Genetics and Genomics Commons^™

Genome-Wide Association Study Of More Than 40,000 Bipolar Disorder Cases Provides New Insights Into The Underlying Biology, Niamh Mullins, Andreas J. Forstner, Kevin S. O’Connell, Brandon Coombes, Ney Alliey Rodriguez

School of Medicine Publications

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets …

Bipolar Multiplex Families Have An Increased Burden Of Common Risk Variants For Psychiatric Disorders, Till F.M. Andlauer, Jose Guzman-Parra, Fabian Streit, Jana Strohmaier, Ney Alliey Rodriguez

School of Medicine Publications

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort …

Polygenic Risk For Anxiety Influences Anxiety Comorbidity And Suicidal Behavior In Bipolar Disorder, Fabiana L. Lopes, Kevin Zhu, Kirstin L. Purves, Christopher Song, Ney Alliey Rodriguez

School of Medicine Publications

Bipolar disorder is often comorbid with anxiety, which is itself associated with poorer clinical outcomes, including suicide. A better etiologic understanding of this comorbidity could inform diagnosis and treatment. The present study aims to test whether comorbid anxiety in bipolar disorder reflects shared genetic risk factors. We also sought to assess the contribution of genetic risk for anxiety to suicide attempts in bipolar disorder. Polygenic risk scores (PRS) were calculated from published genome-wide association studies of samples of controls and cases with anxiety (n = 83,566) or bipolar disorder (n = 51,710), then scored in independent target samples (total n …

Identifying Positive Selection In Multiple Subspecies Of Xylella Fastidiosa, Daniel Doroteo Flores

Theses and Dissertations

For this study, we will be looking to identify positive selection in eight genomes of the bacterial plant pathogen Xylella fastidiosa. A previous study used a branching method that identified 2 genes with positive selection along with a site-specific method identifying 34 genes showing positive selection. This current study focused specifically on the site-specific method, resulting in 28 genes (of 1,039 tested) showing positive selection. Of the 28 genes showing positive selection, 12 of them come from the pathogenicity, virulence and cellular structural categories. The remaining genes are found in the biosynthesis, metabolism, macro metabolism, and cellular process categories. …

The Genetics Of The Mood Disorder Spectrum: Genome-Wide Association Analyses Of More Than 185,000 Cases And 439,000 Controls, Jonathan R. I. Coleman, Héléna A. Gaspar, Julien Bryois, Enda M. Byrne, Ney Alliey Rodriguez

School of Medicine Publications

Background: Mood disorders (including major depressive disorder and bipolar disorder) affect 10% to 20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Multiple approaches have shown considerable sharing of risk factors across mood disorders despite their diagnostic distinction.

Methods: To clarify the shared molecular genetic basis of major depressive disorder and bipolar disorder and to highlight disorder-specific associations, we meta-analyzed data from the latest Psychiatric Genomics Consortium genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: …

Imaging Local Genetic Influences On Cortical Folding, Aaron F. Alexander-Bloch, Armin Raznahan, Simon N. Vandeker, Jakob Seidlitz, Zhixin Lu, Samuel R. Matthias, Emma Knowles, Josephine Mollon, Amanda Rodrigue, Joanne E. Curran, Harald H. H. Goring, Peter T. Fox, John Blangero

School of Medicine Publications

Recent progress in deciphering mechanisms of human brain cortical folding leave unexplained whether spatially patterned genetic influences contribute to this folding. High-resolution in vivo brain MRI can be used to estimate genetic correlations (covariability due to shared genetic factors) in interregional cortical thickness, and biomechanical studies predict an influence of cortical thickness on folding patterns. However, progress has been hampered because shared genetic influences related to folding patterns likely operate at a scale that is much more local (cm) than that addressed in prior imaging studies. Here, we develop methodological approaches to examine local genetic influences on cortical thickness and …

Highly Efficient Induced Pluripotent Stem Cell Reprogramming Of Cryopreserved Lymphoblastoid Cell Lines, Satish Kumar, Joanne E. Curran, Erika C. Espinoza, David C. Glahn, John Blangero

School of Medicine Publications

Tissue culture based in-vitro experimental modeling of human inherited disorders provides insight into the cellular and molecular mechanisms involved and the underlying genetic component influencing the disease phenotype. The breakthrough development of induced pluripotent stem cell (iPSC) technology represents a quantum leap in experimental modeling of human diseases, providing investigators with a self-renewing and thus unlimited source of pluripotent cells for targeted differentiation into functionally relevant disease specific tissue/cell types. The existing rich bio-resource of Epstein-Barr virus (EBV) immortalized lymphoblastoid cell line (LCL) repositories generated from a wide array of patients in genetic and epidemiological studies worldwide, many of them …

Use Of >100,000 Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium Whole Genome Sequences Improves Imputation Quality And Detection Of Rare Variant Associations In Admixed African And Hispanic/Latino Populations, Madeline H. Kowalski, Huijun Qian, Ziyi Hou, Jonathan D. Rosen, Amanda L. Tapia, Yue Shan, Deepti Jain, Maria Argos, John Blangero, Juan M. Peralta

School of Medicine Publications

Most genome-wide association and fine-mapping studies to date have been conducted in individuals of European descent, and genetic studies of populations of Hispanic/Latino and African ancestry are limited. In addition, these populations have more complex linkage disequilibrium structure. In order to better define the genetic architecture of these understudied populations, we leveraged >100,000 phased sequences available from deep-coverage whole genome sequencing through the multi-ethnic NHLBI Trans-Omics for Precision Medicine (TOPMed) program to impute genotypes into admixed African and Hispanic/Latino samples with genome-wide genotyping array data. We demonstrated that using TOPMed sequencing data as the imputation reference panel improves genotype imputation …

Nrxn1 Is Associated With Enlargement Of The Temporal Horns Of The Lateral Ventricles In Psychosis, Ney Alliey-Rodriguez, Tamar A. Grey, Rebecca Shafee, Huma Asif, Ney Alliey Rodriguez

School of Medicine Publications

Schizophrenia, Schizoaffective, and Bipolar disorders share behavioral and phenomenological traits, intermediate phenotypes, and some associated genetic loci with pleiotropic effects. Volumetric abnormalities in brain structures are among the intermediate phenotypes consistently reported associated with these disorders. In order to examine the genetic underpinnings of these structural brain modifications, we performed genome-wide association analyses (GWAS) on 60 quantitative structural brain MRI phenotypes in a sample of 777 subjects (483 cases and 294 controls pooled together). Genotyping was performed with the Illumina PsychChip microarray, followed by imputation to the 1000 genomes multiethnic reference panel. Enlargement of the Temporal Horns of Lateral Ventricles …

Crossover Interference And Sex-Specific Genetic Maps Shape Identical By Descent Sharing In Close Relatives, Madison Caballero, Daniel N. Seidman, Ying Qiao, Jens Sannerud, Thomas D. Dyer, Donna M. Lehman, Joanne E. Curran, Ravindranath Duggirala, John Blangero, Shai Carmi, Amy L. Williams

School of Medicine Publications

Simulations of close relatives and identical by descent (IBD) segments are common in genetic studies, yet most past efforts have utilized sex averaged genetic maps and ignored crossover interference, thus omitting features known to affect the breakpoints of IBD segments. We developed Ped-sim, a method for simulating relatives that can utilize either sex-specific or sex averaged genetic maps and also either a model of crossover interference or the traditional Poisson model for inter-crossover distances. To characterize the impact of previously ignored mechanisms, we simulated data for all four combinations of these factors. We found that modeling crossover interference decreases the …

Rare Degs1 Variant Significantly Alters De Novo Ceramide Synthesis Pathway, Nicholas B. Blackburn, Juan M. Peralta, Satish Kumar, Ana C. Leandro, Marcio Almeida, Michael C. Mahaney, Thomas D. Dyer, Laura Almasy, John L. Vandeberg, Sarah Williams-Blangero, Ravindranath Duggirala, John Blangero, Joanne E. Curran

School of Medicine Publications

The de novo ceramide synthesis pathway is essential to human biology and health but genetic influences remain unexplored. The core function of this pathway is the generation of biologically active ceramide from its precursor, dihydroceramide. Dihydroceramides have diverse, often protective, biological roles; conversely, increased ceramide levels are biomarkers of complex disease. To explore the genetics of the ceramide synthesis pathway, we searched for deleterious nonsynonymous variants in the genomes of 1,020 Mexican Americans from extended pedigrees. We identified a Hispanic ancestry−specific rare functional variant, L175Q, in DEGS1, a key enzyme in the pathway that converts dihydroceramide to ceramide. This amino …

Unimóvil: A Mobile Health Clinic Providing Primary Care To The Colonias Of The Rio Grande Valley, South Texas, Eron G. Manuosv, Vincent P. Diego, Jacob Smith, Jesus R. Garza Ii, John Lowdermilk, John Blangero, Sarah Williams-Blangero, Francisco Fernandez

School of Medicine Publications

Background: We describe a mobile unit (UniMóvil) designed to improve poor healthcare access delivery to residents in two South Texas underserved Colonias. The interprofessional team measured seven clinical outcomes [obesity, diabetes, hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C) levels, and depression], and using the Duke Health Profile, assessed the health-related quality of life (HrQoL).

Methods: The investigators used previously reported disease prevalence, an implementation model, and community needs-assessments to design an outreach healthcare delivery model. A retrospective review of the cohort provides data used to determine potential predictors of clinical variables, 11 domains of HrQOL, and inter/intra Colonia …

Family-Based Analyses Reveal Novel Genetic Overlap Between Cytokine Interleukin-8 And Risk For Suicide Attempt, Emma M. Knowles, Joanne E. Curran, Harald Hh Goring, Samuel R. Mathias, Josephine Mollon, Amanda L. Rodrigue, Rene L. Olvera, Ana C. Leandro, Ravi Duggirala, Laura Almasy, John Blangero, David C. Glahn

School of Medicine Publications

Background: Suicide is major public health concern. It is imperative to find robust biomarkers so that at-risk individuals can be identified in a timely and reliable manner. Previous work suggests mechanistic links between increased cytokines and risk for suicide, but questions remain regarding the etiology of this association, as well as the roles of sex and BMI.

Methods: Analyses were conducted using a randomly-ascertained extended-pedigree sample of 1882 Mexican-American individuals (60% female, mean age = 42.04, range = 18-97). Genetic correlations were calculated using a variance components approach between the cytokines TNF-α, IL-6 and IL-8, and Lifetime Suicide Attempt and …

Efficient Region-Based Test Strategy Uncovers Genetic Risk Factors For Functional Outcome In Bipolar Disorder, Monika Budde, Stefanie Friedrichs, Ney Alliey-Rodriguez, Seth Ament, Judith A. Badner

School of Medicine Publications

Genome-wide association studies of case-control status have advanced the understanding of the genetic basis of psychiatric disorders. Further progress may be gained by increasing sample size but also by new analysis strategies that advance the exploitation of existing data, especially for clinically important quantitative phenotypes. The functionally-informed efficient region-based test strategy (FIERS) introduced herein uses prior knowledge on biological function and dependence of genotypes within a powerful statistical framework with improved sensitivity and specificity for detecting consistent genetic effects across studies. As proof of concept, FIERS was used for the first genome-wide single nucleotide polymorphism (SNP)-based investigation on bipolar disorder …

Polygenic Risk For Schizophrenia And Measured Domains Of Cognition In Individuals With Psychosis And Controls, Rebecca Shafee, Pranav Nanda, Jaya L. Padmanabhan, Neeraj Tandon, Ney Alliey Rodriguez

School of Medicine Publications

Psychotic disorders including schizophrenia are commonly accompanied by cognitive deficits. Recent studies have reported negative genetic correlations between schizophrenia and indicators of cognitive ability such as general intelligence and processing speed. Here we compare the effect of polygenetic risk for schizophrenia (PRSSCZ) on measures that differ in their relationships with psychosis onset: a measure of current cognitive abilities (the Brief Assessment of Cognition in Schizophrenia, BACS) that is greatly reduced in psychotic disorder patients, a measure of premorbid intelligence that is minimally affected by psychosis onset (the Wide-Range Achievement Test, WRAT); and educational attainment (EY), which covaries with both BACS …

Improving Genetic Prediction By Leveraging Genetic Correlations Among Human Diseases And Traits, Robert M. Maier, Zhihong Zhu, Sang Hong Lee, Maciej Trzaskowski, Ney Alliey Rodriguez

School of Medicine Publications

Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases …

Detecting Significant Genotype–Phenotype Association Rules In Bipolar Disorder: Market Research Meets Complex Genetics, René Breuer, Manuel Mattheisen, Josef Frank, Bertram Krumm, Ney Alliey Rodriguez

School of Medicine Publications

Background: Disentangling the etiology of common, complex diseases is a major challenge in genetic research. For bipolar disorder (BD), several genome-wide association studies (GWAS) have been performed. Similar to other complex disorders, major breakthroughs in explaining the high heritability of BD through GWAS have remained elusive. To overcome this dilemma, genetic research into BD, has embraced a variety of strategies such as the formation of large consortia to increase sample size and sequencing approaches. Here we advocate a complementary approach making use of already existing GWAS data: a novel data mining procedure to identify yet undetected genotype–phenotype relationships. We adapted …

Epidermal-Specific Deletion Of Tc-Ptp Promotes Uvb-Induced Epidermal Cell Survival Through The Regulation Of Flk-1/Jnk Signaling, Minwoo Baek, Mihwa Kim, Jae Sung Lim, Liza D. Morales, Joselin Hernandez, Srinivas Mummidi, Sarah Williams-Blangero, Ik-Soon Jang, Andrew Tsin, Dae Joon Kim

School of Medicine Publications

UVB exposure can contribute to the development of skin cancer by modulating protein tyrosine kinase (PTK) signaling. It has been suggested that UVB radiation increases the ligand-dependent activation of PTKs and induces PTP inactivation. Our recent studies have shown that T-cell protein tyrosine phosphatase (TC-PTP) attenuates skin carcinogenesis induced by chemical regimens, which indicates its critical role in the prevention of skin cancer. In the current work, we report that TC-PTP increases keratinocyte susceptibility to UVB-induced apoptosis via the downregulation of Flk-1/JNK signaling. We showed that loss of TC-PTP led to resistance to UVB-induced apoptosis in vivo epidermis. We established …

Genomic Dissection Of Bipolar Disorder And Schizophrenia, Including 28 Subphenotypes, Douglas M. Ruderfer, Stephan Ripke, Andrew Mcquillin, James Boocock, Ney Alliey Rodriguez

School of Medicine Publications

Schizophrenia and bipolar disorder are two distinct diagnoses that share symptomology. Understanding the genetic factors contributing to the shared and disorder-specific symptoms will be crucial for improving diagnosis and treatment. In genetic data consisting of 53,555 cases (20,129 bipolar disorder [BD], 33,426 schizophrenia [SCZ]) and 54,065 controls, we identified 114 genome-wide significant loci implicating synaptic and neuronal pathways shared between disorders. Comparing SCZ to BD (23,585 SCZ, 15,270 BD) identified four genomic regions including one with disorder-independent causal variants and potassium ion response genes as contributing to differences in biology between the disorders. Polygenic risk score (PRS) analyses identified several …

Genetic Analysis Of Deep Phenotyping Projects In Common Disorders, Elliot S. Gershon, Godfrey Pearlson, Matcheri S. Keshavan, Carol Tamminga, Ney Alliey Rodriguez

School of Medicine Publications

Several studies of complex psychotic disorders with large numbers of neurobiological phenotypes are currently under way, in living patients and controls, and on assemblies of brain specimens. Genetic analyses of such data typically present challenges, because of the choice of underlying hypotheses on genetic architecture of the studied disorders and phenotypes, large numbers of phenotypes, the appropriate multiple testing corrections, limited numbers of subjects, imputations required on missing phenotypes and genotypes, and the cross-disciplinary nature of the phenotype measures. Advances in genotype and phenotype imputation, and in genome-wide association (GWAS) methods, are useful in dealing with these challenges. As compared …

Toxoplasma Modulates Signature Pathways Of Human Epilepsy, Neurodegeneration & Cancer, Huân M. Ngô, Ying Zhou, Hernan Lorenzi, Kai Wang, Ney Alliey Rodriguez

School of Medicine Publications

One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii. Approximately fifteen million of these have congenital toxoplasmosis. Although neurobehavioral disease is associated with seropositivity, causality is unproven. To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain: We identified susceptibility genes for congenital toxoplasmosis in our cohort of infected humans and found these genes are expressed in human brain. Transcriptomic and quantitative proteomic analyses of infected human, primary, neuronal stem and monocytic cells revealed effects on neurodevelopment and plasticity in neural, immune, and endocrine networks. …

Genome-Wide Association Studies Of Smooth Pursuit And Antisaccade Eye Movements In Psychotic Disorders: Findings From The B-Snip Study, R. Lencer, L. J. Mills, Ney Alliey-Rodriguez, R. Shafee

School of Medicine Publications

Eye movement deviations, particularly deficits of initial sensorimotor processing and sustained pursuit maintenance, and antisaccade inhibition errors, are established intermediate phenotypes for psychotic disorders. We here studied eye movement measures of 849 participants from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study (schizophrenia N = 230, schizoaffective disorder N = 155, psychotic bipolar disorder N = 206 and healthy controls N = 258) as quantitative phenotypes in relation to genetic data, while controlling for genetically derived ancestry measures, age and sex. A mixed-modeling genome-wide association studies approach was used including ~ 4.4 million genotypes (PsychChip and 1000 Genomes imputation). Across …

Genome-Wide Association Study Of Borderline Personality Disorder Reveals Genetic Overlap With Bipolar Disorder, Major Depression And Schizophrenia, S. H. Witt, F. Streit, M. Jungkunz, J. Frank, Ney Alliey Rodriguez

School of Medicine Publications

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) …

Recombinant Haplotypes Narrow The Arms2/Htra1 Association Signal For Age-Related Macular Degeneration, Felix Grassmann, Felix Grassmann, Iris M. Heid, Bernhard H.F. Weber, L. G. Fritsche, W. Igl, J. N. Bailey, S. Sengupta, J. L. Bragg-Gresham, John Blangero

Human Genetics Publications

Age-related macular degeneration (AMD) is the leading cause of blindness in ageing societies, triggered by both environmental and genetic factors. The strongest genetic signal for AMD with odds ratios of up to 2.8 per adverse allele was found previously over a chromosomal region in 10q26 harboring two genes, ARMS2 and HTRA1, although with little knowledge as to which gene or genetic variation is functionally relevant to AMD pathology. In this study, we analyzed rare recombinant haplotypes in 16,144 AMD cases and 17,832 controls from the International AMD Genomics Consortium and identified variants in ARMS2 but not HTRA1 to exclusively carry …

Protective Effect Of Anti-Phosphatidylserine Antibody In A Guinea Pig Model Of Advanced Hemorrhagic Arenavirus Infection, John M. Thomas, Philip E. Thorpe

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Biology)

Objective: Host derived markers on virally infected cells or virions may provide targets for the generation of antiviral agents. Recently, we identified phosphatidylserine (PS) as a host marker of virions and virally-infected cells.

Methods and Materials: Under normal physiological conditions, PS is maintained on the inner leaflet of the plasma membrane facing the cytosol. Following viral infection, activation or pre-apoptotic changes cause PS to become externalized. We have previously shown that bavituximab, a chimeric human-mouse antibody that binds PS complexed with β2-glycoprotein I (β2GP1), protected rodents against lethal Pichinde virus and cytomegalovirus infections.

Results: Here, we determined the antiviral activity …

A Principal Component Meta-Analysis On Multiple Anthropometric Traits Identifies Novel Loci For Body Shape, Janina S. Ried, Janina Jeff M., Audrey Y. Chu, Jennifer L. Bragg-Gresham, Jennifer E. Huffman, Tarunveer S. Ahluwalia, Gemma Cadby, Niina Eklund, John Blangero

School of Medicine Publications

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. …

Analysis Of Protein-Coding Genetic Variation In 60,706 Humans, Monkol Lek, Konrad J. Karczewski, Eric V. Minikel, Kaitlin E. Samocha, Eric Banks, Timothy Fennell, Anne H. O'Donnell-Luria, James S. Ware, Andrew J. Hill, John Blangero

Human Genetics Publications

Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong …

A Variance Component Method For Integrated Pathway Analysis Of Gene Expression Data, Ellen E. Quillen, John Blangero, Laura Almasy

Human Genetics Publications

Background: The application of pathway and gene-set based analyses to high-throughput data is increasingly common and represents an effort to understand underlying biology where single-gene or single-marker analyses have failed. Many such analyses rely on the a priori identification of genes associated with the trait of interest. In contrast, this variance-component-based approach creates a similarity matrix of individuals based on the expression of genes in each pathway.

Methods: We compared 16 methods of calculating similarity for positive control matrices based on probes for the genes used to model the simulated Genetic Analysis Workshop phenotypes. Results: A simple correlation matrix outperforms …

Independent Test Assessment Using The Extreme Value Distribution Theory, Marcio Almeida, Lucy Blondell, Juan M. Peralta, Jack W. Kent Jr., Goo Jun, Tanya M. Teslovich, Christian Fuchsberger, Andrew R. Wood, Alisa K. Manning, Thomas D. Dyer, Ravindranath Duggirala, John Blangero

School of Medicine Publications

The new generation of whole genome sequencing platforms offers great possibilities and challenges for dissecting the genetic basis of complex traits. With a very high number of sequence variants, a naïve multiple hypothesis threshold correction hinders the identification of reliable associations by the overreduction of statistical power. In this report, we examine 2 alternative approaches to improve the statistical power of a whole genome association study to detect reliable genetic associations. The approaches were tested using the Genetic Analysis Workshop 19 (GAW19) whole genome sequencing data. The first tested method estimates the real number of effective independent tests actually being …

Homology Among The Autosomal Chromosomes Of Boophilus Annulatus (Say) And B. Microplus (Canestrini), Bonnie S. Gunn

Theses and Dissertations - UTB/UTPA

Autosomes of Boophilus annulatus and B. microplus were compared using C- and G-bands to establish the degree of homology. Karyotypes of both species consisted of 20 autosomes and an XX:XO sex determination system with the X being the largest chromosome. All chromosomes of B. annulatus were acrocentric with heterochromatin limited to centromeric regions. The B. microplus karyotype was acrocentric with one band of noncentromeric heterochromatin occurring in three chromosome pairs. Interspecific comparisons indicated seven pairs of G-band homologous autosomes and three G-band homologous pairs when added interstitial heterochromatin was considered. The number three chromosome of both species showed variation in …