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PubMed2000

Susceptibility of sheep for scrapie as assessed by in vitro conversion of nine naturally occurring variants of PrP.

Polymorphisms in the prion protein (PrP) gene are associated with phenotypic expression differences of transmissible spongiform encephalopathies in animals and humans. In sheep, at least 10 different mutually exclusive polymorphisms are present in PrP. In this study, we determined the efficiency of the in vitro formation of protease-resistant PrP of nine sheep PrP allelic variants in order to gauge the relative susceptibility of sheep for scrapie. No detectable spontaneous protease-resistant PrP formation occurred under the cell-free conditions used. All nine host-encoded cellular PrP (PrP(C)) variants had distinct conversion efficiencies induced by PrP(Sc) isolated from sheep with three different homozygous PrP genotypes. In general, PrP allelic variants with polymorphisms at either codon 136 (Ala to Val) or codon 141 (Leu to Phe) and phylogenetic wild-type sheep PrP(C) converted with highest efficiency to protease-resistant forms, which indicates a linkage with a high susceptibility of sheep for scrapie. PrP(C) variants with polymorphisms at codons 171 (Gln to Arg), 154 (Arg to His), and to a minor extent 112 (Met to Thr) converted with low efficiency to protease-resistant isoforms. This finding indicates a linkage of these alleles with a reduced susceptibility or resistance for scrapie. In addition, PrP(Sc) with the codon 171 (Gln-to-His) polymorphism is the first variant reported to induce higher conversion efficiencies with heterologous rather than homologous PrP variants. The results of this study strengthen our views on polymorphism barriers and have further implications for scrapie control programs by breeding strategies.

Alleles↗
PubMed2005

Phylogeography of the threatened crayfish (genus Austropotamobius) in Italy: implications for its taxonomy and conservation.

A nucleotide sequence analysis of a portion of the mitochondrial large ribosomal subunit was performed to define the phylogeography of the threatened crayfish Austropotamobius (Decapoda; Astacidae) in Italy. We collected 61 specimens from 31 localities across the Italian peninsula. For the phylogenetic inference, we combined the 61 Austropotamobius spp sequences obtained from this study with 18 sequences deposited in GenBank and corresponding to Italian, French, Irish, Swiss, and Slovenian locations. Among the analysed sequences, 34 distinct haplotypes were detected. Our results confirmed the presence of both A. pallipes and A. italicus in the Italian peninsula and the existence within the latter species of a strong intraspecific genetic variation, due to the occurrence of four subspecies with a well-defined geographic distribution. From a conservation viewpoint, Italy, with its high haplotype variability, may be considered a 'hot spot' for the genetic diversity of the European native crayfish Austropotamobius. We suggest that re-introduction programs should be conducted with extreme caution in Italy, since not only the two Austropotamobius species but also the four A. italicus subspecies are genetically and taxonomically separate units and require independent conservation plans.

Animals↗
PubMed2006

Eotaxin polymorphisms and serum total IgE levels in children with asthma.

BACKGROUND: Eotaxin (chemokine, CC motif, ligand; CCL11) is a potent eosinophil chemoattractant strongly implicated in the pathobiology of asthma. Genetic variation at the CCL11 locus has been correlated with serum total IgE, blood eosinophil counts, and circulating eotaxin protein levels in several case-control asthma studies. Family-based association studies of CCL11 genetic variants have not been reported to date. OBJECTIVE: To evaluate 9 common CCL11 single nucleotide polymorphisms (SNPs) in nuclear families ascertained through patients with asthma participating in the Childhood Asthma Management Program study. METHODS: Single nucleotide polymorphism genotyping was performed by using minisequencing and probe hybridization platforms. Family-based association analysis for asthma and 4 asthma-related intermediate quantitative phenotypes was performed by using FBAT. RESULTS: One SNP, -384A>G, was associated with asthma among African American families (P = .01). CCL11 SNPs and haplotypes were not associated with asthma among white or Hispanic families. Two low-frequency alleles in strong pairwise linkage disequilibrium, -426C and IVS2+199A, were associated with lower serum total IgE levels (P = .0006 and P = .009, respectively) in white families, whereas 2 more common variants, -576C and g.4438C, were associated with higher IgE levels in African American families (P = .01-.04). Haplotype analysis in the white cohort provided additional evidence of association with serum total IgE, implicating 2 haplotypes. No single SNP or haplotype associations were observed with blood eosinophil levels, FEV(1), or airway responsiveness. CONCLUSION: These findings provide further evidence that genetic variation at the CCL11 locus is an important determinant of serum total IgE levels among patients with asthma.

Adult↗
PubMed2006

Fine mapping of a grain weight quantitative trait locus on rice chromosome 8 using near-isogenic lines derived from a cross between Oryza sativa and Oryza rufipogon.

A quantitative trait locus (QTL) for grain weight (GW) was detected near SSR marker RM210 on chromosome 8 in backcross populations derived from a cross between the Korean japonica cultivar Hwaseongbyeo and Oryza rufipogon (IRGC 105491). The O. rufipogon allele increased GW in the Hwaseongbyeo background despite the fact that O. rufipogon was the small-seeded parent. Using sister BC(3)F(3) near-isogenic lines (NILs), gw8.1 was validated and mapped to a 6.1 cM region in the interval between RM42 and RM210 (P < or = 0.0001). Substitution mapping with eight BC(3)F(4) sub-NILs further narrowed the interval containing gw8.1 to about 306.4 kb between markers RM23201.CNR151 and RM30000.CNR99. A yield trial using homozygous BC(3)F(4) sister sub-NILs and the Hwaseongbyeo recurrent parent indicated that the NIL carrying an O. rufipogon chromosome segment across the entire gw8.1 target region out-yielded its sister NIL (containing Hwaseongbyeo chromosome in the RM42-RM210 interval) by 9% (P=0.029). The higher-yielding NIL produced 19.3% more grain than the Hwaseongbyeo recurrent parent (P=0.018). Analysis of a BC(3)F(4) NIL indicated that the variation for GW is associated with variation in grain shape, specifically grain length. The locus, gw8.1 is of particular interest because of its independence from undesirable height and grain quality traits. SSR markers tightly linked to the GW QTL will facilitate cloning of the gene underlying this QTL as well as marker-assisted selection for variation in GW in an applied breeding program.

Chromosome Mapping↗
PubMed1994

Promoter tagging with a promoterless ipt gene leads to cytokinin-induced phenotypic variability in transgenic tobacco plants:implications of gene dosage effects.

Tobacco plants have been transformed with a T-DNA construct harboring a promoterless cytokinin-synthesizing ipt gene close to the right T-DNA border. Eighteen out of 85 transgenic clones displayed phenotypic alternations typical for an enhanced cytokinin production. Northern blot analysis confirmed the transcriptional activation of the introduced gene by tagged plant promoters. The concentration of cytokinins, expressed as zeatinriboside equivalents, was increased up to sevenfold in transgenic tissues. These increases in cytokinin levels resulted in major developmental changes. Transgenic clones exhibited to different levels traits of a general cytokinin-syndrome, i.e. reduced root growth, reduced apical dominance, reduced leaf surface, reduced growth of the stem and retarded leaf senescence or displayed localized and developmentally specific cytokinin-induced alterations in otherwise normally developing plants. These traits were in particular a simultaneous break of dormancy in all axillary buds before or at the onset of flowering or the reorientation of the developmental pathway of secondary meristems or terminally differentiated cells. This indicates that endogenously produced cytokinins not only influence different growth parameters but have the potential to alter differentiation pattern. The results show that stably inherited developmental alterations due to a general or localized cytokinin overproduction can be obtained by the promoter-tagging approach. The investigation of gene dosage effects in homozygote plants readdresses the question of threshold levels for cytokinin effects on the developmental program of plants.

Adenosine↗
PubMed1998

SWAN: sliding window analysis of nucleotide sequence variability.

RESULTS: This paper describes a new program which reveals, analyses and graphically represents patterns of variability along nucleotide sequences. AVAILABILITY: The program, 'SWAN', is available from the WWW at http://evolve.zoo.ox.ac.uk/ or from the authors upon request. CONTACT: Vitali.Proutski@zoology.oxford.ac.uk

Algorithms↗
PubMed2006

Survival analysis in two lines of rabbits selected for reproductive traits.

The objective of the study was to analyze the reproductive longevity of 2 selected lines of rabbits. The first one was the Prat line, a line selected in Spain on litter size at weaning, and raised in overlapping generations. The second one was a French line, the A1077 line, selected on litter size at birth and individual weight at 63 d of age, managed in batches, and artificially inseminated with discrete generations. Reproductive longevity was measured beginning at the first successful mating, assessed by a pregnancy diagnosis in the Prat line, and at the first kindling in the A1077 line. In the A1077 line, culling for infertility occurred after 3 unsuccessful artificial inseminations. The trait analyzed, defined as the doe length of productive life (LPL), was the time in days between date of the first positive pregnancy diagnosis and date of culling or death in the Prat line. In the A1077 line, the trait was the number of AI after the first kindling. Effects included in the model were year-season, litter size at birth, reproductive cycle or physiological status x cycle interaction, age at first mating, batch (only for the A1077 line), and additive genetic value of the animal as a random effect. Survival analyses were carried out with a Cox model for the Prat line and a discrete model for the A1077 line. The estimated heritability values for LPL were around 0.16 in the Prat and A1077 lines with a model including physiological status x cycle interaction effect. Removing this effect from the model led to an increase in estimated genetic variance with h2 = 0.24 and 0.19 in the Prat and A1077 lines, respectively. Including the traits LPL and number of AI from first fertile mating or AI in selection programs could increase reproductive longevity and decrease the replacement rate.

Animals↗
PubMed1991

Estimated genetic correlations between disease and yield traits in dairy cattle.

Data included observations on more than 200,000 first lactations of Norwegian cattle. Milk yield, fat and protein percentages, and observations on mastitis, ketosis, and presence of disease (binary coding of 0 or 1) were analyzed. Following Bayesian principles and applying the threshold concept, dispersion parameters for the binary traits (on the underlying scale) with continuous production traits were estimated. Heritabilities were .27, .34, and .43 for milk yield, fat percentage, and protein percentage, respectively. Heritabilities for the disease traits were .05 to .13 but may be inconsistent because of methodology problems with small sire by herd-year-season subclass size. Genetic correlations between milk yield and all three disease traits were above .5, indicating an undesirable relationship. Genetic correlations between ketosis and the content traits were -.38 to -.65; low component percentages were associated with high ketosis frequencies. Ignoring diseases in breeding programs may lead to undesirable correlated selection responses when selecting on milk yield.

Animals↗
PubMed2004

Prevalence of spondylosis deformans and estimates of genetic parameters for the degree of osteophytes development in Italian Boxer dogs.

The aim of this study was to assess the prevalence of spondylosis deformans and to investigate genetic aspects of the degree of osteophytes development (DOD) in the Italian Boxer dog population. A total of 849 Boxer dogs was radiographed on the thoracic, lumbar, and sacral regions of the spine and scored for DOD. Grading of DOD was performed for all 20 intervertebral sites comprised within the first thoracic site (site T1-T2) and the site between the seventh lumbar and the first sacral vertebra (site L7-S1). Scores for DOD ranged from 0 (no osteophytes development) to 3 (presence of a bony spur formed by osteophytes on adjoining vertebrae). The first five thoracic sites exhibited no variation for DOD and were not considered in the analysis. The prevalence of spondylosis deformans was 84%, and frequency of dogs showing at least one intervertebral site that scored 3 for DOD was 50%. Scores for DOD at different sites were analyzed as different traits. Nongenetic effects influencing DOD scores were sex, age at screening, and the kennel. Posterior densities of heritability (h2) were estimated using a univariate Bayesian analysis. Eight sites exhibited a posterior probability greater than 0.8 for h2 > 10% and were considered in a multivariate restricted maximum likelihood analysis. Estimated h2 from multivariate analysis ranged from 25 to 48% (SE from 5 to 7%). Three sites exhibited h2 estimates greater than 40%. Genetic correlations for DOD scored at different sites ranged from 0.07 to 0.96. All thoracic sites had estimated correlations larger than 0.85 with other thoracic sites. Genetic correlation between the first and the second lumbar site was 0.91. Correlations between thoracic sites and the first two lumbar sites ranged from 0.5 to 0.9. Sites L6-L7 and L7-S1 also exhibited weak relationships with all remaining sites. Breeding values of dogs for DOD at the eight sites were predicted using estimated covariance matrices. A selection index for DOD was computed from predicted breeding values and a set of relative weighting factors produced by a panel of veterinarians. The index was the most important effect influencing phenotypic differences between dogs for average DOD score, number of affected sites, and number of sites with a DOD score > 1 (P < 0.001). The degree of osteophytes development is a trait showing exploitable additive genetic variance, and breeding programs for decreasing prevalence and severity of spondylosis deformans might focus on this trait.

Age Factors↗
PubMed1995

Comparison of two approaches to analyzing correlated binary data in developmental toxicity studies.

Recently developed statistical methodology is presented for analyzing correlated developmental toxicity data where multiple measures are obtained on individual units such as rat pups. Of particular interest is the assessment of the homogeneity of effects from chemical exposure across different outcomes such as malformation types or non-ossification of forepaw digits. Such contrasts are referred to as within-cluster effects, as they represent differences between observations within a cluster (e.g., pup). Between-cluster effects correspond to comparison of observations from different clusters, e.g., pups exposed to varied doses of chemicals or carcinogens. Two classes of statistical models are available for estimation of these distinct types of effects: (1) cluster-specific models in which regression adjustments are made for cluster effects, and hence all parameters are interpreted as within-cluster effects; and (2) population-averaged models in which no explicit adjustments are made for cluster, and thus all parameters are interpreted as group differences without regard to whether they represent between- or within-cluster effects. Many models in the developmental toxicity literature are population-averaged logistic regression models ignoring variation among clusters which may be significant under strong influences of genetic and environmental factors. Under such conditions, confidence interval-based inference for effect homogeneity will depend upon the class of models. These issues are illustrated with data from two developmental toxicity studies: (1) a National Toxicology Program study of the effects of in utero exposure to di(2ethylhexyl)phthalate among three malformation outcomes in mouse pups; and (2) a study conducted by Hartsfield to investigate the effects of anticonvulsant phenytoin on the risk of non-ossification among digits of the left and right forepaws in rat pups.

Abnormalities, Drug-Induced↗
PubMed2002

Influence of adult domestic violence on children's internalizing and externalizing problems: an environmentally informative twin study.

OBJECTIVE: Externalizing and internalizing problems may aggregate in families because (1) siblings share genetic risks for problem behaviors or (2) siblings are exposed to similar environmental risks. A genetically sensitive design was used to determine whether domestic violence accounted significantly for the variation and covariation of externalizing and internalizing problems, independent of additive genetic effects on these behavior problems. METHOD: Using the Achenbach family of instruments, mothers and teachers reported internalizing and externalizing problems for 1,116 monozygotic and dizygotic 5-year-old twin pairs in the United Kingdom (93% response rate). Mothers reported their experiences of domestic violence in the previous 5 years. Structural equation models were tested to determine the effect of mothers' experiences of domestic violence on children's emotional and conduct problems, controlling for latent genetic and environmental effects on these behaviors. RESULTS: A multivariate model showed that adult domestic violence accounted for 2% and 5% of the variation in children's internalizing and externalizing problems, respectively, independent of genetic effects. The co-occurrence of externalizing and internalizing scores was accounted for by genetic (62.6%) and shared environmental (29.2%) factors and by domestic violence (8%). CONCLUSIONS: Because domestic violence affects children's behavior problems beyond genetic influences, programs that successfully reduce domestic violence should also prevent children's psychopathology.

Biometry↗
PubMed2005

A new intertype recombinant between genotypes C and D of hepatitis B virus identified in China.

Hepatitis B virus (HBV) genotypes have a characteristic geographical distribution. More than 90% of chronic HBV patients in China are infected with genotypes B or C. Here, eight HBV isolates that were initially classified as genotype D by PCR-restriction fragment length polymorphism analysis were analysed in detail. The complete HBV genome was sequenced and compared with 32 sequences retrieved from GenBank, representing HBV genotypes A-G. Phylogenetic analysis of the S gene (nt 10-800) classified all eight isolates as genotype D. However, phylogenetic analyses of nt 800-10 and the open reading frames (ORFs) of the precore/core and X genes classified all eight isolates as genotype C. This discordance between phylogenetic trees reconstructed on different ORFs suggested that intertype recombination has occurred in all eight isolates. By using the simplot program, the site of recombination with genotype D was located in the preS2/S region, spanning nt 10-799 in seven of eight isolates and nt 10-1499 in the other isolate. These results demonstrate that intertype recombination should be considered as a type of variation that increases the genetic diversity of HBV. Hybrids of different HBV genotypes might exhibit specific virological properties and their significance in the diagnosis and management of chronic hepatitis B deserves further investigation.

China↗
PubMed2002

Evaluating sire selection practices using lifetime net income functions.

Dairy farmers do not take full advantage of opportunities available for genetic improvement through use of artificial insemination, perhaps because economic advantages of good sire selection may not be fully recognized or understood. This study was undertaken to document differences between use of AI and non-AI bulls and to develop prediction equations to compare lifetime economic merit of future progeny from alternative sire selection policies. We describe the use of two methods of measuring lifetime economic merit, with and without adjustment for opportunity cost of a postponed replacement. Comparison of lifetime relative net income adjusted for opportunity cost on groups of cows sired by different kinds of bulls showed that daughters of proven AI bulls generated $148 and $120 more lifetime net income under fluid and manufactured milk market conditions than daughters of non-AI bulls. Daughters of proven AI bulls produced $60 more than daughters of AI young sires in progeny testing programs at the time of daughter conception. We developed prediction equations from combinations of genetic evaluations for production, productive life, SCS, and linear type traits on sires to predict lifetime relative net income of progeny produced from alternative sire selection strategies. Prediction equations explained 14 to 18% of variation in relative net income (not adjusted for opportunity cost), but herd and year of first freshening accounted for considerably more variation than did genetic evaluations on the sire of the cow. Finally, two independent data sets were used to develop and test predictions of lifetime relative net income adjusted for opportunity cost using genetic evaluations based on the eight traits included in the Merit indexes for the sire of each cow. Prediction equations from odd numbered herds were used to predict lifetime economic merit in even numbered herds and vice versa. Coefficients of determination ranged from 0.088 to 0.103 and averaged 0.004 higher than prediction equations with Net or Fluid Merit. Accuracy of predictions showed that Net and Fluid Merit were robust and useful indexes that accurately identified bulls whose daughters generated highest lifetime economic merit.

Animals↗
PubMed2002

Tests for sex-biased dispersal using bi-parentally inherited genetic markers.

Understanding why dispersal is sex-biased in many taxa is still a major concern in evolutionary ecology. Dispersal tends to be male-biased in mammals and female-biased in birds, but counter-examples exist and little is known about sex bias in other taxa. Obtaining accurate measures of dispersal in the field remains a problem. Here we describe and compare several methods for detecting sex-biased dispersal using bi-parentally inherited, codominant genetic markers. If gene flow is restricted among populations, then the genotype of an individual tells something about its origin. Provided that dispersal occurs at the juvenile stage and that sampling is carried out on adults, genotypes sampled from the dispersing sex should on average be less likely (compared to genotypes from the philopatric sex) in the population in which they were sampled. The dispersing sex should be less genetically structured and should present a larger heterozygote deficit. In this study we use computer simulations and a permutation test on four statistics to investigate the conditions under which sex-biased dispersal can be detected. Two tests emerge as fairly powerful. We present results concerning the optimal sampling strategy (varying number of samples, individuals, loci per individual and level of polymorphism) under different amounts of dispersal for each sex. These tests for biases in dispersal are also appropriate for any attribute (e.g. size, colour, status) suspected to influence the probability of dispersal. A windows program carrying out these tests can be freely downloaded from http://www.unil.ch/izea/softwares/fstat.html

Alleles↗
PubMed1992

Discrimination as a consequence of genetic testing.

Genetic discrimination refers to discrimination directed against an individual or family based solely on an apparent or perceived genetic variation from the "normal" human genotype. We describe here the results of a case history study designed to assess whether or not genetic discrimination exists. Using the above definition of genetic discrimination and applying stringent criteria for case selection, we find that genetic discrimination exists and is manifested in many social institutions, especially in the health and life insurance industries. Stigmatization, and denial of services or entitlements to individuals who have a genetic diagnosis but who are asymptomatic or who will never become significantly impaired, is noted. Follow-up comprehensive studies on the significance and varieties of genetic discrimination are needed. In order to avoid creating a new social underclass based on genetic discrimination (the "asymptomatic ill"), existing and future genetic testing or screening programs need review by medical, scientific, legal, and social policy experts, as well as the public, and may require modification.

Adult↗
PubMed2026

Swimming Upstream to Understand Congenital Anomalies of the Kidney and Urinary Tract: Zebrafish Models for Developmental Biology, Disease Mechanisms, and Functional Interpretation of Genetic Variation.

Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of pediatric chronic kidney disease (CKD) and comprise a heterogeneous group of developmental disorders with a substantial genetic contribution. Advances in next-generation sequencing have facilitated the identification of numerous candidate genes and rare variants associated with CAKUT. However, establishing causality and defining the biological functions of implicated genes remain major challenges. Functional validation is therefore essential to bridge the gap between gene discovery and mechanistic understanding, enabling the interpretation of genetic variation within the context of kidney development and disease. The zebrafish (Danio rerio) has emerged as a powerful in vivo model for studying renal development and interrogating the function of CAKUT-associated genes. Its utility stems from a high degree of genetic and developmental conservation with humans, conserved nephrogenic pathways, optical transparency during embryogenesis, and the relative ease of genetic manipulation. In this review, we provide an overview of zebrafish kidney development within the broader context of vertebrate nephrogenesis, highlighting the key genetic programs governing intermediate mesoderm specification, nephron segmentation, and pronephric morphogenesis. We then systematically examine CAKUT-associated genes that have been modeled in zebrafish, focusing on studies that have linked genetic perturbations to renal development and structural phenotypes. Finally, we discuss the strengths and limitations of zebrafish models for functional genomics and variant interpretation and consider their emerging role in bridging genetic discovery with mechanistic insights into CAKUT pathogenesis.

Animals↗
PubMed2005

PDCD1: a tissue-specific susceptibility locus for inherited inflammatory disorders.

Variation in genes encoding costimulatory molecules expressed on lymphocytes has been expected to contribute to the genetic component of inflammatory disease, but only the gene encoding the inhibitory protein, CTLA-4, seems consistently to confer disease susceptibility. Studies in murine models implicate the inhibitory product of the pd1 gene, programmed death-1, in the maintenance of peripheral tolerance to self-antigens. We identify 22 single-nucleotide polymorphisms (SNPs) in the equivalent human gene, PDCD1, a number of which show significant associations with the specific immunoglobulin E response to grass allergens in atopic individuals. Stepwise analyses indicate that four of the disease-associated SNPs have independent effects. The two most common haplotypes show positive and negative associations but rarer haplotypes are also likely to be of influence. In a case-control study, multiple regression analysis of genotypic data implies that PDCD1 also confers susceptibility to rheumatoid arthritis. Along with work linking PDCD1 with susceptibility to another autoimmune condition, systemic lupus erythematosus, our data identify PDCD1 as a second immunomodulatory gene with pleiotropic effects in human disease. Genes encoding negative regulators may generally confer a significant fraction of the genetic risk associated with inherited inflammatory disorders.

Alleles↗
PubMed2002

Sequence complexity profiles of prokaryotic genomic sequences: a fast algorithm for calculating linguistic complexity.

MOTIVATION: One of the major features of genomic DNA sequences, distinguishing them from texts in most spoken or artificial languages, is their high repetitiveness. Variation in the repetitiveness of genomic texts reflects the presence and density of different biologically important messages. Thus, deviation from an expected number of repeats in both directions indicates a possible presence of a biological signal. Linguistic complexity corresponds to repetitiveness of a genomic text, and potential regulatory sites may be discovered through construction of typical patterns of complexity distribution. RESULTS: We developed software for fast calculation of linguistic sequence complexity of DNA sequences. Our program utilizes suffix trees to compute the number of subwords present in genomic sequences, thereby allowing calculation of linguistic complexity in time linear in genome size. The measure of linguistic complexity was applied to the complete genome of Haemophilus influenzae. Maps of complexity along the entire genome were obtained using sliding windows of 40, 100, and 2000 nucleotides. This approach provided an efficient way to detect simple sequence repeats in this genome. In addition, local profiles of complexity distribution around the starts of translation were constructed for 21 complete prokaryotic genomes. We hypothesize that complexity profiles correspond to evolutionary relationships between organisms. We found principal differences in profiles of the GC-rich and other (non-GC-rich) genomes. We also found characteristic differences in profiles of AT genomes, which probably reflect individual species variations in translational regulation. AVAILABILITY: The program is available upon request from Alexander Bolshoy or at http://csweb.haifa.ac.il/library/#complex.

Algorithms↗