GA Variant Research Articles

Effects of lysine methylation on gramicidin A channel folding in lipid membranes

Protein-membrane interactions underlie numerous biological processes including folding of ion channels and signal transduction across lipid membranes. A detailed understanding of protein-lipid interactions is critical for designing membrane-active peptides as potential antibiotics, as well. Using gramicidin A (gA) as a model system, we investigated the effects of lysine methylation on peptide folding into transmembrane channels. The results are discussed in terms of the peptides' binding affinity to, translocation across, and structure formation in lipid membranes. The results show that gA mutants with N(ɛ)-trimethylated D-lysines (dMe3 K) are capable of folding into wild type-like channels that are selective for monovalent cations. Surprisingly, N(ɛ)-trimethylation in general reduces the peptide's binding affinity to lipid membranes despite the increased hydrophobicity. Further investigation reveals the critical contribution of the hydrogen bonding potential of lysine side chains to peptide-membrane association, which has previously been underappreciated. Importantly, methylation does give improved therapeutic indices for certain combinations of gA variant and bacterium, indicating that methylation can be an effective strategy to fine tune the performance of peptide antibiotics.

Population pharmacokinetics analysis of cyclophosphamide with genetic effects in patients undergoing hematopoietic stem cell transplantation

To build a population pharmacokinetic (PK) model of cyclophosphamide (CY) and its metabolite, 4-hydroxycyclophosphamide (HCY), in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) and to identify covariates, including genetic polymorphisms, which affect CY and HCY PK parameters. The study cohort comprised 21 patients undergoing HSCT who received CY intravenously between 2009 and 2011. Clinical characteristics and CY and HCY concentration data were collected for all patients, and ABCB1, ABCC2, GSTA1, GSTM1, GSTP1, GSTT1, CYP2B6, CYP2C19, and CYP3A5 genotyping was performed. A hypothetical enzyme compartment was conducted using the NONMEM program. A population PK analysis showed that the ABCC2 1249 genotype and aspartate aminotransferase levels significantly affected non-induced clearance (CL UI) and induced clearance (CL I) of CY, respectively. The final estimate of the mean CL UI and CL I of CY was 15.5 and 0.683L/h, respectively, and the mean volume of distribution (V 1) of CY was 88.0L. The inter-individual variability for CL UI, CL I, and V 1 of CY was 52.8, 200, and 18.0%, respectively. Additionally, the CL UI of CY was significantly decreased to approximately 51% in patients with the 1249 GA heterozygous genotype compared to those with the 1249 GG wild-type genotype (p < 0.05). There were only three heterozygous GA variants of ABCC2 1249 in the study patients. The population PK model developed in this study implies an influence of genetic factors on the clearance of CY. Clearance was moderately reduced in patients with the ABCC2 1249GA heterozygous genotype.

Impact of Vitamin D Receptor VDR rs2228570 Polymorphism in Oldest Old

Background: Calcitriol, a key player in the regulation of mineral metabolism, influences, directly or by increasing plasma Ca²⁺ and phosphate levels, a multitude of physiological functions, such as bone mineralization, cell proliferation, immune response, carbohydrate metabolism, blood pressure, platelet reactivity, gastric acid secretion, cognitive function and mood. Calcitriol is mainly effective by stimulation of the Vitamin D receptor VDR. The responsiveness of VDR may be affected by gene variants, such as the FokI polymorphism (rs2228570). The GG gene variant is expected to be more active than the GA or AA gene variant. The present study explored the impact of VDR rs2228570 on survival and health of oldest old individuals (> 90 years). Methods: 101 individuals > 90 years were examined and genotyped. As a result, the prevalence of GG, GA & AA was 36 (10 ♂, 26♀), 52 (24 ♂, 28♀) and 13 (4 ♂, 9♀), respectively, a prevalence not significantly different from the frequency in public available dbSNP and a population (n = 208) of young volunteers (average age 49 years). Results: As compared to carriers of GG, carriers of AA and/or GA displayed significantly (p<0.05) lower diastolic blood pressure (significant only in ♂), higher instrumental activity of daily life (IADL) score and more frequent hospital visits (significant only in ♂), significantly lower prevalence of depression (significant in ♀+♂), renal disease (significant only in ♀), allergy, peptic ulcer and urolithiasis (significant only in ♂), as well as significantly higher prevalence of transitoric ischemic attacks. In a younger population a German version of the NEO-FFI, allowing reliable and valid assessment of personality, revealed decreased neuroticism (significant only in ♂) and increased extraversion in AA carriers. Conclusion: The Vitamin D receptor gene variant VDR rs2228570 has only little impact on life span but may affect a variety of pathophysiologically relevant functions including mood.

A novel genetic algorithm to solve travelling salesman problem and blocking flow shop scheduling problem

This paper presents a novel genetic algorithm GA to address a wide range of sequencing and scheduling optimisation problems. As for the performance analysis we have applied our algorithm on travelling salesman problems TSPs and flow shop scheduling problems FSPs. Our main objective is to develop an adaptive method which is equally applicable to all kind of optimisation problems with discrete decision variables. Keeping that view in mind we present some new crossover and mutation operators to tackle TSP as well as FSP with GA with path representation. We have also used a new ring parent topology to generate offspring. A new selection procedure, trio-selection procedure is applied to avoid undesirable clustering before reaching the optima. Faster convergence is assured by applying some modified mutation schemes in finding optimal order of cities in TSP and minimising the maximum completion time i.e., makespan for blocking flow shop scheduling problems. This novel GA variant ensures much better results compared to other heuristics, which is apparent from the experimental results and comparisons with other existing algorithms provided below.

The insulin-like growth factor-1 gene is associated with cerebral infarction in Japanese subjects

Atherosclerosis leads to cerebral infarction (CI) and the insulin/insulin-like growth factor-1 (IGF1) signaling pathway plays an important role in this process during adult life. The purpose of this study was to investigate the relationship between the human IGF1 gene and CI in the Japanese population via a case-control study that also included a separate analysis of the two gender groups. A total of 155 CI patients and 316 controls were genotyped for six single nucleotide polymorphisms (SNPs) of the human IGF1 gene (rs2162679, rs7956547, rs2288378, rs2072592, rs978458 and rs6218). All data were analyzed for three separate groups: the total subjects, men and women. The logistic regression analysis revealed that the GG + AG variant of rs2162679 (P = 0.047), the AA + GA variant of rs2072592 (P = 0.005) and the CC + TC variant of rs6218 (P = 0.015) exhibited a protective effect for CI in the total subject group. For the women and the total subjects groups, the overall distribution of the haplotype established by rs7956547-rs978458 was significantly different between the CI patients and the non-CI subjects. For the total subjects, the frequency of the T-G haplotype (rs7956547-rs978458) was also significantly higher (P = 0.034), whereas the frequency of the T-A haplotype (rs7956547-rs978458) was significantly lower (P = 0.008) in the CI patients versus the non-CI subjects. For women, the frequency of the T-A haplotype (rs7956547-rs978458) was significantly lower (P = 0.021) in the CI patients as compared with the non-CI subjects. The specific SNPs and haplotypes can be utilized as genetic markers for CI resistance or CI risk.

Polymorphisms in HIF-1alpha affect presence of lymph node metastasis and can influence tumor size in squamous-cell carcinoma of the glottic larynx

HIF-1alpha plays a key role in the development and progression of cancer. Its polymorphic variants C1772T and G1790A have been associated with greater susceptibility to cancer and increased tumor progression. We determined the distribution of these polymorphisms among 121 patients with glottic cancer and 154 healthy volunteers by PCR-RFLP. We also analyzed the relationship between the presence of these polymorphisms and various clinicopathologic variables. Advanced tumors (T3-T4) were associated with the TT variant (p = 0.036), which was present in 75 % of T4 tumors (p = 0.008). Among patients with nodal metastasis (N+), 41.7 and 22 % were carrying the TT and GA variants, respectively, compared with 9.4 and 2 % of the patients with no metastasis (N0), (p = 0.006 and p = 0.032). The presence of the TT and GA variants were associated with lymph node metastasis, while the presence of the TT variant can be associated with larger tumor size.

New Hybrid Discrete PSO for Solving Non Convex Trim Loss Problem

Trim loss minimization is the most common problem that arises during the cutting process, when products with variable width or length are to be produced in bulk to satisfy customer demands from limited available/stocked materials. The aim is to minimize inevitable waste material. Under various environmental and physical constraints, the trim loss problem is highly constrained, non convex, nonlinear, and with integer restriction on all variables. Due to the highly complex nature of trim loss problem, it is not easy for manufacturers to select an appropriate method that provides a global optimal solution, satisfying all restrictions. This paper proposes a discrete variant of PSO, which embeds a mutation operator, namely power mutation during the position update stage. The proposed variant is named as Hybrid Discrete PSO (HDPSO). Binary variables in HDPSO are generated using sigmoid function with its domain derived from position update equation. Four examples with different levels of complexity are solved and results are compared with two recently developed GA and PSO variants. The computational studies indicate the competitiveness of proposed variant over other considered methods.

E-cadherin (CDH1) gene promoter polymorphism and the risk of colorectal cancer

Published data on the relationship between E-cadherin (CDH1) gene promoter polymorphisms and colorectal cancer (CRC) risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was carried out. In this meta-analysis, we evaluated reported studies of associations between polymorphisms of CDH1 gene promoter -160 C > A and -347 G > GA site, and CRC risk using fixed-effects model and random-effects model. We found decreased CRC risk among subjects carrying CDH1 -160AA (odds ratio [OR] = 0.86, 95 percent confidence interval [95% CI]: 0.75-0.98) and CA + AA (OR = 0.92, 95% CI: 0.87-0.98), using 4,652/4,428 cases/controls and 7,866/7,689 cases/controls from ten studies, respectively. We found a protective effect of the CDH1 -160CA + AA polymorphisms for CRC in distal site tumor population and population-based control in stratified analysis. We found a protective effect of the CDH1 -160AA and CA + AA polymorphisms for CRC in European and American population (OR = 0.87, 95% CI: 0.76-0.99 and OR = 0.91, 95% CI: 0.85-0.98, respectively). We observed that the CDH1 -347 G/GA + GA/GA carrier had an increased risk of CRC, the summary OR was 1.33 (95% CI: 1.08-1.62). Data indicated that certain CDH1 gene promoter -160 C > A and -347 G > GA variants might affect the susceptibility of CRC. Recommendations for further studies include pooling of individual data to facilitate evaluation of multigenic effects and detailed analysis of effect modification by environmental and lifestyle factors.

Thermodynamic characterization of OsGID1‐gibberellin binding using calorimetry and docking simulations

Gibberellins (GAs) are phytohormones regulating various developmental processes in plants. In rice, the initial GA-signaling events involve the binding of a GA to the soluble GA receptor protein, GID1. Although X-ray structures for certain GID1/GA complexes have recently been determined, an examination of the complexes does not fully clarify how GID1s discriminate among different GAs. Herein, we present a study aimed at defining the types of forces important to binding via a combination of isothermal titration calorimetry (ITC) and computational docking studies that employed rice GID1 (OsGID1), OsGID1 mutants, which were designed to have a decreased possible number of hydrogen bonds with bound GA, and GA variants. We find that, in general, GA binding is enthalpically driven and that a hydrogen bond between the phenolic hydroxyl of OsGID1 Tyr134 and the C-3 hydroxyl of a GA is a defining structural element. A hydrogen-bond network that involves the C-6 carboxyl of a GA that directly hydrogen bonds the hydroxyl of Ser198 and indirectly, via a two-water-molecule network, the phenolic hydroxyl of Tyr329 and the NH of the amide side-chain of Asn255 is also important for GA binding. The binding of OsGID1 by GA(1) is the most enthalpically driven association found for the biologically active GAs evaluated in this study. This observation might be a consequence of a hydrogen bond formed between the hydroxyl at the C-13 position of GA(1) and the main chain carbonyl of OsGID1 Phe245. Our results demonstrate that by combining ITC experiments and computational methods much can be learned about the thermodynamics of ligand/protein binding.

A rotary chaotic PSO algorithm for trustworthy scheduling of a grid workflow

In this paper, a rotary chaotic particle swarm optimization (RCPSO) algorithm is presented to solve trustworthy scheduling of a grid workflow. In general, the grid workflow scheduling is a complex optimization problem which requires considering various scheduling criteria so as to meet a wide range of QoS requirements from users. Traditional researches into grid workflow scheduling mainly focus on the optimization constrained by time and cost. The key requirements for reliability, availability and security are not considered adequately. The main contribution of this study is to propose a new approach for trustworthy workflow scheduling in a large-scale grid with rich service resources, and present the RCPSO algorithm to optimize the scheduling performance in a multi-dimensional complex space. Experiments were done in two grid applications with at most 120 candidate services supplied to each task of various workflows. The results show better performance of the RCPSO in solving trustworthy scheduling of grid workflow problems as compared to GA, ACO and other recent variants of PSO.

The association of reduced folate carrier 80G>A polymorphism to outcome in childhood acute lymphoblastic leukemia interacts with chromosome 21 copy number

AbstractThe reduced folate carrier (RFC) is involved in the transport of methotrexate (MTX) across the cell membrane. The RFC gene (SLC19A1) is located on chromosome 21, and we hypothesized that the RFC80 G>A polymorphism would affect outcome and toxicity in childhood leukemia and that this could interact with chromosome 21 copy number in the leukemic clone. A total of 500 children with acute lymphoblastic leukemia treated according to the common Nordic treatment protocols were included, and we found that the RFC AA variant was associated with a 50% better chance of staying in remission compared with GG or GA variants (P = .046). Increased copy numbers of chromosome 21 appear to improve outcome also in children with GA or GG variant. In a subset of 182 children receiving 608 high-dose MTX courses, we observed higher degree of bone marrow toxicity in patients with the RFC AA variant compared with GA/GG variants (platelet 73 vs 99/105 × 109/L, P = .004, hemoglobin 5.6 vs 5.9/6.0 mmol/L, P = .004) and a higher degree of liver toxicity in patients with RFC GG variant (alanine aminotransferase 167 vs 127/124 U/L, P = .05). In conclusion, the RFC 80G>A polymorphism interacts with chromosome 21 copy numbers and affects both efficacy and toxicity of MTX.

Abstract 1662: Association of EGFR and ABCG2 polymorphisms with gefitinib toxicity in non-small cell lung cancer patients

Abstract The use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, in non-small-cell lung cancer (NSCLC) patients is commonly associated with gastrointestinal (diarrhea) and skin (rash) toxicity. These adverse effects have a high interindividual variability, which might be partially explained by pharmacogenetic determinants. In particular, polymorphisms in EGFR and in ABCG2, an efflux transporter higly expressed in the gastrointestinal tract and able to transport gefitinib and other EGFR TKIs, might have an impact on gefitinib-associated toxicity. Therefore, the aim of our study was to evaluate associations between EGFR and ABCG2 polymorphisms with diarrhea and skin rash in gefitinib-treated NSCLC patients. Four polymorphisms in EGFR (CA repeat length in the intron-1 (CA)n, EGFR −191C/A, EGFR −216G/T and EGFR R497K) and one in ABCG2 (ABCG2 421C/A) were assessed in DNA isolated from blood samples and/or paraffin-embedded tumor tissue from 96 NSCLC patients treated with gefitinib. Significant associations between EGFR and ABCG2 variants and toxicity were evaluated using the Fisher's exact test. In total, 87 and 85 patients had available data on polymorphisms and skin and gastrointestinal toxicity, respectively. Diarrhea occurred in 33 (38.8%) of the 85 patients, with 6 of them experiencing high toxicity (grade=2-3 diarrhea). Skin rash was reported for 46 (52.9%) of the 87 patients, with 22 patients having grade&amp;gt;1. The EGFR −191C/A polymorphism was strongly associated with grade&amp;gt;1 diarrhea (P&amp;lt;0.01). Five (33.3%) of the 15 patients carrying the CA or AA genotype developed severe diarrhea compared with only 1 (1.4%) of the 70 CC patients. The EGFR −216G/T polymorphism was also associated with high grade (&amp;gt;1) diarrhea as all the patients who experienced grade 2 or 3 diarrhea carried the GG variant, while only 30.4% (24 out of 79) of the patients with low toxicity carried this variant (P&amp;lt;0.01). Similar findings were found for the EGFR R497K polymorphism, with severe diarrhea being observed in 3 (30%) of the 10 patients with the AA genotype and in 3 (4.1%) of the 74 patients carrying the GG or GA variants (P=0.02). In contrast, none of these EGFR polymorphisms had a significant association with skin toxicity. Additionally, we found no association between EGFR (CA)n and the ABCG2 421C/A polymorphism with either gastrointestinal or skin toxicity. In conclusion, our results demonstrate a clear association between the EGFR −191C/A, −216G/T and R497K with diarrhea in gefitinib-treated NSCLC patients, suggesting that these polymorphisms might be useful as pharmacogenetic markers for the selection of patients for treatment. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1662.

A Scheduling Model with Multi-Objective Optimization for Computational Grids using NSGA-II

Scheduling a job on the grid is an NP Hard problem, and hence a number of models on optimizing one or other characteristic parameters have been proposed in the literature. It is expected from a computational grid to complete the job quickly in most reliable grid environment owing to the number of participants in the grid and the scarcity of the resources available. Genetic algorithm is an effective tool in solving problems that requires sub-optimal solutions and finds uses in multi-objective optimization problems. This paper addresses a multi-objective optimization problem by introducing a scheduling model for a modular job on a computational grid with a dual objective, minimizing the turnaround time and maximizing the reliability of the job execution using NSGA – II, a GA variant. The cost of execution on a node is measured on the basis of the node characteristics, the job attributes and the network properties. Simulation study and a comparison of the results with other similar models reveal the effectiveness of the model.

Analysing the migration effects in nomadic genetic algorithm

Among the several variants of GA, multi-population genetic algorithms (MGA) have created a niche in the literature of genetic algorithms owing to their ability to explore the global optima. But the problem associated with them is the judicious choice of the migration parameters, which when not chosen properly may lead to performance degradation of MGA. This paper discusses the advantages of an adaptive multi-population GA called nomadic genetic algorithm (NGA) with respect to its migration policies and highlights its betterment over other algorithms of the type.

On two types of geometric–arithmetic index

Recently a class of so-called ‘geometric–arithmetic’ topological indices ( GA ) was put forward, defined as the sum over all edges ( uv ) of a (molecular) graph G , of terms Q u Q v / 1 2 ( Q u + Q v ) , where Q u is some quantity associated with the vertex u of G . One variant of GA was obtained for Q u is the number of vertices of G , lying closer to vertex u than to vertex v . We obtain bounds for this GA -index, and also put forward an analogous one, for which Q u is the number of edges of G , lying closer to vertex u than to vertex v .

Reduced folate carrier polymorphism determines methotrexate uptake by B cells and CD4+ T cells

To examine if polymorphism 80G --> A in the Reduced Folate Carrier (RFC) affects uptake of MTX in B- and CD4+ T-cells. Mononuclear cells were isolated from peripheral blood of healthy persons. Real-time PCR was used to detect the RFC80 variants. FITC-labelled MTX was added to cells stimulated with Candida albicans or tetanus toxoid, and the uptake of MTX was measured by flow cytometry. A FITC-conjugated monoclonal antibody against RFC was used to detect the cellular RFC expression. Antigen-stimulated CD4+ T cells and B cells from individuals with the GG variant (n = 9) exhibited lower uptake of MTX than individuals expressing the AA variant (n = 8), or the GA variant (n = 8). No difference could be demonstrated between the three groups with respect to the expression of RFC by CD4+ T cells and B cells, and CD4+ T cells from individuals homozygous for the G allele exhibited lower uptake of MTX per receptor than CD4+ T cells from individuals homozygous for the A allele. MTX is taken up more efficiently via the A allele than via the G allele. This difference between the variant forms of RFC suggests that genotyping could be relevant for determining the relevant dosage of MTX in the treatment of neoplastic and autoimmune disease.

Role of the linker region in the expression of Rhizopus oryzae glucoamylase

BackgroundRhizopus oryzae glucoamylase (RoGA) consists of three domains: an amino (N)-terminal raw starch-binding domain (SBD), a glycosylated linker domain, and a carboxy (C)-terminal catalytic domain. The 36-amino-acid linker region (residues 132–167) connects the two functional domains, but its structural and functional roles are unclear.ResultsTo characterize the linker sequences of RoGA and its involvement in protein expression, a number of RoGA variants containing deletions and mutations were constructed and expressed in Saccharomyces cerevisiae. Deletion analyses demonstrate that the linker region, especially within residues 161 to 167, is required for protein expression. In addition, site-directed mutagenesis and deglycosylation studies reveal that the linker region of RoGA contains both N- and O-linked carbohydrate moieties, and the N-linked oligosaccharides play a major role in the formation of active enzyme. Although the linker segment itself appears to have no ordered secondary structural conformation, the flexible region indeed contributes to the stabilization of functional N- and C-terminal domains.ConclusionOur data provide direct evidence that the length, composition, and glycosylation of the interdomain linker play a central role in the structure and function of RoGA.

Leptin and leptin receptor polymorphisms are associated with increased risk and poor prognosis of breast carcinoma.

BackgroundLeptin (LEP) has been consistently associated with angiogenesis and tumor growth. Leptin exerts its physiological action through its specific receptor (LEPR). We have investigated whether genetic variations in LEP and LEPR have implications for susceptibility to and prognosis in breast carcinoma.MethodsWe used the polymerase chain reaction and restriction enzyme digestion to characterize the variation of the LEP and LEPR genes in 308 unrelated Tunisian patients with breast carcinoma and 222 healthy control subjects. Associations of the clinicopathologic parameters and these genetic markers with the rates of the breast carcinoma-specific overall survival (OVS) and the disease free survival (DFS) were assessed using univariate and multivariate analyses.ResultsA significantly increased risk of breast carcinoma was associated with heterozygous LEP (-2548) GA (OR = 1.45; P = 0.04) and homozygous LEP (-2548) AA (OR = 3.17; P = 0.001) variants. A highly significant association was found between the heterozygous LEPR 223QR genotype (OR = 1.68; P = 0.007) or homozygous LEPR 223RR genotype (OR = 2.26; P = 0.001) and breast carcinoma.Moreover, the presence of the LEP (-2548) A allele showed a significant association with decreased disease-free survival in breast carcinoma patients, and the presence of the LEPR 223R allele showed a significant association with decreased overall survival.ConclusionOur results indicated that the polymorphisms in LEP and LEPR genes are associated with increased breast cancer risk as well as disease progress, supporting our hypothesis for leptin involvement in cancer pathogenesis.

Haemophilia and thrombophilia

For the study presented here 135 pediatric PUP patients with haemophilia consecutively admitted to German pediatric haemophilia treatment centers were investigated. In addition to factor VIII activity, the factor V (FV) G1691A mutation, the factor II (FII) G20210A variant, methylenetetrahydrofolate reductase (MTHFR) T677T genotype, elevated lipoprotein a (Lp a), antithrombin, protein C, and protein S were investigated. 103 out of 122 HA patients (FVIII activity <1%) were suffering from severe HA. The prevalence of prothrombotic risk factors in children with severe haemophilia A (HA) did not differ from previously reported data: FV GA 5.8%, FII GA 3.9%, MTHFR TT 10%, elevated Lp a 7%, protein C type I deficiency 1.1%. The first symptomatic bleeding leading to diagnosis of severe haemophilia occurred with a median age of 1.6 years (range: 0.5-7.1 years) in children carrying prothrombotic risk factors compared to non-carriers (0.9 years (0.1-4.0; p = 0.01). Two patients presenting with neonatal stroke due to elevated Lp a and the FII GA variant showed haemorrhagic stroke transformation triggered by severe haemophilia. In addition, when haemophilia A was corrected by administration of factor VIII concentrates eight out of 25 children with central lines in place developed catheter-related thrombosis. The data of this multicentre cohort study demonstrate that the clinical phenotype of severe haemophilia A in childhood is clearly influenced by the coinheritance of prothrombotic risk factors.

Phase equilibria in the palladium-rich part of the gallium–palladium system. The crystal structures of Ga 3Pd 7 and Ga 1− xPd 2+ x

The phase relations between the palladium-rich phases of the gallium–palladium system are clarified by combining preparative methodologies with powder X-ray diffraction and thermochemical analyses. A modified phase diagram of the palladium-rich part of the system is presented. The structure of Ga 3Pd 7, decomposing peritectoidally at 881(2)°C, was determined by powder X-ray diffraction and refined by a Rietveld profile fit. Ga 3Pd 7 adopts a new structure type with monoclinic space group symmetry: C2/m, Z=2, a=1359.46(2) pm, b=405.510(5) pm, c=544.339(6) pm, β=105.2219(7)°, wR P=0.082. The structure can be seen as a strongly distorted, ordered variant of a respective Ga x Pd 1− x fcc solid solution. It comprises two structural motifs: layers of columns of fused (GaPd 6/2) 2 prisms are formally separated by equiatomic GaPd layers. The impact of the composition on the structure of Co 2Si-type Ga 1− x Pd 2+ x was studied. There exists a symmetry relation between the cubic close-packed arrangement of atoms and the structures of the Co 2Si-type branch of AB 2 phases with Pearson symbol oP12 and space group symmetry Pnma.