Number Of Distinct Haplotypes Research Articles

The many definitions of multiplicity of infection.

The presence of multiple genetically different pathogenic variants within the same individual host is common in infectious diseases. Although this is neglected in some diseases, it is well recognized in others like malaria, where it is typically referred to as multiplicity of infection (MOI) or complexity of infection (COI). In malaria, with the advent of molecular surveillance, data is increasingly being available with enough resolution to capture MOI and integrate it into molecular surveillance strategies. The distribution of MOI on the population level scales with transmission intensities, while MOI on the individual level is a confounding factor when monitoring haplotypes of particular interests, e.g., those associated with drug-resistance. Particularly, in high-transmission areas, MOI leads to a discrepancy between the likelihood of a haplotype being observed in an infection (prevalence) and its abundance in the pathogen population (frequency). Despite its importance, MOI is not universally defined. Competing definitions vary from verbal ones to those based on concise statistical frameworks. Heuristic approaches to MOI are popular, although they do not mine the full potential of available data and are typically biased, potentially leading to misinferences. We introduce a formal statistical framework and suggest a concise definition of MOI and its distribution on the host-population level. We show how it relates to alternative definitions such as the number of distinct haplotypes within an infection or the maximum number of alleles detectable across a set of genetic markers. It is shown how alternatives can be derived from the general framework. Different statistical methods to estimate the distribution of MOI and pathogenic variants at the population level are discussed. The estimates can be used as plug-ins to reconstruct the most probable MOI of an infection and set of infecting haplotypes in individual infections. Furthermore, the relation between prevalence of pathogenic variants and their frequency (relative abundance) in the pathogen population in the context of MOI is clarified, with particular regard to seasonality in transmission intensities. The framework introduced here helps to guide the correct interpretation of results emerging from different definitions of MOI. Especially, it excels comparisons between studies based on different analytical methods.

European context of the diversity and phylogenetic position of SARS-CoV-2 sequences from Polish COVID-19 patients

To provide a comprehensive analysis of the SARS-CoV-2 sequence diversity in Poland in the European context. All publicly available (n = 115; GISAID database) whole-genome SARS-Cov-2 sequences from Polish samples, including those obtained during coronavirus testing performed in our COVID-19 Lab, were examined. Multiple sequence alignment of Polish isolates, phylogenetic analysis (ML tree), and multidimensional scaling (based on the pairwise DNA distances) were complemented by the comparison of the coronavirus clades frequency and diversity in the subset of over 5000 European GISAID sequences. Approximately seventy-seven percent of isolates in the European dataset carried frequent and ubiquitously found haplotypes; the remaining haplotype diversity was population-specific and resulted from population-specific mutations, homoplasies, and recombinations. Coronavirus strains circulating in Poland represented the variability found in other European countries. The prevalence of clades circulating in Poland was shifted in favor of GR, both in terms of the diversity (number of distinct haplotypes) and the frequency (number of isolates) of the clade. Polish-specific haplotypes were rare and could be explained by changes affecting common European strains. The analysis of the whole viral genomes allowed detection of several tight clusters of isolates, presumably reflecting local outbreaks. New mutations, homoplasies, and, to a smaller extent, recombinations increase SARS-CoV-2 haplotype diversity, but the majority of these variants do not increase in frequency and remains rare and population-specific. The spectrum of SARS-CoV-2 haplotypes in the Polish dataset reflects many independent transfers from a variety of sources, followed by many local outbreaks. The prevalence of the sequences belonging to the GR clade among Polish isolates is consistent with the European trend of the GR clade frequency increase.

Mathematical properties and bounds on haplotyping populations by pure parsimony

Although the haplotype data can be used to analyze the function of DNA, due to the significant efforts required in collecting the haplotype data, usually the genotype data is collected and then the population haplotype inference (PHI) problem is solved to infer haplotype data from genotype data for a population. This paper investigates the PHI problem based on the pure parsimony criterion (HIPP), which seeks the minimum number of distinct haplotypes to infer a given genotype data. We analyze the mathematical structure and properties for the HIPP problem, propose techniques to reduce the given genotype data into an equivalent one of much smaller size, and analyze the relations of genotype data using a compatible graph. Based on the mathematical properties in the compatible graph, we propose a maximal clique heuristic to obtain an upper bound, and a new polynomial-sized integer linear programming formulation to obtain a lower bound for the HIPP problem.

Genetic variation in the widespread lichenicolous fungus Marchandiomyces corallinus

The lichenicolous basidiomycete Marchandiomyces corallinus is widely distributed in North America and Europe, where it commonly is found on a variety of lichens. Theoretically either of these characteristics, a wide geographic range or generalized host ecology, could provide opportunities for genetic differentiation within this species. To determine how genetic variation is partitioned in M. corallinus, 12 fungal isolates were obtained from locations in North America and Europe; at two locations, in Washington County, Maine, and on the Isle of Mull in Scotland, fungi also were isolated from different lichen hosts. Vegetative mycelial compatibility tests were used to determine compatibility groupings from among the isolates; in addition, several PCR amplification products (RAPD, nuITS rDNA) were obtained for each isolate. A number of distinct compatibility groups were recognizable based on geography, not host ecology. In addition compatible isolates always were restricted to either North America or Europe. However RAPD markers indicated that compatible isolates are not always genetically identical. The presence of sequence heterozygosity at specific positions indicated that the isolates are heterokaryotic and a number of distinct haplotypes could be identified based on ITS variation at three separate locations. This type of genetic variation in these fungi suggests that sexual recombination is possible and that genetic differentiation has taken place recently as a result of geographic isolation, not host switching.

Genetic variation in the widespread lichenicolous fungus Marchandiomyces corallinus

The lichenicolous basidiomycete Marchandiomyces corallinus is widely distributed in North America and Europe, where it commonly is found on a variety of lichens. Theoretically either of these characteristics, a wide geographic range or generalized host ecology, could provide opportunities for genetic differentiation within this species. To determine how genetic variation is partitioned in M. corallinus, 12 fungal isolates were obtained from locations in North America and Europe; at two locations, in Washington County, Maine, and on the Isle of Mull in Scotland, fungi also were isolated from different lichen hosts. Vegetative mycelial compatibility tests were used to determine compatibility groupings from among the isolates; in addition, several PCR amplification products (RAPD, nuITS rDNA) were obtained for each isolate. A number of distinct compatibility groups were recognizable based on geography, not host ecology. In addition compatible isolates always were restricted to either North America or Europe. However RAPD markers indicated that compatible isolates are not always genetically identical. The presence of sequence heterozygosity at specific positions indicated that the isolates are heterokaryotic and a number of distinct haplotypes could be identified based on ITS variation at three separate locations. This type of genetic variation in these fungi suggests that sexual recombination is possible and that genetic differentiation has taken place recently as a result of geographic isolation, not host switching.

A Comparison of Estimators of the Population Recombination Rate

Three new estimators of the population recombination rate C = 4Nr are introduced. These estimators summarize the data using the number of distinct haplotypes and the estimated minimum number of recombination events, then calculate the value of C that maximizes the likelihood of obtaining the summarized data. They are compared with a number of previously proposed estimators of the recombination rate. One of the newly proposed estimators is generally better than the others for the parameter values considered here, while the three programs that calculate maximum-likelihood estimates give conflicting results.

Mitochondrial DNA variability in viviparous and ovoviviparous populations of the urodele Salamandra salamandra

AbstractMitochondrial DNA analysis of 13 populations of S. salamandra along a transect across the North of the Iberian Peninsula showed values of divergence between haplotypes ranging from d = 0.41% to 5.91%. Phenetic and cladistic analysis grouped the isofemale lineages into two main clusters with contrasting phylogeographic patterns. The first group encompasses populations located at each extreme of the Iberian Peninsula. Despite the large geographic distance separating these populations, they exhibit only a minor degree of divergence among haplotypes. In contrast, much higher diversification, in both number of distinct haplotypes, and overall genetic divergence, was observed in the second group of phylogenetically related populations. Surprisingly, this process of radiation and divergence in mtDNA haplotypes occurred in populations in close geographic proximity. All populations sampled in this group are located within a 300 km range, in the central part of our transect across the Northern edge of the Peninsula. Most populations in the central range of our transect exhibit viviparous reproduction — which is derived and highly unusual among urodeles. The genetic distances measured among Asturian (central portion of our transect), viviparous populations are higher than the distances measured between the two main taxonomic clusters. A viviparous population showing an unusual level of mtDNA heterogenetiy is reported and the potential implications of this focus of localized variability are discussed. The dynamics of isofemale lineages among the two reproductive modes was further explored in combination with the previous allozyme data. Several nuclear markers suggest that major mtDNA divergences could be explained by long‐term extrinsic barriers to gene flow. Isofemale lineages indicate a narrow secondary contact zone among populations with different reproductive patterns. The existence of viviparous and ovovivparous populations sharing a common haplotype suggests that reproductive transition in S. salamandra could have arisen in absence of genetic mtDNA differentiation. We finally outline a genetic model system where the acquisition of water independence from a primitively aquatic dependent amphibian life cycle can be analyzed from a microevolutionary perspective.

Variation in amylase haplotypes among congenic lines of the house mouse.

Pancreatic amylase in the mouse displays considerable quantitative genetic variation. Agar gel electrophoresis reveals that homozygous animals have either one form of the enzyme, type A, or two forms, type AB. Only few animals have been found that contradict this statement, namely among Mus musculus castaneous from Thailand, which has a single-banded B type. Double-banded homozygous specimens of various origins have different relative proportions of the two isoenzymes. By measuring the A:B ratios in such animals, a number of distinct haplotypes or amylase complexes, determining ratios ranging from 61% A:39%, B to 12% A:88% B, have been recognized. These complexes differ also with respect to the total amount of amylase produced. If the reference stock C3H/As is given the value 1, then other haplotypes have values ranging from 1.0 to 0.27. Nineteen amylase haplotypes have been established in congenic lines on a C3H/As background. Some of these lines contain at least four active pancreatic amylase structural genes and breeding experiments have demonstrated that the genetic elements regulating total amylase production and relative proportions of the isoenzymes are located within the amylase complex, cis-acting, and very closely linked to the structural genes.