Genome Genotyping Research Articles

POLYMORPHISMS IN CANDIDATE GENES FOR BEEF QUALITY IN PINZGAU CATTLE

The aim of present study was to identify the polymorphisms in genes encodingcalpastatin (CASTUoG), calpain (CAPN1, CAPN2), diacylglycerol Oacyltransferase(DGAT1), thyroglobulin (TG5), and Stearoyl-CoA Desaturase(SCD) in order to analyse genetic structure of Pinzgau cattle. The genomic DNAfor genotyping was obtained from in total 56 blood samples of Pinzgau bulls. Afterextraction, the concentration of DNA was controlled by the spectrophotometrymeasurement. The genotyping of each individual was carried out by using PCRRFLPmethods. The average value of observed (0.37±0.05) and expectedheterozygosity (0.39±0.06) clearly indicated the prevalence of homozygousindividuals. Observed Wright's fixation indexes showed positive values across allloci (0.03±0.06), which confirmed slight deficiency of heterozygote animalscompared to the Hardy-Weinberg equilibrium expectations. The Hardy-Weinbergequilibrium was found in population, which signalizes only slight impact of factorssuch as selection, migration or inbreeding. The effectiveness of loci allele impact inpopulations has been described also by effective allele numbers (1.68±0.13) thatexpressed the decrease of allele activity in population. The loss of heterozygosityin analysed population was found across all of genetic markers. Each of theevaluated indicators clearly points to the need of genetic diversity monitoring.Moreover, the analyses of single nucleotide polymorphisms in genes significantlyinvolved in control of economically important production traits are still very usablemethods for identification of genetic markers that can be used in marker assistedselection of cattle.

Host genetic susceptibility to Clostridium difficile infections in patients undergoing autologous stem cell transplantation: a genome-wide association study

Clostridium difficile infection (CDI) is the most common hospital-acquired infection. Unfortunately, genes that identify CDI-susceptible patients have not been well described. We performed a genome-wide association study (GWAS) to determine genetic variants associated with the development of CDI. A cohort study of Caucasian patients undergoing autologous stem cell transplantation for multiple myeloma was performed. Patients were genotyped using Illumina® Whole Genome Genotyping Infinium chemistry. We then compared CDI-positive to CDI-negative patients using logistic regression for baseline clinical factors and false discovery rate (FDR) for genetic factors [single nucleotide polymorphisms (SNPs)]. SNPs associated with CDI at FDR of p < 0.01 were then incorporated into a logistic regression model combining clinical and genetic factors. Of the 646 patients analyzed (59.7% male), 57 patients were tested CDI positive (cases) and were compared to 589 patients who were tested negative (controls). Hemoglobin, albumin, and hematocrit were lower for cases (p < 0.05). Eight SNPs on five genes (FLJ16171, GORASP2, RLBP1L1, ASPH, ATP7B) were associated with CDI at FDR p < 0.01. In the combined clinical and genetic model, low albumin and three genes RLBP1L1, ASPH, and ATP7B were associated with CDI. Low serum albumin and genes RLBP1L1 and ASPH located on chromosome 8 and ATP7B on chromosome 13 were associated with CDI. Of particular interest is ATP7B given its copper modulatory role and the sporicidal properties of copper against Clostridium difficile.

Spatial dynamics and mixing of bluefin tuna in the Atlantic Ocean and Mediterranean Sea revealed using next-generation sequencing.

The Atlantic bluefin tuna is a highly migratory species emblematic of the challenges associated with shared fisheries management. In an effort to resolve the species' stock dynamics, a genomewide search for spatially informative single nucleotide polymorphisms (SNPs) was undertaken, by way of sequencing reduced representation libraries. An allele frequency approach to SNP discovery was used, combining the data of 555 larvae and young-of-the-year (LYOY) into pools representing major geographical areas and mapping against a newly assembled genomic reference. From a set of 184,895 candidate loci, 384 were selected for validation using 167 LYOY. A highly discriminatory genotyping panel of 95 SNPs was ultimately developed by selecting loci with the most pronounced differences between western Atlantic and Mediterranean Sea LYOY. The panel was evaluated by genotyping a different set of LYOY (n=326), and from these, 77.8% and 82.1% were correctly assigned to western Atlantic and Mediterranean Sea origins, respectively. The panel revealed temporally persistent differentiation among LYOY from the western Atlantic and Mediterranean Sea (FST =0.008, p=.034). The composition of six mixed feeding aggregations in the Atlantic Ocean and Mediterranean Sea was characterized using genotypes from medium (n=184) and large (n=48) adults, applying population assignment and mixture analyses. The results provide evidence of persistent population structuring across broad geographic areas and extensive mixing in the Atlantic Ocean, particularly in the mid-Atlantic Bight and Gulf of St. Lawrence. The genomic reference and genotyping tools presented here constitute novel resources useful for future research and conservation efforts.

Human beta defensin-1 is involved in the susceptibility to adeno-tonsillar hypertrophy

IntroductionInnate immunity molecules are known to play a pivotal role in the homeostasis of the oral mucosa, permitting the presence of commensal microflora and, at the same time, providing a first line of defense against pathogens attempting to invade the oral cavity.Tonsils represent the local immune tissue in oral cavity, being able to provide a non-specific response to pathogens; however, in the presence of microbes or foreign materials present in the mouth tonsils could became infected and develop chronic inflammation, thus leading to hypertrophy.The etiology of the disease is multifactorial depending upon environmental and host factors, the latter including molecules of mucosal innate immunity. MethodsNinety-five children with adeno-tonsillar hypertrophy subjected to adeno-tonsillectomy were recruited at the pediatric otorhinolaryngology service of the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste (Italy).The specimen discarded from the surgery were used for genomic DNA extraction and genotyping, for mRNA extraction and gene expression analysis, finally the samples were cut and used to prepare slides to perform immunohistochemistry. ResultsFunctional polymorphisms within DEFB1 gene, encoding the human beta defensin-1 (hBD-1), were analyzed finding association between DEFB1 rare haplotypes and susceptibility to adeno-tonsillar hypertrophy. DEFB1 mRNA expression was detected in the tonsils and the hBD-1 protein was localized at the epithelia of tonsils mainly in the proximity of the basal lamina. ConclusionOur findings lead us to hypothesize an involvement of hBD-1 mediated innate immunity in the modulation of the susceptibility towards adeno-tonsillar hypertrophy development.

Scripts for: Inter-chromosomal coupling between vision and pigmentation genes during genomic divergence

This git repository contains all the scripts needed to reproduce our results from the study Inter-chromosomal coupling between vision and pigmentation genes during genomic divergence from raw data to figures. It contains all scripts referenced within the materials & methods section. Related datasets are deposited at ENA (raw sequencing data, acession nr. PRJEB27858) and dryad (genome annotation & genotypes, doi:10.5061/dryad.pg8q56g).

Detection of genomic loci associated with chromosomal recombination using high-density linkage mapping in Setaria

Meiotic recombination is essential to sexual reproduction and the generation of genetic diversity. Variation in recombination rates is presently of particular interest due to efforts being made to increase the rate of genetic gain in agricultural crops by breaking up large linkage disequilibrium blocks containing both beneficial and detrimental alleles. Here, a high-density genetic linkage map of Setaria was constructed using tunable genotyping by sequencing (tGBS) analysis of a population of recombinant inbred lines (RILs). Several regions of the Setaria genome exhibited significant levels of segregation distortion (SD), and recombination crossovers (COs) were also detected. The regions with high SD generally tended to have fewer COs, particularly for pericentromeric chromosomal areas. Recombination crossovers detected in Setaria were unevenly distributed across the genome and occurred more often in intergenic regions. Quantitative trait loci (QTLs) contributing towards the recombination frequency (Type I) and occurrence of COs in designated loci (Type II) were identified, and Type II QTLs garnered higher statistical power. The result of this study suggest that QTLs analysis of Type II traits using RILs might provide an opportunity to further understand meiotic recombination using high throughput genome sequencing and genotyping technologies.

GWAS of agronomic traits in soybean collection included in breeding pool in Kazakhstan

BackgroundIn recent years soybean is becoming one of the most important oilseed crops in Kazakhstan. Only within the last ten years (2006–2016), the area under soybean is expanded from 45 thousand hectares (ha) in 2006 to 120 thousand ha in 2016. The general trend of soybean expansion is from south-eastern to eastern and northern regions of the country, where average temperatures are lower and growing seasons are shorter. These new soybean growing territories were poorly examined in terms of general effects on productivity level among the diverse sample of soybean accessions. In this study, phenotypic data were collected in three separate regions of Kazakhstan and entire soybean sample was genotyped for identification of marker-trait associations (MTA).ResultsIn this study, the collection of 113 accessions representing five different regions of the World was planted in 2015–2016 in northern, eastern, and south-eastern regions of Kazakhstan. It was observed that North American accessions showed the highest yield in four out of six trials especially in Northern Kazakhstan in both years. The entire sample was genotyped with 6 K SNP Illumina array. 4442 SNPs found to be polymorphic and were used for whole genome genotyping purposes. Obtained SNP markers data and field data were used for GWAS (genome-wide association study). 30 SNPs appear to be very significant in 42 MTAs in six studied environments.ConclusionsThe study confirms the efficiency of GWAS for the identification of molecular markers which tag important agronomic traits. Overall thirty SNP markers associated with time to flowering and maturation, plant height, number of fertile nodes, seeds per plant and yield were identified. Physical locations of 32 identified out of 42 total MTAs coincide well with positions of known analogous QTLs. This result indicates importance of revealed MTAs for soybean growing regions in Kazakhstan. Obtained results would serve as required prerequisite for forming and realization of specific breeding programs towards effective adaptation and increased productivity of soybean in three different regions of Kazakhstan.

Identification of copy number variation in French dairy and beef breeds using next-generation sequencing

BackgroundCopy number variations (CNV) are known to play a major role in genetic variability and disease pathogenesis in several species including cattle. In this study, we report the identification and characterization of CNV in eight French beef and dairy breeds using whole-genome sequence data from 200 animals. Bioinformatics analyses to search for CNV were carried out using four different but complementary tools and we validated a subset of the CNV by both in silico and experimental approaches.ResultsWe report the identification and localization of 4178 putative deletion-only, duplication-only and CNV regions, which cover 6% of the bovine autosomal genome; they were validated by two in silico approaches and/or experimentally validated using array-based comparative genomic hybridization and single nucleotide polymorphism genotyping arrays. The size of these variants ranged from 334 bp to 7.7 Mb, with an average size of ~ 54 kb. Of these 4178 variants, 3940 were deletions, 67 were duplications and 171 corresponded to both deletions and duplications, which were defined as potential CNV regions. Gene content analysis revealed that, among these variants, 1100 deletions and duplications encompassed 1803 known genes, which affect a wide spectrum of molecular functions, and 1095 overlapped with known QTL regions.ConclusionsOur study is a large-scale survey of CNV in eight French dairy and beef breeds. These CNV will be useful to study the link between genetic variability and economically important traits, and to improve our knowledge on the genomic architecture of cattle.

Genomic Selection in Plant Breeding: Methods, Models, and Perspectives

Genomic selection (GS) facilitates the rapid selection of superior genotypes and accelerates the breeding cycle. In this review, we discuss the history, principles, and basis of GS and genomic-enabled prediction (GP) as well as the genetics and statistical complexities of GP models, including genomic genotype×environment (G×E) interactions. We also examine the accuracy of GP models and methods for two cereal crops and two legume crops based on random cross-validation. GS applied to maize breeding has shown tangible genetic gains. Based on GP results, we speculate how GS in germplasm enhancement (i.e., prebreeding) programs could accelerate the flow of genes from gene bank accessions to elite lines. Recent advances in hyperspectral image technology could be combined with GS and pedigree-assisted breeding.

Insights Into Onchocerca volvulus Population Biology Through Multilocus Immunophenotyping.

We have developed a serologically based immunophenotyping approach to study Onchocerca volvulus (Ov) population diversity. Using genomic sequence data and polymerase chain reaction-based genotyping, we identified nonsynonymous single-nucleotide polymorphisms (SNPs) in the genes of 16 major immunogenic Ov proteins: Ov-CHI-1/Ov-CHI-2, Ov16, Ov-FAR-1, Ov-CPI-1, Ov-B20, Ov-ASP-1, Ov-TMY-1, OvSOD1, OvGST1, Ov-CAL-1, M3/M4, Ov-RAL-1, Ov-RAL-2, Ov-ALT-1, Ov-FBA-1, and Ov-B8. We assessed the immunoreactivity of onchocerciasis patient sera (n = 152) from the Americas, West Africa, Central Africa, and East Africa against peptides derived from 10 of these proteins containing SNPs. Statistically significant variation in immunoreactivity among the regions was seen in SNP-containing peptides derived from 8 of 10 proteins tested: OVOC1192(1-15), OVOC9988(28-42), OVOC9225(320-334), OVOC7453(22-36), OVOC11517(14-28), OVOC3177(283-297), OVOC7911(594-608), and OVOC12628(174-188). Our data show that differences in immunoreactivity to variant antigenic peptides may be used to characterize Ov populations, thereby elucidating features of Ov population biology previously inaccessible because of the limited availability of parasite material.

Future Directions of Genomics Research in Rheumatic Diseases.

Recent developments in human genome genotyping and sequencing technologies, such as genome-wide association studies and whole-genome sequencing analyses, have successfully identified several risk genes of rheumatic diseases. Fine-mapping studies using the HLA imputation method revealed that classical and non-classical HLA genes contribute to the risk of rheumatic diseases. Integration of human disease genomics with biological, medical, and clinical databases should contribute to the elucidation of disease pathogenicity and novel drug discovery. Disease risk genes identified by large-scale genetic studies are considered to be promising resources for novel drug discovery, including drug repositioning and biomarker microRNA screening for rheumatoid arthritis.

Abstract 4338: The role of IMPACT in survival of cancer cells during tryptophan deprivation by immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO1)

Abstract A broad range of human malignancies overexpress an enzyme called indoleamine 2,3-dioxygenase 1 (IDO1) to suppress antitumor immunity which associates with poor patient prognosis. One mechanism whereby IDO1 activity suppresses the host’s immune cells is mediated by deprivation of the essential amino acid tryptophan (Trp) which raises an intriguing question. How do the cancer cells overcome low levels of the essential amino acid when the immune T-cells are triggered to self-destruct? A protein called IMPACT (product of IMPrinted gene with AnCienT domain) was reported to confer skin cells and neuronal cells increased survival in Trp-deprived environments. Based on these reports, we hypothesise that cancer cells hijack IMPACT to gain survival advantage in Trp-deprived environments. To obtain evidence for this hypothesis, we analysed publicly available genomics datasets and performed experimental assays. Murine GL261 glioblastoma cells overexpressing a full-length mouse IMPACT gene (GL261-IMPACT) were generated by lipofection. IMPACT overexpression was confirmed by Western blot. Metabolic activity and survival of the GL261 cells in Trp deprivation experiments were evaluated using MTT assay and staining with live/dead indicators fluorescein diacetate and propidium iodide, respectively. Meta-analysis of the publicly available RNA-sequencing datasets, The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx), provided evidence that IMPACT was overexpressed in the majority of the 24 analysed human cancers compared to their non-malignant tissue counterparts. Consistent with the high IMPACT expression in prostate cancer patients, 12-25% prostate tumors show amplification of the IMPACT gene (source: cBioPortal for Cancer Genomics). In addition, we found an association of high IMPACT expression with poorer survival for certain leukemia and lung cancer patients in the Gene Expression Omnibus (GEO) portal. To obtain experimental evidence that IMPACT protects cancer cells during Trp deprivation, GL261-IMPACT cells were cultured in media containing 2.5 - 50 μM Trp. Metabolic activity of GL261-IMPACT cells decreased at a slower rate than that of GL261-wild-type cells after 3 to 5 days in media containing limiting Trp concentration (2.5 - 10 μM). On day 5, GL261-wild-type and GL261-IMPACT cells cultivated in 10 μM Trp showed 4.5% and 23% metabolic activity (p = 2.8x10-8), respectively, relative to the same cells grown in 50 μM Trp. Fluorescence microscopy utilising live/dead staining showed that after 5 days of incubation at limiting Trp concentrations (5 - 10 μM), the majority of GL261-wild-type cells were non-viable whereas GL261-IMPACT cells were predominantly viable. Our initial results support the hypothesis that IMPACT aids cancer cells to overcome periods of tryptophan deprivation. Citation Format: Petr Tomek, Ariane Hallermayr, Michael Kilian, Cristin Gregor Print, Lai-Ming Ching. The role of IMPACT in survival of cancer cells during tryptophan deprivation by immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO1) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4338. doi:10.1158/1538-7445.AM2017-4338

Single-Step Genomic and Pedigree Genotype × Environment Interaction Models for Predicting Wheat Lines in International Environments.

Genomic prediction models have been commonly used in plant breeding but only in reduced datasets comprising a few hundred genotyped individuals. However, pedigree information for an entire breeding population is frequently available, as are historical data on the performance of a large number of selection candidates. The single-step method extends the genomic relationship information from genotyped individuals to pedigree information from a larger number of phenotyped individuals in order to combine relationship information on all members of the breeding population. Furthermore, genomic prediction models that incorporate genotype × environment interactions (G × E) have produced substantial increases in prediction accuracy compared with single-environment genomic prediction models. Our main objective was to show how to use single-step genomic and pedigree models to assess the prediction accuracy of 58,798 CIMMYT wheat ( L.) lines evaluated in several simulated environments in Ciudad Obregon, Mexico, and to predict the grain yield performance of some of them in several sites in South Asia (India, Pakistan, and Bangladesh) using a reaction norm model that incorporated G × E. Another objective was to describe the statistical and computational challenges encountered when developing the pedigree and single-step models in such large datasets. Results indicate that the genomic prediction accuracy achieved by models using pedigree only, markers only, or both pedigree and markers to predict various environments in India, Pakistan, and Bangladesh is higher (0.25-0.38) than prediction accuracy of models that use only phenotypic prediction (0.20) or do not include the G × E term.

Mutation in TDRD9 causes non-obstructive azoospermia in infertile men

BackgroundAzoospermia is diagnosed when sperm cells are completely absent in the ejaculate even after centrifugation. It is identified in approximately 1% of all men and in 10%–20% of infertile males....

Target enrichment sequencing in cultivated peanut (Arachis hypogaea L.) using probes designed from transcript sequences.

Enabled by the next generation sequencing, target enrichment sequencing (TES) is a powerful method to enrich genomic regions of interest and to identify sequence variations. The objective of this study was to explore the feasibility of probe design from transcript sequences for TES application in calling sequence variants in peanut, an important allotetraploid crop with a large genome size. In this study, we applied an in-solution hybridization method to enrich DNA sequences of seven peanut genotypes. Our results showed that it is feasible to apply TES with probes designed from transcript sequences in polyploid peanut. Using a set of 31,123 probes, a total of 5131 and 7521 genes were targeted in peanut A and B genomes, respectively. For each genotype used in this study, the probe target capture regions were efficiently covered with high depth. The average on-target rate of sequencing reads was 42.47%, with a significant amount of off-target reads coming from genomic regions homologous to target regions. In this study, when given predefined genomic regions of interest and the same amount of sequencing data, TES provided the highest coverage of target regions when compared to whole genome sequencing, RNA sequencing, and genotyping by sequencing. Single nucleotide polymorphism (SNP) calling and subsequent validation revealed a high validation rate (85.71%) of homozygous SNPs, providing valuable markers for peanut genotyping. This study demonstrated the success of applying TES for SNP identification in peanut, which shall provide valuable suggestions for TES application in other non-model species without a genome reference available.

Integrated genomic analysis of mitochondrial RNA processing in human cancers

BackgroundThe mitochondrial genome is transcribed as continuous polycistrons of RNA containing multiple genes. As a consequence, post-transcriptional events are critical for the regulation of gene expression and therefore all aspects of mitochondrial function. One particularly important process is the m1A/m1G RNA methylation of the ninth position of different mitochondrial tRNAs, which allows efficient processing of mitochondrial mRNAs and protein translation, and de-regulation of genes involved in these processes has been associated with altered mitochondrial function. Although mitochondria play a key role in cancer, the status of mitochondrial RNA processing in tumorigenesis is unknown.MethodsWe measure and assess mitochondrial RNA processing using integrated genomic analysis of RNA sequencing and genotyping data from 1226 samples across 12 different cancer types. We focus on the levels of m1A and m1G RNA methylation in mitochondrial tRNAs in normal and tumor samples and use supervised and unsupervised statistical analysis to compare the levels of these modifications to patient whole genome genotypes, nuclear gene expression, and survival outcomes.ResultsWe find significant changes to m1A and m1G RNA methylation levels in mitochondrial tRNAs in tumor tissues across all cancers. Pathways of RNA processing are strongly associated with methylation levels in normal tissues (P = 3.27 × 10−31), yet these associations are lost in tumors. Furthermore, we report 18 gene-by-disease-state interactions where altered RNA methylation levels occur under cancer status conditional on genotype, implicating genes associated with mitochondrial function or cancer (e.g., CACNA2D2, LMO2, and FLT3) and suggesting that nuclear genetic variation can potentially modulate an individual’s ability to maintain unaltered rates of mitochondrial RNA processing under cancer status. Finally, we report a significant association between the magnitude of methylation level changes in tumors and patient survival outcomes.ConclusionsWe report widespread variation of mitochondrial RNA processing between normal and tumor tissues across all cancer types investigated and show that these alterations are likely modulated by patient genotype and may impact patient survival outcomes. These results highlight the potential clinical relevance of altered mitochondrial RNA processing and provide broad new insights into the importance and complexity of these events in cancer.

Undergraduate Student Research in Quantitative Analysis of Transcription Elongation Perturbation Networks Using Mass Spectrometry

The main goal of this project is to identify how cells respond and adapt to genetic changes that alter the process of RNA synthesis. Using baker's yeast as the study system, experimental approaches provide undergraduate students with early exposure to cutting‐edge research technologies that are broadly applicable in both academia and industry. The project introduces students at all levels of training to the importance of quantitative methods to interrogate biology. The specific focus of the research is to understand the consequences of genetic perturbations that knock out or reduce expression of non‐essential elongation factors on RNA polymerase II‐catalyzed RNA synthesis (transcription). Preliminary data suggest that such genetic perturbations lead to significant adaptations within the RNA polymerase II protein‐protein interaction networks. These adaptations may include (but are not limited to) disruption of interactions with RNA polymerase II, compensation leading to novel protein recruitment, and activation of rescue pathways to dispose of arrested RNA polymerase II. The laboratory portion of an undergraduate course in molecular biology was redesigned to generate elongation factor knock‐out yeast strains with a focus on key molecular biology concepts and techniques including: genomic DNA isolation, oligonucleotide design, PCR, genotyping, protein isolation, and western blotting. In addition to these key concepts, we introduced students to the theory and practice of proteomics analysis through mass spectrometry including discussions of bioinformatics analysis of proteomics data, calculation of false discovery rates, and affinity purification mass spectrometry approaches. Thus far in this study, 9 elongation factor knock out strains have been made and verified by DNA sequencing and are in the process of being analyzed by quantitative mass spectrometry. Data from pre‐ and post‐instructional tests will be presented which demonstrate increased student understanding of mass spectrometry. Additionally, students participated in an 8 week summer internship held at the IU School of Medicine where they extended the project from the classroom lab to performing quantitative mass spectrometry analysis of their elongation factor knock‐outs.Support or Funding InformationDePauw University Student Faculty Research Fund, Showalter Fund (IU), NSF Award Number:1515748 PI Amber Mosley, PhD

Behavior related genes, dietary preferences and anthropometric traits

Food preferences and cognitive control influence dietary habits thus affecting compliance with dietary advice and the risk of chronic diseases. A complex mix of genetic and environmental, cultural and social factors drives these preferences. Therefore, efforts to improve diet and behavior at the individual level should take into consideration this distinct combination of genetic and environmental factors, specifically addressing the psychological component of food consumption with the goal of facilitating long‐term compliance with dietary interventions.ObjectiveTo investigate the association between behavioral candidate genes, food preferences and anthropometric traits.Population and MethodsFor this purpose we used data from the Genetics and Lipid Lowering Drugs and Diet Network (GOLDN) Study including two genetically homogeneous sites (Minneapolis, Minnesota, and Salt Lake City, Utah). In the current study, 818 participants (404 men and 414 women) of European ancestry were included in our analyses. Single nucleotide polymorphisms (SNPs) within 38 loci (1359 SNPs) selected on the basis of previous associations with several behavioral and psychological traits (i.e., stress, addiction, depression, impulsivity, novelty‐seeking, aberrant eating) were extracted from the original genome genotype data that was generated from the Genome‐Wide Human SNP Array 6.0 (Affymetrix). Information about dietary intake was collected with the use of a diet‐history questionnaire, which was developed by the National Cancer Institute.ResultsMultiple nominally significant associations (p&lt;0.05) were observed between genetic variability at the selected loci and the consumption of specific foods and nutrients. However, after adjustment for multiple comparisons, significant associations (Padj&lt;0.05) were observed for the FTO locus with vegetable and total fiber intake; the CREB1 and GABRA2 loci were associated with salt intake; and the SLC6A2 with total fat and monounsaturated fatty acids. Finally, chocolate intake was associated with variation at the OXTR locus. The most significant association with anthropometric traits was found for OXTR and waist circumference.ConclusionOur data indicate that genes implicated in behavioral and psychological traits drive a significant component of an individual's food preferences and dietary habits. This information will contribute to a better understanding of eating behavior and facilitate the implementation of personalized dietary advice that should result in better compliance and more successful prevention and therapy of chronic disorders.Support or Funding InformationNational Heart, Lung, and Blood Institute (NHLBI) grants U01HL072524 (Genetic and Environmental Determinants of Triglycerides), NHLBI R01 HL091357 and by contracts 53‐K06‐5‐10 and 58‐1950‐9‐001 from the USDA, Agriculture Research Service

Exome sequencing identified rare variants in genes HSPG2 and ATP2B4 in a family segregating developmental dysplasia of the hip

BackgroundDevelopmental dysplasia of the hip (DDH) is a common pathological condition of the musculoskeletal system in infants which results in a congenital and developmental malformation of the hip joint. DDH is a spectrum of pathologies affecting the infant hip ranging from asymptomatic subtle radiographic signs through mild instability to frank dislocations with acetabular dysplasia. A Saudi family with three affected individuals with DDH was identified and genetic analysis was performed to detect the possible genetic defect(s) underlying DDH in the affected members of the family.MethodsWe performed whole genome genotyping using Illumina HumanOmni 2.5 M array and whole exome sequencing (WES) using Nextera Rapid capture kit and Illumina NextSeq500 instrument in four individuals of a family with DDH.ResultsSNP data analysis did not identify any runs of homozygosity and copy number variations. Identity-by-descent (IBD) analysis on whole genome genotyping data identified a shared haplotypes on chromosome 1 in affected individuals. An analysis of the WES data identified rare heterozygous variants in HSPG2 and ATP2B4 genes in the affected individuals. Multiple prediction software predicted that the variants identified are damaging. Moreover, in silico analysis showed that HSPG2 regulates ATP2B4 expression using a variety of transcription factors.ConclusionOur results indicate that there might be a functional epistatic interaction between HSPG2 and ATP2B4, and DDH in the family studied is due to a combined effect of both variants. These variants are also present in the asymptomatic mother suggesting that the variants in HSPG2 and ATP2B4 are incompletely penetrant. This study provides the first evidence of digenic inheritance of DDH in a family and extends the spectrum of genetic heterogeneity in this human disorder.

Genomic Loads and Genotypes of Respiratory Syncytial Virus: Viral Factors during Lower Respiratory Tract Infection in Chilean Hospitalized Infants.

The clinical impact of viral factors (types and viral loads) during respiratory syncytial virus (RSV) infection is still controversial, especially regarding newly described genotypes. In this study, infants with RSV bronchiolitis were recruited to describe the association of these viral factors with severity of infection. RSV antigenic types, genotypes, and viral loads were determined from hospitalized patients at Hospital Roberto del Río, Santiago, Chile. Cases were characterized by demographic and clinical information, including days of lower respiratory symptoms and severity. A total of 86 patients were included: 49 moderate and 37 severe cases. During 2013, RSV-A was dominant (86%). RSV-B predominated in 2014 (92%). Phylogenetic analyses revealed circulation of GA2, Buenos Aires (BA), and Ontario (ON) genotypes. No association was observed between severity of infection and RSV group (p = 0.69) or genotype (p = 0.87). After a clinical categorization of duration of illness, higher RSV genomic loads were detected in infants evaluated earlier in their disease (p < 0.001) and also in infants evaluated later, but coursing a more severe infection (p = 0.04). Although types and genotypes did not associate with severity in our children, higher RSV genomic loads and delayed viral clearance in severe patients define a group that might benefit from new antiviral therapies.