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1.  Genome-wide distribution comparative and composition analysis of the SSRs in Poaceae 
BMC Genetics  2015;16:18.
The Poaceae family is of great importance to human beings since it comprises the cereal grasses which are the main sources for human food and animal feed. With the rapid growth of genomic data from Poaceae members, comparative genomics becomes a convinent method to study genetics of diffierent species. The SSRs (Simple Sequence Repeats) are widely used markers in the studies of Poaceae for their high abundance and stability.
In this study, using the genomic sequences of 9 Poaceae species, we detected 11,993,943 SSR loci and developed 6,799,910 SSR primer pairs. The results show that SSRs are distributed on all the genomic elements in grass. Hexamer is the most frequent motif and AT/TA is the most frequent motif in dimer. The abundance of the SSRs has a positive linear relationship with the recombination rate. SSR sequences in the coding regions involve a higher GC content in the Poaceae than that in the other species. SSRs of 70-80 bp in length showed the highest AT/GC base ratio among all of these loci. The result shows the highest polymorphism rate belongs to the SSRs ranged from 30 bp to 40 bp. Using all the SSR primers of Japonica, nineteen universal primers were selected and located on the genome of the grass family. The information of SSR loci, the SSR primers and the tools of mining and analyzing SSR are provided in the PSSRD (Poaceae SSR Database,
Our study and the PSSRD database provide a foundation for the comparative study in the Poaceae and it will accelerate the study on markers application, gene mapping and molecular breeding.
PMCID: PMC4333251
2.  Transcriptome analysis between invasive Pomacea canaliculata and indigenous Cipangopaludina cahayensis reveals genomic divergence and diagnostic microsatellite/SSR markers 
BMC Genetics  2015;16(1):12.
Pomacea canaliculata is an important invasive species worldwide. However, little is known about the molecular mechanisms behind species displacement, adaptational abilities, and pesticide resistance, partly because of the lack of genomic information that is available for this species. Here, the transcriptome sequences for the invasive golden apple snail P. canaliculata and the native mudsnail Cipangopaludina cahayensis were obtained by next-generation-sequencing and used to compare genomic divergence and identify molecular markers.
More than 46 million high quality sequencing reads were generated from P. canaliculata and C. cahayensis using Illumina paired-end sequencing technology. Our analysis indicated that 11,312 unigenes from P. canaliculata and C. cahayensis showed significant similarities to known proteins families, among which a total of 4,320 specific protein families were identified. KEGG pathway enrichment was analyzed for the unique unigenes with 17 pathways (p-value < 10−5) in P. canaliculata relating predominantly to lysosomes and vitamin digestion and absorption, and with 12 identified in C. cahayensis, including cancer and toxoplasmosis pathways, respectively. Our analysis also indicated that the comparatively high number of P450 genes in the P. canaliculata transcriptome may be associated with the pesticide resistance in this species. Additionally, 16,717 simple sequence repeats derived from expressed sequence tags (EST-SSRs) were identified from the 14,722 unigenes in P. canaliculata and 100 of them were examined by PCR, revealing a species-specific molecular marker that could distinguish between the morphologically similar P. canaliculata and C. cahayensis snails.
Here, we present the genomic resources of P. canaliculata and C. cahayensis. Differentially expressed genes in the transcriptome of P. canaliculata compared with C. cahayensis corresponded to critical metabolic pathways, and genes specifically related to environmental stress response were detected. The CYP4 family of P450 cytochromes that may be important factors in pesticide metabolism in P. canaliculata was identified. Overall, these findings will provide valuable genetic data for the further characterization of the molecular mechanisms that support the invasive and adaptive abilities of P. canaliculata.
Electronic supplementary material
The online version of this article (doi:10.1186/s12863-015-0175-2) contains supplementary material, which is available to authorized users.
PMCID: PMC4328836
Biological invasion; Pomacea canaliculata; Cipangopaludina cahayensis; EST-SSR; Transcriptome
3.  A comprehensive linkage map and QTL map for carcass traits in a cross between Giant Grey and New Zealand White rabbits 
BMC Genetics  2015;16:16.
Genomic resources for the rabbit are still limited compared to many other livestock species. The genomic sequence as well as linkage maps have gaps that hamper their use in rabbit genome research. Therefore, the aims of this study were the improvement of existing linkage maps and the mapping of quantitative trait loci (QTL) for carcass and meat quality traits. The study was performed in a F2 population of an initial cross between Giant Grey (GG) and New Zealand White (NZW) rabbits. The population consisted of 363 F2 animals derived from 9 F1 bucks and 33 F1 does. 186 microsatellite and three SNP markers were informative for mapping.
Out of 189 markers, which could be assigned to linkage groups, 110 markers were genetically mapped for the first time. The average marker distance was 7.8 cM. The map across all autosomes reached a total length of 1419 cM. The maternal linkage map was 1.4 times longer than the paternal. All linkage groups could be anchored to chromosomes. On the basis of the generated genetic map, we identified a highly significant QTL (genome-wide significance p < 0.01) for different carcass weights on chromosome 7 with a peak position at 91 cM (157 Mb), a significant QTL (p < 0.05) for bone mass on chromosome 9 at 61 cM (65 Mb), and another one for drip loss on chromosome 12 at 94 cM (128 Mb). Additional suggestive QTL were found on almost all chromosomes. Several genomic loci affecting the fore, intermediate and hind parts of the carcass were identified. The identified QTL explain between 2.5 to 14.6% of the phenotypic variance in the F2 population.
The results present the most comprehensive genetic map and the first genome-wide QTL mapping study for carcass and meat quality traits in rabbits. The identified QTL, in particular the major QTL on chromosome 7, provide starting points for fine mapping and candidate gene search. The data contribute to linking physical and genetic information in the rabbit genome.
Electronic supplementary material
The online version of this article (doi:10.1186/s12863-015-0168-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4330979
Linkage map; QTL; Carcass composition; Meat quality; Rabbit
4.  A haploproficient interaction of the transaldolase paralogue NQM1 with the transcription factor VHR1 affects stationary phase survival and oxidative stress resistance 
BMC Genetics  2015;16:13.
Studying the survival of yeast in stationary phase, known as chronological lifespan, led to the identification of molecular ageing factors conserved from yeast to higher organisms. To identify functional interactions among yeast chronological ageing genes, we conducted a haploproficiency screen on the basis of previously identified long-living mutants. For this, we created a library of heterozygous Saccharomyces cerevisiae double deletion strains and aged them in a competitive manner.
Stationary phase survival was prolonged in a double heterozygous mutant of the metabolic enzyme non-quiescent mutant 1 (NQM1), a paralogue to the pentose phosphate pathway enzyme transaldolase (TAL1), and the transcription factor vitamin H response transcription factor 1 (VHR1). We find that cells deleted for the two genes possess increased clonogenicity at late stages of stationary phase survival, but find no indication that the mutations delay initial mortality upon reaching stationary phase, canonically defined as an extension of chronological lifespan. We show that both genes influence the concentration of metabolites of glycolysis and the pentose phosphate pathway, central metabolic players in the ageing process, and affect osmolality of growth media in stationary phase cultures. Moreover, NQM1 is glucose repressed and induced in a VHR1 dependent manner upon caloric restriction, on non-fermentable carbon sources, as well as under osmotic and oxidative stress. Finally, deletion of NQM1 is shown to confer resistance to oxidizing substances.
The transaldolase paralogue NQM1 and the transcription factor VHR1 interact haploproficiently and affect yeast stationary phase survival. The glucose repressed NQM1 gene is induced under various stress conditions, affects stress resistance and this process is dependent on VHR1. While NQM1 appears not to function in the pentose phosphate pathway, the interplay of NQM1 with VHR1 influences the yeast metabolic homeostasis and stress tolerance during stationary phase, processes associated with yeast ageing.
Electronic supplementary material
The online version of this article (doi:10.1186/s12863-015-0171-6) contains supplementary material, which is available to authorized users.
PMCID: PMC4331311
Chronological lifespan; Pentose phosphate pathway; Transaldolase; NQM1; VHR1; Oxidative stress
5.  GPOPSIM: a simulation tool for whole-genome genetic data 
BMC Genetics  2015;16(1):10.
Population-wide genotypic and phenotypic data is frequently used to predict the disease risk or genetic/phenotypic values, or to localize genetic variations responsible for complex traits. GPOPSIM is a simulation tool for pedigree, phenotypes, and genomic data, with a variety of population and genome structures and trait genetic architectures. It provides flexible parameter settings for a wide discipline of users, especially can simulate multiple genetically correlated traits with desired genetic parameters and underlying genetic architectures.
The model implemented in GPOPSIM is presented, and the code has been made freely available to the community. Data simulated by GPOPSIM is a good mimic to the real data in terms of genome structure and trait underlying genetic architecture.
GPOPSIM would be a useful tool for the methodological and theoretical studies in the population and quantitative genetics and breeding.
Electronic supplementary material
The online version of this article (doi:10.1186/s12863-015-0173-4) contains supplementary material, which is available to authorized users.
PMCID: PMC4328615  PMID: 25652552
Data simulation; SNP; Pedigree; Multiple traits; Mutation-drift equilibrium; Genetic correlation
6.  Mechanisms of amino acid-mediated lifespan extension in Caenorhabditis elegans 
BMC Genetics  2015;16(1):8.
Little is known about the role of amino acids in cellular signaling pathways, especially as it pertains to pathways that regulate the rate of aging. However, it has been shown that methionine or tryptophan restriction extends lifespan in higher eukaryotes and increased proline or tryptophan levels increase longevity in C. elegans. In addition, leucine strongly activates the TOR signaling pathway, which when inhibited increases lifespan.
Therefore each of the 20 proteogenic amino acids was individually supplemented to C. elegans and the effects on lifespan were determined. All amino acids except phenylalanine and aspartate extended lifespan at least to a small extent at one or more of the 3 concentrations tested with serine and proline showing the largest effects. 11 of the amino acids were less potent at higher doses, while 5 even decreased lifespan. Serine, proline, or histidine-mediated lifespan extension was greatly inhibited in eat-2 worms, a model of dietary restriction, in daf-16/FOXO, sir-2.1, rsks-1 (ribosomal S6 kinase), gcn-2, and aak-2 (AMPK) longevity pathway mutants, and in bec-1 autophagy-defective knockdown worms. 8 of 10 longevity-promoting amino acids tested activated a SKN-1/Nrf2 reporter strain, while serine and histidine were the only amino acids from those to activate a hypoxia-inducible factor (HIF-1) reporter strain. Thermotolerance was increased by proline or tryptophan supplementation, while tryptophan-mediated lifespan extension was independent of DAF-16/FOXO and SKN-1/Nrf2 signaling, but tryptophan and several related pyridine-containing compounds induced the mitochondrial unfolded protein response and an ER stress response. High glucose levels or mutations affecting electron transport chain (ETC) function inhibited amino acid-mediated lifespan extension suggesting that metabolism plays an important role. Providing many other cellular metabolites to C. elegans also increased longevity suggesting that anaplerosis of tricarboxylic acid (TCA) cycle substrates likely plays a role in lifespan extension.
Supplementation of C. elegans with 18 of the 20 individual amino acids extended lifespan, but lifespan often decreased with increasing concentration suggesting hormesis. Lifespan extension appears to be caused by altered mitochondrial TCA cycle metabolism and respiratory substrate utilization resulting in the activation of the DAF-16/FOXO and SKN-1/Nrf2 stress response pathways.
Electronic supplementary material
The online version of this article (doi:10.1186/s12863-015-0167-2) contains supplementary material, which is available to authorized users.
PMCID: PMC4328591  PMID: 25643626
Amino acids; Lifespan; Aging; C. elegans; Serine; Proline; Histidine; Tryptophan; Mitochondrial
7.  Associations of the uric acid related genetic variants in SLC2A9 and ABCG2 loci with coronary heart disease risk 
BMC Genetics  2015;16(1):4.
Multiple studies investigated the associations between serum uric acid and coronary heart disease (CHD) risk. However, further investigations still remain to be carried out to determine whether there exists a causal relationship between them. We aim to explore the associations between genetic variants in uric acid related loci of SLC2A9 and ABCG2 and CHD risk in a Chinese population.
A case–control study including 1,146 CHD cases and 1,146 controls was conducted. Association analysis between two uric acid related variants (SNP rs11722228 in SLC2A9 and rs4148152 in ABCG2) and CHD risk was performed by logistic regression model. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Compared with subjects with A allele of rs4148152, those with G allele had a decreased CHD risk and the association remained significant in a multivariate model. However, it altered to null when BMI was added into the model. No significant association was observed between rs11722228 and CHD risk. The distribution of CHD risk factors was not significantly different among different genotypes of both SNPs. Among subjects who did not consume alcohol, the G allele of rs4148152 showed a moderate protective effect. However, no significant interactions were observed between SNP by CHD risk factors on CHD risk.
There might be no association between the two uric acid related SNPs with CHD risk. Further studies were warranted to validate these results.
Electronic supplementary material
The online version of this article (doi:10.1186/s12863-015-0162-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4314773  PMID: 25634581
Coronary heart disease; Uric acid; Polymorphism; Gene-environment interaction
8.  Genome-wide detection and characterization of positive selection in Korean Native Black Pig from Jeju Island 
BMC Genetics  2015;16(1):3.
In the 1980s, Korean native black pigs from Jeju Island (Jeju black pigs) served as representative sample of Korean native black pigs, and efforts were made to help the species rebound from the brink of extinction, which occurred as a result of the introduction of Western pig breeds. Geographical separation of Jeju Island from the Korean peninsula has allowed Jeju black pigs not only to acquire unique characteristics but also to retain merits of rare Korean native black pigs.
To further analyze the Jeju black pig genome, we performed whole-genome re-sequencing (average read depth of 14×) of 8 Jeju black pig and 6 Korean pigs (which live on the Korean peninsula) to compare and identify putative signatures of positive selection in Jeju black pig, the true and pure Korean native black pigs. The candidate genes potentially under positive selection in Jeju black pig support previous reports of high marbling score, rare occurrence of pale, soft, exudative (PSE) meat, but low growth rate and carcass weight compared to Western breeds.
Several candidate genes potentially under positive selection were involved in fatty acid transport and may have contributed to the unique characteristics of meat quality in JBP. Jeju black pigs can offer a unique opportunity to investigate the true genetic resource of once endangered Korean native black pigs. Further genome-wide analyses of Jeju black pigs on a larger population scale are required in order to define a conservation strategy and improvement of native pig resources.
Electronic supplementary material
The online version of this article (doi:10.1186/s12863-014-0160-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4314801  PMID: 25634476
Korean native black pig; Jeju black pig; Positive selection
9.  Association of TNF-alpha, IL-6 and IL-1beta gene polymorphisms with polycystic ovary syndrome: a meta-analysis 
BMC Genetics  2015;16(1):5.
Several studies on the association of TNF-alpha (−308 G/A), IL-6 (−174 G/C) and IL-1beta (−511 C/T) polymorphisms with polycystic ovary syndrome (PCOS) risk have reported conflicting results. The aim of the present study was to assess these associations by meta-analysis.
A total of 14 eligible articles (1665 cases/1687 controls) were included in this meta-analysis. The results suggested that there was no obvious association between the TNF-alpha (−308 G/A) polymorphism and PCOS in the overall population or subgroup analysis by ethnicity, Hardy–Weinberg equilibrium (HWE) in controls, genotyping method, PCOS diagnosis criteria, and study sample size. Also, no obvious association was found between the TNF-alpha (−308 G/A) polymorphism and obesity in patients with PCOS (body mass index [BMI] ≥ 25 kg/m2 vs. BMI < 25 kg/m2). Regarding the IL-6 (−174 G/C) polymorphism, also no association was found in the overall population in heterozygote comparison, dominant model, and recessive model. Even though an allelic model (odds ratio [OR] = 0.63, 95% confidence interval [CI] = 0.41–0.96) and a homozygote comparison (OR = 0.52, 95% CI = 0.30–0.93) showed that the IL-6 (−174 G/C) polymorphism was marginally associated with PCOS. Further subgroup analysis suggested that the effect size was not significant among HWE in controls (sample size ≤ 200) and genotyping method of pyrosequencing under all genetic models. Similarly, there was no association between the IL-1beta (−511 C/T) polymorphism and PCOS in the overall population or subgroup analysis under all genetic models. Furthermore, no significant association was found between the IL-1beta (−511 C/T) polymorphism and several clinical and biochemical parameters in patients with PCOS.
The results of this meta-analysis suggest that the TNF-alpha (−308 G/A), IL-6 (−174 G/C), and IL-1beta (−511 C/T) polymorphisms may not be associated with PCOS risk. However, further case–control studies with larger sample sizes are needed to confirm our results.
Electronic supplementary material
The online version of this article (doi:10.1186/s12863-015-0165-4) contains supplementary material, which is available to authorized users.
PMCID: PMC4314802  PMID: 25634659
Polycystic ovary syndrome; TNF-alpha; IL-6; IL-1beta; Polymorphism; Meta-analysis
10.  Distribution of miRNA genes in the pig genome 
BMC Genetics  2015;16(1):6.
Recent completion of swine genome may simplify the production of swine as a large biomedical model. Here we studied sequence and location of known swine miRNA genes, key regulators of protein-coding genes at the level of RNA, and compared them to human and mouse data to prioritize future molecular studies.
Distribution of miRNA genes in pig genome shows no particular relation to different genomic features including protein coding genes - proportions of miRNA genes in intergenic regions, introns and exons roughly agree with the size of these regions in the pig genome. Our analyses indicate that host genes harbouring intragenic miRNAs are longer from other protein-coding genes, however, no important GO enrichment was found. Swine mature miRNAs show high sequence similarity to their human and mouse orthologues. Location of miRNA genes relative to protein-coding genes is also similar among studied species, however, there are differences in the precise position in particular intergenic regions and within particular hosts. The most prominent difference between pig and human miRNAs is a large group of pig-specific sequences (53% of swine miRNAs). We found no evidence that this group of evolutionary new pig miRNAs is different from old miRNAs genes with respect to genomic location except that they are less likely to be clustered.
There are differences in precise location of orthologues miRNA genes in particular intergenic regions and within particular hosts, and their meaning for coexpression with protein-coding genes deserves experimental studies. Functional studies of a large group of pig-specific sequences in future may reveal limits of the pig as a model organism to study human gene expression.
Electronic supplementary material
The online version of this article (doi:10.1186/s12863-015-0166-3) contains supplementary material, which is available to authorized users.
PMCID: PMC4318388  PMID: 25632794
miRNA; Pig; Genomic location
11.  Heuristic exploitation of genetic structure in marker-assisted gene pyramiding problems 
BMC Genetics  2015;16:2.
Over the last decade genetic marker-based plant breeding strategies have gained increasing attention because genotyping technologies are no longer limiting. Now the challenge is to optimally use genetic markers in practical breeding schemes. For simple traits such as some disease resistances it is possible to target a fixed multi-locus allele configuration at a small number of causal or linked loci. Efficiently obtaining this genetic ideotype from a given set of parental genotypes is known as the marker-assisted gene pyramiding problem. Previous methods either imposed strong restrictions or used black box integer programming solutions, while this paper explores the power of an explicit heuristic approach that exploits the underlying genetic structure to prune the search space.
Gene Stacker is introduced as a novel approach to marker-assisted gene pyramiding, combining an explicit directed acyclic graph model with a pruned generation algorithm inspired by a simple exhaustive search. Both exact and heuristic pruning criteria are applied to reduce the number of generated schedules. It is shown that this approach can effectively be used to obtain good solutions for stacking problems of varying complexity. For more complex problems, the heuristics allow to obtain valuable approximations. For smaller problems, fewer heuristics can be applied, resulting in an interesting quality-runtime tradeoff. Gene Stacker is competitive with previous methods and often finds better and/or additional solutions within reasonable time, because of the powerful heuristics.
The proposed approach was confirmed to be feasible in combination with heuristics to cope with realistic, complex stacking problems. The inherent flexibility of this approach allows to easily address important breeding constraints so that the obtained schedules can be widely used in practice without major modifications. In addition, the ideas applied for Gene Stacker can be incorporated in and extended for a plant breeding context that e.g. also addresses complex quantitative traits or conservation of genetic background. Gene Stacker is freely available as open source software at The website also provides documentation and examples of how to use Gene Stacker.
Electronic supplementary material
The online version of this article (doi:10.1186/s12863-014-0154-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4332449  PMID: 25634328
Plant breeding; Marker-assisted gene pyramiding; Multi-objective optimization; Heuristics
12.  Identification of quantitative trait loci for phosphorus use efficiency traits in rice using a high density SNP map 
BMC Genetics  2014;15(1):155.
Soil phosphorus (P) deficiency is one of the major limiting factors to crop production. The development of crop varieties with improved P use efficiency (PUE) is an important strategy for sustainable agriculture. The objectives of this research were to identify quantitative trait loci (QTLs) linked to PUE traits using a high-density single nucleotide polymorphism (SNP) map and to estimate the epistatic interactions and environmental effects in rice (Oryza sativa L.).
We conducted a two-year field experiment under low and normal P conditions using a recombinant inbred population of rice derived from Zhenshan 97 and Minghui 63 (indica). We investigated three yield traits, biomass (BIOM), harvest index (HI), and grain yield (Yield), and eight PUE traits: total P uptake (PUP), P harvest index (PHI), grain P use efficiency (gPUE) based on P accumulation in grains, straw P use efficiency (strPUE) based on P accumulation in straw, P use efficiency for biomass (PUEb) and for grain yield (PUEg) based on P accumulation in the whole plant, P translocation (PT), and P translocation efficiency (PTE). Of the 36 QTLs and 24 epistatic interactions identified, 26 QTLs and 12 interactions were detected for PUE traits. The environment affected seven QTLs and three epistatic interactions. Four QTLs (qPHI1 and qPHI2 for PHI, qPUEg2 for PUEg, and qPTE8 for PTE) with strong effects were environmentally independent. By comparing our results with similar QTLs in previous studies, three QTLs for PUE traits (qPUP1 and qPUP10 for PUP, and qPHI6 for PHI) were found across various genetic backgrounds. Seven regions were shared by QTLs for yield and PUE traits.
Most QTLs linked to PUE traits were different from those linked to yield traits, suggesting different genetic controls underlying these two traits. Those chromosomal regions with large effects that are not affected by different environments are promising for improving P use efficiency. The seven regions shared by QTLs linked to yield and PUE traits imply the possibility of the simultaneous improvement of yield and PUE traits.
PMCID: PMC4311488  PMID: 25551672
Genotype by environment interaction; Phosphorus use efficiency; Quantitative trait loci; Recombinant inbred lines; Rice; Single nucleotide polymorphism
13.  Distribution of allelic and genotypic frequencies of NAT2 and CYP2E1 variants in Moroccan population 
BMC Genetics  2014;15(1):156.
Several pathogenesis and genetic factors influence predisposition to antituberculosis drug-induced hepatotoxicity (ATDH) especially for isoniazid (INH). However, the major susceptibility genes for ATDH are N-acetyltransferase 2 (NAT2) and cytochrome P450 2E1 (CYP2E1). NAT2 gene determines the individual’s acetylator status (fast, intermediate or slow) to metabolize drugs and xenobiotics, while CYP2E1 c1/c1 genotype carriers had an increased risk of ATDH.
Polymorphisms of the NAT2 and CYP2E1 genes vary remarkably among the populations of different ethnic origins.
The aim of this study was to determine, for the first time, the frequency of slow acetylators in Moroccan population by genotyping of NAT2 gene variants and determining the genotype c1/c1 for CYP2E1 gene, in order to predict adverse effects of Tuberculosis treatment, particularly hepatotoxicity.
The frequencies of specific NAT2 alleles were 53%, 25%, 2% and 4% for NAT2*5, NAT2*6, NAT2*7 and NAT2*14 respectively among 163 Moroccan studied group. Genotyping of CYP2E1 gene, by real-time polymerase chain reaction using TaqMan probes, revealed frequencies of 98.5% for c1/c1 and 1.5% for c1/c2 among 130 Moroccan studied group.
The most prevalent genotypes of NAT2 gene in Moroccans are those which encode slow acetylation phenotype (72.39%), leading to a high risk of ATDH. Most Moroccans are homozygous for c1 allele of CYP2E1 gene which aggravates hepatotoxicity in slow acetylators.
This genetic background should be taken into account in determining the minimum dose of INH needed to treat Moroccan TB patients, in order to decrease adverse effects.
PMCID: PMC4299568  PMID: 25544508
Tuberculosis; CYP2E1 gene; NAT2 gene; Polymorphism; Acetylators; Adverse effects; Moroccans
14.  Accuracy of genome-wide imputation in Braford and Hereford beef cattle 
BMC Genetics  2014;15(1):157.
Strategies for imputing genotypes from the Illumina-Bovine3K, Illumina-BovineLD (6K), BeefLD-GGP (8K), a non-commercial-15K and IndicusLD-GGP (20K) to either Illumina-BovineSNP50 (50K) or to Illumina-BovineHD (777K) SNP panel, as well as for imputing from 50K, GGP-IndicusHD (90iK) and GGP-BeefHD (90tK) to 777K were investigated. Imputation of low density (<50K) genotypes to 777K was carried out in either one or two steps. Imputation of ungenotyped parents (n = 37 sires) with four or more offspring to the 50K panel was also assessed. There were 2,946 Braford, 664 Hereford and 88 Nellore animals, from which 71, 59 and 88 were genotyped with the 777K panel, while all others had 50K genotypes. The reference population was comprised of 2,735 animals and 175 bulls for 50K and 777K, respectively. The low density panels were simulated by masking genotypes in the 50K or 777K panel for animals born in 2011. Analyses were performed using both Beagle and FImpute software. Genotype imputation accuracy was measured by concordance rate and allelic R2 between true and imputed genotypes.
The average concordance rate using FImpute was 0.943 and 0.921 averaged across all simulated low density panels to 50K or to 777K, respectively, in comparison with 0.927 and 0.895 using Beagle. The allelic R2 was 0.912 and 0.866 for imputation to 50K or to 777K using FImpute, respectively, and 0.890 and 0.826 using Beagle. One and two steps imputation to 777K produced averaged concordance rates of 0.806 and 0.892 and allelic R2 of 0.674 and 0.819, respectively. Imputation of low density panels to 50K, with the exception of 3K, had overall concordance rates greater than 0.940 and allelic R2 greater than 0.919. Ungenotyped animals were imputed to 50K panel with an average concordance rate of 0.950 by FImpute.
FImpute accuracy outperformed Beagle on both imputation to 50K and to 777K. Two-step outperformed one-step imputation for imputing to 777K. Ungenotyped animals that have four or more offspring can have their 50K genotypes accurately inferred using FImpute. All low density panels, except the 3K, can be used to impute to the 50K using FImpute or Beagle with high concordance rate and allelic R2.
PMCID: PMC4300607  PMID: 25543517
Braford; Imputation accuracy; Low density panel; Hereford; High density panel
15.  Genetic diversity is a predictor of mortality in humans 
BMC Genetics  2014;15(1):159.
It has been well-established, both by population genetics theory and direct observation in many organisms, that increased genetic diversity provides a survival advantage. However, given the limitations of both sample size and genome-wide metrics, this hypothesis has not been comprehensively tested in human populations. Moreover, the presence of numerous segregating small effect alleles that influence traits that directly impact health directly raises the question as to whether global measures of genomic variation are themselves associated with human health and disease.
We performed a meta-analysis of 17 cohorts followed prospectively, with a combined sample size of 46,716 individuals, including a total of 15,234 deaths. We find a significant association between increased heterozygosity and survival (P = 0.03). We estimate that within a single population, every standard deviation of heterozygosity an individual has over the mean decreases that person’s risk of death by 1.57%.
This effect was consistent between European and African ancestry cohorts, men and women, and major causes of death (cancer and cardiovascular disease), demonstrating the broad positive impact of genomic diversity on human survival.
Electronic supplementary material
The online version of this article (doi:10.1186/s12863-014-0159-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4301661  PMID: 25543667
Heterozygosity; Human; Survival; GWAS
16.  Next generation haplotyping to decipher nuclear genomic interspecific admixture in Citrus species: analysis of chromosome 2 
BMC Genetics  2014;15(1):152.
The most economically important Citrus species originated by natural interspecific hybridization between four ancestral taxa (Citrus reticulata, Citrus maxima, Citrus medica, and Citrus micrantha) and from limited subsequent interspecific recombination as a result of apomixis and vegetative propagation. Such reticulate evolution coupled with vegetative propagation results in mosaic genomes with large chromosome fragments from the basic taxa in frequent interspecific heterozygosity. Modern breeding of these species is hampered by their complex heterozygous genomic structures that determine species phenotype and are broken by sexual hybridisation. Nevertheless, a large amount of diversity is present in the citrus gene pool, and breeding to allow inclusion of desirable traits is of paramount importance. However, the efficient mobilization of citrus biodiversity in innovative breeding schemes requires previous understanding of Citrus origins and genomic structures. Haplotyping of multiple gene fragments along the whole genome is a powerful approach to reveal the admixture genomic structure of current species and to resolve the evolutionary history of the gene pools. In this study, the efficiency of parallel sequencing with 454 methodology to decipher the hybrid structure of modern citrus species was assessed by analysis of 16 gene fragments on chromosome 2.
454 amplicon libraries were established using the Fluidigm array system for 48 genotypes and 16 gene fragments from chromosome 2. Haplotypes were established from the reads of each accession and phylogenetic analyses were performed using the haplotypic data for each gene fragment. The length of 454 reads and the level of differentiation between the ancestral taxa of modern citrus allowed efficient haplotype phylogenetic assignations for 12 of the 16 gene fragments. The analysis of the mixed genomic structure of modern species and cultivars (i) revealed C. maxima introgressions in modern mandarins, (ii) was consistent with previous hypotheses regarding the origin of secondary species, and (iii) provided a new picture of the evolution of chromosome 2.
454 sequencing was an efficient strategy to establish haplotypes with significant phylogenetic assignations in Citrus, providing a new picture of the mixed structure on chromosome 2 in 48 citrus genotypes.
Electronic supplementary material
The online version of this article (doi:10.1186/s12863-014-0152-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4302129  PMID: 25544367
Phylogeny; Haplotype; Evolution; SNP; NGS; Genome admixture
17.  Effect of genotype imputation on genome-enabled prediction of complex traits: an empirical study with mice data 
BMC Genetics  2014;15:149.
Genotype imputation is an important tool for whole-genome prediction as it allows cost reduction of individual genotyping. However, benefits of genotype imputation have been evaluated mostly for linear additive genetic models. In this study we investigated the impact of employing imputed genotypes when using more elaborated models of phenotype prediction. Our hypothesis was that such models would be able to track genetic signals using the observed genotypes only, with no additional information to be gained from imputed genotypes.
For the present study, an outbred mice population containing 1,904 individuals and genotypes for 1,809 pre-selected markers was used. The effect of imputation was evaluated for a linear model (the Bayesian LASSO - BL) and for semi and non-parametric models (Reproducing Kernel Hilbert spaces regressions – RKHS, and Bayesian Regularized Artificial Neural Networks – BRANN, respectively). The RKHS method had the best predictive accuracy. Genotype imputation had a similar impact on the effectiveness of BL and RKHS. BRANN predictions were, apparently, more sensitive to imputation errors. In scenarios where the masking rates were 75% and 50%, the genotype imputation was not beneficial. However, genotype imputation incorporated information about important markers and improved predictive ability, especially for body mass index (BMI), when genotype information was sparse (90% masking), and for body weight (BW) when the reference sample for imputation was weakly related to the target population.
In conclusion, genotype imputation is not always helpful for phenotype prediction, and so it should be considered in a case-by-case basis. In summary, factors that can affect the usefulness of genotype imputation for prediction of yet-to-be observed traits are: the imputation accuracy itself, the structure of the population, the genetic architecture of the target trait and also the model used for phenotype prediction.
PMCID: PMC4333171  PMID: 25544265
Genotype imputation; Genome-enabled prediction; Complex traits; Non-linear models
18.  Assessment of genetic variation within a global collection of lentil (Lens culinaris Medik.) cultivars and landraces using SNP markers 
BMC Genetics  2014;15(1):150.
Lentil is a self-pollinated annual diploid (2n = 2× = 14) crop with a restricted history of genetic improvement through breeding, particularly when compared to cereal crops. This limited breeding has probably contributed to the narrow genetic base of local cultivars, and a corresponding potential to continue yield increases and stability. Therefore, knowledge of genetic variation and relationships between populations is important for understanding of available genetic variability and its potential for use in breeding programs. Single nucleotide polymorphism (SNP) markers provide a method for rapid automated genotyping and subsequent data analysis over large numbers of samples, allowing assessment of genetic relationships between genotypes.
In order to investigate levels of genetic diversity within lentil germplasm, 505 cultivars and landraces were genotyped with 384 genome-wide distributed SNP markers, of which 266 (69.2%) obtained successful amplification and detected polymorphisms. Gene diversity and PIC values varied between 0.108-0.5 and 0.102-0.375, with averages of 0.419 and 0.328, respectively. On the basis of clarity and interest to lentil breeders, the genetic structure of the germplasm collection was analysed separately for cultivars and landraces. A neighbour-joining (NJ) dendrogram was constructed for commercial cultivars, in which lentil cultivars were sorted into three major groups (G-I, G-II and G-III). These results were further supported by principal coordinate analysis (PCoA) and STRUCTURE, from which three clear clusters were defined based on differences in geographical location. In the case of landraces, a weak correlation between geographical origin and genetic relationships was observed. The landraces from the Mediterranean region, predominantly Greece and Turkey, revealed very high levels of genetic diversity.
Lentil cultivars revealed clear clustering based on geographical origin, but much more limited correlation between geographic origin and genetic diversity was observed for landraces. These results suggest that selection of divergent parental genotypes for breeding should be made actively on the basis of systematic assessment of genetic distance between genotypes, rather than passively based on geographical distance.
Electronic supplementary material
The online version of this article (doi:10.1186/s12863-014-0150-3) contains supplementary material, which is available to authorized users.
PMCID: PMC4300608  PMID: 25540077
Grain legume; Genetic diversity; Genotyping; Principal coordinate analysis; Dendrogram; Plant breeding
19.  Normal adult survival but reduced Bemisia tabaci oviposition rate on tomato lines carrying an introgression from S. habrochaites 
BMC Genetics  2014;15(1):142.
Host plant resistance has been proposed as one of the most promising approaches in whitefly management. Already in 1995 two quantitative trait loci (Tv-1 and Tv-2) originating from S. habrochaites CGN1.1561 were identified that reduced the oviposition rate of the greenhouse whitefly (Trialeurodes vaporariorum). After this first study, several others identified QTLs affecting whitefly biology as well. Generally, the QTLs affecting oviposition were highly correlated with a reduction in whitefly survival and the presence of high densities of glandular trichomes type IV. The aim of our study was to further characterize Tv-1 and Tv-2, and to determine their role in resistance against Bemisia tabaci.
We selected F2 plants homozygous for the Tv-1 and Tv-2 QTL regions and did three successive backcrosses without phenotypic selection. Twenty-three F2BC3 plants were phenotyped for whitefly resistance and differences were found in oviposition rate of B. tabaci. The F2BC3 plants with the lowest oviposition rate had an introgression on Chromosome 5 in common. Further F2BC4, F2BC4S1 and F2BC4S2 families were developed, genotyped and phenotyped for adult survival, oviposition rate and trichome type and density. It was possible to confirm that an introgression on top of Chr. 5 (OR-5), between the markers rs-2009 and rs-7551, was responsible for reducing whitefly oviposition rate.
We found a region of 3.06 Mbp at the top of Chr. 5 (OR-5) associated with a reduction in the oviposition rate of B. tabaci. This reduction was independent of the presence of the QTLs Tv-1 and Tv-2 as well as of the presence of trichomes type IV. The OR-5 locus will provide new opportunities for resistance breeding against whiteflies, which is especially relevant in greenhouse cultivation.
Electronic supplementary material
The online version of this article (doi:10.1186/s12863-014-0142-3) contains supplementary material, which is available to authorized users.
PMCID: PMC4301655  PMID: 25539894
Whitefly; Life history traits; Fine mapping; Tv-1; Tv-2; Trichome type IV
20.  Chromosome 16q22 variants in a region associated with cardiovascular phenotypes correlate with ZFHX3 expression in a transcript-specific manner 
BMC Genetics  2014;15(1):136.
The ZFHX3 gene, located in Chromosome 16q22.3, codes for a transcription factor which is widely expressed in human tissues. Genome-wide studies have identified associations between variants within the gene and Kawasaki disease and atrial fibrillation. ZFHX3 has two main transcripts that utilise different transcription start sites. We examined the association between genetic variants in the 16q22.3 region and expression of ZFHX3 to identify variants that regulate gene expression.
We genotyped 65 single-nucleotide polymorphisms to tag genetic variation at the ZFHX3 locus in two cohorts, 451 British individuals recruited in the North East of England and 310 mixed-ancestry individuals recruited in South Africa. Allelic expression analysis revealed that the minor (A) allele of rs8060701, a variant in the first intron of ZFHX3, was associated with a 1.16-fold decrease in allelic expression of both transcripts together, (p = 4.87e-06). The minor (C) allele of a transcribed variant, rs10852515, in the second exon of ZFHX3 isoform A was independently associated with a 1.36-fold decrease in allelic expression of ZFHX3 A (p = 7.06e-31), but not overall ZFHX3 expression. However, analysis of total gene expression of ZFHX3 failed to detect an association with genotype at any variant. Differences in linkage disequilibrium between the two populations allowed fine-mapping of the locus to a 7 kb region overlapping exon 2 of ZFHX3 A. We did not find any association between ZFHX3 expression and any of the variants identified by genome wide association studies.
ZFHX3 transcription is regulated in a transcript-specific fashion by independent cis-acting transcribed polymorphisms. Our results demonstrate the power of allelic expression analysis and trans-ethnic fine mapping to identify transcript-specific cis-acting regulatory elements.
Electronic supplementary material
The online version of this article (doi:10.1186/s12863-014-0136-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4301889  PMID: 25539802
Expression QTL mapping; Trans-ethnic mapping; Atrial fibrillation; Genome-wide association study
21.  Does FTO have a paradoxical effect in fetal life? 
BMC Genetics  2014;15:145.
Low weight at birth is associated with obesity in later life. One hypothesis to explain such an association is that genetic variants that increase the risk of obesity also reduce fetal weight. Recently, obesity in adults was found to be associated with common variants of the fat mass and obesity-associated (FTO) gene. We examined the association between FTO polymorphisms and birth weight in a singleton, full-term birth cohort of 494 newborn-mother pairs without any complications.
The risk alleles for obesity (“A” allele for the rs9939609 FTO variant and “G” allele for the rs9930506 FTO variant) were associated with low weight at birth. The mean differences per risk allele were −79 g (95% CI: −129 to −30; p = 0.002) for rs9939609 and −84 g (95% CI: −131 to −36; P < 0.001) for rs9930506. The level of association remained statistically significant after adjustment for the maternal risk allele and for variables usually associated with birth weight (−50 g, 95% CI: −99 to 0; p = 0.05 for rs9939609 and −48 g, 95% CI: −100 to 0; p = 0.05 for rs9930506). In the follow-up, the allelic difference in weight was attenuated over time.
The FTO variants that confer a predisposition to obesity later in life appear to be associated with low weight at birth. This finding favors the hypothesis of a common genetic denominator that predisposes to a low weight at birth and obesity in adults.
PMCID: PMC4332444
Obesity, FTO; Newborn; Mother; Birth weight; Adiposity
22.  Genetic variation, heritability and genotype by environment interaction of morphological traits in a tetraploid rose population 
BMC Genetics  2014;15(1):146.
Global trade has ensured that the ornamental horticulture continues to grow worldwide, with rose hybrids being the most economically important genus (Rosa x hybrida). Due to changes in global trade and an increase in energy costs the ornamental industry has seen a shift in the production and sale of flowers from the US and Europe alone to production in Africa and Latin America. As Kenya is a major exporter of roses to Europe we studied the genetic variation and heritability of specific morphological traits in a tetraploid population grown in the Netherlands and in Kenya. The aim was to estimate genotype by environment interaction (G × E) and to investigate the implications of (G × E) for rose breeding.
A tetraploid rose population (K5) from a cross between two tetraploid parents was field tested over two seasons in the Netherlands (summer and winter) and two locations in Kenya (Nairobi and Njoro). Ten traits were compared per genotype across the four environments. There were differences in trait association across the four environments showing that the traits were partially influenced by the environment.
The traits that had a low ratio of σ2ge/σ2g also showed a high value for heritability. For the traits number of petals, prickles on petioles, prickles on stems the interaction is minimal. For the traits chlorophyll content, stem width and side shoots we observed a much higher interaction ratio of 0.83, 1.43 and 3.13 respectively. The trait number of petals had the highest heritability of 0.96 and the lowest σ2ge/σ2g ratio (0.08). The trait number of side shoots (SS) with the lowest heritability (0.40) also had the highest σ2ge/σ2g ratio of 3.13.
Attained by this experiment showed that we have different magnitudes of non-crossover G × E interactions. For the traits number of petals, prickles on stems and prickles on petioles with a low interaction and high heritability, selection can be done at any of the environments. Thus, these traits can be confirmed at the breeding site. For the traits stem width, side shoots and chlorophyll content that had a higher interaction selection for or against these traits should be done at the production location or at least be verified there.
Electronic supplementary material
The online version of this article (doi:10.1186/s12863-014-0146-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4293809  PMID: 25526782
Rose; Tetraploid; Genetics; Morphological traits; Heritability; Correlations; Genotype x environment
23.  Recombination of the porcine X chromosome: a high density linkage map 
BMC Genetics  2014;15(1):148.
Linkage maps are essential tools for the study of several topics in genome biology. High density linkage maps for the porcine autosomes have been constructed exploiting the high density data provided by the PorcineSNP60 BeadChip. However, a high density SSCX linkage map has not been reported up to date. The aim of the current study was to build an accurate linkage map of SSCX to provide precise estimates of recombination rates along this chromosome and creating a new tool for QTL fine mapping.
A female-specific high density linkage map was built for SSCX using Sscrofa10.2 annotation. The total length of this chromosome was 84.61 cM; although the average recombination rate was 0.60 cM/Mb, both cold and hot recombination regions were identified. A Bayesian probabilistic to genetic groups and revealed that the animals used in the current study for linkage map construction were likely to be carriers of X chromosomes of European origin. Finally, the newly generated linkage map was used to fine-map a QTL at 16 cM for intramuscular fat content (IMF) measured on longissimus dorsi. The sulfatase isozyme S gene constitutes a functional and positional candidate gene underlying the QTL effect.
The current study presents for the first time a high density linkage map for SSCX and supports the presence of cold and hot recombination intervals along this chromosome. The large cold recombination region in the central segment of the chromosome is not likely to be due to structural differences between X chromosomes of European and Asian origin. In addition, the newly generated linkage map has allowed us to fine-map a QTL on SSCX for fat deposition.
Electronic supplementary material
The online version of this article (doi:10.1186/s12863-014-0148-x) contains supplementary material, which is available to authorized users.
PMCID: PMC4293812  PMID: 25526890
Porcine linkage maps; Recombination; X chromosome; European and Asian X chromosome
24.  Genetic influence of dopamine receptor, dopamine transporter, and nicotine metabolism on smoking cessation and nicotine dependence in a Japanese population 
BMC Genetics  2014;15(1):151.
This study investigated whether polymorphisms of the ankyrin repeat and kinase domain containing 1 gene (ANKK1), which is adjacent to the dopamine D2 receptor gene (DRD2), and the dopamine transporter (SLC6A3) and cytochrome P450 2A6 (CYP2A6) genes influence smoking cessation and nicotine dependence in a Japanese population. In 96 current and former smokers, genotyping frequencies for the ANKK1/DRD2 TaqIA, SLC6A3 VNTR, and CYP2A6 polymorphisms were subjected to chi-square analysis, and regression analyses were used to determine the association of the genotypes of current smokers with a Heavy Smoking Index, in addition to evaluating the effect of the subjects’ smoking history on the association.
Genotyping results suggested that nicotine dependence among current smokers homozygous for the SLC6A3 10r allele was lower than that of smokers carrying the minor alleles, and that the CYP2A6 polymorphism might mediate this association. Furthermore, the age at which current smokers began smoking might moderate the association between their genetic polymorphisms and nicotine dependence.
This study provides preliminary findings on the influence of genetic variants on the smoking phenotypes in a Japanese population.
PMCID: PMC4307219  PMID: 25526961
ANKK1/DRD2 TaqIA polymorphism; CYP2A6*4 polymorphism; Nicotine dependence SLC6A3 VNTR polymorphism; Smoking cessation
25.  Identification of skin-expressed genes possibly associated with wool growth regulation of Aohan fine wool sheep 
BMC Genetics  2014;15(1):144.
Sheep are valuable resources for the animal fibre industry. Therefore, identifying genes which regulate wool growth would offer strategies for improving the quality of fine wool. In this study, we employed Agilent sheep gene expression microarray and proteomic technology to compare the gene expression patterns of the body side (hair-rich) and groin (hairless) skins of Aohan fine wool sheep (a Chinese indigenous breed).
Comparing the body side to the groin skins (S/G) of Aohan fine wool sheep, the microarray study revealed that 1494 probes were differentially expressed, including 602 more highly expressed and 892 less highly expressed probes. The microarray results were verified by means of quantitative PCR. Cluster analysis could distinguish the body side skin and the groin skin. Based on the Database for Annotation, Visualization and Integrated Discovery (DAVID), 38 of the differentially expressed genes were classified into four categories, namely regulation of receptor binding, multicellular organismal process, protein binding and macromolecular complex. Proteomic study revealed that 187 protein spots showed significant (p < 0.05) differences in their respective expression levels. Among them, 46 protein entries were further identified by MALDI-TOF/MS analyses.
Microarray analysis revealed thousands of differentially expressed genes, many of which were possibly associated with wool growth. Several potential gene families might participate in hair growth regulation. Proteomic analysis also indentified hundreds of differentially expressed proteins.
Electronic supplementary material
The online version of this article (doi:10.1186/s12863-014-0144-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4272822  PMID: 25511509
Microarray; Proteomic technology; Wool growth; Differential expression

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