Genetics Commons^™

Wnt And Egf Pathways Act Together To Induce C. Elegans Male Hook Development, Hui Yu, Adeline Seah, Michael A. Herman, Edwin L. Ferguson, H. Robert Horvitz, Paul W. Sternberg

School of Biological Sciences: Faculty Publications

Comparative studies of vulva development between Caenorhabditis elegans and other nematode species have provided some insight into the evolution of patterning networks. However, molecular genetic details are available only in C. elegans and Pristionchus pacificus. To extend our knowledge on the evolution of patterning networks, we studied the C. elegans male hook competence group (HCG), an equivalence group that has similar developmental origins to the vulval precursor cells (VPCs), which generate the vulva in the hermaphrodite. Similar to VPC fate specification, each HCG cell adopts one of three fates (1°, 2°, 3°), and 2° HCG fate specification …

Efficient Gene Replacements In Toxoplasma Gondii Strains Deficient For Nonhomologous End Joining, Barbara A. Fox, Jessica G. Ristuccia, Jason P. Gigley, David J. Bzik

Dartmouth Scholarship

A high frequency of nonhomologous recombination has hampered gene targeting approaches in the model apicomplexan parasite Toxoplasma gondii. To address whether the nonhomologous end-joining (NHEJ) DNA repair pathway could be disrupted in this obligate intracellular parasite, putative KU proteins were identified and a predicted KU80 gene was deleted. The efficiency of gene targeting via double-crossover homologous recombination at several genetic loci was found to be greater than 97% of the total transformants in KU80 knockouts. Gene replacement efficiency was markedly increased (300- to 400-fold) in KU80 knockouts compared to wild-type strains. Target DNA flanks of only approximately 500 bp were …

Associaton Tests That Accommodate Genotyping Errors, Ingo Ruczinski, Qing Li, Benilton Carvalho, M. Daniele Fallin, Rafael A. Irizarry, Thomas A. Louis

Johns Hopkins University, Dept. of Biostatistics Working Papers

High-throughput SNP arrays provide estimates of genotypes for up to one million loci, often used in genome-wide association studies. While these estimates are typically very accurate, genotyping errors do occur, which can influence in particular the most extreme test statistics and p-values. Estimates for the genotype uncertainties are also available, although typically ignored. In this manuscript, we develop a framework to incorporate these genotype uncertainties in case-control studies for any genetic model. We verify that using the assumption of a “local alternative” in the score test is very reasonable for effect sizes typically seen in SNP association studies, and show …

Sparse Linear Discriminant Analysis For Simultaneous Testing For The Significance Of A Gene Set/Pathway And Gene Selection, Michael C. Wu, Lingson Zhang, Zhaoxi Wang, David C. Christiani, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

A Hidden Markov Random Field Model For Genome-Wide Association Studies, Hongzhe Li, Zhi Wei, J M. Maris

UPenn Biostatistics Working Papers

Genome-wide association studies (GWAS) are increasingly utilized for identifying novel susceptible genetic variants for complex traits, but there is little consensus on analysis methods for such data. Most commonly used methods include single SNP analysis or haplotype analysis with Bonferroni correction for multiple comparisons. Since the SNPs in typical GWAS are often in linkage disequilibrium (LD), at least locally, Bonferonni correction of multiple comparisons often leads to conservative error control and therefore lower statistical power. In this paper, we propose a hidden Markov random field model (HMRF) for GWAS analysis based on a weighted LD graph built from the prior …

Genetic And Environmental Contributions To Body Mass Index: Comparative Analysis Of Monozygotic Twins, Dizygotic Twins And Same-Age Unrelated Siblings, Nancy Segal, R. Feng, Shirley Mcguire, D. Allison, S. Miller

Psychology

Background—Earlier studies have established that a substantial percentage of variance in obesity-related phenotypes is explained by genetic components. However, only one study has used both virtual twins (VTs) and biological twins and was able to simultaneously estimate additive genetic, non-additive genetic, shared environmental and unshared environmental components in body mass index (BMI). Our current goal was to re-estimate four components of variance in BMI, applying a more rigorous model to biological and virtual multiples with additional data. Virtual multiples share the same family environment, offering unique opportunities to estimate common environmental influence on phenotypes that cannot be separated from …

Thirty-Seven Additional Microsatellite Loci In The Pacific Lion-Paw Scallop (Nodipecten Subnodosus) And Cross-Amplification In Other Pectinids, Jessica Lynn Petersen, Ana M. Ibarra, Bernie May

Department of Animal Science: Faculty Publications

We characterized 37 new microsatellite markers in the Pacific lion-paw scallop (Nodipecten subnodosus) and tested for cross-amplification in four other species. Genetic diversity was estimated using 24 individuals from the Lagoon Ojo de Liebre, B.C.S., Mexico. Allelic richness varied from 5 to 27 alleles per locus and the average expected heterozygosity was 0.76. Ten loci exhibited significant departure from Hardy–Weinberg equilibrium likely due to the presence of null alleles. Sixteen of these markers cross-amplified in closely related N. nodosus, while little or no amplification was observed in three Argopecten species.

Multiple Imputation To Correct For Measurement Error In Admixture Estimates In Genetic Structured Association Testing, Miguel A. Padilla, Jamin Divers, Laura K. Vaughan, David B. Allison, Hemant K. Tiwari

Psychology Faculty Publications

Objectives: Structured association tests ( SAT), like any statistical model, assumes that all variables are measured without error. Measurement error can bias parameter estimates and confound residual variance in linear models. It has been shown that admixture estimates can be contaminated with measurement error causing SAT models to suffer from the same afflictions. Multiple imputation (MI) is presented as a viable tool for correcting measurement error problems in SAT linear models with emphasis on correcting measurement error contaminated admixture estimates. Methods: Several MI methods are presented and compared, via simulation, in terms of controlling Type I error rates for both …

Electroporation For The Delivery Of Dna-Based Vaccines And Immunotherapeutics: Current Clinical Developments, Angela M. Bodles-Brakhop, Richard Heller, Ruxandra Draghia-Akli

Bioelectrics Publications

Electroporation (EP) has been used in basic research for the past 25 years to aid in the transfer of DNA into cells in vitro. EP in vivo enhances transfer of DNA vaccines and therapeutic plasmids to the skin, muscle, tumors, and other tissues resulting in high levels of expression, often with serological and clinical benefits. the recent interest in nonviral gene transfer as treatment options for a vast array of conditions has resulted in the refinement and optimization of EP technology. current research has revealed that EP can be successfully used in many species, including humans. clinical trials are …

Proactive Procreation : Ethical Implications Of New Genetic Technologies For Parental Obligations To Future Offspring, L Syd M. Johnson

Legacy Theses & Dissertations (2009 - 2024)

This dissertation examines the ethical implications of recent genetic innovations, particularly preimplantation genetic diagnosis, for the obligations and duties of parents to future children. I critique common but uncompelling objections to the use of genetic information, diagnosis, and technology to influence the characteristics of future offspring, and conclude that genetic selection and enhancement are not different in kind or degree from other means of selection, direction, and enhancement that parents engage in to shape the lives of their children. Procreation is morally risky -- it risks imposing substantial burdens on persons who would not otherwise have to bear those burdens, …

Role Of Cyp2a5 In Drug Metabolism, Chemical Toxicity, And Maintenance Of Steroid Hormone Homeostasis : Insights From Studies On A Novel Cyp2a5-Null Mouse Model, Xin Zhou

Legacy Theses & Dissertations (2009 - 2024)

The central hypothesis is that CYP2A5 plays an important role in the metabolism of xenobiotic substrates, and in the toxicity induced by over-exposure to drugs, as well as in the metabolism of endogenous compounds and regulation of steroid hormone homeostasis. The specific aims are: 1) to generate and characterize a Cyp2a5-null mouse; 2) to determine the role of CYP2A5 in the systemic clearance of nicotine and cotinine; and 3) to explore the mechanisms underlying the resistance of the lateral nasal gland (LNG) of male Cyp2g1-null/Cyp2a5-low mouse and Cyp2a5-null mouse to acetaminophen (AP) toxicity.

An Rnai Screen Targeting The Protein Tyrosine Kinases Identifies Bruton's Tyrosine Kinase (Btk) As A Breast Cancer Cell Survival Factor, Cheryl Lynne Eifert

Legacy Theses & Dissertations (2009 - 2024)

The receptor protein tyrosine kinases (RPTKs) and the non- receptor protein tyrosine kinases (PTKs) are among the most commonly up-regulated genes found in all types of cancers. Although, a large body of data implicates a majority of tyrosine kinases (TKs) in cancer, few have been extensively evaluated for any potential therapeutic benefit in any of the many subtypes of breast cancer. We have used RNA interference (RNAi) to perform a large-scale loss-of-function analysis to facilitate the identification of individual factors necessary for the survival of an ErbB2 positive breast cancer cell line. We have found that 30% of the TKs …

Estrogenic Compounds Downstream From Three Small Cities In Eastern Nebraska: Occurrence And Biological Effect, Marlo K. Sellin, Daniel D. Snow, Debbie L. Akerly, Alan S. Kolok

Biology Faculty Publications

Recent studies have detected estrogenic compounds in surface waters in North America and Europe. Furthermore, the presence of estrogenic compounds in surface waters has been attributed, in some cases, to the discharge of wastewater treatment plant (WWTP) effluent. The primary objective of the current study was to determine if WWTP effluent contributes estrogens to the surface waters of Nebraska. A second objective of this study was to determine if estrogens were found in concentrations sufficient enough to manifest feminizing effects on fish. These objectives were satisfied by deploying polar organic chemical integrative samplers (POCIS) and caged fathead minnows at eight …

Letter From The Dean, Lalit Verma

Discovery, The Student Journal of Dale Bumpers College of Agricultural, Food and Life Sciences

No abstract provided.

Inheritance Of Shoulder Spotting In The Tetra, Hyphessobrycon Bentosi Characidae, Jack Frankel

Department of Biology Faculty Publications

The tetra (Hyphessobrycon bentosi) exhibits two phenotypes associated with shoulder spotting. Fish possess ei-ther a prominent black vertical spot located directly behind the operculum (H. b. bentosi,  bentosi  white  tip  tetra) or  lack  this spot (H. b. rosaceus, rosy tetra). Segregation patterns observed from the progenies of ten different crosses suggest that the  inheritance  of  these  phenotypes  is  controlled  by  two  autosomal  loci  acting  in  a complementary  fashion,  with  domi-nance at both loci required for the expression of the spotted phenotype. 

Construction Of A Transgene To Analyze The Function Of The 3’Utr Of The Hdc Gene On Spatial Expression Of Histidine Decarboxylase In Drosophila Melanogaster, Embriette Hyde, Martin G. Burg

Student Summer Scholars Manuscripts

Histamine has been shown to be an important neurotransmitter used in the nervous system of Drosophila melanogaster. Histidine decarboxylase (HDC) is the enzyme that catalyzes the synthesis of histamine. All genetic information necessary for Hdc gene expression has been shown to be present in a 9.4kb genomic DNA fragment. A previous study fused the 5'-UTR of Hdc to the gene encoding eGFP. Microscopic analysis of flies transformed with the pHdc-eGFP transgene showed a weak pattern of eGFP expression in the nervous system as compared to histamine localization, indicating that another genomic region may be necessary for robust Hdc expression. Studies …

Patterning Defects In Silkworm Embryos Analysed Through Cuticle Preparations, Amit Singh, Madhuri Kango-Singh, K. P. Gopinathan

Biology Faculty Publications

The mulberry silkworm, Bombyx mori, a holometabolous lepidopteran insect, has a metameric body plan. Due to its functional adaptation, B. mori presents some unique deviations in its pal/ern from the evolutionarily advanced dipteran insect, Drosophila melanogaster. Previous studies on mutant phenotype analysis in B. mori have been carried out in late stages of larval development. Here we employ, the cuticle preparation approach during embryonic development to study morphological landmarks associated with B. mori, Eri, another race a/silkworm, and pattern defects associated with Ekp mutant of B.mori. The homeotic mutant Ekp, generates ectopic abdominallegs, a feature …

Intradermal Delivery Of Plasmid Vegf(165) By Electroporation Promotes Wound Healing, Bernadette Ferraro, Yolmari Cruz, Domenico Coppola, Richard Heller

Bioelectrics Publications

Skin flaps are extensively used in reconstructive surgeries to repair large defects and deep wounds, but severe ischemia and necrosis often results in loss of the transplanted tissue. Thus, skin flap models are often used to study the biology of healing and necrosis of acute ischemic wounds. Delivery of exogenous vascular endothelial growth factor (VEGF) to areas of ischemia has shown promise for promoting therapeutic angiogenesis, but its expression must be tightly regulated to avoid adverse effects. In this study, plasmid DNA encoding VEGF₁₆₅ (pVEGF) was delivered to the ischemic skin of a rat skin flap model by intradermal …

Development Of Pcr Assays To Detect And Characterise Salmonella Isolates From Cheese And Meat Products By Utilizing An Integrated Genomics Approach, Noelle Geraldine Mccarthy

Theses

Salmonella is an extremely important foodborne pathogen which is responsible for millions of cases of gastroenteritis annually. Salmonella outbreaks have been associated with numerous common food stuffs such as meat, dairy and seafood. Traditional culture based methods for the detection Salmonella are labourious and costly. Rapid detection and serovar identification would dramatically decrease the time required to identify Salmonella outbreaks and potential health risks.

In the US 99% of all Salmonella infections are caused by members of Salmonella enterica subspecies 1. Serovars within subspecies 1 can vary due to host specificity and pathogenicity. DNA sequencing projects have provided valuable genomic …

The Association Of Human Leukocyte Antigen(Hla) Alleles And Type 2 Diabetes Mellitus (T2dm) Among Mexican Americans (Ma), Kantibhai Motiram Patel

Open Access Theses & Dissertations

The epidemic of type 2 diabetes mellitus (T2DM) is ranked as a major public health priority across the United States and especially in the El Paso, Texas region. The risk for the development of T2DM is greater in minority groups, particularly among Mexican Americans (MA) who comprise approximately 78% of El Paso's population. The growing incidence of T2DM in this group is typically attributed to increase in weight (obesity). The incidence of diabetes may also be influenced by genetic factors that are unique to this group. Several earlier studies have identified genetic markers for type 1 diabetes mellitus (T1DM). These …

When Did The Ancestors Of Polynesia Begin To Migrate To Polynesia? The Mtdna Evidence, David Lesniewski

UNLV Theses, Dissertations, Professional Papers, and Capstones

The timing and nature of the migration of the ancestors of the Polynesian people is debated by two competing theories. The "Express Train" and "Slow Boat" theories assert that the migration of the Proto-Polynesian people began around 6,000 years before present (BP) or around 10,000 years BP respectively. Through the use of haplogroups and specific genetic mutations a direct relationship between the Proto-Polynesians and modern Polynesians was attempted to test which of these theories was correct. The ancient skeletal remains from the island of Borneo currently housed at UNLV were used in this study as their dates fall within both …

Dna Before Proteins? Recent Discoveries In Nucleic Acid Catalysis Strengthen The Case, Aaron Steven Burton, Niles Lehman

Chemistry Faculty Publications and Presentations

An RNA-DNA World could arise from an all-RNA system with the development of as few as three ribozymes— a DNA-dependent RNA polymerase, an RNA-dependent DNA polymerase, and a catalyst for the production of DNA nucleotides. A significant objection to DNA preceding proteins is that RNA has not been shown to catalyze the production of DNA. However, RNA- and DNAzymes have been recently discovered that catalyze chemical reactions capable of forming deoxyribose, such as mixed aldol condensation of 5’-glyceryl- and 3’- glycoaldehyde-terminated DNA strands. Thus, the only remaining obstacles to RNA-catalyzed in vitro DNA synthesis are alterations of substrate and template …

Choosing The Right Path: Enhancement Of Biologically Relevant Sets Of Genes Or Proteins Using Pathway Structure, Reuben Thomas, Julia M. Gohlke, Geffrey F. Stopper, Frederick M. Parham, Christopher J. Portier

Biology Faculty Publications

A method is proposed that finds enriched pathways relevant to a studied condition using the measured molecular data and also the structural information of the pathway viewed as a network of nodes and edges. Tests are performed using simulated data and genomic data sets and the method is compared to two existing approaches. The analysis provided demonstrates the method proposed is very competitive with the current approaches and also provides biologically relevant results.