Identification Of Genomic Regions Research Articles

Towards Precision Medicine for Hypertension: A Review of Genomic, Epigenomic, and Microbiomic Effects on Blood Pressure in Experimental Rat Models and Humans.

Compelling evidence for the inherited nature of essential hypertension has led to extensive research in rats and humans. Rats have served as the primary model for research on the genetics of hypertension resulting in identification of genomic regions that are causally associated with hypertension. In more recent times, genome-wide studies in humans have also begun to improve our understanding of the inheritance of polygenic forms of hypertension. Based on the chronological progression of research into the genetics of hypertension as the "structural backbone," this review catalogs and discusses the rat and human genetic elements mapped and implicated in blood pressure regulation. Furthermore, the knowledge gained from these genetic studies that provide evidence to suggest that much of the genetic influence on hypertension residing within noncoding elements of our DNA and operating through pervasive epistasis or gene-gene interactions is highlighted. Lastly, perspectives on current thinking that the more complex "triad" of the genome, epigenome, and the microbiome operating to influence the inheritance of hypertension, is documented. Overall, the collective knowledge gained from rats and humans is disappointing in the sense that major hypertension-causing genes as targets for clinical management of essential hypertension may not be a clinical reality. On the other hand, the realization that the polygenic nature of hypertension prevents any single locus from being a relevant clinical target for all humans directs future studies on the genetics of hypertension towards an individualized genomic approach.

XCAVATOR: accurate detection and genotyping of copy number variants from second and third generation whole-genome sequencing experiments

BackgroundWe developed a novel software package, XCAVATOR, for the identification of genomic regions involved in copy number variants/alterations (CNVs/CNAs) from short and long reads whole-genome sequencing experiments.ResultsBy using simulated and real datasets we showed that our tool, based on read count approach, is capable to predict the boundaries and the absolute number of DNA copies CNVs/CNAs with high resolutions. To demonstrate the power of our software we applied it to the analysis Illumina and Pacific Bioscencies data and we compared its performance to other ten state of the art tools.ConclusionAll the analyses we performed demonstrate that XCAVATOR is capable to detect germline and somatic CNVs/CNAs outperforming all the other tools we compared. XCAVATOR is freely available at http://sourceforge.net/projects/xcavator/.

Abstract 1378: Identification of genomic regions associated with temozolomide resistance in glioblastoma through analysis of histone marks on chromatin

Abstract Glioblastoma (GBM) is an aggressive and fatal primary brain tumor. Temozolomide (TMZ) is a critical component of the standard care of newly diagnosed GBM patients, but unfortunately preexisting primary resistance and rapid emergence of secondary resistance invariably limits the therapeutic benefit of TMZ in GBM. Prior studies have identified genetic and epigenetic alterations that can modulate TMZ sensitivity and treatment outcome. However, comprehensive analysis of histone marks and knowledge of epigenetic regulation of genes associated with TMZ sensitivity or resistance is lacking. To identify epigenetic states associated with TMZ resistance, we performed an epigenetic profiling of eight different histone marks in GBM xenografts. Using chromatin immunoprecipitation combined with high throughput sequencing (ChIP-seq), distribution of H3K4me1, H3K4me3, H3K9ac, H3K9me2, H3K9me3, H3K27ac, H3K27me3 and H3K36me3 histone marks was compared in a panel of GBM patient-derived xenograft sub-lines derived by treating TMZ sensitive GBM12 tumors with placebo (n=2 sublines) or temozolomide (n=6 sub-lines) and then propagating resulting recurrent tumors. Our analysis revealed that H3K4me1 and H3K27ac modification patterns varied globally across individual sub-lines, while distribution of H3K4me3, H3K36me3 histone marks was specifically altered in discrete genomic regions in resistant sub-lines depending on the mechanisms of resistance. To find how epigenetic modifications affect TMZ sensitivity, we analyzed ChIP-Seq data using Hidden Markov Model to test if one or a combination of histone marks relates to TMZ resistance. The effect of histone modifications on transcription was simultaneously determined by RNA sequencing. These analyses helped identify specific histone modifications which could be functionally related to TMZ resistance. Through these analyses we have identified 1142 genomic regions governed by a specific epigenetic pattern. We subsequently analyzed a candidate genomic region on top of the list. By using Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated nucleases 9 system (CRISPR/Cas9 system), we have generated clones from an intrinsically TMZ resistant SKMG3 cell line with deletion up to four-kilo base genomic region. Clonogenic growth assays showed that deletion of this genomic region enhanced TMZ sensitivity, reducing the IC50 from 186 μM to less than 60μM, p<0.05. This finding indicates that this genomic region is functionally related with TMZ sensitivity. Taken together, our study reveals epigenetic modifications related to TMZ resistance in GBM cells and a specific genomic region involved in regulating TMZ sensitivity. The analysis of epigenetic state at this genomic region could potentially be useful in predicting treatment response and may help in designing TMZ sensitizing therapy in GBM. Citation Format: Xiaoyue Chen, Haiyun Gan, Jeong Heong Lee, Dong Fang, Gaspar Kitange, Jann Sarkaria, Zhiguo Zhang. Identification of genomic regions associated with temozolomide resistance in glioblastoma through analysis of histone marks on chromatin [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 1378. doi:10.1158/1538-7445.AM2017-1378

Identification of genomic regions for grain yield and yield stability and their epistatic interactions

The task of identifying genomic regions conferring yield stability is challenging in any crop and requires large experimental data sets in conjunction with complex analytical approaches. We report findings of a first attempt to identify genomic regions with stable expression and their individual epistatic interactions for grain yield and yield stability in a large elite panel of wheat under multiple environments via a genome wide association mapping (GWAM) approach. Seven hundred and twenty lines were genotyped using genotyping-by-sequencing technology and phenotyped for grain yield and phenological traits. High gene diversity (0.250) and a moderate genetic structure (five groups) in the panel provided an excellent base for GWAM. The mixed linear model and multi-locus mixed model analyses identified key genomic regions on chromosomes 2B, 3A, 4A, 5B, 7A and 7B. Further, significant epistatic interactions were observed among loci with and without main effects that contributed to additional variation of up to 10%. Simple stepwise regression provided the most significant main effect and epistatic markers resulting in up to 20% variation for yield stability and up to 17% gain in yield with the best allelic combination.

Genome-wide association study for conformation traits in three Danish pig breeds

BackgroundSelection for sound conformation has been widely used as a primary approach to reduce lameness and leg weakness in pigs. Identification of genomic regions that affect conformation traits would help to improve selection accuracy for these lowly to moderately heritable traits. Our objective was to identify genetic factors that underlie leg and back conformation traits in three Danish pig breeds by performing a genome-wide association study followed by meta-analyses.MethodsData on four conformation traits (front leg, back, hind leg and overall conformation) for three Danish pig breeds (23,898 Landrace, 24,130 Yorkshire and 16,524 Duroc pigs) were used for association analyses. Estimated effects of single nucleotide polymorphisms (SNPs) from single-trait association analyses were combined in two meta-analyses: (1) a within-breed meta-analysis for multiple traits to examine if there are pleiotropic genetic variants within a breed; and (2) an across-breed meta-analysis for a single trait to examine if the same quantitative trait loci (QTL) segregate across breeds. SNP annotation was implemented through Sus scrofa Build 10.2 on Ensembl to search for candidate genes.ResultsAmong the 14, 12 and 13 QTL that were detected in the single-trait association analyses for the three breeds, the most significant SNPs explained 2, 2.3 and 11.4% of genetic variance for back quality in Landrace, overall conformation in Yorkshire and back quality in Duroc, respectively. Several candidate genes for these QTL were also identified, i.e. LRPPRC, WRAP73, VRTN and PPARD likely control conformation traits through the regulation of bone and muscle development, and IGF2BP2, GH1, CCND2 and MSH2 can have an influence through growth-related processes. Meta-analyses not only confirmed many significant SNPs from single-trait analyses with higher significance levels, but also detected several additional associated SNPs and suggested QTL with possible pleiotropic effects.ConclusionsOur results imply that conformation traits are complex and may be partly controlled by genes that are involved in bone and skeleton development, muscle and fat metabolism, and growth processes. A reliable list of QTL and candidate genes was provided that can be used in fine-mapping and marker assisted selection to improve conformation traits in pigs.

Expression quantitative locus mapping for identification of hotspots using an empirical Bayes mixture model

Identification of genomic regions that regulate gene expression can help our understanding of the mechanisms underlying genetic contributions to phenotypic variations. Hence, we consider a mixture model to locate candidate genomic regions that are more frequently associated with gene expression traits. A modified two-sample t-statistic was used, and single-nucleotide polymorphisms (SNPs) with P-values <10-5 were considered for a subsequent two-component negative binomial mixture model. An expectation-maximisation algorithm was adopted to identify the parameters involved in the model. The SNPs were then ranked based on their false discovery rate (FDR) values. Any SNP with a FDR value <1% was considered as a potential hotspot. Three independent datasets were used to replicate the findings. A number of common hotspots were identified, and many hotspots have annotated function as the binding site of transcription factors or histone proteins.

In vitro Engineered DNA-binding Molecule-mediated Chromatin Immunoprecipitation (in vitro enChIP) Using CRISPR Ribonucleoproteins in Combination with Next-generation Sequencing (in vitro enChIP-Seq) for the Identification of Chromosomal Interactions

We have developed locus-specific chromatin immunoprecipitation (locus-specific ChIP) technologies consisting of insertional ChIP (iChIP) and engineered DNA-binding molecule-mediated ChIP (enChIP). Locus-specific ChIP is a method to isolate a genomic region of interest from cells while it also identifies what binds to this region using mass spectrometry (for protein) or next generation sequencing (for RNA or DNA) as described in Fujita et al. (2016a). Recently, we identified genomic regions that physically interact with a locus using an updated form of enChIP, in vitro enChIP, in combination with NGS (in vitro enChIP-Seq) ( Fujita et al., 2017a ). Here, we describe a protocol on in vitro enChIP to isolate a target locus for identification of genomic regions that physically interact with the locus.

Development of genetic maps and QTL analyses inCynara cardunculusL.: state of the art

Cynara cardunculus (2n=2x=34) is a member of the Asteraceae family, which is the largest and one of the most ecologically successful botanical families, and possesses a medium-sized genome (flow cytometry estimation = 1.07 Gb). The species is native to the Mediterranean Basin and, in addition to globe artichoke (var. scolymus L), it includes the cultivated cardoon (var. altilis DC) and the wild cardoon [var. sylvestris (Lamk) Fiori]. The two cultivated and the wild forms are fully cross-compatible and their F1 segregating progenies have been developed for linkage studies on the basis of the two-way pseudo-testcross approach as well as for QTL analyses. Here, we report a survey on the state of the art of map development and the identification of genomic region influencing key agronomic traits in the species.

Refining genomewide association for growth and fat deposition traits in an F pig population.

The identification of genomic regions that affect additive genetic variation and contain genes involved in controlling growth and fat deposition has enormous impact in the farm animal industry (e.g., carcass merit and meat quality). Therefore, a genomewide association study was implemented in an F pig population using a 60,000 SNP marker panel for traits related to growth and fat deposition. Estimated genomic EBV were linearly transformed to calculate SNP effects and to identify genomic positions possibly associated with the genetic variability of each trait. Genomic segments were then defined considering the markers included in a region 1 Mb up- and downstream from the SNP with the smallest -value and a false discovery rate < 0.05 for each trait. The significance for each 2-Mb segment was tested using the Bonferroni correction. Significant SNP were detected on SSC2, SSC3, SSC5, and SSC6, but 2-Mb segment significant effects were observed on SSC3 for weight at birth (wt_birth) and on SSC6 for 10th-rib backfat and last-rib backfat measured by ultrasound at different ages. Furthermore, a 6-Mb segment on SSC6 was also considered because the 2-Mb segments for 10 different fat deposition traits were overlapped. Although the segment effects for each trait remain significant, the proportion of additive variance explained by this larger segment was slightly smaller in some traits. In general, the results confirm the presence of genetic variability for wt_birth on SSC3 (18.0-20.2 Mb) and for fat deposition traits on SSC6 (133.8-136.0 Mb). Within these regions, fibrosin () and myosin light chain, phosphorylatable, fast skeletal muscle () genes could be considered as candidates for the wt_birth signal on SSC3, and the SERPINE1 mRNAbinding protein 1 gene () may be a candidate for the fat deposition trait signals on SSC6.

Crossbred steer temperament as yearlings and whole genome association of steer temperament as yearlings and calf temperament post-weaning.

cattle often have the reputation for a poor or dangerous temperament. Identification of genomic regions that associate with temperament of such cattle may be useful for genetic improvement strategies. The objectives of this study were to evaluate subjective temperament scores (1 to 9; higher scores indicated more unfavorable temperament) for aggressiveness, nervousness, flightiness, gregariousness, and overall temperament of one-half steers in feedlot conditions at 1 yr of age and compare those scores of those steers when evaluated approximately 1 mo postweaning, and conduct whole genome association analyses using SNP markers and the temperament traits of those steers at 1 yr of age and for temperament traits of all calves at weaning. Contemporary groups ( < 0.001) were steers born in the same year and season, and fed in the same feedlot pen. Aggressiveness of steers at 1 yr of age was not associated with aggressiveness at weaning (linear regression coefficient did not differ from 0; = 0.96), but regressions of all other yearling scores of steers on the scores at weaning were positive (coefficients ranged from 0.26 ± 0.04 to 0.32 ± 0.04; < 0.001). Estimates of Pearson correlation coefficients (using unadjusted values and residual values) of the different traits measured at 1 yr of age were large ( > 0.63; < 0.008) except for aggressiveness with nervousness, flightiness, or gregariousness, which did not differ from 0 ( > 0.1). Five SNP on BTA 1, 24, and 29 had suggestive associations (0.17 < [adjusted for FDR] < 0.24) with aggressiveness, nervousness, or flightiness at evaluation postweaning and 13 SNP on 11 chromosomes had suggestive associations (0.07 < [adjusted for FDR] < 0.24) with aggressiveness, nervousness, flightiness, or overall temperament score of steers at 1 yr of age. Genes close to these loci with roles in neural systems of various organisms included synaptotagmin 4 (BTA 24), FAT atypical cadhedrin 3 (BTA 29), tubulin tyrosine ligase-like 1 (BTA 5), spermatogenesis associated 17 (BTA 16), stanniocalcin 2 (BTA 20), and GABA receptor γ 3 (BTA 21).

Signatures of selection identify loci associated with fat tail in sheep.

Identification of genomic regions that have been targets of selection for phenotypic traits is one of the most challenging applications of dense marker panels in animal genetics. In this study, a genomewide scan using approximately 50,000 SNP was performed in an attempt to identify genomic regions associated with fat deposition in sheep, the importance of this not only being limited to livestock facing future climate changes but also for elucidating the physiology of lipid metabolism. The genotyping results obtained with the Ovine SNP50K BeadChip in 2 fat tail breeds were compared with those obtained in 13 thin tail breeds. Direct sequencing of the annotated genes located in proximity to the markers with opposite allele frequency in thin tail vs. fat tail sheep gave additional SNP of interest. To further confirm the results of the genomewide scan, we genotyped the SNP within these genes in the 2 groups of sheep. A missense mutation in the gene, with different allele frequency in the 2 groups, was detected. The results indicated and as the most probable genes involved in the fat tail phenotype.

Identification of genomic regions and candidate genes associated with growth ofEriocheir Sinensisby QTL mapping and marker annotation

Eriocheir sinensis is a valuable economic fishery resource in Asia and an invasive species of the world. A genome-wide quantitative trait loci (QTLs) scan for 10 growth traits was performed, resulting in 61 significant QTLs with phenotypic variance explained by a QTL from 11.2% to 42.2%. Most of the QTLs were restricted to narrow regions (<1 cM) and confirmed by genome wide association study. By blasting all markers on the linkage map with available transcriptomic and genomic sequences of E. sinensis, 15 markers on 14 linkage groups were found to be resided in gene sequences related to animal growth. A hypothetical protein gene (marker f1459) and a C-type lectin domain family 2 member D3 (marker m44) gene were detected to be located within the QTL intervals on LG11 and LG57 respectively. In addition, marker f2745 on LG34 was identified to be within intron 2 of Molting-inhibiting hormone 1, a moulting associated gene; two marker-containing genes, Adenomatous polyposis coli protein and Proto-oncogene tyrosine-protein kinase ROS were detected to be located on LG21 and LG44, which were involved in the growth-related pathways ‘Wnt signaling pathway’ and ‘mitogen-activated protein kinase signaling pathway’ respectively. The results are expected to be useful in marker-assisted selection and provide valuable information for the study of gene network regulation for growth of the crab.

Genome-wide selection signatures in Pinzgau cattle

The aim of this study was to identify the evidence of recent selection based on estimation of the integrated Haplotype Score (iHS), population differentiation index (FST) and characterize affected regions near QTL associated with traits under strong selection in Pinzgau cattle. In total 21 Austrian and 19 Slovak purebreed bulls genotyped with Illumina bovineHD and bovineSNP50 BeadChip were used to identify genomic regions under selection. Only autosomal loci with call rate higher than 90%, minor allele frequency higher than 0.01 and Hardy-Weinberg equlibrium limit of 0.001 were included in the subsequent analyses of selection sweeps presence. The final dataset was consisted from 30538 SNPs with 81.86 kb average adjacent SNPs spacing. The iHS score were averaged into non-overlapping 500 kb segments across the genome. The FST values were also plotted against genome position based on sliding windows approach and averaged over 8 consecutive SNPs. Based on integrated Haplotype Score evaluation only 7 regions with iHS score higher than 1.7 was found. The average iHS score observed for each adjacent syntenic regions indicated slight effect of recent selection in analysed group of Pinzgau bulls. The level of genetic differentiation between Austrian and Slovak bulls estimated based on FST index was low. Only 24% of FST values calculated for each SNP was greather than 0.01. By using sliding windows approach was found that 5% of analysed windows had higher value than 0.01. Our results indicated use of similar selection scheme in breeding programs of Slovak and Austrian Pinzgau bulls. The evidence for genome-wide association between signatures of selection and regions affecting complex traits such as milk production was insignificant, because the loci in segments identified as affected by selection were very distant from each other. Identification of genomic regions that may be under pressure of selection for phenotypic traits to better understanding of the relationship between genotype and phenotype is one of the challenges for livestock genetics.

Identification of QTLs for Rust Resistance in the Peanut Wild Species Arachis magna and the Development of KASP Markers for Marker-Assisted Selection.

Rust is a major pathogen of the peanut crop. Development and adoption of rust-resistant cultivars is the most cost efficient and effective way to control the spread of the disease and reduce yield losses. Some cultivated peanut germplasm accessions have a degree of resistance, but the secondary gene pool is a source of much stronger resistance alleles. Wild species, however, have undesirable agronomic traits that are a disincentive to their use in breeding. The identification of genomic regions that harbor disease resistance in wild species is the first step in the implementation of marker-assisted selection that can speed the introgression of wild disease resistances and the elimination of linkage drag. In this work, we identify genome regions that control different components of rust resistance in a recombinant inbred line population developed from a cross between two Arachis species, the susceptible most probable B genome ancestor of cultivated peanut, Arachis ipaënsis, and an accession of its closest relative, Arachis magna, which is resistant to rust. Quantitative trait loci for several components of resistance were placed in the same position on linkage group B08. Single-nucleotide polymorphism Kompetitive allele-specific polymerase chain reaction markers for rust resistance region were designed and validated for marker function in both diploid and tetraploid contexts.

GENETIC MAPPING OF ACIDITY-RELEVANT TRAITS

Organic acids are an important determinant for wine quality. A mapping population from a cross between the breeding strain Gf.Ga-47-42 (?Bacchus? × ?Seyval?) and the cultivar ?Villard Blanc? (?Seibel 6468? × ?Subereux?) was investigated in detail regarding differences in the acidity level of the must. The acidity profile was recorded in three consecutive years under field conditions at Geilweilerhof (Palatinate, Germany). The obtained data were subjected to QTL analysis in order to identify genetic regions involved in acidity regulation. Investigated traits included total acidity, tartaric and malic acid levels as well as pH values in musts and wines. The identification of genomic regions which carry genes with a significant influence on these traits will give new insights into the acidity characteristics of grape cultivars. Newly identified trait-linked molecular markers are intended for application in marker-assisted selection (MAS) during the breeding process. This will contribute to accelerate grapevine breeding by early selection for quality traits.

Identification of genomic regions and the isoamylase gene for reduced grain chalkiness in rice.

Grain chalkiness is an important grain quality related to starch granules in the endosperm. A high percentage of grain chalkiness is a major problem because it diminishes grain quality in rice. Here, we report quantitative trait loci identification for grain chalkiness using high-throughput single nucleotide polymorphism genotyping of a chromosomal segment substitution line population in which each line carried one or a few introduced japonica cultivar Nipponbare segments in the genetic background of the indica cultivar ZS97. Ten quantitative trait loci regions were commonly identified for the percentage of grain chalkiness and the degree of endosperm chalkiness. The allelic effects at nine of these quantitative trait loci reduced grain chalkiness. Furthermore, a quantitative trait locus (qPGC8-2) on chromosome 8 was validated in a chromosomal segment substitution line–derived segregation population, and had a stable effect on chalkiness in a multiple-environment evaluation of the near-isogenic lines. Residing on the qPGC8-2 region, the isoamylase gene (ISA1) was preferentially expressed in the endosperm and revealed some nucleotide polymorphisms between two varieties, Nipponbare and ZS97. Transgenic lines with suppression of ISA1 by RNA interference produced grains with 20% more chalkiness than the control. The results support that the gene may underlie qPGC8-2 for grain chalkiness. The multiple-environment trials of the near-isogenic lines also show that combination of the favorable alleles such as the ISA1 gene for low chalkiness and the GS3 gene for long grains considerably improved grain quality of ZS97, which proves useful for grain quality improvement in rice breeding programs.

Construction of a high-density DArTseq SNP-based genetic map and identification of genomic regions with segregation distortion in a genetic population derived from a cross between feral and cultivated-type watermelon.

Watermelon [Citrullus lanatus (Thunb.) Matsum. & Nakai] is an economically important vegetable crop grown extensively worldwide. To facilitate the identification of agronomically important traits and provide new information for genetic and genomic research on this species, a high-density genetic linkage map of watermelon was constructed using an F2 population derived from a cross between elite watermelon cultivar K3 and wild watermelon germplasm PI 189225. Based on a sliding window approach, a total of 1,161 bin markers representing 3,465 SNP markers were mapped onto 11 linkage groups corresponding to the chromosome pair number of watermelon. The total length of the genetic map is 1,099.2 cM, with an average distance between bins of 1.0 cM. The number of markers in each chromosome varies from 62 in chromosome 07 to 160 in chromosome 05. The length of individual chromosomes ranged between 61.8 cM for chromosome 07 and 140.2 cM for chromosome 05. A total of 616 SNP bin markers showed significant (P < 0.05) segregation distortion across all 11 chromosomes, and 513 (83.3 %) of these distorted loci showed distortion in favor of the elite watermelon cultivar K3 allele and 103 were skewed toward PI 189225. The number of SNPs and InDels per Mb varied considerably across the segregation distorted regions (SDRs) on each chromosome, and a mixture of dense and sparse SNPs and InDel SDRs coexisted on some chromosomes suggesting that SDRs were randomly distributed throughout the genome. Recombination rates varied greatly among each chromosome, from 2.0 to 4.2 centimorgans per megabase (cM/Mb). An inconsistency was found between the genetic and physical positions on the map for a segment on chromosome 11. The high-density genetic map described in the present study will facilitate fine mapping of quantitative trait loci, the identification of candidate genes, map-based cloning, as well as marker-assisted selection (MAS) in watermelon breeding programs.

Identification of genome regions and important variations associated with expression level of MYH genes and its correlation with meat quality traits in pigs

Meat quality is one of the most important economic traits in pig breeding. It has been reported that the composition of type II muscle fibers is correlated with meat quality in pigs. Type II muscle fibers contain three isoforms, IIa, IIb and IIx, which contain specific myofibrillar proteins MYH2, MYH4 and MYH1, respec- tively. In this study, the expression levels of MYH1, MYH2, and MYH4 genes in the Longissimus thoracis (LT) muscle were measured in 114 Yorkshire pigs. Further, the correlations between the expression level of MYH genes and the meat quality traits of intramuscular fat, drip loss, water-holding capacity and postmortem pH values were analyzed. The results showed that the expression level of MYH2 was positively correlated with the intramuscular fat (R= 0.20, P<0.05). The expression levels of MHY1 and MYH4 were negatively correlated with the pH at 24 h post mortem (pH24h ; R = -0.28, P<0.01; R= -0.25, P<0.01, respectively). Besides, the 60K SNP chip was used for genotyping the individuals. Genome wide association analysis indicated that 15 SNPs were significantly asso- ciated with the expression levels of these three MYH genes. The results indicated the expression levels of MYH1, MYH2 and MYH4 genes could be useful markers for improvement of meat quality in pigs.

Genome-wide association study using deregressed breeding values for cryptorchidism and scrotal/inguinal hernia in two pig lines.

BackgroundCryptorchidism and scrotal/inguinal hernia are the most frequent congenital defects in pigs. Identification of genomic regions that control these congenital defects is of great interest to breeding programs, both from an animal welfare point of view as well as for economic reasons. The aim of this genome-wide association study (GWAS) was to identify single nucleotide polymorphisms (SNPs) that are strongly associated with these congenital defects. Genotypes were available for 2570 Large White (LW) and 2272 Landrace (LR) pigs. Breeding values were estimated based on 1 359 765 purebred and crossbred male offspring, using a binary trait animal model. Estimated breeding values were deregressed (DEBV) and taken as the response variable in the GWAS.ResultsHeritability estimates were equal to 0.26 ± 0.02 for cryptorchidism and to 0.31 ± 0.01 for scrotal/inguinal hernia. Seven and 31 distinct QTL regions were associated with cryptorchidism in the LW and LR datasets, respectively. The top SNP per region explained between 0.96% and 1.10% and between 0.48% and 2.77% of the total variance of cryptorchidism incidence in the LW and LR populations, respectively. Five distinct QTL regions associated with scrotal/inguinal hernia were detected in both LW and LR datasets. The top SNP per region explained between 1.22% and 1.60% and between 1.15% and 1.46% of the total variance of scrotal/inguinal hernia incidence in the LW and LR populations, respectively. For each trait, we identified one overlapping region between the LW and LR datasets, i.e. a region on SSC8 (Sus scrofa chromosome) between 65 and 73 Mb for cryptorchidism and a region on SSC13 between 34 and 37 Mb for scrotal/inguinal hernia.ConclusionsThe use of DEBV in combination with a binary trait model was a powerful approach to detect regions associated with difficult traits such as cryptorchidism and scrotal/inguinal hernia that have a low incidence and for which affected animals are generally not available for genotyping. Several novel QTL regions were detected for cryptorchidism and scrotal/inguinal hernia, and for several previously known QTL regions, the confidence interval was narrowed down.Electronic supplementary materialThe online version of this article (doi:10.1186/s12711-015-0096-6) contains supplementary material, which is available to authorized users.

Selection footprints in barley breeding lines detected by combining genotyping-by-sequencing with reference genome information

This study is a retrospective analysis of an elite cross from the Spanish National Barley Breeding Program. This was the most successful cross produced in the breeding program in the past 20 years. The progeny from this cross has been investigated at two points in the program, before and after selection, through the analysis of allelic frequencies at a number of genetic loci with molecular markers. Shifts in allelic frequencies after selection allowed the identification of genomic regions with selection footprints likely due to the breeding process. The cross was replicated in three different years, and therefore, the three progenies represent different selection histories but, in all cases, were preferentially selected compared to the lines from other crosses used in the program. The progenies were sampled at two generations, before conscious selection (F2) and after six generations of selection (F8). The F2 plants were genotyped with microsatellites, whereas 31 F8 lines were surveyed for SNP and presence/absence variation polymorphisms using a genotyping-by-sequencing system (DArTseq). The DArTseq markers were aligned to the barley physical map, and, after curation, over 3,000 were still available for the analysis. Overall, 15 genomic regions in the F8 lines had allele frequencies beyond chosen thresholds, indicating selection, eight toward parent Orria and seven toward Plaisant. These selection footprints partially validated QTLs detected through classical linkage mapping in a RIL population of the same cross. These validated selection footprints convey useful information for barley breeding, either through marker-assisted selection or through genomic selection.