Number Of Single Nucleotide Polymorphisms Research Articles

Estimation of inbreeding and identification of regions under heavy selection based on runs of homozygosity in a Large White pig population

BackgroundRuns of homozygosity (ROHs) are homozygous segments of the genome where the two haplotypes inherited from the parents are identical. The current availability of genotypes for a very large number of single nucleotide polymorphisms (SNPs) is leading to more accurate characterization of ROHs in the whole genome. Here, we investigated the occurrence and distribution of ROHs in 3,692 Large White pigs and compared estimates of inbreeding coefficients calculated based on ROHs (FROH), homozygosity (FHOM), genomic relationship matrix (FGRM) and pedigree (FPED). Furthermore, we identified genomic regions with high ROH frequencies and annotated their candidate genes.ResultsIn total, 176,182 ROHs were identified from 3,569 animals, and all individuals displayed at least one ROH longer than 1 Mb. The ROHs identified were unevenly distributed on the autosomes. The highest and lowest coverages of Sus scrofa chromosomes (SSC) by ROH were on SSC14 and SSC13, respectively. The highest pairwise correlation among the different inbreeding coefficient estimates was 0.95 between FROH_total and FHOM, while the lowest was − 0.083 between FGRM and FPED. The correlations between FPED and FROH using four classes of ROH lengths ranged from 0.18 to 0.37 and increased with increasing ROH length, except for ROH > 10 Mb. Twelve ROH islands were located on four chromosomes (SSC1, 4, 6 and 14). These ROH islands harboured genes associated with reproduction, muscular development, fat deposition and adaptation, such as SIRT1, MYPN, SETDB1 and PSMD4.ConclusionFROH can be used to accurately assess individual inbreeding levels compared to other inbreeding coefficient estimators. In the absence of pedigree records, FROH can provide an alternative to inbreeding estimates. Our findings can be used not only to effectively increase the response to selection by appropriately managing the rate of inbreeding and minimizing the negative effects of inbreeding depression but also to help detect genomic regions with an effect on traits under selection.

Epidemic of venereal treponematosis in wild monkeys: a paradigm for syphilis origin.

Treponema pallidum infections have been primarily known as slightly contagious mucocutaneous infections called yaws (tropical Africa and America) and bejel (subtropical North Africa). T. pallidum emerged as a highly infectious venereal syphilis agent in South America, probably about 500 years ago, and because of its venereal transmission, it quickly caused a worldwide pandemic. The disease manifests as lesions, including a chancre; then antibodies become detectable when or slightly after the chancre appears, and before the development of a rash and other systemic manifestations. Venereal diseases are poorly known in monkeys. During fieldwork in Senegal, we discovered an epizootic outbreak of venereal disease that we explored. We detected a venereal form of T. pallidum subsp. pertenue infection in green monkeys (Chlorocebus sabaeus), then observed an epizootic outbreak in Senegal and its spread among baboons a year later. Comparative analysis of T. pallidum genomes from the monkeys' chancres and other Treponema genomes showed an acceleration of the number of single nucleotide polymorphisms, comparable to that observed in syphilis. Identified T. pallidum clones seem to be epizootic through the acceleration of their mutation rate, which is linked to their larger diffusion.

Reconstructing the blood metabolome and genotype using long-range chromatin interactions

Background—Maintenance of tight controls on circulating blood metabolites is crucial to normal, healthy tissue and organismal function. A number of single nucleotide polymorphisms (SNPs) have been associated with changes in the levels of blood metabolites. However, the impacts of the metabolite-associated SNPs are largely unknown because they fall within non-coding regions of the genome. Objective—We aimed to identify genes and tissues that are linked to changes in circulating blood metabolites by characterizing genome-wide spatial regulatory interactions involving blood metabolite-associated SNPs. Method—We systematically integrated chromatin interaction (Hi-C), expression quantitative trait loci (eQTL), gene ontology, drug interaction, and literature-supported connections to deconvolute the genetic regulatory influences of 145 blood metabolite-associated SNPs. Findings—We identified 577 genes that are regulated by 130 distal and proximal metabolite-associated SNPs across 48 different human tissues. The affected genes are enriched in categories that include metabolism, enzymes, plasma proteins, disease development, and potential drug targets. Our results suggest that regulatory interactions in other tissues contribute to the modulation of blood metabolites. Conclusions—The spatial SNP-gene-metabolite associations identified in this study expand on the list of genes and tissues that are influenced by metabolic-associated SNPs and improves our understanding of the molecular mechanisms underlying pathologic blood metabolite levels.

The German Shorthair Pointer Dog Breed (Canis lupus familiaris): Genomic Inbreeding and Variability.

Simple SummaryIn order to protect domestic animals’ biodiversity, a deep knowledge of the genomic makeup is required. The authors describe the genomic architecture of the German Short Hair Pointer breed and analyze the inbreeding levels under a genomic and a genealogic perspective. Twenty-four dogs from Italy were genotyped and analyzed jointly with 10 dogs from USA, whose genotypes were available from a published research. The authors investigated the genomic structural variation of the breed using runs of homozygosity—the direct measurement of the proportion of homozygous DNA, i.e., genomic inbreeding. Some traits clearly revealed the selection objectives addressed in the breed. The results describe a low inbred population with quite good levels of genetic variability.The German Shorthaired Pointer (GSHP) is a breed worldwide known for its hunting versatility. Dogs of this breed are appreciated as valuable companions, effective trackers, field trailers and obedience athletes. The aim of the present work is to describe the genomic architecture of the GSHP breed and to analyze inbreeding levels under a genomic and a genealogic perspective. A total of 34 samples were collected (24 Italian, 10 USA), and the genomic and pedigree coefficients of inbreeding have been calculated. A total of 3183 runs of homozygosity (ROH) across all 34 dogs have been identified. The minimum and maximum number of Single Nucleotide Polymorphisms (SNPs) defining all ROH are 40 and 3060. The mean number of ROH for the sample was 93.6. ROH were found on all chromosomes. A total of 854 SNPs (TOP_SNPs) defined 11 ROH island regions (TOP_ROH), in which some gene already associated with behavioral and morphological canine traits was annotated. The proportion of averaged observed homozygotes estimated on total number of SNPs was 0.70. The genomic inbreeding coefficient based on ROH was 0.17. The mean inbreeding based on genealogical information resulted 0.023. The results describe a low inbred population with quite a good level of genetic variability.

A Turkey-origin H9N2 Avian Influenza Virus Shows Low Pathogenicity but Different Within-Host Diversity in Experimentally Infected Turkeys, Quail and Ducks.

Avian influenza virus (AIV) is a highly diverse and widespread poultry pathogen. Its evolution and adaptation may be affected by multiple host and ecological factors, which are still poorly understood. In the present study, a turkey-origin H9N2 AIV was used as a model to investigate the within-host diversity of the virus in turkeys, quail and ducks in conjunction with the clinical course, shedding and seroconversion. Ten birds were inoculated oculonasally with a dose of 106 EID50 of the virus and monitored for 14 days. Virus shedding, transmission and seroconversion were evaluated, and swabs collected at selected time-points were characterized in deep sequencing to assess virus diversity. In general, the virus showed low pathogenicity for the examined bird species, but differences in shedding patterns, seroconversion and clinical outcome were noted. The highest heterogeneity of the virus population as measured by the number of single nucleotide polymorphisms and Shannon entropy was found in oropharyngeal swabs from quail, followed by turkeys and ducks. This suggests a strong bottleneck was imposed on the virus during replication in ducks, which can be explained by its poor adaptation and stronger selection pressure in waterfowl. The high within-host virus diversity in quail with high level of respiratory shedding and asymptomatic course of infection may contribute to our understanding of the role of quail as an intermediate host for adaptation of AIV to other species of poultry. In contrast, low virus complexity was observed in cloacal swabs, mainly from turkeys, showing that the within-host diversity may vary between different replication sites. Consequences of these observations on the virus evolution and adaptation require further investigation.

Single nucleotide polymorphism rs110861313 in the intergenic region of chromosome 23 is associated with the development of leukosis in the Russian Black Pied cattle

In recent years, using a genome-wide association study (GWAS), a number of single nucleotide polymorphisms (SNPs) have been suggested to be associated with susceptibility to leukemia in cattle. However, all studies have been done with purebred Holstein cows and their hybrids. In this regard, it is important to confirm the functional role of polymorphisms previously identified in a GWAS study in Russian cattle breeds. The aim of this study was to verify the association between rs110861313 in the intergenic region of bovine chromosome 23 and leukemia in the Russian Black Pied cattle. Based on the levels of bovine leukemia virus (BLV)-specific antibodies detected in serum using serodiagnostic techniques, animals were divided into three groups: healthy animals (n = 115), asymptomatic virus carriers (n = 145) and animals with leukemia (n = 107). Genotyping of rs110861313 was carried out using polymerase chain reaction followed by analysis of restriction fragment length polymorphisms. A significant decrease in the frequency of the A/A genotype (11.2 %) was revealed in animals with persistent lymphocytosis compared to virus carriers (27.6 %) (p < 0.002). At the same time, the frequency of animals with the C/C genotype in animals with persistent lymphocytosis (41.1 %) was significantly higher than that of virus carriers (21.4 %) (p < 0.001). In this case, asymptomatic virus carriers can be considered a more suitable control than healthy animals that have not been in contact with the virus. According to bioinformatics analysis, resistance to BLV can be due to the presence of the transcription factor FOXM1 binding site in the region of rs110861313. FOXM1 is expressed in immune cells and can potentially affect the expression of the neighboring genes (LY6G5B, GPANK1, ABHD16A, LY6G6F, LY6G6E, CSNK2B, ApoM). Thus, we found that SNP rs110861313 in the intergenic region of bovine chromosome 23 is associated with the development of leukemia following BLV infection in the Russian Black Pied cattle.

Associations of chronotype with clock genes polymorphisms

AbstractIntroductionIndividuals with a later timing of circadian rhythms (evening types) tend to have unhealthier behaviors compared to those with an earlier timing (morning types). Previous studies have shown that evening types have unhealthier diets and later eating times than morning types. Furthermore, evening types bear higher odds for type 2 diabetes and weight gain (women). Circadian rhythms are controlled by clock genes which have an important role in regulating energy homeostasis. Thus far, a number of single nucleotide polymorphisms (SNP) of clock genes have been associated with metabolic disturbances, obesity and dietary habits (e.g., breakfast skipping and macronutrient intakes). Our aim was to examine chronotype associations with SNPs of the 20 known key clock genes which could help to clarify the underlying mechanisms behind chronotype phenotype.MethodsOur data included 8558 participants (aged 25–74 years, 52% of women) from the cross-sectional population-based National FINRISK 2007 and 2012 surveys. Chronotype was assessed with a shortened six-item version of Horne and Östberg's Morningness-Eveningness Questionnaire (sMEQ) accounting for 83% of the total variance of the original questionnaire. For comparison we used a single self-evaluation question on chronotype from the questionnaire. Genotyping was done using Illumina arrays (HumanCoreExome, Omniexpress and 610K). Linear and logistic regression was used for statistical analysis with the additive genetic model. The analyses were adjusted for age, sex, batch effects and five principal components to account for population structure. The false discovery rate method by the Benjamini-Yekutieli procedure was applied to correct for multiple comparisons.ResultsWe found 27 SNPs in two clock genes that were significantly (P < 0.05) associated with chronotype when assessed with the single question. Minor allele carriers of the NR1D2 (Rev-erbβ) polymorphisms (rs4131403A, rs4858095T, rs6794922G, rs4619734A, rs4589882A, rs4321479C, rs6779476A, rs6790557A, rs13095392A, rs4858098G, rs4858567C, rs11717862G, rs7431301A, rs5023610G, rs5847265C, rs5847266G, rs6550823A, rs9882735C, rs7371944A, rs55792500G) were associated with evening type, whereas minor allele carriers of the NFIL3 polymorphisms (rs2482704T, rs2989836T, rs2482356C, rs2440589T, rs9409419G, rs2482702G, rs2482357A) were more likely morning types. Findings were similar when chronotype was assessed with sMEQ but did not reach statistical significance.DiscussionOur findings indicated novel genetic associations of chronotype with two clock genes that have previously been associated with carbohydrate and lipid metabolism (NR1D2), and with lipid absorption and export in intestinal epithelial cells and hepatic gluconeogenesis (NFIL3). These results expand our knowledge of the genetic basis of chronotype and warrant further studies to replicate these findings.

Whole-genome resequencing using genomic DNA extracted from horsehair roots for gene-doping control in horse sports.

ABSTRACTGene doping is prohibited in horseracing and equestrian sports. In previous studies, we developed non-targeted transgene and genome editing detection methods based on whole genome resequencing (WGR) using genomic DNA extracted from whole blood. In this study, we aimed to develop a WGR method using DNA extracts from hair roots. Hair roots are a preferred substrate because their collection is less invasive than blood collection. Hair is also easier to store for long periods of time. Although almost all genomic DNA extracted from hair root samples stored for years at room temperature was degraded, the quality of genomic DNA from samples stored for years at refrigerated temperatures (4–8°C) was maintained. High-molecular-weight genomic DNA was isolated from hair roots using a magnetic silica beads method of extraction, enabling WGR from horsehair root extracts. Nucleotide sequencing results and numbers of single-nucleotide polymorphisms and insertions/deletions concurred with those previously reported for WGR of DNA extracted from whole blood. Therefore, we consider that storing hair samples at refrigerated temperatures prevents degradation of DNA, allowing the detection of gene doping in these samples based on WGR. It is likely this finding will also have a deterrent effect, as it is now possible to test horses with archived samples even if they or their parents are deceased. To our knowledge, this is the first report employing WGR on horsehair roots stored for a long term.

Profile of bNRAMP1 Gene Sequence as the Candidate Gene for Pathogenic Bacterial Resistance Trait in Cattle

Bovine Natural Resistance Associated Macrophage Protein 1 (bNRAMP1) gene is one of the candidate gene that widely used to control the infectious disease in dairy and beef cattle. In mouse, the bNRAMP1 gene is important to confer resistance or suspectibility to Mycobacterium bovis, Salmonella typhimurium and Leishmania donovani. This article was carried out to explain the profile of bNRAMP gene such as genes structure, number of Single Nucleotide Polymorphisms (SNPs) and its relationship to pathogenic bacterial diseases evidence such as bovine Tuberculosis, mastitis and Brucellosis. The mutations (SNPs) in bNRAMP1 gene were occured in intron, exon and 3UTR regions. Previous studies reported that some SNPs in bNRAMP1 gene affected to many pathogenic bacterial disease incidences in cattle. Hence, the bNRAMP1 gene can be used as the genetic marker for pathogenic bacterial resistance trait

Investigating the drivers of the spatio-temporal patterns of genetic differences between Plasmodium falciparum malaria infections in Kilifi County, Kenya

Knowledge of how malaria infections spread locally is important both for the design of targeted interventions aiming to interrupt malaria transmission and the design of trials to assess the interventions. A previous analysis of 1602 genotyped Plasmodium falciparum parasites in Kilifi, Kenya collected over 12 years found an interaction between time and geographic distance: the mean number of single nucleotide polymorphism (SNP) differences was lower for pairs of infections which were both a shorter time interval and shorter geographic distance apart. We determine whether the empiric pattern could be reproduced by a simple model, and what mean geographic distances between parent and offspring infections and hypotheses about genotype-specific immunity or a limit on the number of infections would be consistent with the data. We developed an individual-based stochastic simulation model of households, people and infections. We parameterized the model for the total number of infections, and population and household density observed in Kilifi. The acquisition of new infections, mutation, recombination, geographic location and clearance were included. We fit the model to the observed numbers of SNP differences between pairs of parasite genotypes. The patterns observed in the empiric data could be reproduced. Although we cannot rule out genotype-specific immunity or a limit on the number of infections per individual, they are not necessary to account for the observed patterns. The mean geographic distance between parent and offspring malaria infections for the base model was 0.4 km (95% CI 0.24, 1.20), for a distribution with 58% of distances shorter than the mean. Very short mean distances did not fit well, but mixtures of distributions were also consistent with the data. For a pathogen which undergoes meiosis in a setting with moderate transmission and a low coverage of infections, analytic methods are limited but an individual-based model can be used with genotyping data to estimate parameter values and investigate hypotheses about underlying processes.

Associations between microRNA (miR-25, miR-32, miR-125, and miR-222) polymorphisms and recurrent implantation failure in Korean women

BackgroundRecurrent implantation failure (RIF) is the failure of embryos to implant more than two times in a given individual. There is debate about a precise definition for RIF, but we consider more than two implantation failures for individuals who undergo in vitro fertilization-embryo transfer (IVF-ET) to constitute RIF. There are many potential reasons for RIF, including embryonic factors, immunological factors, uterine factors, coagulate factors, and genetic factors. Genetic variation has been suggested as one of the contributing factors leading to RIF, and a number of single-nucleotide polymorphisms (SNPs) have been reported to be associated with RIF. The recent elucidation of miRNA functions has provided new insight into the regulation of gene expression.MethodsWe investigated associations between polymorphisms in four miRNAs and RIF in 346 Korean women: 118 patients with RIF and 228 controls. We determined the genotypes of the miRNAs in the study participants by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) analysis. We analyzed the effects of genotypes, allele combinations, and environmental and clinical factors on the risk of RIF.ResultsThe miR-25 T/miR-125aT/miR-222G (odds ratio (OR), 0.528; 95% confidence interval (CI), 0.282–0.990; P = 0.044) and miR-25 T/miR-125aT allele combinations were associated with a reduced risk of RIF. The miR-25 T/miR-32C/miR-125aC/miR-222 T allele combination was associated with an increased risk of RIF. The miR-222GT+TT genotypes interacted with high prothrombin time (≥ 12 s) to increase the risk of RIF.ConclusionsMicroRNA polymorphisms are significantly different between patients that experience RIF and healthy controls. Combinations of microRNA polymorphisms were associated with the risk of RIF. Interactions between environmental factors and genotypes increased the risk of RIF in Korean women.

Process-based species delimitation leads to identification of more biologically relevant species.

Most approaches to species delimitation to date have considered divergence-only models. Although these models are appropriate for allopatric speciation, their failure to incorporate many of the population-level processes that drive speciation, such as gene flow (e.g., in sympatric speciation), places an unnecessary limit on our collective understanding of the processes that produce biodiversity. To consider these processes while inferring species boundaries, we introduce the R-package delimitR and apply it to identify species boundaries in the reticulate taildropper slug (Prophysaon andersoni). Results suggest that secondary contact is an important mechanism driving speciation in this system. By considering process, we both avoid erroneous inferences that can be made when population-level processes such as secondary contact drive speciation but only divergence is considered, and gain insight into the process of speciation in terrestrial slugs. Further, we apply delimitR to three published empirical datasets and find results corroborating previous findings. Finally, we evaluate the performance of delimitR using simulation studies, and find that error rates are near zero when comparing models that include lineage divergence and gene flow for three populations with a modest number of Single Nucleotide Polymorphisms (SNPs; 1500) and moderate divergence times (<100,000 generations). When we apply delimitR to a complex model set (i.e., including divergence, gene flow, and population size changes), error rates are moderate (∼0.15; 10,000 SNPs), and, when present, misclassifications occur among highly similar models.

Campylobacter jejuni isolated from poultry meat in Brazil: in silico analysis and genomic features of two strains with different phenotypes of antimicrobial susceptibility.

Campylobacter jejuni is the most common bacterial cause of foodborne diarrheal disease worldwide and is among the antimicrobial resistant "priority pathogens" that pose greatest threat to public health. The genomes of two C. jejuni isolated from poultry meat sold on the retail market in Southern Brazil phenotypically characterized as multidrug-resistant (CJ100) and susceptible (CJ104) were sequenced and analyzed by bioinformatic tools. The isolates CJ100 and CJ104 showed distinct multilocus sequence types (MLST). Comparative genomic analysis revealed a large number of single nucleotide polymorphisms, rearrangements, and inversions in both genomes, in addition to virulence factors, genomic islands, prophage sequences, and insertion sequences. A circular 103-kilobase megaplasmid carrying virulence factors was identified in the genome of CJ100, in addition to resistance mechanisms to aminoglycosides, beta-lactams, macrolides, quinolones, and tetracyclines. The molecular characterization of distinct phenotypes of foodborne C. jejuni and the discovery of a novel virulence megaplasmid provide useful data for pan-genome and large-scale studies to monitor the virulent C. jejuni in poultry meat is warranted.

Genomics of Early Cardiac Dysfunction and Mortality in Obese Drosophila melanogaster.

In experimental evolution, we impose functional demands on laboratory populations of model organisms using selection. After enough generations of such selection, the resulting populations constitute excellent material for physiological research. An intense selection regime for increased starvation resistance was imposed on 10 large outbred Drosophila populations. We observed the selection responses of starvation and desiccation resistance, metabolic reserves, and heart robustness via electrical pacing. Furthermore, we sequenced the pooled genomes of these populations. As expected, significant increases in starvation resistance and lipid content were found in our 10 intensely selected SCO populations. The selection regime also improved desiccation resistance, water content, and glycogen content among these populations. Additionally, the average rate of cardiac arrests in our 10 obese SCO populations was double the rate of the 10 ancestral CO populations. Age-specific mortality rates were increased at early adult ages by selection. Genomic analysis revealed a large number of single nucleotide polymorphisms across the genome that changed in frequency as a result of selection. These genomic results were similar to those obtained in our laboratory from less direct selection procedures. The combination of extensive genomic and phenotypic differentiation between these 10 populations and their ancestors makes them a powerful system for the analysis of the physiological underpinnings of starvation resistance.

Analysis of single nucleotide polymorphisms (SNPs) associated with antibiotic resistance genes in Chilean Piscirickettsia salmonis strains.

The aetiological agent of Piscirickettsiosis is Piscirickettsia salmonis, a Gram-negative intracellular pathogen, and high doses of antibiotics have regularly been employed to treat this infection. Seven florfenicol and/or oxytetracycline resistance genes (tet pump, tetE, Tclor/flor, Tbcr, TfloR, ompF and mdtN) were identified in strains by in silico genome analyses. Later, the number of single nucleotide polymorphisms (SNPs) and its relationship with the resistance to these antibiotics were identified and analysed, using the original LF-89 strain as reference. Trials to determine and compare the minimum inhibitory concentration (MIC) of oxytetracycline and florfenicol in each strain, as well as to quantify the gPCR transcripts levels in the selected genes, were performed. Therefore, variations in the resistance to both antibiotics were observed, where the strain with fewer SNPs showed the highest susceptibility. Consistently, the in silico 3D analyses of proteins encoded by the selected genes revealed structural changes, evident in the sequences with the highest number of SNPs. These results showed that the bacterial resistance to oxytetracycline was mainly linked to the presence of SNPs in relevant sites, antibiotic resistance genes and an OmpF porin, leading to important changes in the protein structure.

P1233Differential effects of five risk variants for atrial fibrillation at the 4q25 region on L-type calcium current and transient inward currents in human atrial myocytes

Abstract Background An increasing number of single nucleotide polymorphisms (SNPs) at the chromosomal region 4q25 have been associated with risk of atrial fibrillation (AF) and we have recently reported that carriers of the rs13143308 risk variant have an increased incidence of spontaneous calcium release-induce transient inward currents (ITI). However, it is not known if different 4q25 variants have similar effects. Purpose This study aimed to compare the effects of five SNPs at 4q25 on L-type calcium current (ICa) and ITI frequency, features that are altered in patients with AF. Methods To avoid confounding effects of AF on calcium homeostasis, atrial samples from 63 patients without AF were genotyped and divided into groups according to the genotype of the SNPs rs1448818, rs6817105, rs13143308, rs6843082, rs3853443 ordered according to their location and identified by the three last digits + an R for risk or N for normal variants. ICa density and ITI frequency were measured with perforated patch clamp technique in atrial myocytes from these patients. Results Three SNPs 818, 308 and 443 segregated independently of the genotype at the other loci. The 105 and 082 loci always co-segregated with 308 but never together. The ICa density was smaller in carriers of 818R and 443N variants (−1.6±0.3pA/pF, p=0.01) or 818N and 443R variants (−1.6±0.4pA/pF, p=0.02) than in patients with 818N and 443N variants (−3.2±0.4pA/pF), independently of the genotype at 105, 308 and 082 (these loci did not affect ICa). In contrast, to this, the ITI frequency was increased only in myocytes from patients carrying 105R, 308R and 082N (1.4±0.2events/min, p&lt;0.001) or 105N, 308R and 082R (1.6±0.5events/min, p=0.002) when compared to patients with 105N, 308N and 082N (0.36±0.09events/min) independently of the genotypes at 818 and 443, or when compared to patients without risk at any of the five loci (0.55±0.30events/min). The table shows schematically the qualitative effects of the different risk variants. Risk variant rs1448818C rs6817105C rs13143308T rs6843082T rs3853445C ICa Decreased Unchanged Unchanged Unchanged Decreased ITI Unchanged Increased Increased Increased Unchanged Conclusion Different SNPs at the chromosomal region 4q25 are associated with differential pathological changes in intracellular calcium homeostasis. Risk variants at rs1448818 or rs3853445 cause loss of ICa without affecting ITI frequency while a risk variant at rs13143308 elevates the ITI frequency without affecting ICa. These findings afford a framework for stratification of pharmacological therapy based on the functional effects of the 4q25 risk variants Acknowledgement/Funding SAF2017-88019; Marato2015-20-30; SGR2017-1769; CIBERCV

Application of different DNA extraction procedures, library preparation protocols and sequencing platforms: impact on sequencing results

In this study three DNA extraction procedures, two library preparation protocols and two sequencing platforms were applied to analyse six bacterial cultures and their corresponding DNA obtained as part of a proficiency test. The impact of each variable on sequencing results was assessed using the following parameters: reads quality, assembly and alignment statistics; number of single nucleotide polymorphisms (SNPs), detected applying assembly- and alignment-based strategies; antimicrobial resistance genes (ARGs), identified on de novo assemblies of all sequenced genomes. The investigated nucleic acid extraction procedures, library preparation kits and sequencing platforms do not significantly affect de novo assembly statistics and number of SNPs and ARGs. The only exception was observed for two duplicates, which were associated to one PCR-based library preparation kit. Results from this comparative study can support researchers in the choice toward the available pre-sequencing and sequencing options, and might suggest further comparisons to be performed.

Association analysis between genomic variants within advanced glycation end product specific receptor (AGER) gene and risk of breast cancer in Iranian women

The advanced glycation end product specific receptor (AGER) gene codes for a cell surface receptor which is one of the immunoglobulin superfamily members. This gene has a number of single nucleotide polymorphisms (SNPs) whose variants are associated with altered function of the encoded protein. In the current project, we examined association between rs184003 and rs1800625 SNPs and susceptibility to breast cancer in an Iranian population. The current study excludes participation of rs184003 AGER variant in conferring cancer risk. However, for the rs1800625, based on the calculated P value, the results should be assessed in larger cohorts. Primarily, the rs1800625 SNP was associated with breast cancer risk in dominant model (OR (95% CI) = 1.79 (1.03–3.11)), but after correction for multiple comparisons it did not reach the level of significance (adjusted P value = 0.07). The other SNP was not associated with breast cancer risk in any inheritance model. Haplotype analyses revealed a trend toward association between the GC haplotype (rs184003 and rs1800625 respectively) and risk of breast cancer (OR (95% CI) = 1.77 (1.09–2.88), adjusted P value = 0.08)). The current study excludes participation of rs184003 AGER variants in conferring cancer risk. However, for the rs1800625, based on the calculated P value, the results should be assessed in larger cohorts.

Extension of a haplotype-based genomic prediction model to manage multi-environment wheat data using environmental covariates.

A multi-environment genomic prediction model incorporating environmental covariates increased the prediction accuracy of wheat grain protein content. The advantage of the haplotype-based model was dependent upon the trait of interest. The inclusion of environment covariates (EC) in genomic prediction models has the potential to precisely model environmental effects and genotype-by-environment interactions. Together with EC, a haplotype-based genomic prediction approach, which is capable of accommodating the interaction between local epistasis and environment, may increase the prediction accuracy. The main objectives of our study were to evaluate the potential of EC to portray the relationship between environments and the relevance of local epistasis modelled by haplotype-based approaches in multi-environment prediction. The results showed that among five traits: grain yield (GY), plant height, protein content, screenings percentage (SP) and thousand kernel weight, protein content exhibited a 2.1% increase in prediction accuracy when EC was used to model the environmental relationship compared to treatment of the environment as a regular random effect without a variance-covariance structure. The approach used a Gaussian kernel to characterise the relationship among environments that displayed no advantage in contrast to the use of a genomic relationship matrix. The prediction accuracies of haplotype-based approaches for SP were consistently higher than the genotype-based model when the numbers of single-nucleotide polymorphisms (SNP) in a haplotype were from three to ten. In contrast, for GY, haplotype-based models outperformed genotype-based methods when two to four SNPs were used to construct the haplotype.

Papel de la variabilidad genética en las enfermedades mendelianas y multifactoriales.

The first draft of the human genome sequencing published in 2001 reported a large number of single nucleotide polymorphisms (SNPs). Given that these polymorphisms could practically represent all the variability involved in the susceptibility, protection, severity, among other aspects, of various common diseases, as well as in their response to medications, it was thought that they might be "the biomarkers of choice" in personalized genomic medicine. With the new information obtained from the sequencing of a larger number of genomes, we have understood that SNPs are only an important part of the genetic markers involved in these traits. In addition to SNPs, other variants have been identified, such as insertions/deletions (INDELs) and copy number variants (CNVs), which - in addition to classic variable number tandem repeats (VNTRs) and short tandem repeats (STRs) - originate or contribute to the development of diseases. The use of these markers has served to identify regions of the genome involved in Mendelian diseases (one gene-one disease) or genes directly associated with multifactorial diseases. This review has the purpose to describe the role of STRs, VNTRs, SNPs, CNVs and INDELs in linkage and association studies and their role in Mendelian and multifactorial diseases.