The structure of genetic linkage data: from LIPED to 1M SNPs

There are three assumptions of independence or conditional independence that underlie linkage likelihood computations on sets of related individuals. The first is the independence of meioses, which gives rise to the conditional independence of haplotypes carried by offspring, given those of their parents. The second derives from the assumption of absence of genetic interference, which gives rise to the conditional independence of inheritance vectors, given the inheritance vector at an intermediate location. The third is the assumption of independence of allelic types, at the population level, both among haplotypes of unrelated individuals and also over the loci along a given haplotype. These three assumptions have been integral to likelihood computations since the first lod scores were computed, and remain key components in analysis of modern genetic data. In this paper we trace the role of these assumptions through the history of linkage likelihood computation, through to a new framework of genetic linkage analysis in the era of dense genomic marker data.     

Parent-offspring conflict over duration of parental care and its consequences in tawny owls Strix aluco

In species defending territories, fitness of newly independent juveniles could depend on phenotypic quality or early access to vacant resources as a result of rapid dispersal. In the first case, parent-offspring conflict will arise when parents cease feeding maturing offspring while these still demand provisioning. In the latter case, the young should decide when to stop begging to search for vacant territories. I radio-tracked 72 juvenile tawny owls from independence to sexual maturity to investigate whether parents or offspring decided the timing of the onset of independence and compare effects of age versus date of independence on survival and reproductive status. Juvenile owls stopped begging when 90–123 d old. This was synchronous within broods, independent of gender or age rank. Independence age of cross-fostered young varied across foster nests but was independent of hatching nest. After independence, young roosted in their parents' territory for 18 d on average before dispersal. This suggests that juvenile owls would rather extend dependency than disperse early. As predicted from this behaviour, age of independence had a positive influence on survival and reproductive status at maturity, whereas there were no effects of date of independence.     

A comparison of tests for independence in the FBI RFLP data bases

Several tests of independence of alletic frequencies within and between loci have been compared, and it has been found that Fisher's exact test is the best test to use. When this test is applied to RFLP databases established by the FBI, paying no attention to the single-band problem, there is generally evidence for independence at one locus but not at two loci. When the test is restricted to double-banded entries in the databases; there is overall evidence for independence.     

Effects of hypoxia and body size on the oxygen consumption of the bivalve Arctica islandica (L.)

The relationship between oxygen consumption and body weight has been examined in Arctica islandica (L.).Large Arctica exhibit a high degree of respiratory independence under hypoxic conditions; like other species studied, respiratory independence increases markedly with increasing body size. Respiratory independence can also be modified by temperature and physiological condition and it is concluded that the division of species per se into oxygen regulators and oxygen conformers is not merited. These terms describe only the extremes of what is a variable capacity to maintain respiratory independence during hypoxia.     

Physical properties of VNTR data, and their impact on a test of allelic independence.

In this article we describe the physical properties of VNTR data, as well as their effects on the two-dimensional distribution of fragment pairs. Tests of independence of alleles at a locus may confound those physical properties with allele independence. A recently proposed test by Geisser and Johnson is an example. We show that alleles can be strictly independent, yet the proposed test suggests large violations of allele independence because it is sensitive to well-known electrophoretic phenomena.     

Density‐dependent offspring interactions do not explain macroevolutionary scaling of adult size and offspring size

Most life forms exhibit a correlated evolution of adult size (AS) and size at independence (SI), giving rise to AS–SI scaling relationships. Theory suggests that scaling arises because relatively large adults have relatively high reproductive output, resulting in strong density‐dependent competition in early life, where large size at independence provides a competitive advantage to juveniles. The primary goal of our study is to test this density hypothesis, using large datasets that span the vertebrate tree of life (fishes, amphibians, reptiles, birds, and mammals). Our secondary goal is to motivate new hypotheses for AS–SI scaling by exploring how subtle variation in life‐histories among closely related species is associated with variation in scaling. Our phylogenetically informed comparisons do not support the density hypothesis. Instead, exploration of AS–SI scaling among life‐history variants suggests that steeper AS–SI scaling slopes are associated with evolutionary increases in size at independence. We suggest that a positive association between size at independence and juvenile growth rate may represent an important mechanism underlying AS–SI scaling, a mechanism that has been underappreciated by theorists. If faster juvenile growth is a consequence of evolutionary increases in size at independence, this may help offset the cost of delayed maturation, leading to steeper AS–SI scaling slopes.     

Independence Training from a Cross-Cultural Perspective

Studies relating age of independence training with achievement motivation and achievement have resulted in contradictory findings. The responses of fifty-two Chinese mothers in Hawaii to the independence training questionnaire were analyzed in conjunction with ethnographic data on child rearing practices. The lack of significant relationships between the index of independence training and measures of boys' achievement motivation and achievement behaviors was explained by the failure of the questionnaire to tap the mother's underlying motives for stating particular ages. The Chinese data revealed that cultural factors, such as values, strongly affect the mothers' responses.     

It can't happen here - can it?

If scientific advice is to have any value, it must come from sources that are not under any obligation to any organisation, public or private. Most principal scientific organisations in Western countries have similar ideas about the importance of independence but the independence of American science is being eroded.     

The adsorptive characteristics of proteins for polystyrene and their significance in solid-phase immunoassays

The adsorptive characteristics of polystyrene tubes for seven proteins of different molecular weight and ionic charge have been studied. The stability of these adsorbed proteins was monitored throughout the various steps of the amplified-enzyme-linked immunosorbent assay (a-ELISA). Using ¹²⁵I-labeled proteins, it was observed that each had a characteristic adsorptive behavior not explainable by simple charge differences. The proportion of protein bound to a 6.5-cm² tube surface was independent of the amount added up to an input of about 100 ng. Binding increased proportionately with temperature and incubation time. Beyond the range of concentrations where the proportion bound was independent of input, i.e., the region of independence, the kinetics of adsorption changed. The amount of protein adsorbed at the upper limit of the region of independence was inversely proportional to molecular weight for all except α-lactalbumin. Quantitative measurement of bound protein using the a-ELISA suggests that beyond the region of independence, protein-to-protein rather than protein-to-polystyrene adsorption occurred. This was suggested by computation using the Stokes radii of the proteins which implied that the amount of protein bound at the upper limit of the region of independence was a layer of protein one molecule thick. The upper limit of the region of independence determines, therefore, the maximun amount of functional antigen for such assays. Once adsorbed, proteins remained stably bound throughout the assay steps. The presence of competing proteins had no effect on the adsorptive characteristics of a given protein provided that the total protein concentration of the mixture was within the range of independence. The results indicate that the adsorptive characteristics of proteins for polystyrene tubes routinely used in solid-phase immunoassays should be taken into consideration when designing and interpreting data obtained with such assays.     

Dependent competing risks: a stochastic process model

Analyses of human mortality data classified according to cause of death frequently are based on competing risk theory. In particular, the times to death for different causes often are assumed to be independent. In this paper, a competing risk model with a weaker assumption of conditional independence of the times to death, given an assumed stochastic covariate process, is developed and applied to cause specific mortality data from the Framingham Heart Study. The results generated under this conditional independence model are compared with analogous results under the standard marginal independence model. Under the assumption that this conditional independence model is valid, the comparison suggests that the standard model overestimates by 4% the effect on life expectancy at age 30 due to the hypothetical elimination of cancer and by 7% the effect for cardiovascular/cerebrovascular disease. By age 80 the overestimates were 11% for cancer and 16% for heart disease. These results suggest the importance of avoiding the marginal independence assumption when appropriate data are available — especially when focusing on mortality at advanced ages.     

Thoughts on clonal integration: Facing the evolutionary context

Summary In this essay, I have pointed out that the appropriate evolutionary context for plant clonality dictates a focus on the impact of the derived trait of potential independence of subunits on the evolutionarily primitive trait of obligate interdependence of plant subunits, i.e. the advantages of independence. This fact prescribes a major shift in approach from previous lines of investigation which have assumed that clonal plants should fall apart and sought to determine the advantages of interdependence. The delineated reorientation calls for a significant change in the investigation of the ecology of clonality in higher plants, emphasizing factors that select for physical and physiological disintegration of the genet and de-emphasizing the need to derive ecological explanations for properties a plant will possess entirely by reason of its phylogenetic and developmental heritage. I suggest that (1) patterns of ramet independence may result from selective pressures on the cost of interconnections (2) programmed ramet independendence may be a response to the selective pressure of a high possibility of traumatic breakage and (3) programmed ramet independence may allow escape of the genet from mortality due to pathogen infestation.     

Nondetectability of restriction fragments and independence of DNA fragment sizes within and between loci in RFLP typing of DNA.

We provide experimental evidence showing that, during the restriction-enzyme digestion of DNA samples, some of the HaeIII-digested DNA fragments are small enough to prevent their reliable sizing on a Southern gel. As a result of such nondetectability of DNA fragments, individuals who show a single-band DNA profile at a VNTR locus may not necessarily be true homozygotes. In a population database, when the presence of such nondetectable alleles is ignored, we show that a pseudodependence of alleles within as well as across loci may occur. Using a known statistical method, under the hypothesis of independence of alleles within loci, we derive an efficient estimate of null allele frequency, which may be subsequently used for testing allelic independence within and across loci. The estimates of null allele frequencies, thus derived, are shown to agree with direct experimental data on the frequencies of HaeIII-null alleles. Incorporation of null alleles into the analysis of the forensic VNTR database suggests that the assumptions of allelic independence within and between loci are appropriate. In contrast, a failure to incorporate the occurrence of null alleles would provide a wrong inference regarding the independence of alleles within and between loci.     

Survival to independence in relation to pre‐fledging development and latitude in songbirds across the globe

Species differ strongly in their life histories, including the probability of survival. Annual adult survival was investigated extensively in the past, whereas juvenile survival, and especially survival to independence, received much less attention. Yet, they are critical for our understanding of population demography and life‐history evolution. We investigated post‐fledging survival to independence (i.e. survival upon leaving the nest until nutritional independence) in 74 species of passerine birds worldwide based on 100 population level estimates extracted from published literature. Our comparative analyses revealed that survival to independence increased with the length of nestling period and relative fledging mass (ratio of fledging mass to adult body mass). At the same time, species with higher nest predation rates had shorter nestling periods and lower relative fledging mass. Thus, we identify an important trade‐off in life history strategies: staying longer in the nest may improve post‐fledging survival due to enhanced flight ability and sensory functions, but at the cost of a longer exposure to nest predators and increased mortality due to nest predation. Additionally, post‐fledging survival to independence did not differ between species from the northern temperate zone vs species from the tropics and southern hemisphere. However, analyses of post‐fledging survival curves suggest that 1) daily survival rates are not constant and improve quickly upon leaving the nest, and 2) species in the tropics and southern hemisphere have higher daily post‐fledging survival rates than northern temperate species. Nevertheless, due to the accumulation of mortality risk during their much longer periods of post‐fledging care, overall survival until independence is comparable across latitudes. Obtaining high‐quality demographic data across latitudes to evaluate the generality of these findings and mechanisms underlying them should be a research priority.     

Visual contrast sensitivity in patients with impairment of functional independence after stroke

ABSTRACT: BACKGROUND: Stroke has been considered a serious public health problem in many countries, accounting for complex disorders involving perception, such as visual, cognitive and functional deficits. The impact of stroke on the visual perception of individuals with impairments in functional independence was investigated. METHODS: We measured changes in functional independence and visual function in 40 patients with stroke (M = 52.3, SD = 0.65) and 10 controls (M = 52.5, SD = 0.66). The patients were divided into four subgroups following the Barthel Index (Group A: 20--35, serious dependence; Group B: 40--55, moderate dependence; Group C: 60--95, mild dependence; and Group D: 100 points, independence). Visual function was evaluated using the Contrast Sensitivity Function (CSF). The contrast threshold was measured using a temporal, two-alternative, forced-choice psychophysical method. RESULTS: The results show significant differences in CSF between healthy volunteers and patients with stroke (F (1.56) = 151.2, p < 0.001) for all frequencies (F (2.56) = 125.96, p < 0.001). The results also show that patients with low functional independence had lower contrast sensitivity than those with greater functional independence (F (3.56) = 344.82, p < 0.001). CONCLUSIONS: An association exists between CSF and a worsening in the functional potential for performing daily living activities. Our results suggest that the CSF can be used as a diagnostic tool to analyze visual function associated with deficits in functional independence after stroke. These findings should be considered across the continuum of care for these patients.     

Testing the independent species' arrangement assertion made by theories of stochastic geometry of biodiversity

The assertion that the spatial location of different species is independent of each other is fundamental in major ecological theories such as neutral theory that describes a stochastic geometry of biodiversity. However, this assertion has rarely been tested. Here we use techniques of spatial point pattern analysis to conduct a comprehensive test of the independence assertion by analysing data from three large forest plots with different species richness: a species-rich tropical forest at Barro Colorado Island (Panama), a tropical forest in Sinharaja (Sri Lanka), and a temperate forest in Changbaishan (China). We hypothesize that stochastic dilution effects owing to increasing species richness overpower signals of species associations, thereby yielding approximate species independence. Indeed, the proportion of species pairs showing: (i) no significant interspecific association increased with species richness, (ii) segregation decreased with species richness, and (iii) small-scale interspecific interaction decreased with species richness. This suggests that independence may indeed be a good approximation in the limit of very species-rich communities. Our findings are a step towards a better understanding of factors governing species-rich communities and we propose a hypothesis to explain why species placement in species-rich communities approximates independence.     

Enrichment analysis in high-throughput genomics - accounting for dependency in the NULL

Translating the overwhelming amount of data generated in high-throughput genomics experiments into biologically meaningful evidence, which may for example point to a series of biomarkers or hint at a relevant pathway, is a matter of great interest in bioinformatics these days. Genes showing similar experimental profiles, it is hypothesized, share biological mechanisms that if understood could provide clues to the molecular processes leading to pathological events. It is the topic of further study to learn if or how a priori information about the known genes may serve to explain coexpression. One popular method of knowledge discovery in high-throughput genomics experiments, enrichment analysis (EA), seeks to infer if an interesting collection of genes is 'enriched' for a Consortium particular set of a priori Gene Ontology Consortium (GO) classes. For the purposes of statistical testing, the conventional methods offered in EA software implicitly assume independence between the GO classes. Genes may be annotated for more than one biological classification, and therefore the resulting test statistics of enrichment between GO classes can be highly dependent if the overlapping gene sets are relatively large. There is a need to formally determine if conventional EA results are robust to the independence assumption. We derive the exact null distribution for testing enrichment of GO classes by relaxing the independence assumption using well-known statistical theory. In applications with publicly available data sets, our test results are similar to the conventional approach which assumes independence. We argue that the independence assumption is not detrimental.     

Circularity and Independence in Phylogenetic Tests of Ecological Hypotheses

It has been asserted that in order to avoid circularity in phylogenetic tests of ecological hypotheses, one must exclude from the cladistic analysis any characters that might be correlated with that hypothesis. The argument assumes that selective correlation leads to lack of independence among characters and may thus bias the analysis. This argument conflates the idea of independence between the ecological hypothesis and the phylogeny with independence among characters used to construct the tree. We argue that adaptation or selection does not necessarily result in the non-independence of characters, and that characters for a cladistic analysis should be evaluated as homology statements rather than functional ones. As with any partitioning of data, character exclusion may lead to weaker phylogenetic hypotheses, and the practice of mapping characters onto a tree, rather than including them in the analysis, should be avoided. Examples from pollination biology are used to illustrate some of the theoretical and practical problems inherent in character exclusion.     

Metabolomic changes in cats with renal disease and calcium oxalate uroliths

Metabolomics - The global population is aging. Preserving function and independence of our aging population is paramount. A key component to maintaining independence is the preservation of...     

Evidence for direct involvement of the capsid protein in HIV infection of nondividing cells

HIV and other lentiviruses can productively infect nondividing cells, whereas most other retroviruses, such as murine leukemia virus, require cell division for efficient infection. However, the determinants for this phenotype have been controversial. Here, we show that HIV-1 capsid (CA) is involved in facilitating HIV infection of nondividing cells because amino acid changes on CA severely disrupt the cell-cycle independence of HIV. One mutant in the N-terminal domain of CA in particular has lost the cell-cycle independence in all cells tested, including primary macrophages. The defect in this mutant appears to be at a stage past nuclear entry. We also find that the loss of cell-cycle independence can be cell-type specific, which suggests that a cellular factor affects the ability of HIV to infect nondividing cells. Our data suggest that CA is directly involved at some step in the viral life cycle that is important for infection of nondividing cells.