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RESEARCH ARTICLE Open Access
"... Entropy-based selection for maternal-fetal genotype incompatibility with application to preterm prelabor rupture of membranes Shaoyu Li1*, Yuehua Cui2,3 * and Roberto Romero4,5,6 Background: Maternal-fetal genotype incompatibility (MFGI) is increasingly reported to influence human diseases, especial ..."
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Entropy-based selection for maternal-fetal genotype incompatibility with application to preterm prelabor rupture of membranes Shaoyu Li1*, Yuehua Cui2,3 * and Roberto Romero4,5,6 Background: Maternal-fetal genotype incompatibility (MFGI) is increasingly reported to influence human diseases, especially pregnancy-related complications. In practice, it is challenging to identify the ideal incompatibility model for analysis, since the true MFGI mechanism is generally unknown. The underlying MFGI mechanism for different genetic variants can vary, and to use a single incompatibility model for all circumstances would cause power loss in testing MFGI. Results: In this article, we propose a practical 2-step procedure that incorporates a model selection strategy based on an entropy measurement to select the most appropriate MFGI model represented by data and test the significance of the MFGI effect using the chosen model within the generalized linear regression framework. Conclusions: Our simulation studies show that the proposed two-step procedure controls the type I error rate and increase the testing power under various scenarios. In a real data application, our analysis reveals genes having an MFGI effect, which may not be detected with a non-model selection counterpart.
iPLACENTAL MORPHOLOGY AND THE CELLULAR BRAIN IN MAMMALIAN EVOLUTION
"... ii I, Eric Lewitus confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. iii – Harpo iv A major focus of evolutionary neurobiology has been on whether different regions of the eutherian b ..."
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ii I, Eric Lewitus confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. iii – Harpo iv A major focus of evolutionary neurobiology has been on whether different regions of the eutherian brain evolve in concert, and how free the brain is to evolve independently of body plans. Since the eutherian brain is loosely modularized, such that one region is rarely isolated for specialization at the expense of others, but the design of modularization itself can be adapted by tweaking developmental programs, the degree to which brain regions must evolve in concert and can evolve independently may carry a deep phylogenetic signal. Using data collected from preserved brain tissue of 37 primate, 21 carnivore, and 15 other eutherian species (spanning 11 orders), I examined the phylogenetic level at which the proliferation of neurons and glia in the primary visual cortex and hippocampus proper, as well as granular layer volumes of the dentate gyrus and cerebellum, may be constrained by conserved
Correspondence
, 2011
"... mating systems; natural selection; sexual selection; parthenogenesis; asexuality; dual sexuality; parental investment; brooding. ..."
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mating systems; natural selection; sexual selection; parthenogenesis; asexuality; dual sexuality; parental investment; brooding.
Correspondence
, 2010
"... doi:10.1111/j.1752-4571.2010.00156.x In this review, I describe how evolutionary genomics is uniquely suited to spearhead advances in understanding human disease risk, owing to the privileged position of genes as fundamental causes of phenotypic variation, and the ability of population genetic and p ..."
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doi:10.1111/j.1752-4571.2010.00156.x In this review, I describe how evolutionary genomics is uniquely suited to spearhead advances in understanding human disease risk, owing to the privileged position of genes as fundamental causes of phenotypic variation, and the ability of population genetic and phylogenetic methods to robustly infer processes of natural selection, drift, and mutation from genetic variation at the levels of family, population, species, and clade. I first provide an overview of models for the origins and maintenance of genetically based disease risk in humans. I then discuss how analyses of genetic disease risk can be dovetailed with studies of positive and balancing selection, to evaluate the degree to which the ‘genes that make us human ’ also represent the genes that mediate risk of polygenic disease. Finally, I present four basic principles for the nascent field of human evolutionary medical genomics, each of which represents a process that is nonintuitive from a proximate perspective. Joint consideration of these principles compels novel forms of interdisciplinary analyses, most notably studies that (i) analyze tradeoffs at the level of molecular genetics, and (ii) identify genetic variants that are derived in the human lineage or in specific populations, and then compare individuals with derived versus ancestral alleles.
Genes, Brain and Behavior (2011) doi: 10.1111/j.1601-183X.2011.00710.x Review Comparative immunogenetics of autism and schizophrenia
, 2011
"... Autism and schizophrenia are highly heritable neurodevelopmental disorders, each mediated by a diverse suite of genetic and environmental risk factors. Comorbidity and familial aggregation of such neurodevelopmental disorders with other disease-related conditions can provide important insights into ..."
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Autism and schizophrenia are highly heritable neurodevelopmental disorders, each mediated by a diverse suite of genetic and environmental risk factors. Comorbidity and familial aggregation of such neurodevelopmental disorders with other disease-related conditions can provide important insights into their etiology. Epidemiological studies have documented reduced rates of rheumatoid arthritis, a systemic autoimmune condition, in schizophrenia, and recent work has shown increased rates of rheumatoid arthritis in first-degree relatives of autistic individuals, especially mothers. Advances in understanding the genetic basis of rheumatoid arthritis have shown that much of the genetic liability to this condition is due to risk and protective alleles at the HLA DRB1 locus. These data allow robust testing of the hypotheses that allelic variation at DRB1 pleiotropically modulates risk of rheumatoid arthritis, autism and schizophrenia. Systematic review of the literature indicates that reported associations of DRB1 variants with these three conditions are congruent with a pleiotropic model: DRB1*04 alleles have been associated with increased risk of rheumatoid arthritis and autism but decreased risk of schizophrenia, and DRB1*13 alleles have been associated with protection from rheumatoid arthritis and autism but higher risk of schizophrenia. These convergent findings from genetics and epidemiology imply that a subset of autism and schizophrenia cases may be underlain by genetically based neuroimmune alterations, and that analyses of the causes of risk and protective effects from DRB1 variants may provide new approaches to therapy.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Issue: The Year in Evolutionary Biology
"... The origins and evolution of genetic disease risk in modern humans ..."
modern
"... Year in Evolutionary Biology, in review, 2010, please do not circulate or cite 1 ..."
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Year in Evolutionary Biology, in review, 2010, please do not circulate or cite 1
