight adjusted to 210 days and preweaning weight gain, could complement the genetic evaluations of this breed through marker-assisted management strategies.

Summary Single nucleotide polymorphisms (SNPs) are the most abundant type of molecular genetic marker and can be used for producing high-resolution genetic maps, marker-trait association studies and marker-assisted breeding. Large polyploid genomes such as wheat present a challenge for SNP discovery because of the potential presence of multiple homoeologs for each gene. AutoSNPdb has been successfully applied to identify SNPs from Sanger sequence data for several species, including barley, rice and Brassica, but the ...

С 2013 г. компанией FTDNA была введена новая коммерческая услуга Big-Y, которая позволила более глубоко исследовать результаты ДНК-тестирования Y-хромосомы, вплоть до выявления приватных и терминальных снипов, характерных различным субкладам и подветвям гаплогрупп.

Исследование на Big-Y было проведено и представителями сако-динлинской подветви (СДП), которые по классификации этногеномико-исторического проекта (ЭИП) «Суюн» относятся вместе с массагето-аланской (МАП) и усуньской (УП) подветвями к туранским[1] линиям группы Z2123.

Abstract Proteogenomics provide opportunities for proteomic validation of gene structures, genomic alterations and functional relevance of novel findings obtained from genomic data analysis. However, for effective proteogenomic data integration, an extensive proteome profiling, approaching the gene coverage of genomics data, is critical. Here we developed a multi-stage database search method for comprehensive proteomics data analysis to complement whole transcriptome sequencing data. The method utilizes two complementary database search engines, MS-GF+ and MODa/MODi, in tandem. The MS/MS data were first subjected to MS-GF+ database search (1st stage search) and the unidentified MS/MS data from the 1st stage search were subsequently analyzed with the combined use of MODa and MODi (2nd stage search), tools for blind and unrestrictive modification search, respectively. When combined with m PE-MMR, a tool for accurate and extensive precursor masses assignments to MS/MS data, the multi-stage method exhibited a significant increase in identified peptides, modified peptides, mutated peptides, identified proteins and coding genes, compared to a conventional single-stage method. With the increased coverage of proteome profile, the genomics and proteomics data obtained from the same gastric tumor tissue were effectively integrated as evidenced by proBAMsuite analysis results, which showed abundant examples of peptides uniquely mapped to genomic locations as well as increased coverages of exon-exon junctions and coding regions with the multi-stage search method.

Previous studies have shown that genetic variants of the CLOCK gene have been associated with a risk of obesity. The aim of the study was to investigate the relationship of CLOCK SNPs o hypertension and coronary artery disease in Russian population. We genotyped 1139 individuals of Russian ethnicity including healthy subjects, patients with hypertension and patients with coronary artery disease. In addition, we studied effect of SNPs on the structure of the CLOCK mRNA using computational models. Blood pressure, total cholesterol (TC), triglycerides (TG), high-and low-density lipoprotein levels (mg/dl), glucose (mg/dl) and body mass index (BMI, kg/m2) were analyzed. There was no association between polymorphism in the BMAL1 gene with diseases given. Computational mRNA structure analysis has revealed changes in promoter and G2121A sites. Genetic variants of the CLOCK gene rs1801260, rs34789226, rs4865010 were positively associated with essential hypertension and coronary artery disease  in the sample of Russian population.

Genome-wide patterns of variation across individuals provide most powerful source of data for uncovering the history of migration, expansion, and adaptation of the human population. The arrival of new technologies that type more than millions of the single nucleotide polymorphisms (SNPs) in a single experiment has made SNP in genome-wide association (GWA) assay a prudent venture. SNPs represent the most widespread type of sequence variation in genomes, and known as valuable genetic markers for revealing the evolutionary history and common genetic polymorphisms that explain the heritable risk for common diseases. Characterizing the nature of gene variation in human populations and assembling an extensive catalog of SNPs in candidate genes in association with particular diseases are the major goals of human genetics. In this article we explore the recent discovery of SNP–GWA to revolutionize not only the process of genetic variation and disease detection but also the convention of preventative and curative medicine for future prospects.

Single nucleotide polymorphisms (SNPs) are the most abundant type of molecular genetic marker and can be used for producing high-resolution genetic maps, marker-trait association studies and marker-assisted breeding. Large polyploid genomes such as wheat present a challenge for SNP discovery because of the potential presence of multiple homoeologs for each gene. AutoSNPdb has been successfully applied to identify SNPs from Sanger sequence data for several species, including barley, rice and Brassica, but the volume of data required to accurately call SNPs in the complex genome of wheat has prevented its application to this important crop. DNA sequencing technology has been revolutionized by the introduction of next-generation sequencing, and it is now possible to generate several million sequence reads in a timely and cost-effective manner. We have produced wheat transcriptome sequence data using 454 sequencing technology and applied this for SNP discovery using a modified autoSNPdb...

Unravelling the molecular mechanisms underlying gastric carcinogenesis is one of the major challenges in cancer genomics. Gastric cancer is a very complex and heterogeneous disease, and although much has been learned about the different genetic changes that eventually lead to its development, the detailed mechanisms still remain unclear. Malignant transformation of gastric cells is the consequence of a multistep process involving different genetic and epigenetic changes in numerous genes in combination with host genetic background and environmental factors. The majority of gastric adenocarcinomas are characterized by genetic instability, either microsatellite instability (MSI) or chromosomal instability (CIN). It is believed that chromosome destabilizations occur early in tumour progression. This review summarizes the most common genetic alterations leading to instability in sporadic gastric cancers and its consequences.

In order to increase the efficiency of cacao tree resistance to witches' broom disease, which is caused by Moniliophthora perniciosa (Tricholomataceae), we looked for molecular markers that could help in the selection of resistant cacao genotypes. Among the different markers useful for developing marker-assisted selection, single nucleotide polymorphisms (SNPs) constitute the most common type of sequence difference between alleles and can be easily detected by in silico analysis from expressed sequence tag libraries. We report the first detection and analysis of SNPs from cacao-M. perniciosa interaction expressed sequence tags, using bioinformatics. Selection based on analysis of these SNPs should be useful for developing cacao varieties resistant to this devastating disease.

SNPs are known to be the most abundant source of sequence variation in the human
genome. The SNPs in the NRY (non-recombining Y-chromosome) region which passes from father to son as
unchanged haplotype-blocks escaping recombination, provides important advantages in the investigations of
sexual assault crimes, in the cases of parentage testing especially if the mother or alleged father is unavailable
for testing and in the evolutionary studies. The aim of this study, was to determine the frequencies of Y SNP
markers and the haplogroups, in order to define the Y-chromosome SNP markers which are polymorphic, have
high discrimination power and can be used in forensic investigations in the Antalya population. For each of 75
unrelated males from Antalya, 35 different Y-SNP markers were amplified in a single reaction using multiplex
minisequencing method. In the study, 18 markers of them were found to be polymorphic. The most frequent YSNP
markers with mutations were M139 (100%), SRY10831/SRY1532 (92%), M89 (85.3%), M213 (85.3%), M9
(44%), 92R7 (30.6%), 12F2 (30.6%), M45 (29.3%), M172 (26.6%) and M173 (22.6%). The Y-chromosome
haplogroups of Antalya population were defined by these 18 Y-SNP polymorphic loci and the frequencies and
the distribution of haplogroups were determined. J2*(xJ2F2) (26.6%), K*(xN3,O,P) (13.3%), E3b (9.3%),
F*(xH,I,J,K) (8%), R1a1*(xR1a1b) (8%), R1b*(xR1b1, R1b6, R1b8) (8%), P*(xQ3a,R1) (8%) haplogroups
were identified as the most abundant in Antalya population. These haplogroups are reported as widespread also
in European and neighboring Near Eastern populations.

To analyse the association of high sensitivity C-reactive (hsCRP) protein levels and -717A/G single nucleotide polymorphism of CRP with acute myocardial infarction (AMI) in the Indian population. Study population included 100 MI cases wherein 32 patients had experienced previous MI (MI-Group-1), 68 MI cases were recruited at presentation (MI-Group-2) and equal number of age and gender matched healthy individuals. hsCRP levels were determined by ELISA and genotyping of -717A/G was carried out by polymerase chain reactionbased restriction digestion method. The -717A/G genotypes did not influence hsCRP level and their distribution did not differ between groups. However, in the present study hsCRP demonstrated significant correlation with BMI in controls of both the genders and with triglycerides in females of AMI at presentation who otherwise are with low risk profile. Identifying traditional risk factors associated with inflammation may help in controlling the acute event.

A high level of inbreeding has deleterious effects on animal productive and reproductive traits. The effect of inbreeding by CAPN316, CAST282, GH L127V, GHR F279Y, GHR A257G, and CYP3A28 C994G markers on reproductive characteristics, weight dynamics (0-5 years of age), and exterior traits were studied. The genealogical analysis showed that the population includes seven lines of cattle. For the SNP genotyping, PCR-RFLP methods were set up. Testing deviation from the Hardy-Weinberg equilibrium was performed using Pearson's chi-squared test. The estimation of inbreeding depression by Fst coefficients of SNPs for traits studied was performed via multiple regression models with forward stepwise. The tested population was analyzed in Hardy-Weinberg equilibrium for all SNPs, except GHR F279Y. The cattle lines Bryalhil Sau and Southome Extra were considered the best lines as they showed the lowest level of heterozygosity. A negative effect of inbreeding level for different markers was seen for regression coefficients: calf birth weight =-1.08±0.30 (GHR F279Y), body weight at 8 months =-0.71±0.11 (CAPN316),-0.49±0.11 (GHR F279Y), and 15 months =-0.54±0.04 (CAST282),-0.36±0.06 (GHR F279Y). Increased inbreeding had a positive influence on regression coefficients for calf average daily gain = 0.86±0.26 (GH L127V), weight at 8 and 15 months = 1.43±0.13, 1.05±0.05 (GHR A257G), and exterior traits-shoulder, back and low back, rump, and hindquarter = 1.09±0.11, 0.77±0.22, and 1.10±0.30 (CYP3A28 C994G), respectively.

Plant breeding leads to the genetic improvement of target traits by selecting a small number of genotypes from among typically large numbers of candidate genotypes after careful evaluation. In this study, we first investigated how mutations at conserved nucleotide sites normally viewed as deleterious, such as nonsynonymous sites, accumulated in a wheat, Triticum aestivum, breeding lineage. By comparing a 150 year old ancestral and modern cultivar, we found recent nucleotide polymorphisms altered amino acids and occurred within conserved genes at frequencies expected in the absence of purifying selection. Mutations that are deleterious in other contexts likely had very small or no effects on target traits within the breeding lineage. Second, we investigated if breeders selected alleles with favorable effects on some traits and unfavorable effects on others and used different alleles to compensate for the latter. An analysis of a segregating population derived from the ancestral and modern parents provided one example of this phenomenon. The recent cultivar contains the Rht-B1b green revolution semi-dwarfing allele and compensatory alleles that reduce its negative effects. However, improvements in traits other than plant height were due to pleiotropic loci with favorable effects on traits and to favorable loci with no detectable pleiotropic effects. Wheat breeding appears to tolerate mutations at conserved nucleotide sites and to only select for alleles with both favorable and unfavorable effects on traits in exceptional situations.

Objectives Pharmacogenetic testing is projected to
improve health outcomes and reduce the cost of care by
increasing therapeutic efficacy and minimizing drug toxicity.
American Indian and Alaska Native (AI/AN) people
historically have been excluded from pharmacogenetic
research and its potential benefits, a deficiency we sought
to address. The vitamin K antagonist warfarin is prescribed
for prevention of thromboembolic events, although its
narrow therapeutic index and wide interindividual variability
necessitate close monitoring of drug response. Therefore,
we were interested in variation in CYP2C9, VKORC1,
CYP4F2, CYP4F11, and GGCX, which encode enzymes
important for the activity of warfarin and synthesis of
vitamin K-dependent blood clotting factors.

Background: Eosinophilic infiltration and peripheral blood eosinophilia in asthma require the cooperation of eosinophilspecific cytokines and chemokines and their receptors. Objective: We investigated the association of polymorphisms in CCR3 and IL5RA with asthma susceptibility or peripheral blood eosinophilia and the effects of the polymorphisms on receptor expression. Methods: Polymorphisms in CCR3 and IL5RA were identified and genotyped in 576 asthmatic patients and 180 healthy control subjects. CCR3 and IL-5 receptor a (IL-5Ra) protein expression on eosinophils was measured by means of flow cytometry. Results: Although polymorphisms in CCR3 were not associated with asthma susceptibility, the CCR3 haplotype ht2 showed a negative gene dose effect on the eosinophil count (P 5 .003-.009). IL5RA c.25091G>A was weakly associated with eosinophil count. The effects of ht2 were greater when paired with IL5RA c.25091A (P 5 .001-.002). CCR3 protein expression was higher on eosinophils of asthmatic patients without ht2 than in those with ht2. Asthmatic patients with the IL5RA c.25091A allele showed higher IL-5Ra expression than those who were homozygous for the G allele. Conclusion: The genetic association between CCR3 polymorphisms and the number of circulating eosinophils was revealed as a novel finding. These associations were more pronounced when the CCR3 polymorphisms were paired with polymorphisms in IL5RA. The protein expression levels of CCR3 and IL-5Ra on peripheral blood eosinophils are associated with the polymorphisms on their own genes.

The development of an assay for the detection of gene mutations has been attempted based on surface-enhanced Raman scattering (SERS). Using multiplexing property and high sensitivity of SERS technique, the detection of all mutation possibilities on one given spot is achievable. To test the feasibility of approach, SNPs and other types of mutations such as insertion and deletion are investigated. The PCR amplified and isolated genomic DNA without PCR amplification is immobilized on poly-L/D-lysine coated glass surface after denaturing with heating. The SERS probes are prepared by simultaneous attachment of oligonucleotides complementary to the target mutation regions and Raman active dyes to 13 nm gold nanoparticles (GNPs). After the hybridization of SERS probes on the poly-L/D-lysine surfaces, it was stained with silver colloidal nanoparticles for further enhancement of Raman scattering. In the second approach, Raman active dyes are chemically attached on gold nanoparticles and a thin layer of silver film is deposited on top of it to prepare core-shell nanoparticles. The complementary oligonucleotides to the target regions of the gene are chemically attached to silver surfaces of the nanoparticles. The promising results indicate that it is possible to detect certain mutation types without PCR amplification using the approach.

Nutrigenomics is the science of analyzing and understanding gene–nutrient interactions, which because of the genetic heterogeneity, varying degrees of interaction among gene products, and the environmental diversity is a complex science. Although much knowledge of human diversity has been accumulated, estimates suggest that ~90% of genetic variation has not yet been characterized. Identification of the DNA sequence variants that contribute to nutrition-related disease risk is essential for developing a better understanding of the complex causes of disease in humans, including nutrition-related disease. The Human Variome Project (HVP; http://www.humanvariomeproject.org/) is an international effort to systematically identify genes, their mutations, and their variants associated with phenotypic variability and indications of human disease or phenotype. Since nutrigenomic research uses genetic information in the design and analysis of experiments, the HVP is an essential collaborator for ongoing studies of gene–nutrient interactions. With the advent of next generation sequencing methodologies and the understanding of the undiscovered variation in human genomes, the nutrigenomic community will be generating novel sequence data and results. The guidelines and practices of the HVP can guide and harmonize these efforts.

Background: The first case of the novel coronavirus disease-2019 (COVID-19) in West Africa was first confirmed in Nigeria in February 2020. Since then, several public health interventions and preventive measures have been implemented to curtail transmission of the causative agent, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Therefore, this study was performed to assess the knowledge, attitudes, and perceptions of West Africans towards COVID-19. Methods: An online survey was conducted between 29 September to 29 October 2020 among West Africans. Thirtythree survey questions were designed to collect sociodemographic data and participants' knowledge, attitude and perception towards COVID-19. The study targeted all West African nationals who were 18 years and above, and willing to participate in the study. Participants were either in-country or abroad. Results: Overall, 1106 respondents (≥18 years) from 16 West African countries, with about 12.1% of them residing outside the West African subregion, participated in the survey. The respondents had an average COVID-19 knowledge score of 67.82 ± 8.31, with knowledge of the disease significantly associated with the country of residence (p = 0.00) and marginally (p = 0.05) so with settlement types (i.e., urban, suburban and rural areas). Most respondents (93.4%) could identify the main COVID-19 symptoms, and 73.20% would consult a healthcare professional if infected with SARS-CoV-2. Also, 75.2% of the respondents are willing to receive the COVID-19 vaccine, whereas 10.40% and 14.40% are unwilling and undecided, respectively. Perceptions of what constitute COVID-19 preventive measures were highly variable. Approximately, 8% of the respondents felt that their government responded excellently in managing the pandemic while a third felt that the response was just good. Also, more than half (54%) opined that isolation and treatment of COVID-19 patients is a way of curbing SARS-CoV-2 spread. Conclusions: Most West Africans have basic knowledge of COVID-19 and showed a positive attitude, with likely proactive practice towards the disease. However, results showed that these varied across countries and are influenced by

Faba bean (Vicia faba) is a grain legume, which is globally grown for both human consumption as well as feed for livestock. Despite its agro-ecological importance the usage of Vicia faba is severely hampered by its anti-nutritive seed-compounds vicine and convicine (V+C). The genes responsible for a low V+C content have not yet been identified. In this study, we aim to computationally identify regulatory SNPs (rSNPs), i.e., SNPs in promoter regions of genes that are deemed to govern the V+C content of Vicia faba. For this purpose we first trained a deep learning model with the gene annotations of seven related species of the Leguminosae family. Applying our model, we predicted putative promoters in a partial genome of Vicia faba that we assembled from genotyping-by-sequencing (GBS) data. Exploiting the synteny between Medicago truncatula and Vicia faba, we identified two rSNPs which are statistically significantly associated with V+C content. In particular, the allele substitutions regarding these rSNPs result in dramatic changes of the binding sites of the transcription factors (TFs) MYB4, MYB61, and SQUA. The knowledge about TFs and their rSNPs may enhance our understanding of the regulatory programs controlling V+C content of Vicia faba and could provide new hypotheses for future breeding programs.

Aims Thioredoxin interacting protein (TXNIP) is an attractive candidate gene for diabetes or diabetic dyslipidaemia, since TXNIP is the strongest glucoseresponsive gene in pancreatic B-cells, TXNIP deficiency in a mouse model is associated with hyperlipidaemia and TXNIP is located in the 1q21-1q23 chromosomal Type 2 diabetes mellitus (DM) locus. We set out to investigate whether metabolic effects of TXNIP that were previously reported in a murine model are also relevant in human Type 2 DM.

Genetic mapping of quantitative traits requires genotypic data for large numbers of markers in many individuals. For such studies, the use of large single nucleotide polymorphism (SNP) genotyping arrays still offers the most cost-effective solution. Herein we report on the design and performance of a SNP genotyping array for Populus trichocarpa (black cottonwood). This genotyping array was designed with SNPs pre-ascertained in 34 wild accessions covering most of the species latitudinal range. We adopted a candidate gene approach to the array design that resulted in the selection of 34 131 SNPs, the majority of which are located in, or within 2 kb of, 3543 candidate genes. A subset of the SNPs on the array (539) was selected based on patterns of variation among the SNP discovery accessions. We show that more than 95% of the loci produce high quality genotypes and that the genotyping error rate for these is likely below 2%. We demonstrate that even among small numbers of samples (n = 10) from local populations over 84% of loci are polymorphic. We also tested the applicability of the array to other species in the genus and found that the number of polymorphic loci decreases rapidly with genetic distance, with the largest numbers detected in other species in section Tacamahaca. Finally, we provide evidence for the utility of the array to address evolutionary questions such as intraspecific studies of genetic differentiation, species assignment and the detection of natural hybrids.

First-generation selection (FGS) and secondgeneration selection (SGS) breeding populations of loblolly pine from east Texas were studied to estimate the genetic diversity, population structure, linkage disequilibrium (LD), signatures of selection and association of breeding traits with a genome-wide panel of 4,264 single nucleotide polymorphisms (SNPs). Relatively high levels of observed (Ho= 0.178–0.198) and expected (He=0.180–0.198) heterozygosities were observed in all populations. The amount of inbreeding was very low with many populations exhibiting a slight excess of heterozygotes. The population structure was weak, but FST indicated more pronounced differentiation in the SGS populations. As expected for outcrossing natural populations, the genome-wide LD was low, but marker density was insufficient to deduce the decay rate. Numerous associations were found between various phenotypic traits and SNPs, but only a few remained significant after false positive correction. Signatures of diversifying and balancing selection were found in markers representing important biological functions. These results present the first step in the application of markerassisted selection (MAS) to the Western Gulf Forest Tree Improvement Program (WGFTIP) for loblolly pine and will contribute to the knowledgebase necessary for genomic selection technology.

With the recent advent of genomic tools for cattle, several recessive conditions affecting fertility have been identified and selected against, such as deficiency of uridine monophosphate synthase, complex vertebral malformation, and brachyspina. The current report refines the location of a recessive haplotype affecting fertility in Jersey cattle using crossover haplotypes, discovers the causative mutation using whole genome sequencing, and examines the gene's role in embryo loss. In an attempt to identify unknown recessive lethal alleles in the current dairy population, a search using deep Mendelian sampling of 5,288 Jersey cattle was conducted for high-frequency haplotypes that have a deficit of homozygotes at the population level. This search led to the discovery of a putative recessive lethal in Jersey cattle on Bos taurus autosome 15. The haplotype, denoted JH1, was associated with reduced fertility, and further investigation identified one highly-influential Jersey bull as the putative source ancestor. By combining SNP analysis of whole-genome sequences aligned to the JH1 interval and subsequent SNP validation a nonsense mutation in CWC15 was identified as the likely causative mutation underlying the fertility phenotype. No homozygous recessive individuals were found in 749 genotyped animals, whereas all known carriers and carrier haplotypes possessed one copy of the mutant allele. This newly identified lethal has been responsible for a substantial number of spontaneous abortions in Jersey dairy cattle throughout the past half-century. With the mutation identified, selection against the deleterious allele in breeding schemes will aid in reducing the incidence of this defect in the population. These results also show that carrier status can be imputed with high accuracy. Whole-genome resequencing proved to be a powerful strategy to rapidly identify a previously mapped deleterious mutation in a known carrier of a recessive lethal allele.

Genomic studies may generate massive amounts of data, bringing interpretation challenges. Efforts for the differentiation of benign and pathogenic variants gain importance. In this article, we used segregation analysis and other molecular data to reclassify to benign or likely benign several rare clinically curated variants of autosomal dominant inheritance from a cohort of 500 Brazilian patients with rare diseases. This study included only symptomatic patients who had undergone molecular investigation with exome sequencing for suspected diseases of genetic etiology. Variants clinically suspected as the causative etiology and harbored by genes associated with highly-penetrant conditions of autosomal dominant inheritance underwent Sanger confirmation in the proband and inheritance pattern determination because a “de novo” event was expected. Among all 327 variants studied, 321 variants were inherited from asymptomatic parents. Considering segregation analysis, we have reclassified 51...

After the completion of Human Genome Project in 2003, it is now possible to associate genetic variations in the human genome with common and complex diseases. The current challenge now is to utilize the genomic data efficiently and to develop tools to improve our understanding of etiology of complex diseases. Many For the Alzheimer's Disease Neuroimaging Initiative: Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.ucla.edu).

Human settlement and migrations along sides of Bay-of-Bengal have played a vital role in shaping the genetic landscape of Bangladesh, Eastern India and Southeast Asia. Bangladesh and Northeast India form the vital land bridge between the South and Southeast Asia. To reconstruct the population history of this region and to see whether this diverse region geographically acted as a corridor or barrier for human interaction between South Asia and Southeast Asia, we, for the first time analyzed high resolution uniparental (mtDNA and Y chromosome) and biparental autosomal genetic markers among aboriginal Bangladesh tribes currently speaking Tibeto-Burman language. All the three studied populations; Chakma, Marma and Tripura from Bangladesh showed strikingly high homogeneity among themselves and strong affinities to Northeast Indian Tibeto-Burman groups. However, they show substantially higher molecular diversity than Northeast Indian populations. Unlike Austroasiatic (Munda) speakers of India, we observed equal role of both males and females in shaping the Tibeto-Burman expansion in Southern Asia. Moreover, it is noteworthy that in admixture proportion, TB populations of Bangladesh carry substantially higher mainland Indian ancestry component than Northeast Indian Tibeto-Burmans. Largely similar expansion ages of two major paternal haplogroups (O2a and O3a3c), suggested that they arose before the differentiation of any language group and approximately at the same time. Contrary to the scenario proposed for colonization of Northeast India as male founder effect that occurred within the past 4,000 years, we suggest a significantly deep colonization of this region. Overall, our extensive analysis revealed that the population history of South Asian Tibeto-Burman speakers is more complex than it was suggested before.

The article highlights the results of the analysis of the L127V GH, F279Y, and A257G GHR gene's polymorphic variants, that influence milk and meat bull’s offspring characteristics. The effects of genotype SNPs L127V F279Y on fat (genotype VV SNP L127V) and protein (genotype FF SNP F279Y) content in milk was demonstrated. The effects of L127V and F279Y genotypes on the fat content in milk (genotype VV SNP L127V) and milk yield (genotype FF SNP F279Y) were shown. Birth weight was determined higher in calves from bulls with genotypes FY (F279Y) and AG (A257G).

RESUMO Tendo em vista que, no Panamá, grande parte dos programas de melhoramento genético se estabelecem com o uso de germoplasma introduzido, é necessário informar sobre quais doenças genéticas podem estar inadvertidamente circulando, como nas raças crioulas Guaymí panamenhas. e Guabalá, portanto, o objetivo deste trabalho é identificar o polimorfismo de quatro doenças genéticas em Guaymí, Guabalá e raças transfronteiriças no Panamá. Foi estabelecida a presença de polimorfismos e frequência alélica de quatro marcadores relacionados a distúrbios genéticos, fator de transcrição da microftalmia (MITF), olho rosa (PE), sindactilia ou pé de mula (LRP4) e gene da queratina 74 (KRT74).) por sequenciamento de próxima geração, NGS. Com algumas exceções, novos polimorfismos de variantes SNP dos genes MITF02, PE, LRP440 e KRT74 foram identificados. No entanto, foi observada ligação ao alelo de MITF89, LRP435, LRP452, LRP431. A raça Guabalá foi a única que apresentou alta frequência gênica no alelo T alternativo do gene KRT74. Este trabalho é apresentado como o primeiro relato de polimorfismos marcadores associados a doenças genéticas no Panamá, para os quais é necessária a expansão e o monitoramento oportuno dos genótipos estudados e não incluídos neste trabalho.

Resistance to fluoroquinolones (FQ) is being increasingly reported and found to be mediated by efflux pumps, plasmid-mediated quinolone resistance genes (PMQR) and mutations in gyrA, gyrB, parC and parE. However, studies reporting on FQ resistance mechanisms (FQRM), particularly in Africa, are focused mostly on Salmonella. This study used a whole-genome-based approach to describe FQRM in forty-eight clinical Enterobacteriaceae isolates comprising of Klebsiella pneumoniae (n = 21), Serratia marcescens (n = 12), Entero-bacter spp. (n = 10), Citrobacter freundii (n = 3), Escherichia coli (n = 1), and Klebsiella michiganensis (n = 1) with reduced susceptibility to FQ in Enterobacteriaceae. All the isolates exhibited exceptionally high-level resistance (MIC of 4-512mg/L) to all three FQs, which could not be reversed by carbonyl cyanide m-chlorophenyl hydrazine (CCCP), verap-amil (VRP) or reserpine (RSP). PMQR genes such as oqxAB (n = 43), aac(6')-Ib-cr (n = 28), and qnr(S1, B1, B2, B9, B49, B66) (n = 23) were identified without transposons or integrons in their immediate environments. Multiple and diverse mutations were found in gyrA (including S83I/Y and T/I83I/T), gyrB, parC and parE, which were clonally specific. There were vertical and horizontal transmission of high-level FQ resistance in Enterobacteriaceae in hospitals in Durban, South Africa, which are mediated by efflux, PMQR genes, and gyrA, gyrB, parC and parE mutations.

Single nucleotide polymorphisms (SNPs) are the most abundant type of molecular genetic marker and can be used for producing high-resolution genetic maps, marker-trait association studies and marker-assisted breeding. Large polyploid genomes such as wheat present a challenge for SNP discovery because of the potential presence of multiple homoeologs for each gene. AutoSNPdb has been successfully applied to identify SNPs from Sanger sequence data for several species, including barley, rice and Brassica, but the volume of data required to accurately call SNPs in the complex genome of wheat has prevented its application to this important crop. DNA sequencing technology has been revolutionized by the introduction of next-generation sequencing, and it is now possible to generate several million sequence reads in a timely and cost-effective manner. We have produced wheat transcriptome sequence data using 454 sequencing technology and applied this for SNP discovery using a modified autoSNPdb method, which integrates SNP and gene annotation information with a graphical viewer. A total of 4 694 141 sequence reads from three bread wheat varieties were assembled to identify a total of 38 928 candidate SNPs. Each SNP is within an assembly complete with annotation, enabling the selection of polymorphism within genes of interest. Figure 3 Venn diagram displaying the number of reads with combinations of SwissProt, GenBank and Brachypodium ortholog annotation.