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PubMed2005

Integration of stochastic effects and data uncertainties into the design of process equipment.

Stochastic effects and data uncertainties are present in any engineering calculation. Their impact may be particularly important if they concern the design of process equipment. A calculation model for the dynamic behavior of a heat exchanger and procedures to deal with the related uncertainties are presented. Their propagation through the calculation by means of a Monte Carlo approach is shown. The temperature at the heat exchanger outlet and the step response of a sudden variation in the heat exchanger inlet temperature are simulated and evaluated by way of example. It is demonstrated that the inclusion of stochastic effects and uncertainties provides a more reliable basis for design decisions and hence reduces the probability of errors.

Journal Article↗
PubMed2006

Phloem flow strongly influences the systemic spread of silencing in GFP Nicotiana benthamiana plants.

The term 'RNA silencing' describes a process that results in the specific degradation of an RNA target. In plants, silenced tissues can initiate the spreading of the process into non-silenced regions by a mobile signal that can be transmitted over long distances. In the present work, we made use of a modified grafting approach to elucidate the driving force behind long-distance transport of the silencing signal. We made reciprocal grafts of two GFP-transgenic Nicotiana benthamiana lines, the non-silenced line 16c (sensor) and the silenced line 6.4 (inducer). We show that the direction of systemic spread of silencing from inducer to sensor can be manipulated by altering sink/source relations in the plant. Using radioactive phosphate as a phloem tracer, we demonstrated that plants that transmitted silencing from silenced scion to non-silenced rootstock had developed a persisting phloem flow from scion to rootstock. These data provide experimental proof of what has been hypothesized so far, that the silencing signal travels via phloem from source to sink. We present here evidence that the appearance of systemic silencing is not an accidental stochastic process, but can be predicted on the basis of the direction of phloem flow.

Gene Expression Regulation, Plant↗
PubMed2000

Stochastic simulation of processive and oscillatory sliding using a two-headed model for axonemal dynein.

Computer simulations have been used in an attempt to understand experimental observations of processive and oscillatory sliding by one or a few axonemal dyneins. A simple two-headed model has been examined using stochastic simulation methods. To explain the experimental observations, the model must be capable of taking backward steps, as well as forward steps, and there must be hysteresis in switching between forward or backward stepping. When the effects of Brownian movement on motor strain are included, it is not possible to obtain oscillations as regular as the experimental records by using motor strain to regulate switching between forward or backward stepping.

Biological Clocks↗
PubMed1996

Kinetics and locus of failure of receptor-ligand-mediated adhesion between latex spheres. I. Protein-carbohydrate bond.

We previously described the use of a counter-rotating cone and plate rheoscope to measure the time and force dependence of break-up of doublets of sphered, swollen, and fixed red cells (SSRC) cross-linked by monoclonal IgM antibody. It has been shown that doublet break-up can occur by extraction of receptors from the membrane, rather than by antibody-antigen bond break-up, and is a stochastic process. We therefore prepared 4.62-microns carboxyl modified latex spheres with a covalently coupled synthetic blood group B antigen trisaccharide. Using a two-step carbodiimide process, ethylene diamine was covalently linked to the carboxyl modified latex spheres, and the trisaccharide, having an eight carbon spacer modified to bear a terminal carboxyl group, was linked to the ethylene diamine. Using these antigen spheres we carried out studies in Couette flow, in a transparent cone and plate rheoscope, of the shear-induced break-up of doublets cross-linked by monoclonal IgM anti-B antibody in 19% and 15% Dextran 40. As previously found with SSRC, over a range of normal force from 55 to 175 pN, there was a distribution in times to break-up. However, the fraction of antigen sphere doublets broken up, which increased from 0.08 to 0.43 at 75 pM IgM, and from 0.06 to 0.20 at 150 pM IgM, was significantly lower than that for the SSRC, where the fraction broken up at 150 pM IgM increased from 0.10 to 0.47. Thus, significantly higher forces were required to achieve the same degree of break-up for doublets of antigen-linked spheres than for SSRC. Computer simulation using a stochastic model of break-up showed that the differences between antigen sphere and SSRC doublet break-up were due to a change in bond character (the range and depth of the bond energy minimum) rather than to an increase in the number of bonds linking antigen-sphere doublets. This supports the notion that antibody-antigen bonds are ruptured in the case of antigen spheres, whereas antigen is able to be extracted from the membrane of SSRC, although changes of receptor substrate from cell to latex and the possibility of latex strand extraction from the microspheres are potential complicating factors.

ABO Blood-Group System↗
PubMed2000

Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype.

Colorectal cancers (CRCs) are characterized by multiple genetic (mutations) and epigenetic (CpG island methylation) alterations, but it is not known whether these evolve independently through stochastic processes. We have recently described a novel pathway termed CpG island methylator phenotype (CIMP) in CRC, which is characterized by the simultaneous methylation of multiple CpG islands, including several known genes, such as p16, hMLH1, and THBS1. We have now studied mutations in K-RAS, p53, DPC4, and TGFbetaRII in a panel of colorectal tumors with or without CIMP. We find that CIMP defines two groups of tumors with significantly different genetic lesions: frequent K-RAS mutations were found in CIMP(+) CRCs (28/41, 68%) compared with CIMP(-) cases (14/47, 30%, P = 0.0005). By contrast, p53 mutations were found in 24% (10/41) of CIMP(+) CRCs vs. 60% (30/46) of CIMP(-) cases (P = 0.002). Both of these differences were independent of microsatellite instability. These interactions between CIMP, K-RAS mutations, and p53 mutations were preserved in colorectal adenomas, suggesting that they occur early in carcinogenesis. The distinct combinations of epigenetic and genetic alterations in each group suggest that activation of oncogenes and inactivation of tumor suppressor genes is related to the underlying mechanism of generating molecular diversity in cancer, rather than simply accumulate stochastically during cancer development.

Adenoma↗
PubMed1983

Neoplastic conversion of preneoplastic Syrian hamster cells: rate estimation by fluctuation analysis.

Analysis of the role of gene mutations in the multistep process of neoplastic transformation requires that the discrete steps in carcinogenesis first be dissected. Toward this end, we have isolated and characterized preneoplastic Syrian hamster cells which exhibit in vitro a trait highly correlated with neoplastic conversion in vivo. Previous findings (J. C. Barrett, Cancer Res. 40:91-94, 1980) indicate that spontaneous neoplastic transformation of Syrian hamster cells occurs in at least two steps. An intermediate stage, characterized by an aneuploid established cell line which has a propensity to become neoplastic spontaneously upon further growth in vitro, has been described. These preneoplastic cells differ from diploid early-passage Syrian hamster cells in becoming capable of anchorage-independent growth in semisolid agar, as well as becoming neoplastic in vivo when attached to a solid substrate. Evidence presented here demonstrates that anchorage-independent conversion in vitro is a reliable marker for neoplastic conversion in this cell system. Fluctuation analyses, patterned after those described by Luria and Delbruck for microbial genetics, demonstrate that anchorage-independent variants are generated randomly from clonally derived preneoplastic cells at the rate of 10(-8) to 10(-7) variants per cell per generation. These results establish a multistep stochastic process for transformation in vitro and indicate that conversion to anchorage independence may be necessary for Syrian hamster cells to become tumorigenic. The possible role of gene mutation in this step during neoplastic progression is discussed.

Aneuploidy↗
PubMed1998

An allele-specific, stochastic gene expression process controls the expression of multiple Ly49 family genes and generates a diverse, MHC-specific NK cell receptor repertoire.

Mouse NK cells express MHC class I-specific inhibitory Ly49 receptors. Since these receptors display distinct ligand specificities and are clonally distributed, their expression generates a diverse NK cell receptor repertoire specific for MHC class I molecules. We have previously found that the Dd (or Dk)-specific Ly49A receptor is usually expressed from a single allele. However, a small fraction of short-term NK cell clones expressed both Ly49A alleles, suggesting that the two Ly49A alleles are independently and randomly expressed. Here we show that the genes for two additional Ly49 receptors (Ly49C and Ly49G2) are also expressed in a (predominantly) mono-allelic fashion. Since single NK cells can co-express multiple Ly49 receptors, we also investigated whether mono-allelic expression from within the tightly linked Ly49 gene cluster is coordinate or independent. Our clonal analysis suggests that the expression of alleles of distinct Ly49 genes is not coordinate. Thus Ly49 alleles are apparently independently and randomly chosen for stable expression, a process that directly restricts the number of Ly49 receptors expressed per single NK cell. We propose that the Ly49 receptor repertoire specific for MHC class I is generated by an allele-specific, stochastic gene expression process that acts on the entire Ly49 gene cluster.

Alleles↗
PubMed2000

Disturbance Frequency and Community Stability in Native Tallgrass Prairie.

Ecological communities are spatially and temporally variable in response to a variety of biotic and abiotic forces. It is not always clear, however, if spatial and temporal variability leads to instability in communities. Instability may result from strong biotic interactions or from stochastic processes acting on small populations. I used 10-15 yr of annual data from the Konza Prairie Long-Term Ecological Research site to examine whether plant, breeding bird, grasshopper, and small mammal communities in tallgrass prairie exhibit stability or directional change in response to different experimentally induced fire frequencies. Based on ordination and ANOVA, plant and grasshopper communities on annually burned sites differed significantly from plant and grasshopper communities on less frequently burned sites. Breeding birds and small mammals differed among sites as well, but these differences were not clearly related to disturbance frequency. A modified time series analysis indicated that plant communities were undergoing directional change (unstable) on all watersheds, regardless of fire frequency. Contrary to expectations, directional change was greatest on the annually burned sites and lowest on the infrequently burned sites. Unlike the plant communities, breeding bird, grasshopper, and small mammal communities were temporally stable, despite high-compositional variability from 1 yr to the next. Stability among the consumer communities within these dynamic plant communities occurs because three-dimensional vegetation structure does not change over time, despite changes in plant species composition. Evidence suggests that instability in the plant community results from strong biotic interactions among temporally persistent core species and stochastic dynamics among infrequent satellite species. Overall, community stability cannot be assessed if the pattern of temporal dynamics is unknown. Long-term empirical studies of different taxa under different disturbance regimes are needed to determine over what time frames and spatial scales communities may be stable. Such studies are essential for the development of generalities regarding the relationship between disturbance frequency and community stability in terrestrial and aquatic systems.

community dynamics↗
PubMed1989

Pathways of human cell post-replication repair.

Mutagenesis, clastogenesis, and carcinogenesis, may all be S-phase dependent processes within carcinogen-damaged human cells. Carcinogens have been shown to inhibit replicative DNA synthesis in S phase cells and the mechanisms of inhibition have been identified. It is proposed that the sequelae of carcinogen action (mutations, sister-chromatid exchanges, chromosome aberrations) are the consequence of the production of lesions in the DNA template which interfere with the ability of DNA polymerase to synthesize a complementary strand without error. Mis-instructive lesions in the template give rise to base-substitution mutations in nascent strands as DNA polymerase inserts an incorrect but complementary base. Non-instructive base lesions and sterically interfering bulky adducts in the template inhibit DNA polymerase and cause the growing points of nascent DNA strands to be blocked. This blockage perpetuates discontinuities in daughter strands. These discontinuities are eliminated by a process known as post-replication repair. Blocked growing points may be relieved by un-directed insertion of DNA precursors to span the non-instructive lesions. Transient dislocation of the primer terminus from the damaged template may occur at palindromic or repetitive sequences. Reannealing of the primer terminus beyond the site of damage may allow bypass of blocking lesions with a consequence of deletion or insertion of genetic information. DNA at the site of blocked growing points may be a substrate for other enzymes involved in DNA metabolism. Single-strand gaps in daughter strands may be recognized by Rec A-like proteins which catalyze paranemic invasion of sister duplex strands. Recombination intermediates generated at sites of blocked growing points may be resolved by a pathway that produces either sister-chromatid exchanges or the insertion of a patch of parental template DNA within the daughter strand. Single-strand-specific endonuclease may attack regions of denatured DNA at blocked growing points producing double-strand breaks which appear to be intermediates in the formation of chromatid aberrations. The utilization of each of these pathways of post-replication repair will depend upon the precise structure of the template lesion, the sequence context in which the lesion is embedded in the template strand, and stochastic processes.

Cell Cycle↗
PubMed1987

The morphogenesis of the chick primary corneal stroma. I. New observations on collagen organization in vivo help explain stromal deposition and growth.

The primary stroma of the avian cornea contains collagen fibrils in orthogonal array. While investigating the processes underlying its morphogenesis, we have found that stromal organization is not as expected in three important respects. First, the fibrils are not uniform: those near the epithelium (newly laid down) have a maximum diameter of about 20 nm (mean: 17.7 nm), while those near the endothelium (laid down for approx. 40 h) have diameters up to 40 nm (mean: 22.8 nm). Fibrils thus grow rapidly to 20 nm and then continue to enlarge slowly, presumably by diffusion of collagen molecules from the epithelium. Second, the collagen, although orthogonally organized, does not contain layers of parallel fibrils. Instead, SEM observation shows that only a few fibrils lie in a parallel array before this short-range order is broken by orthogonal fibrils in the same plane. Furthermore, fibrils in corneas that had been freeze dried but not critical-point dried for SEM were widely spaced and the intervening gaps were filled by an extensive matrix that was probably composed of the proteoglycans known to be in the stroma. Third, we have shown experimentally that the stromal undulations seen in sections are not present in vivo but are shrinkage artifacts: the less corneas were shrunk for SEM preparation, the less pronounced were the stromal undulations. We also noted that, even after the distortions required for the stroma to undulate, the constituent fibrils remained orthogonally organized. These results give insight into the mechanisms underlying stromal morphogenesis and growth. The observations on the growth of collagen fibrils and on collagen organization show that stromal deposition is a more stochastic process than previously thought and, hence, provides support for the view that a complex self-assembly mechanism underlies both fibrillogenesis and the generation of orthogonal organization. The experiments on, and the analysis of, stromal folding show that fibrils slide over one another as undulations form, with the extensive matrix of hydrated proteoglycans being the likely lubricant. This fluidity of the stromal components probably explains how growth can occur without the structure being distorted.

Animals↗
PubMed1989

Spatial patterns of human gene frequencies in Europe.

The aims of this study of spatial patterns of human gene frequencies in Europe are twofold. One is to present new methodology developed for the analysis of such data. The other is to report on the diversity of spatial patterns observed in Europe and their interpretation as evidence of population processes. Spatial variation in 59 allele and haplotype frequencies (26 genetic systems) for polymorphisms in blood antigens, enzymes, and proteins is analyzed for an aggregate of 3,384 localities, using homogeneity tests, one-dimensional and directional spatial correlograms, and SYMAP interpolated surfaces. The data matrices are reduced to reveal the principal patterns by clustering techniques. The findings of this study can be summarized as follows: 1) There is significant heterogeneity in allele frequencies among the localities for all but one genetic system. 2) There are significant spatial patterns for most allele frequencies. 3) There is a substantial minority of clinal patterns in these populations. Clinal trends are found more frequently in HLA alleles than for other variables. North-south and northwest-southwest gradients predominate. 4) There is a strong decline in overall genetic similarity with geographic distance for most variables. 5) There are few, if any, appreciable correlations in pairs of allele frequencies over the continent, and there is little interesting correlation structure in the resulting correlation matrix. 6) Few spatial correlograms are markedly similar to each other, yet they form well-defined clusters. Spatial variation patterns, therefore, differ among allele frequencies. Patterns of human gene frequencies in modern Europe are diverse and complex. No single model suffices for interpretation of the observed genetic structure. Some clinal patterns reported here support the Neolithic demic-expansion hypothesis, others suggest latitudinal selection. Most of the clinal patterns are in HLA alleles, but there is also evidence from ABO for east-west migration diffusion. The majority of patterns are patchy, consistent with hypotheses of isolation by distance or of settlement of genetically differing, subsequently expanding ethnic groups. While undoubtedly there has been an ongoing stochastic process of differentiation consistent with the isolation-by-distance model, this has not obscured the directional patterns caused by migration (demic diffusion), and has perhaps only reinforced the contribution from settlement of ethnic units to patterns of genetic variation. However, the impact of the latter is most difficult to discern and requires further methodological developments.

ABO Blood-Group System↗
PubMed1996

Phenotypic variability in monozygotic twins with neurofibromatosis 2.

Mutations in the neurofibromatosis 2 (NF2) tumor suppressor gene on chromosome 22q12 cause a clinically variable autosomal dominant syndrome characterized by bilateral vestibular schwannomas (VSs), other nervous system tumors, and early onset lenticular cataracts. We studied three pairs of monozygotic (MZ) twins with NF2, all with bilateral VSs, to separate genetic from nongenetic causes of clinical variability. The evaluation included gadolinium-enhanced high-resolution magnetic resonance imaging of the head and spine, neuro-ophthalmic examination with slit lamp, physical examination, and zygosity testing with microsatellite markers. Each MZ pair was concordant for general phenotypic subtype (mild or severe) and often for the affected organ systems. However, the MZ pairs were discordant for some features of disease presentation or progression. For example, all three pairs were discordant for presence or type of associated cranial tumors. We hypothesize that phenotypic differences between NF2 MZ twins are at least partly due to stochastic processes, such as the loss of the second NF2 allele or alleles of other genes.

Adult↗
PubMed1996

Molecular phylogeny of the New World monkeys (Platyrrhini, primates) based on two unlinked nuclear genes: IRBP intron 1 and epsilon-globin sequences.

Nuclear sequences of the 1.8 kilobase (kb) long intron 1 of the interstitial retinol-binding protein gene (IRBP), previously determined for 11 of the 16 extant genera of New World monkeys (superfamily Ceboidea, infraorder Platyrrhini), have now been determined for the remaining 5 genera. The maximum parsimony trees found, first with IRBP sequences alone and then with tandemly combined IRBP and epsilon-globin gene sequences from the same species, supported a provisional cladistic classification with the following clusters. Subtribes Callitrichina (Callithrix, Cebuella), Callimiconina (Callimico), Leontopithecina (Leontopithecus) and Saguina (Saguinus) constitute subfamily Callitrichinae, and subfamilies Callitrichinae, Aotinae (Aotus), and Cebinae (Cebus, Saimiri) constitute family Cebidae. Subtribes Chiropotina (Chiropotes, Cacajao) and Pitheciina (Pithecia) constitute tribe Pitheciini; and tribes Pitheciini and Callicebini (Callicebus) constitute subfamily Pitheciinae. Subtribes Brachytelina (Brachyteles, Lagothrix) and Atelina (Ateles) constitute tribe Atelini, and tribes Atelini and Alouattini (Alouatta) constitute subfamily Atelinae. The parsimony results were equivocal as to whether Pitheciinae should be grouped with Atelinae in family Atelidae or have its own family Pitheciidae. The cladistic groupings of extant ceboids were also examined by different stochastic evolutionary models that employed the same stochastic process of nucleotide substitutions but alternative putative phylogenetic trees on which the nucleotide substitutions occurred. Each model, i.e., each different tree, predicted a different multinomial distribution of nucleotide character patterns for the contemporary sequences. The predicted distributions that were closest to the actual observed distributions identified the best fitting trees. The cladistic relationships depicted in these best fitting trees agreed in almost all cases with those depicted in the maximum parsimony trees.

Animals↗
PubMed1998

Conditions for fibronectin fibril formation in the early Xenopus embryo.

Fibronectin fibril formation on a multilayered cohesive cell sheet is studied in the Xenopus embryo. In the blastula, secreted fibronectin accumulates in the blastocoel, where it associates with mucous material. At the onset of gastrulation, a fibrillar fibronectin matrix develops on the blastocoel roof. Cells engage in this process stochastically within a 2-hr period. Fibril network formation requires more than 60 microg/ml of fibronectin, but the timing of fibrillogenesis is not regulated through the availability of fibronectin. With the exception of a few isolated mesoderm cells, only the cells of the blastocoel roof are able to form fibronectin fibrils. However, this requires that cells are provided with a free surface and, at the same time, with lateral adhesive cell contacts, i.e. fibril assembly occurs only on the surface of cohesive cells aggregates. This explains the observed restriction of fibronectin matrix formation to the inner surface of the blastocoel roof in the embryo. In addition, a minimum blastocoel roof size is required for fibril formation.

Animals↗
PubMed1999

A hierarchical Bayesian approach to age-specific back-calculation of cancer incidence rates.

We propose a Bayesian hierarchical model to estimate age-specific cancer incidence per year from age-specific cancer mortality. The model is based upon the empirical Bayesian approach of Liao and Brookmeyer (1995) and extends that model by consideration of the dependence on age. The incident cases per year are considered as observations from a discrete-time stochastic process following an autoregressive structure within a Poisson regression model. The model assumes that the survival probability among those with cancer is known. We have investigated the sensitivity of the model to the choice of this distribution and have found that this is the most sensitive part of the model. By comparison the predictions of the model are relatively robust to changes in other key areas, such as the number of years an incident case contributes before death, assumptions about parameter equality for identification and the initial prior distributions. The proposed methodology has been investigated using lung cancer mortality data from Scotland. Parameter estimates were obtained through Markov chain Monte Carlo methods, implemented using BUGS.

Age Factors↗
PubMed1999

Secretion of zona pellucida glycoprotein mZP2 by growing oocytes from mZP3(+/+) and mZP3(-/-) mice.

The mouse egg extracellular coat, or zona pellucida (ZP), is composed of three glycoproteins, called mZP1-3, which are synthesized and secreted concomitantly by growing oocytes. Disruption of the mZP3 gene by targeted mutagenesis yields mice that are homozygous nulls (mZP3(-/-)). Growing oocytes from mZP3(-/-) mice do not synthesize mZP3 mRNA or protein and, as a result, do not assemble a ZP. Here, we examined secretion of mZP2 by growing oocytes and eggs from mZP3(-/-) mice, as well as incorporation of mZP2 into the ZP of oocytes from mZP3(+/+) mice. Laser scanning confocal microscopy (LSCM) of antibody-labeled samples showed that, indeed, mZP2 was synthesized and secreted by oocytes isolated from mZP3(-/-) mice and cultured in vitro. Nascent mZP2 was found in the culture medium, associated with the surface of the plasma membrane of growing oocytes, and in the oocyte cytoplasm. By contrast, mZP2 was barely detectable at any of these sites when ovulated eggs from mZP3(-/-) mice were examined. Examination of oocytes from wild-type (mZP3(+/+)) mice showed that, while a portion of nascent mZP2 was assembled into the ZP (approximately 40%), here too a significant fraction was secreted into the culture medium (approximately 60%). Similar results also were obtained when intact pre-antral follicles were isolated from mZP3(+/+) mice and cultured in vitro. Several of these observations are consistent with previous results obtained with oocytes from heterozygous null mice (mZP3(+/-)). Furthermore, the results suggest that ZP assembly from nascent glycoproteins may be a stochastic process that requires the presence of both mZP2 and mZP3 and occurs completely outside the growing oocyte.

Animals↗
PubMed2000

Orderliness of hormone release.

ApEn, approximate entropy, is a recently formulated family of parameters and statistics quantifying regularity (orderliness) in serial data, with developments both within theoretical mathematics, as well as numerous applications to multiple biological contexts. ApEn appears to have broad application to hormone pulsatility analysis within endocrinology, bringing a new perspective to the assessment of secretory patterns. ApEn is complementary to pulse detection algorithms widely employed to evaluate hormone secretion time-series--it is scale-invariant and model-independent, evaluates both dominant and subordinant patterns in data, discriminates series for which clear pulse recognition is difficult, and often provides a direct barometer of feedback between subsystems. ApEn is applicable to systems with at least 50 data points and to broad classes of models: it can be applied to discriminate both general classes of correlated stochastic processes, as well as noisy deterministic systems. Moreover, ApEn is complementary to spectral and autocorrelation analyses, providing effective discriminatory capability in instances in which the aforementioned measures exhibit minimal distinctions. We present some basic background on the above, and illustrate various facets of ApEn utility via several representative endocrinological studies.

Animals↗
PubMedDate not supplied

Genetic structure of Algerian populations.

Blood samples were collected in Algeria from 4,444 army recruits and tested for 10 genetic polymorphic systems. These samples were collected from territorial Wilayas (administrative units of Algeria) from which the young soldiers had originated. Based on similar geography and economic and political history, these Wilayas were clustered into 10 regions. These regions, not part of the governmental administrative units, were characterized by allelic frequencies, and analyzed using R-matrix principal components, Wright's F(ST), spatial autocorrelation, and Mantel tests. Hierarchical relationships between the culturally defined regions were examined using two different analytical methods of phylogenetic tree constructions: neighbor-joining, and unweighted pair group average arithmetic (UPGMA). These results indicated the predominance of genetic homogeneity due to the gene flow between regions, but with some migration emanating from sub-Saharan Africa and Mediterranean Europe. Wright's F(ST) value of 0.0063, based on 16 alleles, suggested a relatively small genetic microdifferentiation of the regions. In Algeria, gene flow apparently swamped most of the effects of stochastic processes and disrupted the relationship between geography and genetics, as characterized by the isolation-by-distance model. Some genetic differences and similarities were observed between regions or clusters of regions. The resulting genetic structure of the Algerian populations is best explained by a combination of gene flow, ecology, and history.

Algeria↗