http://www.biomedcentral.com/bmcgenet/ The editor's pick of recent articles published by BMC Genetics 2012-04-27T00:00:00Z Background: The mammalian cochlea receives and analyzes sound at specific places along the cochlea coil, commonly referred to as the tonotopic map. Although much is known about the cell-level molecular defects responsible for severe hearing loss, the genetics responsible for less severe and frequency-specific hearing loss remains unclear. We recently identified quantitative trait loci (QTLs) Hfhl1 and Hfhl2 that affect high-frequency hearing loss in NIH Swiss mice. Here we used 2f1-f2 distortion product otoacoustic emissions (DPOAE) measurements to refine the hearing loss phenotype. We crossed the high frequency hearing loss (HFHL) line of NIH Swiss mice to three different inbred strains and performed linkage analysis on the DPOAE data obtained from the second-generation populations. Results: We identified a QTL of moderate effect on chromosome 7 that affected 2f1-f2 emissions intensities (Hfhl1), confirming the results of our previous study that used auditory brainstem response (ABR) thresholds to identify QTLs affecting HFHL. We also identified a novel significant QTL on chromosome 9 (Hfhl3) with moderate effects on 2f1-f2 emissions intensities. By partitioning the DPOAE data into frequency subsets, we determined that Hfhl1 and Hfhl3 affect hearing primarily at frequencies above 24 kHz and 35 kHz, respectively. Furthermore, we uncovered additional QTLs with small effects on isolated portions of the DPOAE spectrum. Conclusions: This study identifies QTLs with effects that are isolated to limited portions of the frequency map. Our results support the hypothesis that frequency-specific hearing loss results from variation in gene activity along the cochlear partition and suggest a strategy for creating a map of cochlear genes that influence differences in hearing sensitivity and/or vulnerability in restricted portions of the cochlea. http://www.biomedcentral.com/1471-2156/13/32 James M Keller Konrad Noben-Trauth BMC Genetics 2012, 13:32 2012-04-27T00:00:00Z 10.1186/1471-2156-13-32 Sounding out the genetics of hearing loss The identification of two quantitative trait loci (QTL) with frequency-specific effects on the hearing spectrum of NIH Swiss mice supports the hypothesis that frequency-specific hearing loss is the result of regionally specific gene activity in the cochlea. /content/figures/1471-2156-13-32-toc.gif BMC Genetics 1471-2156 13 32 2012-04-27T00:00:00Z PDF Background: A defense system against transposon activity in the human germline based on PIWI proteins and piRNA has recently been discovered. It represses the activity of LINE-1 elements via DNA methylation by a largely unknown mechanism. Based on the dispersed distribution of clusters of piRNA genes in a strand-specific manner on all human chromosomes, we hypothesized that this system might work preferentially on local and proximal sequences. We tested this hypothesis with a methylation-associated SNP (mSNP) marker which is based on the density of C-T transitions in CpG dinucleotides as a surrogate marker for germline methylation. Results: We found significantly higher density of mSNPs flanking piRNA clusters in the human genome for flank sizes of 1-16 Mb. A dose-response relationship between number of piRNA genes and mSNP density was found for up to 16 Mb of flanking sequences. The chromosomal density of hypermethylated LINE-1 elements had a significant positive correlation with the chromosomal density of piRNA genes (r = 0.41, P = 0.05). Genome windows of 1-16 Mb containing piRNA clusters had significantly more hypermethylated LINE-1 elements than windows not containing piRNA clusters. Finally, the minimum distance to the next piRNA cluster was significantly shorter for hypermethylated LINE-1 compared to normally methylated elements (14.4 Mb vs 16.1 Mb). Conclusions: Our observations support our hypothesis that the piRNA-PIWI system preferentially methylates sequences in close proximity to the piRNA clusters and perhaps physically adjacent sequences on other chromosomes. Furthermore they suggest that this proximity effect extends up to 16 Mb. This could be due to an unknown localization signal, transcription of piRNA genes near the nuclear membrane or the presence of an unknown RNA molecule that spreads across the chromosome and targets the methylation directed by the piRNA-PIWI complex. Our data suggest a region specific molecular mechanism which can be sought experimentally. http://www.biomedcentral.com/1471-2156/13/31 Martin I Sigurdsson Albert V Smith Hans T Bjornsson Jon J Jonsson BMC Genetics 2012, 13:31 2012-04-24T00:00:00Z 10.1186/1471-2156-13-31 Preferential methylation of proximal piRNA clusters Significantly high densities of methylation-associated SNPs flanking clusters of RNAs that interact with regulatory PIWI genes (piRNAs), supports the hypothesis that the piRNA-PIWI system preferentially methylates sequences in close proximity to the piRNA clusters /content/figures/1471-2156-13-31-toc.gif BMC Genetics 1471-2156 13 31 2012-04-24T00:00:00Z XML Background: A detailed genetic study of the pre-Columbian population inhabiting the Tompullo 2 archaeological site (department Arequipa, Peru) was undertaken to resolve the kin relationships between individuals buried in six different chullpas. Kin relationships were an important factor shaping the social organization in the pre-Columbian Andean communities, centering on the ayllu, a group of relatives that shared a common land and responsibilities. The aim of this study was to evaluate whether this Andean model of a social organization had an influence on mortuary practices, in particular to determine whether chullpas served as family graves. Results: The remains of forty-one individuals were analyzed with both uniparental (mtDNA, Y-chromosome) and biparental (autosomal microsatellites) markers. Reproducible HVRI sequences, autosomal and Y chromosomal STR profiles were obtained for 24, 16 and 11 individuals, respectively. Mitochondrial DNA diversity was comparable to that of ancient and contemporary Andean populations. The Tompullo 2 population exhibited the closest relationship with the modern population from the same region. A kinship analysis revealed complex pattern of relations within and between the graves. However mean relatedness coefficients regarding the pairs of individuals buried in the same grave were significantly higher than those regarding pairs buried in different graves. The Y chromosome profiles of 11 males suggest that only members of one male line were buried in the same grave. Conclusions: Genetic investigation of the population that inhabited Tompullo 2 site shows continuity between pre-Columbian and modern Native Amerindian populations inhabiting the Arequipa region. This suggests that no major demographic processes have influenced the mitochondrial DNA diversity of these populations during the past five hundred years. The kinship analysis involving uni- and biparental markers suggests that the community that inhabited the Tompullo 2 site was organized into extended family groups that were buried in different graves. This finding is in congruence with known models of social organization of Andean communities. http://www.biomedcentral.com/1471-2156/13/30 Mateusz Baca Karolina Doan Maciej Sobczyk Anna Stankovic Piotr Weglenski BMC Genetics 2012, 13:30 2012-04-23T00:00:00Z 10.1186/1471-2156-13-30 Ancient DNA reveals Andean family values Ancient DNA retrieved from 15-16th Century Andean burial mounds confirms historical and ethnographic evidence that communities were organized into social structures with extended family groups buried in a single grave. /content/figures/1471-2156-13-30-toc.gif BMC Genetics 1471-2156 13 30 2012-04-23T00:00:00Z PDF Background: With the considerable growth of available nucleotide sequence data over the last decade, integrated and flexible analytical tools have become a necessity. In particular, in the field of population genetics, there is a strong need for automated and reliable procedures to conduct repeatable and rapid polymorphism analyses, coalescent simulations, data manipulation and estimation of demographic parameters under a variety of scenarios. Results: In this context, we present EggLib (Evolutionary Genetics and Genomics Library), a flexible and powerful C++/Python software package providing efficient and easy to use computational tools for sequence data management and extensive population genetic analyses on nucleotide sequence data. EggLib is a multifaceted project involving several integrated modules: an underlying computationally efficient C++ library (which can be used independently in pure C++ applications); two C++ programs; a Python package providing, among other features, a high level Python interface to the C++ library; and the egglib script which provides direct access to pre-programmed Python applications. Conclusions: EggLib has been designed aiming to be both efficient and easy to use. A wide array of methods are implemented, including file format conversion, sequence alignment edition, coalescent simulations, neutrality tests and estimation of demographic parameters by Approximate Bayesian Computation (ABC). Classes implementing different demographic scenarios for ABC analyses can easily be developed by the user and included to the package. EggLib source code is distributed freely under the GNU General Public License (GPL) from its website http://egglib.sourceforge.net/ where a full documentation and a manual can also be found and downloaded. http://www.biomedcentral.com/1471-2156/13/27 Stéphane De Mita Mathieu Siol BMC Genetics 2012, 13:27 2012-04-11T00:00:00Z 10.1186/1471-2156-13-27 Free range of tools for population genetics EggLib (Evolutionary Genetics and Genomics Library) is a new freely available software package providing a wide range of user-friendly computational tools for sequence data management and population genetic analyses on nucleotide sequence data. /content/figures/1471-2156-13-27-toc.gif BMC Genetics 1471-2156 13 27 2012-04-11T00:00:00Z XML Background: For anurans, knowledge of 5S rDNA is scarce. For Engystomops species, chromosomal homeologies are difficult to recognize due to the high level of inter- and intraspecific cytogenetic variation. In an attempt to better compare the karyotypes of the Amazonian species Engystomops freibergi and Engystomops petersi, and to extend the knowledge of 5S rDNA organization in anurans, the 5S rDNA sequences of Amazonian Engystomops species were isolated, characterized, and mapped. Results: Two types of 5S rDNA, which were readily differentiated by their NTS (non-transcribed spacer) sizes and compositions, were isolated from specimens of E. freibergi from Brazil and E. petersi from two Ecuadorian localities (Puyo and Yasuní). In the E. freibergi karyotypes, the entire type I 5S rDNA repeating unit hybridized to the pericentromeric region of 3p, whereas the entire type II 5S rDNA repeating unit mapped to the distal region of 6q, suggesting a differential localization of these sequences. The type I NTS probe clearly detected the 3p pericentromeric region in the karyotypes of E. freibergi and E. petersi from Puyo and the 5p pericentromeric region in the karyotype of E. petersi from Yasuní, but no distal or interstitial signals were observed. Interestingly, this probe also detected many centromeric regions in the three karyotypes, suggesting the presence of a satellite DNA family derived from 5S rDNA. The type II NTS probe detected only distal 6q regions in the three karyotypes, corroborating the differential distribution of the two types of 5S rDNA. Conclusions: Because the 5S rDNA types found in Engystomops are related to those of Physalaemus with respect to their nucleotide sequences and chromosomal locations, their origin likely preceded the evolutionary divergence of these genera. In addition, our data indicated homeology between Chromosome 5 in E. petersi from Yasuní and Chromosomes 3 in E. freibergi and E. petersi from Puyo. In addition, the chromosomal location of the type II 5S rDNA corroborates the hypothesis that the Chromosomes 6 of E. petersi and E. freibergi are homeologous despite the great differences observed between the karyotypes of the Yasuní specimens and the others. http://www.biomedcentral.com/1471-2156/13/17 Débora Rodrigues Miryan Rivera Luciana Lourenço BMC Genetics 2012, 13:17 2012-03-20T00:00:00Z 10.1186/1471-2156-13-17 Cytogenetics of Amazonian Anurans Two different types of 5S rDNA sequences are identified from two species of Engystomops frog, differentiated by their non-transcribed spacer sizes and compositions, facilitating the identification of possible homeologous chromosomes in this genus /content/figures/1471-2156-13-17-toc.gif BMC Genetics 1471-2156 13 17 2012-03-20T00:00:00Z XML Background: Identification of genomic regions that have been targets of selection for phenotypic traits is one of the most important and challenging areas of research in animal genetics. However, currently there are relatively few genomic regions identified that have been subject to positive selection. In this study, a genome-wide scan using ~50,000 Single Nucleotide Polymorphisms (SNPs) was performed in an attempt to identify genomic regions associated with fat deposition in fat-tail breeds. This trait and its modification are very important in those countries grazing these breeds. Results: Two independent experiments using either Iranian or Ovine HapMap genotyping data contrasted thin and fat tail breeds. Population differentiation using FST in Iranian thin and fat tail breeds revealed seven genomic regions. Almost all of these regions overlapped with QTLs that had previously been identified as affecting fat and carcass yield traits in beef and dairy cattle. Study of selection sweep signatures using FST in thin and fat tail breeds sampled from the Ovine HapMap project confirmed three of these regions located on Chromosomes 5, 7 and X. We found increased homozygosity in these regions in favour of fat tail breeds on chromosome 5 and X and in favour of thin tail breeds on chromosome 7. Conclusions: In this study, we were able to identify three novel regions associated with fat deposition in thin and fat tail sheep breeds. Two of these were associated with an increase of homozygosity in the fat tail breeds which would be consistent with selection for mutations affecting fat tail size several thousand years after domestication. http://www.biomedcentral.com/1471-2156/13/10 Mohammad Hossein Moradi Ardeshir Nejati-Javaremi Mohammad Moradi-Shahrbabak Ken G Dodds John C McEwan BMC Genetics 2012, 13:10 2012-02-26T00:00:00Z 10.1186/1471-2156-13-10 Genomic regions correlated with fat deposition in sheep Three novel regions associated with fat deposition in thin and fat tailed sheep have been identified from a genome-wide scan of selective sweeps using 50,000 SNPs from the Ovine HapMap project /content/figures/1471-2156-13-10-toc.gif BMC Genetics 1471-2156 13 10 2012-02-26T00:00:00Z XML Background: Hundreds of new loci have been discovered by genome-wide association studies of human traits. These studies mostly focused on associations between single locus and a trait. Interactions between genes and between genes and environmental factors are of interest as they can improve our understanding of the genetic background underlying complex traits. Genome-wide testing of complex genetic models is a computationally demanding task. Moreover, testing of such models leads to multiple comparison problems that reduce the probability of new findings. Assuming that the genetic model underlying a complex trait can include hundreds of genes and environmental factors, testing of these models in genome-wide association studies represent substantial difficulties.We and Pare with colleagues (2010) developed a method allowing to overcome such difficulties. The method is based on the fact that loci which are involved in interactions can show genotypic variance heterogeneity of a trait. Genome-wide testing of such heterogeneity can be a fast scanning approach which can point to the interacting genetic variants. Results: In this work we present a new method, SVLM, allowing for variance heterogeneity analysis of imputed genetic variation. Type I error and power of this test are investigated and contracted with these of the Levene's test. We also present an R package, VariABEL, implementing existing and newly developed tests. Conclusions: Variance heterogeneity analysis is a promising method for detection of potentially interacting loci. New method and software package developed in this work will facilitate such analysis in genome-wide context. http://www.biomedcentral.com/1471-2156/13/4 Maksim V Struchalin Najaf Amin Paul HC Eilers Cornelia M van Duijn Yurii S Aulchenko BMC Genetics 2012, 13:4 2012-01-24T00:00:00Z 10.1186/1471-2156-13-4 Genome-wide detection of interacting loci Squared Residual Value Linear Modeling (SVLM) is a new method for the detection of potentially interacting loci that extends variance heterogeneity analysis to imputed genetic data, and is available as an open-source software package, VariABEL. /content/figures/1471-2156-13-4-toc.gif BMC Genetics 1471-2156 13 4 2012-01-24T00:00:00Z XML