An >Open Source< Perspective of earliest hominid origins

The >Open Source< Perspective deals with the spatio-temporal distribution pattern of Miocene hominids and suggests a pan-African perspective on the evolution of bipedalism. The shrinking of the rainforest from the Middle Miocene resulted in a selection pressure that was similar along its wide-stretched margin. The earliest hominids might represent co-existing geographic variants.     

Multiple loci associated with canine hip dysplasia (CHD) in German shepherd dogs

Canine hip dysplasia (CHD) is the most common hereditary skeletal disorder in dogs. To identify common alleles associated with CHD, we developed 37 informative single nucleotide polymorphisms (SNPs) within 13 quantitative trait loci (QTL) previously identified for German shepherd dogs. These SNPs were genotyped in 95 German shepherd dogs affected by CHD and 95 breed, sex, and birth year-matched controls. A total of ten SNPs significant at a nominal P value of 0.05 were validated in 843 German shepherd dogs including 277 unaffected dogs and 566 CHD-affected dogs. Cases and controls were sampled from the whole German shepherd dog population in Germany in such a way that mean coancestry coefficients were below 0.1 % within cases and controls as well as among cases and controls. We identified nine SNPs significantly associated with CHD within five QTL on dog chromosomes (CFA) 3, 9, 26, 33, and 34. Genotype effects of these nine SNPs explained between 22 and 34 % of the phenotypic variance of hip dysplasia in German shepherd dogs. The strongest associated SNPs were located on CFA33 and 34 within the candidate genes PNCP, TRIO, and SLC6A3. Thus, the present study validated positional candidate genes within five QTL for CHD.     

Next generation sequencing gives an insight into the characteristics of highly selected breeds versus non-breed horses in the course of domestication

Background

Domestication has shaped the horse and lead to a group of many different types. Some have been under strong human selection while others developed in close relationship with nature. The aim of our study was to perform next generation sequencing of breed and non-breed horses to provide an insight into genetic influences on selective forces.

Results

Whole genome sequencing of five horses of four different populations revealed 10,193,421 single nucleotide polymorphisms (SNPs) and 1,361,948 insertion/deletion polymorphisms (indels). In comparison to horse variant databases and previous reports, we were able to identify 3,394,883 novel SNPs and 868,525 novel indels. We analyzed the distribution of individual variants and found significant enrichment of private mutations in coding regions of genes involved in primary metabolic processes, anatomical structures, morphogenesis and cellular components in non-breed horses and in contrast to that private mutations in genes affecting cell communication, lipid metabolic process, neurological system process, muscle contraction, ion transport, developmental processes of the nervous system and ectoderm in breed horses.

Conclusions

Our next generation sequencing data constitute an important first step for the characterization of non-breed in comparison to breed horses and provide a large number of novel variants for future analyses. Functional annotations suggest specific variants that could play a role for the characterization of breed or non-breed horses.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-562) contains supplementary material, which is available to authorized users.     

Signal Transduction in the Footsteps of Goethe and Schiller

The historical town of Weimar in Thuringia, the "green heart of Germany" was the sphere of Goethe and Schiller, the two most famous representatives of German literature's classic era. Not yet entirely as influential as those two cultural icons, the Signal Transduction Society (STS) has nevertheless in the last decade established within the walls of Weimar an annual interdisciplinary Meeting on "Signal Transduction – Receptors, Mediators and Genes", which is well recognized as a most attractive opportunity to exchange results and ideas in the field.The 12^th STS Meeting was held from October 28 to 31 and provided a state-of-the-art overview of various areas of signal transduction research in which progress is fast and discussion lively. This report is intended to share with the readers of CCS some highlights of the Meeting Workshops devoted to specific aspects of signal transduction.     

Genetic correlations between conformation traits and radiographic findings in the limbs of German Warmblood riding horses

Studbook inspection (SBI) data of 20 768 German Warmblood mares and radiography results (RR) data of 5102 Hanoverian Warmblood horses were used for genetic correlation analyses. The scores on a scale from 0 to 10 were given for conformation and basic quality of gaits, resulting in 14 SBI traits which were used for the correlation analyses. The radiographic findings considered included osseous fragments in fetlock (OFF) and hock joints (OFH), deforming arthropathy in hock joints (DAH) and distinct radiographic findings in the navicular bones (DNB) which were analyzed as binary traits, and radiographic appearance of the navicular bones (RNB) which was analyzed as a quasi-linear trait. Genetic parameters were estimated multivariately in linear animal models with REML using information on 24 448 horses with SBI and/or RR records. The ranges of heritability estimates were h² = 0.14–0.34 for the RR traits and h² = 0.09–0.50 for the SBI traits. Negative additive genetic correlations of r_g = -0.19 to -0.56 were estimated between OFF and conformation of front and hind limbs and walk at hand, and between DNB and hind limb conformation. There were indications of negative additive genetic correlations between DAH and all SBI traits, but because of low prevalence and low heritability of DAH, these results require further scrutiny. Positive additive genetic correlations of r_g = 0.37–0.52 were estimated between OFF and withers height and between OFH and withers height, indicating that selection for taller horses will increase disposition to develop OFF and OFH. Selection of broodmares with regards to functional conformation will assist, but cannot replace possible selection against radiographic findings in the limbs of young Warmblood riding horses, particularly with regards to OFF.     

Regulation of FasL expression: a SH3 domain containing protein family involved in the lysosomal association of FasL

As a death factor of T cells and Natural Killer (NK) cells, Fas Ligand (FasL) is stored in association with secretory lysosomes. Upon stimulation, these cytotoxic granules are transported to the cell membrane where FasL is exposed on the cell surface, shed or secreted. It has been noted before that the proline-rich domain within the cytosolic part of FasL is required for its vesicular association. However, the molecular interactions involved in targeting FasL to secretory lysosomes or to the plasma membrane have not been elucidated. We now identified a family of structurally related proteins that upon co-expression with FasL reallocate the death factor from a membrane to an intracellular localization. Members of this protein family are characterized by a similar domain structure and include FBP17, PACSIN1-3, CD2BP1, CIP4, Rho-GAP C1 and several hypothetical proteins. We show that all tested members of this "FCH/SH3-family" co-precipitate FasL from transfectants. The interactions strictly depend on functional SH3 domains within the FCH/SH3 proteins. Since co-expression of FasL with individual FCH/SH3 proteins dramatically alters the intracellular localization of FasL especially in non-hematopoietic cells, our data suggest that FCH/SH3 proteins might play an important role for the subcellular distribution and lysosomal association of FasL.     

Brief communication: comparing loading scenarios in lower first molar supporting bone structure using 3D finite element analysis

Finite element analysis (FEA) is a widespread technique to evaluate the stress/strain distributions in teeth or dental supporting tissues. However, in most studies occlusal forces are usually simplified using a single vector (i.e., point load) either parallel to the long tooth axis or oblique to this axis. In this pilot study we show how lower first molar occlusal information can be used to investigate the stress distribution with 3D FEA in the supporting bone structure. The LM₁ and the LP²‐LM¹ of a dried modern human skull were scanned by μCT in maximum intercuspation contact. A kinematic analysis of the surface contacts between LM₁ and LP²‐LM¹ during the power stroke was carried out in the occlusal fingerprint analyzer (OFA) software to visualize contact areas during maximum intercuspation contact. This information was used for setting the occlusal molar loading to evaluate the stress distribution in the supporting bone structure using FEA. The output was compared to that obtained when a point force parallel to the long axis of the tooth was loaded in the occlusal basin. For the point load case, our results indicate that the buccal and lingual cortical plates do not experience notable stresses. However, when the occlusal contact areas are considered, the disto‐lingual superior third of the mandible experiences high tensile stresses, while the medio‐lingual cortical bone is subjected to high compressive stresses. Developing a more realistic loading scenario leads to better models to understand the relationship between masticatory function and mandibular shape and structures. Am J Phys Anthropol, 2012. © 2011 Wiley Periodicals, Inc.