http://www.biomedcentral.com/bmcgenet/ The latest research articles published by BMC Genetics 2009-07-07T00:00:00Z This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ Background: In several biological contexts, parameter inference often relies on computationally-intensive techniques. "Approx-imate Bayesian Computation", or ABC, methods based on summary statistics have become increasingly popular.A particular avor of ABC based on using a linear regression to approximate the posterior distribution of theparameters, conditional on the summary statistics, is computationally appealing, yet no standalone tool exists toautomate the procedure. Here, I describe a program to implement the method. Results: The software package ABCreg implements the local linear-regression approach to ABC. The advantages are: 1.The code is standalone, and fully-documented. 2. The program will automatically process multiple data sets, andcreate unique output les for each (which may be processed immediately in R), facilitating the testing of inferenceprocedures on simulated data, or the analysis of multiple data sets. 3. The program implements two dierenttransformation methods for the regression step. 4. Analysis options are controlled on the command line by theuser, and the program is designed to output warnings for cases where the regression fails. 5. The program doesnot depend on any particular simulation machinery (coalescent, forward-time, etc.), and therefore is a generaltool for processing the results from any simulation. 6. The code is open-source, and modular.Examples of applying the software to empirical data from Drosophila melanogaster, and testing the procedureon simulated data, are shown. Conclusions: In practice, the ABCreg simplies implementing ABC based on local-linear regression. http://www.biomedcentral.com/1471-2156/10/35 Kevin Thornton BMC Genetics 2009, 10:35 2009-07-07T00:00:00Z doi:10.1186/1471-2156-10-35 BMC Genetics 1471-2156 10 35 2009-07-07T00:00:00Z PDF Background: Seven karyomorphs of the fish, Hoplias malabaricus (A-G) were previously included in two major groups, Group I (A, B, C, D) and Group II (E, F, G), based on their similar karyotype structure. In this paper, karyomorphs from Group I were analyzed by means of distinct chromosomal markers, including silver-stained nucleolar organizer regions (Ag-NORs) and chromosomal location of repetitive sequences (18S and 5S rDNA, and satellite 5SHindIII-DNA), through fluorescence in situ hybridization (FISH), in order to evaluate the evolutionary relationships among them. Results: The results showed that several chromosomal markers had conserved location in the four karyomorphs. In addition, some other markers were only conserved in corresponding chromosomes of karyomorphs A-B and C-D. These data therefore reinforced and confirmed the proposed grouping of karyomorphs A-D in Group I and highlight a closer relationship between karyomorphs A-B and C-D. Moreover, the mapping pattern of some markers on some autosomes and on the chromosomes of the XY and X1X2Y systems provided new evidence concerning the possible origin of the sex chromosomes. Conclusion: The in situ investigation of repetitive DNA sequences adds new informative characters useful in comparative genomics at chromosomal level and provides insights into the evolutionary relationships among Hoplias malabaricus karyomorphs. http://www.biomedcentral.com/1471-2156/10/34 Marcelo Cioffi Cesar Martins Luiz Bertollo BMC Genetics 2009, 10:34 2009-07-07T00:00:00Z doi:10.1186/1471-2156-10-34 BMC Genetics 1471-2156 10 34 2009-07-07T00:00:00Z PDF Background: Polled animals are valued in cattle industry because the absence of horns has a significant economic impact. However, some cattle are neither polled nor horned but have so-called scurs on their heads, which are corneous growths loosely attached to the skull. A better understanding of the genetic determinism of the scurs phenotype would help to fine map the polled locus. To date, only one study has attempted to map the scurs locus in cattle. Here, we have investigated the inheritance of the scurs phenotype in the French Charolais breed and examined whether the previously proposed localisation of the scurs locus on bovine chromosome 19 could be confirmed or not. Results: Our results indicate that the inheritance pattern of the scurs phenotype in the French Charolais breed is autosomal recessive with complete penetrance in both sexes, which is different from what is reported for other breeds. The frequency of the scurs allele (Sc) reaches 69.9% in the French Charolais population. Eleven microsatellite markers on bovine chromosome 19 were genotyped in 267 offspring (33 half-sib and full-sib families). Both non-parametric and parametric linkage analyses suggest that in the French Charolais population the scurs locus may not map to the previously identified region. A new analysis of an Angus-Hereford and Hereford-Hereford pedigree published in 1978 enabled us to calculate the frequency of the Sc allele in the Hereford breed (89.4%) and to study the penetrance of this allele in males heterozygous for both polled and scurs loci (40%). This led us to revise the inheritance pattern of the scurs phenotype proposed for the Hereford breed and to suggest that allele Sc is not fully but partially dominant in double heterozygous males while it is always recessive in females. Crossbreeding involving the Charolais breed and other breeds gave results similar to those reported in the Hereford breed. Conclusions: Our results suggest the existence of unknown genetics factors modifying the expression of the scurs locus in double heterozygous Hereford and Angus males. The specific inheritance pattern of the scurs locus in the French Charolais breed represents an opportunity to map this gene and to identify the molecular mechanisms regulating the growth of horns in cattle. http://www.biomedcentral.com/1471-2156/10/33 Aurelien Capitan Cecile Grohs Mathieu Gautier Andre Eggen BMC Genetics 2009, 10:33 2009-07-06T00:00:00Z doi:10.1186/1471-2156-10-33 BMC Genetics 1471-2156 10 33 2009-07-06T00:00:00Z PDF Background: Boar taint is an unpleasant odour and flavour of the meat from some uncastrated male pigs primarily caused by elevated levels of androstenone and skatole in adipose tissue. Androstenone is produced in the same biochemical pathway as testosterone and estrogens, which represents a particular challenge when selecting against high levels of androstenone in the breeding programme, without simultaneously decreasing levels of other steroids. Detection of single nucleotide polymorphisms (SNPs) associated with compounds affecting boar taint is important both for gaining a better understanding of the complex regulation of the trait and for the purpose of identifying markers that can be used to improve the gain of breeding. The beneficial SNPs to be used in breeding would have the combinational effects of reducing levels of boar taint without affecting fertility of the animals. The aim of this study was to detect SNPs in boar taint candidate genes and to perform association studies for both single SNPs and haplotypes with levels of boar taint compounds and phenotypes related to reproduction. Results: An association study involving 275 SNPs in 121 genes and compounds related to boar taint and reproduction were carried out in Duroc and Norwegian Landrace boars. Phenotypes investigated were levels of androstenone, skatole and indole in adipose tissue, levels of androstenone, testosterone, estrone sulphate and 17beta-estradiol in plasma, and length of bulbo urethralis gland. The SNPs were genotyped in more than 2800 individuals and several SNPs were found to be significantly (LRT > 5.4) associated with the different phenotypes. Genes with significant SNPs in either of the traits investigated include cytochrome P450 members CYP2E1, CYP21, CYP2D6 and CYP2C49, steroid 5alpha-reductase SRD5A2, nuclear receptor NGFIB, catenin CTNND1, BRCA1 associated protein BAP1 and hyaluronoglucosaminidase HYAL2. Haplotype analysis provided additional evidence for an effect of CYP2E1 on levels of skatole and indole, and for BAP1, HYAL2 and SRD5A2 on levels of androstenone. Conclusion: The findings in this study indicate that polymorphisms in CYP2E1, CYP21, CYP2D6, CYP2C49, NGFIB and CTNND1 might be used to reduce levels of boar taint without affecting levels of testosterone, estrone sulphate, 17beta-estradiol or length of bulbo urethralis gland. http://www.biomedcentral.com/1471-2156/10/32 Maren Moe Sigbjorn Lien Torunn Aasmundstad Theo Meuwissen Marianne Hansen Christian Bendixen Eli Grindflek BMC Genetics 2009, 10:32 2009-07-05T00:00:00Z doi:10.1186/1471-2156-10-32 BMC Genetics 1471-2156 10 32 2009-07-05T00:00:00Z PDF Background: Lactase non-persistence is a condition where lactase activity is decreased in the intestinal wall after weaning. In European derived populations a single nucleotide polymorphism (SNP) C/T-13910 residing 13.9 kb upstream from the lactase gene has been shown to define lactase activity, and several other single nucleotide polymorphisms (G/C-14010, T/G-13915, C/G-13907 and T/C-13913) in the same region have been identified in African and Middle East populations. Results: The T-13910 allele most common in European populations was present in 21.8% mixed ancestry (N=62) individuals and was it was absent in the Xhosa (N=109) and Ghana (N=196) subjects. Five other substitutions were also found in the region covering the previously reported variants in African and Middle East populations. These included the G/C-14010 variant common in Kenyan and Tanzanian populations, which was present in 12.8% of Xhosa population and in 8.1% of mixed ancestry subjects. Two novel substitutions (C/T-14091 and A/C-14176) and one previously reported substitution G/A-13937 (rs4988234) were less common and present only in the Xhosa population. One novel substitution G/A-14107 was present in the Xhosa and Ghanaian populations. None of the other previously reported variants were identified. Conclusions: Identification of the G/C-14010 variant in the Xhosa population, further confirms their genetic relatedness to other nomadic populations members that belong to the Bantu linguistic group in Tanzania and Kenya. Further studies are needed to confirm the possible relationship of the novel substitutions to the lactase persistence trait. http://www.biomedcentral.com/1471-2156/10/31 Suvi Torniainen M Parker Ville Holmberg Elisa Lahtela Collet Dandara Irma Jarvela BMC Genetics 2009, 10:31 2009-07-05T00:00:00Z doi:10.1186/1471-2156-10-31 BMC Genetics 1471-2156 10 31 2009-07-05T00:00:00Z PDF Background: The aim of this paper is to develop a flexible model for analysis of quantitative trait loci (QTL) in outbred line crosses, which includes both additive and dominance effects. Our flexible intercross analysis (FIA)model accounts for QTL that are not fixed within founder lines and is based on the variance component framework. Genome scans with FIA are performed using a score statistic, which does not require variance component estimation. Results: Simulations of a pedigree with 800 F2 individuals showed that the power of FIA including both additive and dominance effects was almost 50% for a QTL with equal allele frequencies in both lines with complete dominance and a moderate effect, whereas the power of a traditional regression model was equal to the chosen signifficance value of 5%. The power of FIA without dominance effects included in the model was close to those obtained for FIA with dominance for all simulated cases except for QTL with overdominant effects. A genome-wide linkage analysis of experimental data from an F2 intercross between Red Jungle Fowl and White Leghorn was performed with both additive and dominance effects included in FIA. The score values for chicken body weight at 200 days of age were similar to those obtained in FIA analysis without dominance. Conclusions: We have extended FIA to include QTL dominance effects. The power of FIA was superior, or similar, to standard regression methods for QTL effects with dominance. The difference in power for FIA with or without dominance is expected to be small as long as the QTL effects are not overdominant. We suggest that FIA with only additive effects should be the standard model to be used, especially since it is more computationally efficient. http://www.biomedcentral.com/1471-2156/10/30 Lars Ronnegard Francois Besnier Orjan Carlborg BMC Genetics 2009, 10:30 2009-06-28T00:00:00Z doi:10.1186/1471-2156-10-30 BMC Genetics 1471-2156 10 30 2009-06-28T00:00:00Z PDF Background: Progress in the field of human ancient DNA studies has been severely restricted due to the myriad sources of potential contamination, and because of the pronounced difficulty in identifying authentic results. Improving the robustness of human aDNA results is a necessary pre-requisite to vigorously testing hypotheses about human evolution in Europe, including possible admixture with Neanderthals. This study approaches the problem of distinguishing between authentic and contaminating sequences from common European mtDNA haplogroups by applying a multiplexed Single-Base-Extension assay, containing both control and coding region sites, to DNA extracted from the Tyrolean Iceman. Results: The multiplex assay developed for this study was able to test sufficient polymorphisms in one reaction to unequivocally demonstrate that the Iceman's mtDNA belongs to a new European mtDNA clade with a very limited distribution amongst modern data sets. Controlled contamination experiments show that the correct results are returned by the multiplex assay even in the presence of substantial amounts of exogenous DNA. The overall level of discrimination achieved by targeting both control and coding region polymorphisms in a single reaction provides a methodology capable of dealing with most cases of homoplasy prevalent in European haplogroups. Conclusions: The new genotyping results for the Iceman confirm the extreme fallibility of human aDNA studies in general, even when authenticated by independent replication. The sensitivity and accuracy of the multiplex Single-Base-Extension methodology forms part of an emerging suite of alternative techniques for the accurate retrieval of ancient DNA sequences from both anatomically modern humans and Neanderthals. The contamination of laboratories remains a pressing concern in aDNA studies, both in the pre and post-PCR environments, and the adoption of a forensic style assessment of a priori risks would significantly improve the credibility of results. http://www.biomedcentral.com/1471-2156/10/29 Phillip Endicott Juan Sanchez Irene Pichler Paul Brotherton Jerome Brooks Eduard Egarter-Vigl Alan Cooper Peter Pramstaller BMC Genetics 2009, 10:29 2009-06-19T00:00:00Z doi:10.1186/1471-2156-10-29 BMC Genetics 1471-2156 10 29 2009-06-19T00:00:00Z PDF Background: The Isolation by Distance Web Service (IBDWS) is a user-friendly web interface for analyzing patterns of isolation by distance in population genetic data. IBDWS enables researchers to perform a variety of statistical tests such as Mantel tests and reduced major axis regression (RMA), and returns vector based graphs. The more than 90 citations since 2005 confirm the popularity and utility of this website. Despite its usefulness, the computational intensity of the statistical tests means that data sets with over 65 populations can take hours or days to complete due to the computational intensity of the statistical tests. This is especially troublesome for web-based software analysis, since users tend to expect real-time results on the order of seconds or at most, minutes. Moreover, as genetic data continue to increase and diversify, so does the demand for more processing power. In order to increase the speed and efficiency of IBDWS, we first determined which aspects of the code were most time consuming and whether they might be amenable to improvements by parallelization or algorithmic optimization. Results: Runtime tests uncovered two areas of IBDWS that consumed significant amounts of time: randomizations within the Mantel test and the RMA calculations. We found that these sections of code could be restructured and parallelized to improve efficiency. The code was first optimized by combining two similar randomization routines, implementing a Fisher-Yates shuffling algorithm, and then parallelizing those routines. Tests of the parallelization and Fisher-Yates algorithmic improvements were performed on a variety of data sets ranging from 10 to 150 populations. All tested algorithms showed runtime reductions and a very close fit to the predicted speedups based on time-complexity calculations. In the case of 150 populations with 10,000 randomizations, data were analyzed 23 times faster. Conclusions: Since the implementation of the new algorithms in late 2007, datasets have continued to increase substantially in size and many exceed the largest population sizes we used in our test sets. The fact that the website has continued to work well in "real-world" tests, and receives a considerable numbers of new citations, provides the strongest testimony to the effectiveness of our improvements. However, we soon expect the need to upgrade the number of nodes in our cluster significantly as dataset sizes continue to expand. The parallel implementation can be found at http://ibdws.sdsu.edu/. http://www.biomedcentral.com/1471-2156/10/28 Julia Turner Scott Kelley James Otto Faramarz Valafar Andrew Bohonak BMC Genetics 2009, 10:28 2009-06-19T00:00:00Z doi:10.1186/1471-2156-10-28 BMC Genetics 1471-2156 10 28 2009-06-19T00:00:00Z PDF Background: Although high-throughput genotyping arrays have made whole-genome association studies (WGAS) feasible, only a small proportion of SNPs in the human genome are actually surveyed in such studies. In addition, various SNP arrays assay different sets of SNPs, which leads to challenges in comparing results and merging data for meta-analyses. Genome-wide imputation of untyped markers allows us to address these issues in a direct fashion. Methods: 384 Caucasian American liver donors were genotyped using Illumina 650Y (Ilmn650Y) arrays, from which we also derived genotypes from the Ilmn317K array. On these data, we compared two imputation methods: MACH and BEAGLE. We imputed 2.5 million HapMap Release22 SNPs, and conducted GWAS on ~40,000 liver mRNA expression traits (eQTL analysis). In addition, 200 Caucasian American and 200 African American subjects were genotyped using the Affymetrix 500K array plus a custom 164K fill-in chip. We then imputed the HapMap SNPs and quantified the accuracy by randomly masking observed SNPs. Results: MACH and BEAGLE perform similarly with respect to imputation accuracy. The Ilmn650Y results in excellent imputation performance, and it outperforms Affx500K or Ilmn317K sets. For Caucasian Americans, 90% of the HapMap SNPs were imputed at 98% accuracy. As expected, imputation of poorly tagged SNPs (untyped SNPs in weak LD with typed markers) was not as successful. It was more challenging to impute genotypes in the African American population, given (1) shorter LD blocks and (2) admixture with Caucasian populations in this population. To address issue (2), we pooled HapMap CEU and YRI data as an imputation reference set, which greatly improved overall performance. The approximate 40,000 phenotypes scored in these populations provide a path to determine empirically how the power to detect associations is affected by the imputation procedures. That is, at a fixed false discovery rate, the number of cis-eQTL discoveries detected by various methods can be interpreted as their relative statistical power in the GWAS. In this study, we find that imputation offer modest additional power (by 4%) on top of either Ilmn317K or Ilmn650Y, much less than the power gain from Ilmn317K to Ilmn650Y (13%). Conclusions: Current algorithms can accurately impute genotypes for untyped markers, which enables researchers to pool data between studies conducted using different SNP sets. While genotyping itself results in a small error rate (e.g. 0.5%), imputing genotypes is surprisingly accurate. We found that dense marker sets (e.g. Ilmn650Y) outperform sparser ones (e.g. Ilmn317K) in terms of imputation yield and accuracy. We also noticed it was harder to impute genotypes for African American samples, partially due to population admixture, although using a pooled reference boosts performance. Interestingly, GWAS carried out using imputed genotypes only slightly increased power on top of assayed SNPs. The reason is likely due to adding more markers via imputation only results in modest gain in genetic coverage, but worsens the multiple testing penalties. Furthermore, cis-eQTL mapping using dense SNP set derived from imputation achieves great resolution, and locate associate peak closer to causal variants than conventional approach. http://www.biomedcentral.com/1471-2156/10/27 Ke Hao Eugene Chudin Joshua McElwee Eric Schadt BMC Genetics 2009, 10:27 2009-06-16T00:00:00Z doi:10.1186/1471-2156-10-27 BMC Genetics 1471-2156 10 27 2009-06-16T00:00:00Z PDF Background: Linkage disequilibrium (LD) mapping is commonly used to evaluate markers for genome-wide association studies. Most types of LD software focus strictly on LD analysis and visualization, but lack supporting services for genotyping. Results: We developed a freeware called LD2SNPing, which provides a complete package of mining tools for genotyping and LD analysis environments. The software provides SNP ID- and gene-centric online retrievals for SNP information and tag SNP selection from dbSNP/NCBI and HapMap, respectively. Restriction fragment length polymorphism (RFLP) enzyme information for SNP genotype is available to all SNP IDs and tag SNPs. Single and multiple SNP inputs are possible in order to perform LD analysis by online retrieval from HapMap and NCBI. An LD statistics section provides D, D', r2, δQ, ρ, and the P values of the Hardy-Weinberg Equilibrium for each SNP marker, and Chi-square and likelihood-ratio tests for the pair-wise association of two SNPs in LD calculation. Finally, 2D and 3D plots, as well as plain-text output of the results, can be selected. Conclusion: LD2SNPing thus provides a novel visualization environment for multiple SNP input, which facilitates SNP association studies. The software, user manual, and tutorial are freely available at http://bio.kuas.edu.tw/LD2NPing. http://www.biomedcentral.com/1471-2156/10/26 Hsueh-Wei Chang Li-Yeh Chuang Yan-Jhu Chang Yu-Huei Cheng Yu-Chen Hung Hsiang-Chi Chen Cheng-Hong Yang BMC Genetics 2009, 10:26 2009-06-06T00:00:00Z doi:10.1186/1471-2156-10-26 BMC Genetics 1471-2156 10 26 2009-06-06T00:00:00Z XML