Biology subjects

Goldberg, A.

Publications and source records attributed to Goldberg, A..

23 records · Page 2Linked to original sources

bioRxiv2020

Distinct Hierarchical Alterations of Intrinsic Neural Timescales Account for Different Manifestations of Psychosis

Hierarchical perceptual-inference models of psychosis may provide a holistic framework for understanding psychosis in schizophrenia including heterogeneity in clinical presentations. Particularly, hypothesized alterations at distinct levels of the perceptual-inference hierarchy may explain why hallucinations and delusions tend to cluster together yet sometimes manifest in isolation. To test this, we used a recently developed resting-state fMRI measure of intrinsic neural timescale (INT), which reflects the time window of neural integration and captures hierarchical brain gradients. In analyses examining extended sensory hierarchies that we first validated, we found distinct hierarchical INT alterations for hallucinations versus delusions in the auditory and somatosensory systems, thus providing support for hierarchical perceptual-inference models of psychosis. Simulations using a large-scale biophysical model suggested local elevations of excitation-inhibition ratio at different hierarchical levels as a potential mechanism. More generally, our work highlights the robustness and utility of INT for studying hierarchical processes relevant to basic and clinical neuroscience.

neuroscience↗

bioRxiv2019

Assortative mating and the dynamical decoupling of genetic admixture levels from phenotypes that differ between source populations

Source populations for an admixed population can possess distinct patterns of genotype and pheno-type at the beginning of the admixture process. Such differences are sometimes taken to serve as markers of ancestry--that is, phenotypes that are initially associated with the ancestral background in one source population are taken to reflect ancestry in that population. Examples exist, however, in which genotypes or phenotypes initially associated with ancestry in one source population have decoupled from overall admixture levels, so that they no longer serve as proxies for genetic ancestry. We develop a mechanistic model for describing the joint dynamics of admixture levels and phenotype distributions in an admixed population. The approach includes a quantitative-genetic model that relates a phenotype to underlying loci that affect its trait value. We consider three forms of mating. First, individuals might assort in a manner that is independent of the overall genetic admixture level. Second, individuals might assort by a quantitative phenotype that is initially correlated with the genetic admixture level. Third, individuals might assort by the genetic admixture level itself. Under the model, we explore the relationship between genetic admixture level and phenotype over time, studying the effect on this relationship of the genetic architecture of the phenotype. We find that the decoupling of genetic ancestry and phenotype can occur surprisingly quickly, especially if the phenotype is driven by a small number of loci. We also find that positive assortative mating attenuates the process of dissociation in relation to a scenario in which mating is random with respect to genetic admixture and with respect to phenotype. The mechanistic framework suggests that in an admixed population, a trait that initially differed between source populations might be a reliable proxy for ancestry for only a short time, especially if the trait is determined by relatively few loci. The results are potentially relevant in admixed human populations, in which phenotypes that have a perceived correlation with ancestry might have social significance as ancestry markers, despite declining correlations with ancestry over time.\n\nAuthor SummaryAdmixed populations are populations that descend from two or more populations that had been separated for a long time at the beginning of the admixture process. The source populations typically possess distinct patterns of genotype and phenotype. Hence, early in the admixture process, phenotypes of admixed individuals can provide information about the extent to which these individuals possess ancestry in a specific source population. To study correlations between admixture levels and phenotypes that differ between source populations, we construct a genetic and phenotypic model of the dynamical process of admixture. Under the model, we show that correlations between admixture levels and these phenotypes dissipate over time--especially if the genetic architecture of the phenotypes involves only a small number of loci, or if mating in the admixed population is random with respect to both the admixture levels and the phenotypes. The result has the implication that a trait that once reflected ancestry in a specific source population might lose this ancestry correlation. As a consequence, in human populations, after a sufficient length of time, salient phenotypes that can have social meaning as ancestry markers might no longer bear any relationship to genome-wide genetic ancestry.

evolutionary biology↗

bioRxiv2019

Assortative mating by population of origin in a mechanistic model of admixture

Populations whose mating pairs have levels of similarity in phenotypes or genotypes that differ systematically from the level expected under random mating are described as experiencing assortative mating. Excess similarity in mating pairs is termed positive assortative mating, and excess dissimilarity is negative assortative mating. In humans, empirical studies suggest that mating pairs from various admixed populations--whose ancestry derives from two or more source populations--possess correlated ancestry components that indicate the occurrence of positive assortative mating on the basis of ancestry. Generalizing a two-sex mechanistic admixture model, we devise a model of one form of ancestry-assortative mating that occurs through preferential mating based on source population. Under the model, we study the moments of the admixture fraction distribution for different assumptions about mating preferences, including both positive and negative assortative mating by population. We consider the special cases of assortative mating by population that involve a single admixture event and that consider a model of constant contributions to the admixed population over time. We demonstrate that whereas the mean admixture under assortative mating is equivalent to that of a corresponding randomly mating population, the variance of admixture depends on the level and direction of assortative mating. In contrast to standard settings in which positive assortment increases variation within a population, certain assortative mating scenarios allow the variance of admixture to decrease relative to a corresponding randomly mating population: with the three populations we consider, the variance-increasing effect of positive assortative mating within a population might be overwhelmed by a variance-decreasing effect emerging from mating preferences involving other pairs of populations. The effect of assortative mating is smaller on the X chromosome than the autosomes because inheritance of the X in males depends only on the mothers ancestry, not on the mating pair. Because the variance of admixture is informative about the timing of admixture and possibly about sex-biased admixture contributions, the effects of assortative mating are important to consider in inferring features of population history from distributions of admixture values. Our model provides a framework to quantitatively study assortative mating under flexible scenarios of admixture over time.

evolutionary biology↗

bioRxiv2017

Coalescent theory of migration network motifs

Natural populations display a variety of spatial arrangements, each potentially with a distinctive impact on genetic diversity and genetic differentiation among subpopulations. Although the spatial arrangement of populations can lead to intricate migration networks, theoretical developments have focused mainly on a small subset of such networks, emphasizing the island-migration and stepping-stone models. In this study, we investigate all small network motifs: the set of all possible migration networks among populations subdivided into at most four subpopulations. For each motif, we use coalescent theory to derive expectations for three quantities that describe genetic variation: nucleotide diversity, FST, and half-time to equilibrium diversity. We describe the impact of network properties on these quantities, finding that motifs with a large mean node degree have the largest nucleotide diversity and the longest time to equilibrium, whereas motifs with small density have the largest FST. In addition, we show that the motifs whose pattern of variation is most strongly influenced by loss of a connection or a subpopulation are those that can be split easily into several disconnected components. We illustrate our results using two example datasets--sky island birds of genus Brachypteryx and Indian tigers--identifying disturbance scenarios that produce the greatest reduction in genetic diversity; for tigers, we also compare the benefits of two assisted gene flow scenarios. Our results have consequences for understanding the effect of geography on genetic diversity and for designing strategies to alter population migration networks to maximize genetic variation in the context of conservation of endangered species.

genetics↗

bioRxiv2017

Reply To Lazaridis And Reich: Robust Model-Based Inference Of Male-Biased Admixture During Bronze Age Migration From The Pontic-Caspian Steppe

Comparing the sex-specifically inherited X chromosome to the autosomes in ancient genetic samples, we (1) studied sex-specific admixture for two prehistoric migrations. For each migration, we used several admixture estimation procedures--including ADMIXTURE model-based clustering (2)--comparing X-chromosomal and autosomal ancestry in contemporaneous Central Europeans, and interpreting greater admixture from the migrating population on the autosomes as male-biased migration. For migration into late Neolithic/Bronze Age Central Europeans (\"BA\") from the Pontic-Caspian steppe (\"SP\"), we inferred male-biased admixture at 5-14 males per migrating female.\n\nLazaridis & Reich (3) contest this male-biased migration claim. For simulated individuals, they claim that ADMIXTURE provides biased X-chromosomal ancestry estimates. They argue that if the bias is taken into account, the ...

genetics↗