Biogeographic origin prediction of three continental populations through 42 ancestry informative SNPs

A biogeographic estimate of a certain population can not only discern population substructure in the whole genome association study, but also provide informative clues for forensic investigations when obtained DNA genotypes do not find a match in the available forensic DNA database. In this study, 100 ancestry informative single nucleotide polymorphisms (AISNPs) were first presented to differentiate three continental ancestries (African, East Asian and European). Ultimately, forty-two AISNPs were chosen from the 100 AISNPs. Distinguishing power of the 100 and 42 AISNPs for differentiating continental populations was further evaluated with population cluster analyses. Results indicated both of AISNP sets could efficiently differentiate 11 training populations from the three continents. Further validation of 42 AISNPs in testing population set indicated these 42 AISNPs performed well for ancestry inferences of these testing individuals. Ancestry components of Uyghur group were assessed by comparing with different continental populations based on these 42 AISNPs. Results revealed that East Asian populations contributed more ancestry components to the studied Uyghur group than European populations. In conclusion, our study is expected to provide more AISNP markers and enrich extant reference database.     

Systematic selection of ancestry informative SNPs for differentiating Han,Japanese, Dai,and Kinh populations

Biogeographical origin inferences of different populations can provide valuable clues in the forensic investigation by narrowing down the detection scope. However, much research mainly focuses on forensic ancestral origin analyses of major continental populations, which may provide limited information in forensic practice. To improve the ancestral resolution of East Asian populations, we systematically selected ancestry informative single-nucleotide polymorphisms (AISNPs) for differentiating Han, Dai, Japanese, and Kinh populations. In addition, we evaluated the performance of the selected AISNPs to differentiate these populations via multiple methods. Totally 116 AISNPs were selected from the genome-wide data to infer the population origins of these four populations. Results of principle component analysis and population genetic structure of these populations indicated that the selected 116 AISNPs could achieve ancestral resolution of most individuals. Furthermore, the machine learning model built by 116 AISNPs unveiled that most individuals from these four populations could be assigned to correct population origins. To sum up, the selected 116 SNPs could be available for ancestral origin predictions of Han, Dai, Japanese, and Kinh populations, which could provide valuable information for forensic research and genome-wide association study in East Asian populations to some extent.     

A targeted ancestry informative InDels panel on capillary electrophoresis for ancestry inference in Asian populations

CE is the primary methodology used in forensic DNA typing. Alleles of commonly used types of genetic markers could be separated and detected via CE based on dye color and migration time. Insertion/deletion (InDel) is an ideal genetic marker for forensic DNA analysis due to their abundance in the human genome, low mutation rate, availability of their allele types via CE, and elimination of stutter peaks. Moreover, InDels could be used as ancestry informative markers since allele frequencies of InDels is different among geographically separated populations. Several ancestry informative insertion/deletion panels have been established based on CE platform to achieve the intercontinental populations distinction. However, improvements to differentiate intracontinental populations is few. In this study, 21 InDels with fixation index (F_ST) > 0.15 were selected and assembled into one ancestry informative insertion/deletion panel. Using well-designed primers, those 21 InDels could be amplified successfully and genotyped on the CE platform accurately and completely. The panel showed a large F_ST distance distinction among the ten Asian populations. Using clustering analysis, ten Asian populations were classified into three subgroups: East Asian, Southeast Asian, and South Asian subgroups. To evaluate the panel's capability in ancestry inference, a validation experiment was undertaken with 319 individuals from four geographically separated populations in China. Four Chinese populations were classified into different ancestry subgroups and 81.8% test individuals’ ancestry could be inferred correctly. Our result showed that development of high ancestry informative InDels panel based on CE platform is a potential for individual ancestry inference among intracontinental populations.     

A small NGS–SNP panel of ancestry inference designed to distinguish African,European, East,and South Asian populations

In this study, a small set of ancestry informative SNPs was selected to differentiate African, European, East and South Asian samples, which was detected by the next-generation sequencing technology. A total of 127 Chinese Shaanxi Han individuals were collected as test samples. No statistically significant linkage disequilibrium of any pair of loci or departure from Hardy–Weinberg equilibrium of each locus was observed in the test population. To evaluate the performance of ancestry assignment using this panel, admixture analysis, principal component analysis, and likelihood ratio calculations were conducted based on the 1000 genome data and test samples. All populations were clustered into four groups, African, European, South and East Asian populations, which were consistent with their geographical origins. The pairwise fixation index (F_ST) between populations from different continental groups ranged from 0.140 to 0.621 with average 0.415, and the pairwise F_ST between populations from the same continent ranged from 0.000 to 0.056 with average 0.012. The likelihood ratio results of 125 test individuals indicated that their ancestry components were highly possible from East Asia. In conclusion, this small set of ancestry informative SNPs can be used as a reliable tool to identify and quantify ancestry components of unknown samples.     

A high-performance SNP panel developed by machine-learning approaches for characterizing genetic differences of Southern and Northern Han Chinese,Korean, and Japanese individuals

Population stratification analyses targeting genetically closely related East Asians have revealed that distinguishable differentiation exists between Han Chinese, Korean, and Japanese individuals, as well as between southern (S-) and northern (N-) Han Chinese. Previous studies offer a number of choices for ancestry informative single nucleotide polymorphisms (AISNPs) to discriminate East-Asian populations. In this study, we collected and examined the efficiency of 1185 AISNPs using frequency and genotype data from various publicly available databases. With the aim to perform fine-scale classification of S-Han, N-Han, Korean, and Japanese subjects, machine-learning methods (Softmax and Random Forest) were used to screen a panel of highly informative AISNPs and to develop a superior classification model. Stepwise classification was implemented to increase and balance the discrimination in the process of AISNP selection, first discriminating Han, Korean, and Japanese individuals, and then characterizing stratification between S-Han and N-Han. The final 272-AISNP panel is an alternative optimization of various previous works, which promises reliable and >90% accuracy in classification of the four East-Asian groups. This AISNP panel and the machine-learning model could be a useful and superior choice in medical genome-wide association studies and in forensic investigations for unknown suspect identity.     

Distinguishing three distinct biogeographic regions with an in‐house developed 39‐AIM‐InDel panel and further admixture proportion estimation for Uyghurs

In the forensic field, ancestry‐informative markers (AIMs) showing remarkable allele frequency discrepancies can be useful in deducing the likely ancestral origin of a person or estimating the ancestry component proportions of an admixed population or individual. Diallelic single nucleotide polymorphisms are genetic markers commonly used for ancestry inference, but the genotyping methods of single nucleotide polymorphisms fail to fulfil the demands of cost‐effectiveness and simplicity of experimental manipulation. To overcome the limitations, a 39 ancestry‐informative insertion/deletion polymorphism multiplex panel was developed in the present study to perform ancestry assignment of individuals from three distinct biogeographic regions (Africa, Europe, East Asia). And in the panel design, we also attempted to incorporate AIM‐insertion/deletion polymorphisms exhibiting allelic frequency differences in Han, Uyghur, and Tibetan populations into the multiplex assay, further expecting to provide valuable information for refining ancestry inference within Chinese populations. Statistical analyses were performed to estimate efficiency of this panel in clustering individuals from three continents mentioned above into their corresponding populations, which indicated the potential of the panel in ancestry inference. Besides, we also estimated the ancestral component proportions of Uyghur group and STRUCTURE analysis revealed that Uyghurs from Urumchi city of northern Xinjiang exhibited a distinctly admixed pattern of East Asian and European ancestry components with a ratio of 49:44, reflecting the relatively higher East Asian ancestry component contribution in the gene pool of the Uyghur group.     

Autosomal deletion/insertion polymorphisms for global stratification analyses and ancestry origin inferences of different continental populations by machine learning methods

A lot of population data of 30 deletion/insertion polymorphisms (DIPs) of the Investigator DIPplex kit in different continental populations have been reported. Here, we assessed genetic distributions of these 30 DIPs in different continental populations to pinpoint candidate ancestry informative DIPs. Besides, the effectiveness of machine learning methods for ancestry analysis was explored. Pairwise informativeness (In) values of 30 DIPs revealed that six loci displayed relatively high In values (>0.1) among different continental populations. Besides, more loci showed high population-specific divergence (PSD) values in African population. Based on the pairwise In and PSD values of 30 DIPs, 17 DIPs in the Investigator DIPplex kit were selected to ancestry analyses of African, European, and East Asian populations. Even though 30 DIPs provided better ancestry resolution of these continental populations based on the results of PCA and population genetic structure, we found that 17 DIPs could also distinguish these continental populations. More importantly, these 17 DIPs possessed more balanced cumulative PSD distributions in these populations. Six machine learning methods were used to perform ancestry analyses of these continental populations based on 17 DIPs. Obtained results revealed that naïve Bayes manifested the greatest performance; whereas, k nearest neighbor showed relatively low performance. To sum up, these machine learning methods, especially for naïve Bayes, could be used as the valuable tool for ancestry analysis.     

Inference of population structure and admixture proportion from Y chromosomal data of Chinese population

In the past two decades, Y chromosome data has been generated for human population genetic studies. These Y chromosome datasets were produced with various testing methods and markers, thus difficult to combine them for a comprehensive analysis. In this study, we combine four human Y chromosomal datasets of Han, Tibetan, Hui, and Li ethnic groups. The dataset contains 27 microsatellites and 137 single nucleotide polymorphisms these populations share in common. We assembled a single dataset containing 2439 individuals from 25 nationwide populations in China. A systematic analysis of genetic distance and clustering was performed. To determine the gene flow of the studied population with worldwide populations, we modeled the ancestry informative markers. The reference panel was regarded as a mixture of South Asian (SAS), East Asian (EAS), European (EUR), African (AFR), and American (AMR) populations from 1000 Genomes data of Y chromosome using nonlinear data-fitting. We then calculated the admixture proportion of these four studied populations with 26 worldwide populations. The results showed that the Han and Hui have great genetic affinity, and Hui is the most admixed ethnic group, with 61.53% EAS, 34.65% SAS, 1.91% AFR, 1.56% AMR, and 0.04% EUR ancestry component (the AMR is highly admixed and thus should be ignored). All the other three ethnic groups contained more than 97% EAS ancestry component. The Li is the least admixed population in this study. The combined dataset in this study is the largest of this kind reported to date and proposes reference population data for use in future paternal genetic studies and forensic genealogical identification.     

Forensic efficacy evaluation and genetic structure exploration of the Yunnan Miao group by a multiplex InDel panel

The aim of the study was to better understand the genetic characteristics of the Miao group in China. Herein, genetic characteristics and forensic application values of 57 autosomal insertion–deletion (InDel) loci were investigated in 210 unrelated healthy individuals from the Chinese Yunnan Miao (YM) group. Meanwhile, the genetic differences in these InDels were compared among the YM group and 26 reference populations. The results of forensic statistical analyses showed that all 57 autosomal InDels were in accordance with the Hardy–Weinberg and linkage equilibria of pairwise loci in the Chinese YM group. Moreover, the combined probability of discrimination and probability of exclusion in the YM group were 0.9999999999999999999999801 and 0.999928, respectively, which indicated that the multiplex amplification including 57 autosomal InDels was suitable for forensic individual identification and paternity testing in the Chinese YM group. In addition, the results of allelic frequency distribution differential analyses, principal component analyses, phylogenetic tree reconstruction, and genetic structure analyses between the Chinese YM group and 26 reference populations revealed that the genetic similarities between the YM group and East Asian populations were more than that between the YM group and other geographical populations. This 57 autosomal InDels system can also effectively distinguish East Asian, European, and African populations.     

Development of a novel forensic STR multiplex for ancestry analysis and extended identity testing

There is growing interest in developing additional DNA typing techniques to provide better investigative leads in forensic analysis. These include inference of genetic ancestry and prediction of common physical characteristics of DNA donors. To date, forensic ancestry analysis has centered on population‐divergent SNPs but these binary loci cannot reliably detect DNA mixtures, common in forensic samples. Furthermore, STR genotypes, forming the principal DNA profiling system, are not routinely combined with forensic SNPs to strengthen frequency data available for ancestry inference. We report development of a 12‐STR multiplex composed of ancestry informative marker STRs (AIM‐STRs) selected from 434 tetranucleotide repeat loci. We adapted our online Bayesian classifier for AIM‐SNPs: Snipper, to handle multiallele STR data using frequency‐based training sets. We assessed the ability of the 12‐plex AIM‐STRs to differentiate CEPH Human Genome Diversity Panel populations, plus their informativeness combined with established forensic STRs and AIM‐SNPs. We found combining STRs and SNPs improves the success rate of ancestry assignments while providing a reliable mixture detection system lacking from SNP analysis alone. As the 12 STRs generally show a broad range of alleles in all populations, they provide highly informative supplementary STRs for extended relationship testing and identification of missing persons with incomplete reference pedigrees. Lastly, mixed marker approaches (combining STRs with binary loci) for simple ancestry inference tests beyond forensic analysis bring advantages and we discuss the genotyping options available.     

A set of novel multi-allelic SNPs for forensic application developed through massively parallel sequencing and its examples of population genetic studies

Massively parallel sequencing (MPS) technology allows to simultaneously type multitudinous molecular genetic markers for many samples in one run with the feature of high detection resolution, and thereby arouses the increasing attention from forensic science. Herein, multiple allelic single nucleotide polymorphisms (multi-allelic SNPs) were screened for personal identification and parentage testing, and then were genotyped using MPS platform. Unrelated individuals of Chinese Mongolian and Kazakh groups were investigated to further estimate forensic effectiveness and applicability of these multi-allelic SNPs. The results of sequencing efficiency estimations and forensic genetic statistical parameters demonstrated that this MPS panel of multi-allelic SNPs was expected to be work for forensic applications. Subsequently, the exploration of population genetic variation patterns among the two investigated groups and other 26 reference populations revealed that these Chinese Mongolian and Kazakh groups had the similar population genetic patterns with the populations from East Asian, but European ancestral composition in the Kazakh group was higher than that in the Mongolian group. Currently, the present results were the preliminary research to scrutinize genetic information of these two ethnic minority groups employing multi-allelic SNPs.     

Genome-wide association studies combined with k-fold cross-validation identify rs17822931 as an ancestry-informative marker in Han Chinese population

DNA-based ancestry inference has long been a research hot spot in forensic science. The differentiation of Han Chinese population, such as the northern-to-southern substructure, would benefit forensic practice. In the present study, we enrolled participants from northern and southern China, each participant was genotyped at ∼400 K single-nucleotide polymorphisms (SNPs) and data of CHB and CHS from 1000 Genomes Project were used to perform genome-wide association analyses. Meanwhile, a new method combining genome-wide association study (GWAS) analyses with k-fold cross-validation in a small sample size was introduced. As a result, one SNP rs17822931 emerged with a p-value of 7.51E − 6. We also simulated a huge dataset to verify whether k-fold cross-validation could reduce the false-negative rate of GWAS. The identified ABCC11 rs17822931 has been reported to have allele frequencies varied with the geographical gradient distribution in humans. We also found a great difference in the allele frequency distributions of rs17822931 among five different cohorts of the Chinese population. In conclusion, our study demonstrated that even small-scale GWAS can also have potential to identify effective loci with implemented k-fold cross-validation method and shed light on the potential maker of rs17822931 in differentiating the north-to-south substructure of the Han Chinese population.     

Development of a novel multiplex polymerase chain reaction system for forensic individual identification using insertion/deletion polymorphisms

Insertion/deletion (InDel) polymorphisms have been widely used in the fields of population genetics, genetic map constructions, and forensic investigations owing to the advantages of their low mutation rates, widespread distributions in the human genome, and small amplicon sizes. In order to provide more InDels with high discrimination power in Chinese populations, we selected and constructed one novel multiplex PCR‐InDel panel for forensic individual identification. Genetic distributions of these 35 InDels in five reference populations from East Asia showed low genetic differentiations among these populations. Forensic efficiency evaluations of these InDels revealed that these loci could perform well for forensic individual identifications in these reference populations. In the meantime, genetic diversities and forensic parameters of these InDels were further investigated in the studied Kazak group. Mean value of polymorphism information content for 35 InDels was 0.3611. Cumulative power of discrimination of 35 InDels was 0.99999999999999603 in Kazak group. Given these results, the panel is suitable for individual identifications in the studied Kazak and these reference populations.     

The Electrochemical Behavior of α‐Ketoglutarate at the Hanging Mercury Drop Electrode in Acidic Aqueous Solution and Its Practical Application in Environmental and Biological Samples

The voltammetric behavior of α‐ketoglutarate (α‐KG) at the hanging mercury drop electrode (HMDE) has been investigated in acetate buffer solution. Under the optimum experimental conditions (pH 4.5, 0.2 M NaAc‐HAc buffer solution), a sensitive reductive wave of α‐KG was obtained by linear scan voltammetry (LSV) and the peak potential was ?1.18 V (vs. SCE), which was an irreversible adsorption wave. The kinetic parameters of the electrode process were α=0.3 and k_s=0.72 1/s. There was a linear relationship between peak current i_{p, α‐KG} and α‐KG concentration in the range of 2×10^?6–8×10^?4 M α‐KG. The detection limit was 8×10^?7 M and the relative standard deviation was 2.0% (C_α‐KG=8×10^?4 M, n=10). Applications of the reductive wave of α‐KG for practical analysis were addressed as follows: (1) It can be used for the quantitative analysis of α‐KG in biological samples and the results agree well with those obtained from the established ultraviolet spectrophotometric method. (2) Utilizing the complexing effect between α‐KG and aluminum, a linear relationship holds between the decrease of peak current of α‐KG Δi_p and the added Al concentration Cequation/tex2gif-inf-5.gif in the range of 5.0×10^?6–2.5×10^?4 M. The detection limit was 2.2×10^?6 M and the relative standard deviation was 3.1% (Cequation/tex2gif-inf-6.gif=4×10^?5 M, n=10). It was successfully applied to the detection of aluminum in water and synthetic biological samples with satisfactory results, which were consistent with those of ICP‐AES. (3) It was also applied to study the effect of Al^III on the glutamate dehydrogenase (GDH) activity in the catalytically reaction of α‐KG+NH +NADH?L ‐glutamate+NAD⁺+H₂O by differential pulse polarography (DPP) technique. By monitoring DPP reductive currents of NAD⁺ and α‐KG, an elementary important result was found that Al could greatly affect the activity of GDH. This study could be attributed to intrinsic understanding of the aluminum's toxicity in enzyme reaction processes.     

Evaluation of ForenSeq™ Signature Prep Kit B on predicting eye and hair coloration as well as biogeographical ancestry by using Universal Analysis Software (UAS) and available web‐tools

This study examined 266 individuals from various populations including African American, East Asian, South Asian, European, and mixed populations to evaluate the ForenSeq? Signature Prep Kit Primer Mix B. Focus was placed on phenotypic and biogeographical ancestry predictions by Illumina's Universal Analysis Software (UAS). These outcomes were compared to those obtained through web‐tools developed at the Erasmus Medical Center (EMC) and available from the Forensic Resource/Reference on Genetics‐knowledge base (FROG‐kb), as well as to eye color predictions by the 8‐plex system. Due to drop‐outs, predictions for eye and hair color by UAS failed for various samples in each run. By including reads below thresholds, predictions could be obtained for all samples through the web‐tools. Eye and hair color predictions for African Americans, East Asians, and South Asians showed no errors. Difficulties however, were noted in intermediate (neither blue nor brown) eye color predictions. These were mitigated by the 8‐plex system through exclusion of one eye color (e.g. “not brown”). Additionally, notable discrepancies were observed in hair color predictions, where some black/dark‐brown haired individuals were predicted to have blond hair. Overall, ancestry predictions were more accurate by FROG‐kb compared to UAS, which did not predict South Asian ancestry, particularly Indian individuals.     

Development a multiplex panel of AISNPs,multi-allelic InDels,microhaplotypes, and Y-SNP/InDel loci for multiple forensic purposes via the NGS

Recently, next generation sequencing has shown the promising application value in forensic research. In this study, we constructed a multiplex amplification system of different molecular genetic markers based on the previous selected ancestry informative single nucleotide polymorphisms (SNPs), multi-allelic insertion/deletion (InDel) polymorphisms, microhaplotypes, and Y-chromosomal SNP/InDel loci, and evaluated forensic efficiencies of the system in Chinese Shaanxi Han, Chinese Hui, and Chinese Mongolian groups via the next generation sequencing platform. Ancestry information analyses of Shaanxi Han, Hui, and Mongolian groups revealed that most Mongolian individuals could be differentiated from Shaanxi Hans and Huis based on the selected ancestry informative SNPs. Multi-allelic InDels and microhaplotypes showed the multiple allele variations and possessed relatively high genetic polymorphisms in these three groups, indicating these loci could provide higher forensic efficiencies for individual identification and paternity testing. Based on Y-chromosomal SNPs, different haplogroup distributions were observed among Shaanxi Han, Hui, and Mongolian groups. In conclusion, the self-developed system could be used to simultaneously carry out the individual identification, paternity analysis, mixture deconvolution, forensic ancestry information analysis, and Y-chromosomal haplogroup inference, which could provide more valuable investigative clues in forensic practices.     

Development and validation of a new 18 X-STR typing assay for forensic applications

With a unique inheritance pattern compared to autosomal short tandem repeats (A-STRs), X chromosomal STRs (X-STRs) have special usage in forensic relationship testing. In this study, we designed a multiplex amplification system (named TYPER-X19 multiplex assay) consisting of 18 STR loci spreading from 7.837 to 149.460 Mb on the X chromosomes (DXS9895, DXS8378, DXS9902, DXS6810, DXS7132, DXS10079, DXS6789, DXS7424, DXS101, DXS6797, DXS7133, DXS6804, GATA165B12, DXS10103, HPRTB, GATA31E08, DXS8377, and DXS7423), and the amelogenin. PCR primers were marked with four kinds of fluorophores including FAM, HEX, TAMRA, and ROX. The multiplex system was optimized and tested for precision, concordance, reproducibility, sensitivity, stability, DNA mixture, and species specificity according to the conventional validation guidelines. The results indicated that the system was accurate, reliable, and sensitive enough, and was suitable for common forensic case-type samples. In the population genetic study, a total of 148 alleles were detected at the 18 X-STR loci in 398 Southern Han Chinese. Relatively high combined power of discrimination in male (PD_m), power of discrimination in female (PD_f), mean paternity exclusion chance in trios (MEC_trio), and mean paternity exclusion chance in duos (MEC_Duo) by Desmarais were detected, and HPRTB-DXS10103 was in linkage disequilibrium. The results suggested that the TYPER-X19 multiplex assay was suitable for forensic applications.     

Developing and population analysis of a new multiplex panel of 18 microhaplotypes and compound markers using next generation sequencing and its application in the Shaanxi Han population

Compound marker consists of two different types of genetic markers, like deletion/insertion polymorphism and single nucleotide polymorphism in the genomic region of 200 bp, and microhaplotype consists of a series of closely linked single nucleotide polymorphisms in a small DNA segment (<300 bp), which show great potential for human identifications and mixture analyses. In this study, we initially selected 23 novel genetic markers comprising 10 microhaplotypes and 13 compound markers according to previously reported single nucleotide polymorphism or deletion/insertion polymorphism loci. Genetic distributions of these 23 loci in different continental populations showed that they could be used as valuable loci for forensic human identification purpose. Besides, high informativeness values (>0.1) were observed in six loci which could be further employed for forensic ancestry analyses. Finally, 18 loci were successfully developed into a multiplex panel and detected by the next generation sequencing (NGS) technology. Further analyses of these 18 loci in the studied Shaanxi Han population showed that 15 loci exhibited relatively high expected heterozygosities (>0.5). Cumulative power of discrimination (0.999 999 999 99 4835) of these 18 loci revealed that the multiplex panel could also be utilized for human identifications in the studied Shaanxi Han population.     

Multiplex amplified product-length polymorphism analysis of 36 mitochondrial single-nucleotide polymorphisms for haplogrouping of East Asian populations

We present a reliable, rapid, and economical multiplex amplified product-length polymorphism (APLP) method for analyzing the haplogroup-diagnostic mitochondrial single-nucleotide polymorphisms (mtSNPs) in East Asian populations. By examining only 36 haplogroup-specific mtSNPs in the coding region by using four 9-multiplex polymerase chain reaction (PCR) and subsequent electrophoresis, we could safely assign 1815 individuals from 8 populations of Japanese, Korean, Chinese, and Germans to 45 relevant haplogroups. This multiplex APLP analysis of coding-region mtSNPs for haplogrouping is especially useful not only for molecular phylogenetic studies but also for large-scale association studies due to its rapid and economical nature. This is the first panel of mtSNPs in the coding region to be used for haplogrouping of East Asian populations.     

First principles study of small palladium cluster growth and isomerization

Structures and physical properties of small palladium clusters Pd_n up to n = 15 and several selected larger clusters were studied using density functional theory under the generalized gradient approximation. It was found that small Pd_n clusters begin to grow 3‐dimensionally at n = 4 and evolve into symmetric geometric configurations, such as icosahedral and fcc‐like, near n = 15. Several isomers with nearly degenerate average binding energies were found to coexist and the physical properties of these clusters were calculated. For several selected isomers, relatively moderate energy barriers for structural interchange for a given cluster size were found, implying that isomerization could readily occur under ambient conditions. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007