Validation Of SNPs Research Articles

Probing Genetics and Environmental Factors underlying Uterine Fibroid Tumorigenesis in Ghana, West Africa

Uterine fibroid (UF) is the most prevalent benign tumour that affects millions of women globally, with a high incidence of 70% amongst women of reproductive age. UF has been associated with various complications, such as recurrent surgeries, infertility, anemia and pregnancy loss. Notably, women of African descent often experience more severe symptoms and complications. Although hormones, growth factors, and genetic alterations are widely associated with UF, the precise mechanism underlying its pathogenesis is not fully understood. Recent evidence suggests altered microbiota may serve as a potential risk factor for UF development. Altered microbiota can contribute to tumorigenesis via epigenetic changes to host cells or toxic effects from invasion. The lack of curative-drug treatment poses significant challenges to patients with UF. Patients often undergo surgeries that require the removal of the uterus or tumour, which can negatively impact fertility. Furthermore, uterine fibroids’ diagnosis relies on expensive imaging technologies such as ultrasound, which may not be readily available in developing countries. Moreso, diagnosis is often conducted only after patients’ symptoms become severe. Although late presentation may contribute to severe symptoms and complications among women with UF in Africa, other factors that influence severity and increase incidence in this population remain unknown. A comprehensive assessment of UF predisposing factors in high-risk populations such as Ghana could give better insights into disease pathogenesis. Hence, this study aims to assess: UF-associated demographic factors, the role of uterine microbiota dysbiosis on UF tumorigenesis; and molecular markers associated with UF in the Ghanaian population. Epidemiological data and clinical samples (tissues, blood and cervico-vaginal swabs) will be obtained. The characterization of samples will involve metagenomics, whole genome sequencing, functional validation of SNPs and SNP genotyping. The association of risk alleles with disease phenotypes will be assessed via regression analysis using PLINK v.1.9. The findings will provide information on potential disease markers that can be explored for better management strategies for UF in high-risk populations.

Abstract 1516 Computational Prediction and Biochemical Validation of CVD-associated SNPs Altering NKX2-5 DNA-binding

Abstract 1516 Computational Prediction and Biochemical Validation of CVD-associated SNPs Altering NKX2-5 DNA-binding

Computational Identification and Validation of Non-Synonymous SNPs in Progesterone Receptor Membrane Complex 1 Linked to Lung Cancer

Numerous gene polymorphisms have been attributed to Lung cancer, but PGRMC1 (Progesterone receptor membrane component 1) is a lesser-known candidate among them. However, emerging research is slowly suggesting the role of polymorphisms in PGRMC1 gene-associated tumorigenesis. Nevertheless, phenotypic changes still need to be studied. The main aim of this study is to identify the most deleterious nsSNPs (non-synonymous single nucleotide polymorphisms) in PGRMC1 that can potentially increase the susceptibility to lung cancer progression. In this work, we scrutinized highly detrimental nsSNPs for PGRMC1 from the available dbSNP database. We further categorized using the FATHMM server to enlist the nsSNPs, which are driver mutants capable of affecting the function of the PGRMC1 protein. We employed clinical evidence from the COSMIC database for further evaluation and confirming the presence of nsSNPs in lung cancer patients. There are 12 nsSNPs reported in lung cancer patients, which are L32M, R47C, D141N, G20W, S57C, R70P, I89V, G118V, A191D, G95V, E157K, and G168V predicted to damage the functions. Conclusively, through a comprehensive comparison of the outcomes obtained through these computational methods, we identified novel I89V, D120E, G95V and G168V nsSNPs that pose substantial risks to the functionality of the PGRMC1 protein. Focusing on the importance of PGRMC1 in lung cancer, analyzing its function was conceded to unveil the interlink between genetic mutation and phenotypic changes. Thus, this study provides insights into the influence of PGRMC1variants in Lung cancer. The evaluated nsSNPs can significantly aid future research on the gene and its association with lung cancer progression in large population distribution frequencies of genotypes among different subgroups.

Evaluation of SNPs from human IGFBP6 associated with gene expression: an in-silico study

In the bloodstream and in local tissues, most IGF molecules are associated with the one of the members of the IGF-binding protein (IGFBP) family, which are divided into six distinct types. IGF-binding proteins have been demonstrated to either decrease or increase the growth-promoting effects of IGFs on cell culture, by extending their half-life. They alter how IGFs interact with the receptors on their cell surfaces. IGFBP6 gene is associated with disease in-situ carcinoma. Upregulation or downregulation of IGFBP6 gene has been implicated in different types of cancer in humans. Nonsynonymous SNPs changes have the potential to affect the protein’s structure and function. Potential functional SNPs can be assessed before undertaking studies in larger populations because validation of these functional SNPs can be a crucial problem. So, in this in-silico investigation, we used a variety of sequence- and structure-based bioinformatics methods to separate the potential nsSNPs of the IGFBP6 gene from the neutral ones. In total of 216 nsSNPs, 5 were found to have potential effects using 5 prediction tools. From which, 2 nsSNPs (R128G and R164H) were selected as potentially damaging due to their presence in highly conserved region and ability to decrease protein stability. Among these 2 nsSNPs, only R164H was found to be associated with Uterine corpus endometrial carcinoma. It was also found that both, upregulation or downregulation of IGFBP6 gene can lead to the different types of cancers. The findings of the present study will certainly be valuable in the future large population-based investigations as well as drug discovery, especially developing personalized medicine.Communicated by Ramaswamy H. Sarma

Validation of SNPs Identified by Amplicon Sequencing and their Association with Egg Production and Egg Weight in Anand Synthetic White Leghorn and Anand Bantamised White Leghorn Chicken

The present study was aimed to validate the previously found SNPs using NGS-based amplicon sequencing and investigate of their association with egg production and egg weight by PCR-RFLP in Anand Synthetic White Leghorn (ASWLH) and Anand Bantamised White Leghorn (ABWLH) chicken. A total of 500 blood samples were collected including, 227 samples of ASWLH and 273 of ABWLH maintained at the Poultry Research Station, Anand Agricultural University, Anand, Gujarat. The study was conducted for a total of eight SNP markers located across the four genes involved in physiological pathways related to egg production and egg weight, viz., GnRHII (T88170424C), GnRHII (G88170427A), VIPR1 (C1826542A), VIPR1 (C1826555T), OCX32 (C21912308T), OCX32 (T21912084G), OCX32 (C21912423A) and GHR (C13415980T). Out of eight SNPs, C21912423A of the OCX32 gene was significantly associated with egg weight at the 40 weeks of age (EW40) in the whole population. The G88170427A of the GnRHII gene was significantly associated with egg weight at the 28 weeks of age (EW28) and C21912308T of the OCX-32 gene was significantly associated with total egg number at the age of 64 weeks (TWN64) in the whole population.

Validation of SNPs associated with late severe toxicity after radiotherapy for prostate cancer

Validation of SNPs associated with late severe toxicity after radiotherapy for prostate cancer

Systems analysis of avascular necrosis of femoral head using integrative data analysis and literature mining delineates pathways associated with disease

Avascular necrosis of femoral head (AVNFH) is a debilitating disease, which affects the middle aged population. Though the disease is managed using bisphosphonate, it eventually leads to total hip replacement due to collapse of femoral head. Studies regarding the association of single nucleotide polymorphisms with AVNFH, transcriptomics, proteomics, metabolomics, biophysical, ultrastructural and histopathology have been carried out. Functional validation of SNPs was carried out using literature. An integrated systems analysis using the available datasets might help to gain further insights into the disease process. We have carried out an analysis of transcriptomic data from GEO-database, SNPs associated with AVNFH, proteomic and metabolomic data collected from literature. Based on deficiency of vitamins in AVNFH, an enzyme-cofactor network was generated. The datasets are analyzed using ClueGO and the genes are binned into pathways. Metabolomic datasets are analyzed using MetaboAnalyst. Centrality analysis using CytoNCA on the data sets showed cystathionine beta synthase and methylmalonyl-CoA-mutase to be common to 3 out of 4 datasets. Further, the genes common to at least two data sets were analyzed using DisGeNET, which showed their involvement with various diseases, most of which were risk factors associated with AVNFH. Our analysis shows elevated homocysteine, hypoxia, coagulation, Osteoclast differentiation and endochondral ossification as the major pathways associated with disease which correlated with histopathology, IHC, MRI, Micro-Raman spectroscopy etc. The analysis shows AVNFH to be a multi-systemic disease and provides molecular signatures that are characteristic to the disease process.

Genome-Wide Epistatic Interaction Networks Affecting Feed Efficiency in Duroc and Landrace Pigs

Interactions among genomic loci have often been overlooked in genome-wide association studies, revealing the combinatorial effects of variants on phenotype or disease manifestation. Unexplained genetic variance, interactions among causal genes of small effects, and biological pathways could be identified using a network biology approach. The main objective of this study was to determine the genome-wide epistatic variants affecting feed efficiency traits [feed conversion ratio (FCR) and residual feed intake (RFI)] based on weighted interaction SNP hub (WISH-R) method. Herein, we detected highly interconnected epistatic SNP modules, pathways, and potential biomarkers for the FCR and RFI in Duroc and Landrace purebreds considering the whole population, and separately for low and high feed efficient groups. Highly interacting SNP modules in Duroc (1,247 SNPs) and Landrace (1,215 SNPs) across the population and for low feed efficient (Duroc—80 SNPs, Landrace—146 SNPs) and high feed efficient group (Duroc—198 SNPs, Landrace—232 SNPs) for FCR and RFI were identified. Gene and pathway analyses identified ABL1, MAP3K4, MAP3K5, SEMA6A, KITLG, and KAT2B from chromosomes 1, 2, 5, and 13 underlying ErbB, Ras, Rap1, thyroid hormone, axon guidance pathways in Duroc. GABBR2, GNA12, and PRKCG genes from chromosomes 1, 3, and 6 pointed towards thyroid hormone, cGMP-PKG and cAMP pathways in Landrace. From Duroc low feed efficient group, the TPK1 gene was found involved with thiamine metabolism, whereas PARD6G, DLG2, CRB1 were involved with the hippo signaling pathway in high feed efficient group. PLOD1 and SETD7 genes were involved with lysine degradation in low feed efficient group in Landrace, while high feed efficient group pointed to genes underpinning valine, leucine, isoleucine degradation, and fatty acid elongation. Some SNPs and genes identified are known for their association with feed efficiency, others are novel and potentially provide new avenues for further research. Further validation of epistatic SNPs and genes identified here in a larger cohort would help to establish a framework for modelling epistatic variance in future methods of genomic prediction, increasing the accuracy of estimated genetic merit for FE and helping the pig breeding industry.

TCTEX1D1 is a genetic modifier of disease progression in Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is caused by pathogenic variants in the DMD gene leading to the lack of dystrophin. Variability in the disease course suggests that other factors influence disease progression. With this study we aimed to identify genetic factors that may account for some of the variability in the clinical presentation. We compared whole-exome sequencing (WES) data in 27 DMD patients with extreme phenotypes to identify candidate variants that could affect disease progression. Validation of the candidate SNPs was performed in two independent cohorts including 301 (BIO-NMD cohort) and 109 (CINRG cohort of European ancestry) DMD patients, respectively. Variants in the Tctex1 domain containing 1 (TCTEX1D1) gene on chromosome 1 were associated with age of ambulation loss. The minor alleles of two independent variants, known to affect TCTEX1D1 coding sequence and induce skipping of its exon 4, were associated with earlier loss of ambulation. Our data show that disease progression of DMD is affected by a new locus on chromosome 1 and demonstrate the possibility to identify genetic modifiers in rare diseases by studying WES data in patients with extreme phenotypes followed by multiple layers of validation.

Transcriptional profiling of contrasting genotypes revealed key candidates and nucleotide variations for drought dissection in Camellia sinensis (L.) O. Kuntze

Tea is popular health beverage consumed by millions of people worldwide. Drought is among the acute abiotic stress severely affecting tea cultivation, globally. In current study, transcriptome sequencing of four diverse tea genotypes with inherent contrasting genetic response to drought (tolerant & sensitive) generated more than 140 million reads. De novo and reference-based assembly and functional annotation of 67,093 transcripts with multifarious public protein databases yielded 54,484 (78.2%) transcripts with significant enrichment of GO and KEGG drought responsive pathways in tolerant genotypes. Comparative DGE and qRT analysis revealed key role of ABA dependent & independent pathways, potassium & ABC membrane transporters (AtABCG22, AtABCG11, AtABCC5 & AtABCC4) and antioxidant defence system against oxidative stress in tolerant genotypes, while seems to be failed in sensitive genotypes. Additionally, highly expressed UPL3HECT E3 ligases and RING E3 ligases possibly enhance drought tolerance by actively regulating functional modification of stress related genes. Further, ascertainment of, 80803 high quality putative SNPs with functional validation of key non-synonymous SNPs suggested their implications for developing high-throughput genotyping platform in tea. Futuristically, functionally relevant genomic resources can be potentially utilized for gene discovery, genetic engineering and marker-assisted genetic improvement for better yield and quality in tea under drought conditions.

Assessment of OvineSNP50 in Nigerian and Kenyan sheep populations

Deciphering genomic information requires markers that are polymorphic and sufficient enough to capture its vast array of genetic data. Polymorphic loci can differ greatly between breeds of the same species and the exclusion of the Nigerian and some African sheep breeds during the development of the OvineSNP50 chip necessitated the validation of SNPs included on the chip to allow for genomic applications of the excluded breeds. A total of sixty sheep samples were genotyped [10 each of the Balami, Uda, West African Dwarf and Yankasa from Nigeria, Dorper and Red Maasai from Kenya (East Africa)] using the Ovine 50k Illumina SNP bead chip. Results revealed that 33,994 SNPs (97.47%) of the called 34,876 SNPs were validated for downstream analysis. Mean heterozygosity values of 0.154 and 0.153 were obtained for polymorphic SNPs on sex and autosomal chromosomes respectively, while the values of 0.662 and 0.054 were obtained on the sex and autosomal chromosomes respectively for the mean identity-bystate (IBS). Six and three individuals violated the per ID and identity-by-state (IBS) thresholds, respectively. It was observed that the Ovine 50k Illumina SNP bead chip was informative in the Nigerian and East African sheep that were studied, and should be useful in examining the underlying genetic variation. Keywords: Sheep, OvineSNP50, genome-wide, call rate, minor allele frequency

DEVELOPMENT OF SNP MARKERS PRESENT IN EXPRESSED GENES OF THE PLANT-PATHOGEN INTERACTION: Theobroma cacao - Moniliophtora perniciosa

We report the detection, validation and analysis of SNPs in the plant-pathogen interaction between cacao and Moniliophthora perniciosa ESTs using resequencing. This analysis in 73 EST sequences allowed the identification of 185 SNPs, 57% of them corresponding to transversion, 29% to transition and 14% to indels. The ESTs containing SNPs were classified into 14 main functional categories. After validation, 91 SNPs were confirmed, categorized and the parameters of nucleotide diversity and haplotype were calculated. Haplotype-based gene diversity and polymorphic information content (PIC) ranged from 0.559 to 0.56 and 0.115 to 0.12; respectively. Also, it was the advantage when considering haplotypes structure for each locus in place of single SNPs. Most of the gene fragments had a major haplotype combined to a series of low frequency haplotypes. Thus, the re-sequencing approach proved to be a valuable resource to identify useful SNPs for wide genetic applications. Furthermore, the cacao genome sequence availability allow a positional selection of DNA fragments to be re-sequenced enhancing the usefulness of the discovered SNPs. These results indicate the potential use of SNPs markers to identify allelic status of cacao resistance genes through marker-assisted selection to support the development of promising genotypes with high resistance to witch's broom disease. (Resume d'auteur)

Predicting the functional consequences of non-synonymous single nucleotide polymorphisms in IL8 gene

Here we report an in-silico approach for identification, characterization and validation of deleterious non-synonymous SNPs (nsSNPs) in the interleukin-8 gene using three steps. In first step, sequence homology-based genetic analysis of a set of 50 coding SNPs associated with 41 rsIDs using SIFT (Sorting Intolerant from Tolerant) and PROVEAN (Protein Variation Effect Analyzer) identified 23 nsSNPs to be putatively damaging/deleterious in at least one of the two tools used. Subsequently, structure-homology based PolyPhen-2 (Polymorphism Phenotyping) analysis predicted 9 of 23 nsSNPs (K4T, E31A, E31K, S41Y, I55N, P59L, P59S, L70P and V88D) to be damaging. According to the conditional hypothesis for the study, only nsSNPs that score damaging/deleterious prediction in both sequence and structural homology-based approach will be considered as ‘high-confidence’ nsSNPs. In step 2, based on conservation of amino acid residues, stability analysis, structural superimposition, RSMD and docking analysis, the possible structural-functional relationship was ascertained for high-confidence nsSNPs. Finally, in a separate analysis (step 3), the IL-8 deregulation has also appeared to be an important prognostic marker for detection of patients with gastric and lung cancer. This study, for the first time, provided in-depth insights on the effects of amino acid substitutions on IL-8 protein structure, function and disease association.

Computational identification of non-synonymous polymorphisms within regions corresponding to protein interaction sites

BackgroundProtein-protein interactions (PPI) play an important role in function of all organisms and enable understanding of underlying metabolic processes. Computational predictions of PPIs are an important aspect in proteomics, as experimental methods may result in high degree of false positive results and are more expensive. Although there are many databases collecting predicted PPIs, exploration of genetics information underlying PPI interactions has not been investigated thoroughly. The aim of the present study was to identify genomic locations corresponding to regions involved in predicted PPIs and to collect non-synonymous polymorphisms (nsSNPs) located within those regions; which we termed PPI-SNPs. MethodsPredicted PPIs were obtained from PiSITE database (http://pisite.hgc.jp). Non-synonymous SNPs mapped on protein structural data (PDBs) were obtained from the UCSC server. Polymorphism locations on protein structures were mapped to predicted PPI regions. DAVID tool was used for pathway enrichment and gene cluster analysis (https://david.ncifcrf.gov/). ResultsWe collected 544 polymorphisms located within predicted PPI sites that map to 197 genes. We identified 9 SNPs, previously associated with diseases, but not yet associated with PPI sites. We also found examples in which polymorphisms located within predicted PPI regions are also occurring within previously experimentally validated PPIs and within experimentally determined functional domains. ConclusionsOur study provides the first catalog of nsSNPs located within predicted PPIs. These prioritized SNPs present the basis for planning experimental validation of SNPs that cause gain or loss of PPIs. Our implementation is expandable, as datasets used are constantly updated.

Evolutionary divergence in Chenopodium and validation of SNPs in chloroplast rbcL and matk genes by allele-specific PCR for development of Chenopodium quinoa-specific markers

The genus Chenopodium comprises about 150 species, of which Chenopodium quinoa and C. album are important for their nutritional value. Evaluation of variation in qualitative morphological traits of plants and SNPs in chloroplast rbcL and matK gene sequences in 19 accessions representing C. quinoa and C. album indicated that the accessions IC-411824 and IC-411825, which have white seeds, belong to C. quinoa rather than C. album. This observation was also supported by a time tree that indicated IC-411824 and IC-411825 to be a sister clade to accessions of C. quinoa with an estimated age of 1.2Mya. Whereas multiple alignments of rbcL gene sequences from the 19 accessions revealed 1.26% parsimony-informative sites with 0.68% interspecific sequence diversity, alignment of nucleotide sequences of amplicons representing the matK gene revealed 4.97% parsimony-informative sites and 2.81% interspecific sequence diversity. Validation of SNPs in the cp rbcL and matK regions of 36 accessions belonging to C. quinoa and C. album was performed by allele-specific PCR with primers carrying a single base change at the 3′ end. We report the first C. quinoa-specific SNP-based primer, R1RQ-AFR, designed from rbcL sequences, that could differentiate quinoa from 64 genera including 13 species of the genus Chenopodium. With an estimated age of 10.5–4.1million years (Myr), the Himalayan chenopods are evolutionarily younger than the Andean chenopods. The results establish the paraphyletic origin of the genus Chenopodium.

Melanoma Expression Genes Identified through Genome-Wide Association Study of Breslow Tumor Thickness

rs12203592 falls within an enhancer region of IRF4; the T allele impairs transcription factor binding, leading to reduced expression of IRF4 and tyrosinase (Praetorius et al., 2013). In a recent meta-analysis, the association between rs12203592 polymorphism and SCC was significant in dominant, recessive, and codominant models (Wu et al., 2016). The additive genetic model was selected a priori for our study, but exploration of the codominant model confirmed the association between SCC risk and the TT versusCCgenotype (HR1⁄4 2.24, 95% confidence interval 1⁄4 1.22e4.09, P 1⁄4 0.009). Previous studies investigating genetic risks for cSCC in OTRs have been limited by small sample sizes and candidate gene approach; the recent GWAS for cSCC has informed our candidate gene selection in this cohort. Our study design enabled investigation of these genes in the context of Fitzpatrick skin type, an important risk factor. Our data show that genotype data can improve risk stratification for posttransplantation cSCC beyond the clinical pigmentation phenotype. Strengths of this study include a wellcharacterized cohort with Fitzpatrick type and histopathologic confirmation of cSCC outcomes. The genotyping array is the same as that used in Asgari et al. (2016), allowing direct validation of SNPs reported in that publication. The primary limitation is small sample size, but this pilot data supports development of cohort studies to generate

Genome-Wide Association Studies for Taxane-Induced Peripheral Neuropathy in ECOG-5103 and ECOG-1199.

Taxane-induced peripheral neuropathy (TIPN) is an important survivorship issue for many cancer patients. Currently, there are no clinically implemented biomarkers to predict which patients might be at increased risk for TIPN. We present a comprehensive approach to identification of genetic variants to predict TIPN. We performed a genome-wide association study (GWAS) in 3,431 patients from the phase III adjuvant breast cancer trial, ECOG-5103 to compare genotypes with TIPN. We performed candidate validation of top SNPs for TIPN in another phase III adjuvant breast cancer trial, ECOG-1199. When evaluating for grade 3-4 TIPN, 120 SNPs had a P value of <10(-4) from patients of European descent (EA) in ECOG-5103. Thirty candidate SNPs were subsequently tested in ECOG-1199 and SNP rs3125923 was found to be significantly associated with grade 3-4 TIPN (P = 1.7 × 10(-3); OR, 1.8). Race was also a major predictor of TIPN, with patients of African descent (AA) experiencing increased risk of grade 2-4 TIPN (HR, 2.1; P = 5.6 × 10(-16)) and grade 3-4 TIPN (HR, 2.6; P = 1.1 × 10(-11)) compared with others. An SNP in FCAMR, rs1856746, had a trend toward an association with grade 2-4 TIPN in AA patients from the GWAS in ECOG-5103 (OR, 5.5; P = 1.6 × 10(-7)). rs3125923 represents a validated SNP to predict grade 3-4 TIPN. Genetically determined AA race represents the most significant predictor of TIPN.

LOXL1 gene variants and their association with pseudoexfoliation glaucoma (XFG) in Spanish patients.

BackgroundLOXL1 gene is the most important genetic risk factor known so far for pseudoexfoliation glaucoma (XFG). Our purpose was to evaluate the potential association of individual genetic variants of the lysyl oxidase-like 1 (LOXL1) gene and haplotypes with XFG in Spanish patients.MethodsBlood samples were collected from a total of 105 Spanish patients with XFG and 200 healthy controls. The entire LOXL1 gene along with the promoter, coding and non-coding regions including the 5´- and 3´-untranslated regions, were sequenced using next-generation sequencing in 99 XFG patients. SNPs rs16958477 (promoter), rs1048661 (exon 1), rs3825942 (exon 1), rs2165241 (intron 1) and rs3522 (exon 7) in LOXL1 were genotyped by restriction fragment-length polymorphism (RFLP) in all Spanish control participants and in six additional XFG patients, and a case–control association study was performed.Comparisons of the allelic and genotypic frequencies were performed using standard χ2 test with Bonferroni and Pearson corrections. Logistic regression analyses were permormed using Sigmaplot v11. Haplotypes frequencies were performed using HaploView 4.0.ResultsSequencing of the LOXL1 gene in XFG participants identified a total of 212 SNPs, of which 49 exhibited allelic frequencies with significant differences between cases and controls, and 66 were not previously described. The allele frequencies of SNPs rs16958477, rs1048661, rs3825942, rs2165241, were significantly associated with an increased risk for XFG, however the SNP rs3522 was not.The haplotype frequencies of SNPs rs16958477, rs1048661, rs3825942 and rs2165241 and their association with XFG indicated that the CGGT haplotype, containing all four risk alleles, and the AGGT haplotype, which carries the protective allele of rs16958477 and three risk alleles of the other three SNPs, were significantly associated with XFG (p = 4.5×10−6, and p = 8.8×10−6), conferring more than 2-fold increased disease susceptibility.ConclusionsSNPs of the LOXL1 gene are associated with XFG in the Spanish population. This information adds new support to the distinct risk association frequencies of LOXL1 alleles with XFG in Western European and Asian populations. Identification and validation of additional SNPs along the entire LOXL1 gene of XFG cases may provide insightful information on their potential role in the pathogenesis of this disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-015-0221-y) contains supplementary material, which is available to authorized users.

Validation of the 50k Illumina goat SNP chip in the South African Angora goat

Tools for the genomic evaluation of goats have generally lagged behind those for other species. However, the recent availability of the goat SNP50 consortium bead chip has marked a positive change for this small ruminant species. Polymorphic loci can differ greatly between breeds of the same species. Exclusion of fibre-producing breeds, such as the Angora goat, during the development of this genotyping array necessitates the validation of SNPs included on the chip to allow for genomic applications that would accelerate genetic progress in mohair yield and quality. Forty eight unrelated Angora goats, displaying phenotypic variation in two important price-determining traits, namely fibre diameter and fleece weight, were genotyped with the goat SNP50 consortium bead chip. Results revealed that 46 983 SNP (88.1%) of the 53 347 called SNPs were polymorphic (MAF&gt;0.05). After quality control, 3 960 SNP were filtered from further analysis for violating Hardy-Weinberg and call-rate parameter thresholds, leaving 43 759 (82%) of the 53 347 SNPs to be validated for downstream analysis. Observed and expected heterozygosity values of 0.365 and 0.370, respectively, were obtained for polymorphic SNPs. A total of 30 357 SNPs in linkage disequilibrium (LD) were removed to obtain a set of independent markers, resulting in a final SNP density of 1 SNP/ ~226 kb. Results indicate that the goat SNP50 bead chip was informative in the Angora goats that were studied, and should be useful in examining the underlying genetic variationKeywords: Call rate, Hardy-Weinberg equilibrium, linkage disequilibrium, minor allele frequency

Validation of the 50k Illumina goat SNP chip in the South African Angora goat : short communication

Tools for the genomic evaluation of goats have generally lagged behind those for other species. However, the recent availability of the goat SNP50 consortium bead chip has marked a positive change for this small ruminant species. Polymorphic loci can differ greatly between breeds of the same species. Exclusion of fibre-producing breeds, such as the Angora goat, during the development of this genotyping array necessitates the validation of SNPs included on the chip to allow for genomic applications that would accelerate genetic progress in mohair yield and quality. Forty eight unrelated Angora goats, displaying phenotypic variation in two important price-determining traits, namely fibre diameter and fleece weight, were genotyped with the goat SNP50 consortium bead chip. Results revealed that 46 983 SNP (88.1%) of the 53 347 called SNPs were polymorphic (MAF>0.05). After quality control, 3 960 SNP were filtered from further analysis for violating Hardy-Weinberg and call-rate parameter thresholds, leaving 43 759 (82%) of the 53 347 SNPs to be validated for downstream analysis. Observed and expected heterozygosity values of 0.365 and 0.370, respectively, were obtained for polymorphic SNPs. A total of 30 357 SNPs in linkage disequilibrium (LD) were removed to obtain a set of independent markers, resulting in a final SNP density of 1 SNP/ ~226 kb. Results indicate that the goat SNP50 bead chip was informative in the Angora goats that were studied, and should be useful in examining the underlying genetic variation.