Matching Items (20)

132424-Thumbnail Image.png

Characterization of the Notch Ligand Deltalike 3 from A. carolinensis

Description

The highly conserved Notch signaling pathway regulates cell-cell communication pathways, cell fate, cell determination, cell death, embryonic development, and adult tissue pathways in metazoans. The Notch receptors and ligands that bind to Notch are single pass, transmembrane proteins that communicate

The highly conserved Notch signaling pathway regulates cell-cell communication pathways, cell fate, cell determination, cell death, embryonic development, and adult tissue pathways in metazoans. The Notch receptors and ligands that bind to Notch are single pass, transmembrane proteins that communicate cell to cell via juxtacrine signaling. There are reports of the divergent function and localization of the Deltalike 3 (Dll3) ligand. In Mus musculus (an eutherin mammal) the DLL3 protein inhibits the Notch signaling pathway and is localized in the Golgi apparatus. In contrast, the DLL3 protein from zebrafish, Danio rerio (a teleost) activates Notch and is located on the cell surface. This study will focus on examining the evolutionary pathway/evolutionary similarities, localization, and function of the A. carolinensis dll3 gene in comparison to other vertebrate species. This is important because there is not much known about the evolutionary divergence of the DLL3 A. carolinensis protein, its function in Notch signaling, and its subcellular localization.
Evolutionary analysis of vertebrate DLL3 protein sequences using phylogenetic trees showed that D. rerio and A. carolinensis are more evolutionarily similar in comparison to M. musculus suggesting that they may have similar intracellular localization. However, immunofluorescence staining experiments showed that the A. carolinensis DLL3 protein co-localized significantly with an endoplasmic reticulum (ER) specific primary antibody. Since this protein is localized in the secretory system, similar to that of M. musculus DLL3, it suggests that its function is to inhibit the Notch signaling pathway. Protein sequence alignments were created that suggested that there is a region in the protein sequences where the lizard and mouse sequence are conserved, while the zebrafish sequence simultaneously varies. This region of the amino acid sequence could be responsible for the difference in localization and function of the protein in these two species.

Contributors

Agent

Created

Date Created
2019-05

128462-Thumbnail Image.png

Variable Autosomal and X Divergence Near and Far From Genes Affects Estimates of Male Mutation Bias in Great Apes

Description

Male mutation bias, when more mutations are passed on via the male germline than via the female germline, is observed across mammals. One common way to infer the magnitude of male mutation bias, α, is to compare levels of neutral

Male mutation bias, when more mutations are passed on via the male germline than via the female germline, is observed across mammals. One common way to infer the magnitude of male mutation bias, α, is to compare levels of neutral sequence divergence between genomic regions that spend different amounts of time in the male and female germline. For great apes, including human, we show that estimates of divergence are reduced in putatively unconstrained regions near genes relative to unconstrained regions far from genes. Divergence increases with increasing distance from genes on both the X chromosome and autosomes, but increases faster on the X chromosome than autosomes. As a result, ratios of X/A divergence increase with increasing distance from genes and corresponding estimates of male mutation bias are significantly higher in intergenic regions near genes versus far from genes. Future studies in other species will need to carefully consider the effect that genomic location will have on estimates of male mutation bias.

Contributors

Created

Date Created
2016-11-09

132484-Thumbnail Image.png

The Effects of Sex Chromosome Complement Aware Read Mapping on Variant Calling in Hepatocellular Carcinoma

Description

Hepatocellular carcinoma (HCC) is a type of liver cancer common in Sub-Saharan Africa and South East Asian countries. Each year more than 700,000 new cases and more than 600,000 deaths are recorded worldwide due to HCC. According to the American

Hepatocellular carcinoma (HCC) is a type of liver cancer common in Sub-Saharan Africa and South East Asian countries. Each year more than 700,000 new cases and more than 600,000 deaths are recorded worldwide due to HCC. According to the American Cancer Society HCC is ranked the 5th most common cancer worldwide with a male:female susceptibility ratio ranging between 2:1 and 8:1. HCC risk factors include lifestyle behaviors, such as persistent alcohol abuse and smoking, prolonged exposure to aflatoxins, chronic viral hepatitis infections, inherited metabolic diseases and non-alcoholic fatty liver diseases. To understand the genetic effects underlying sex-bias in HCC, it is necessary to include the sex chromosomes in genomics analyses. X and Y chromosomes are often discluded in genomics studies because of the technical and analytical challenges: sequence homology. The purpose of this thesis is to analyze the effects of sex chromosome complement aware read mapping to germline variant calling. 10 male and 10 female tumor adjacent samples from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA LIHC) cohort were processed using sex-aware and default reference and the concordance of the two approaches was examined. We detected a higher disconcordance of 0.69% on variants called on the X chromosome and a disconcordance of 0.51% on variants called on the Y chromosomes for the reference and alternative alleles respectively compared to autosomes. Variants called on the REF/ALT genotypes had a disconcordances of 1.00%, 1.05%, 1.35% and 12.34% for the autosomes, chromosome 7, the X, and the Y chromosome, respectively. At the end of the project we concluded that the generated datasets showed the effect of sex-aware read mapping on variant calling. Though the data did not show the sites that can be called as variants in one dataset but not in the other, rather the concordance looked at sites that were called as variants in both data sets.

Contributors

Agent

Created

Date Created
2019-05

133149-Thumbnail Image.png

The Genomics of Cancer Resistance in Long-Lived Vesper Bats

Description

Bats (order Chiroptera) are the longest lived mammals for their size, with particularly extreme longevity evolving in the family Vespertilionidae, or vesper bats. Because of this, researchers have proposed using bats to study ageing and cancer suppression. Here, we study

Bats (order Chiroptera) are the longest lived mammals for their size, with particularly extreme longevity evolving in the family Vespertilionidae, or vesper bats. Because of this, researchers have proposed using bats to study ageing and cancer suppression. Here, we study gene duplications across mammalian genomes and show that, similar to previous findings in elephants, bats have experienced duplications of the tumor suppressor gene TP53, including five genomic copies in the genome of the little brown bat (Myotis lucifugus) and two copies in Brandt's bat (Myotis brandtii). These species can live 37 and 41 years, respectively, despite having an adult body mass of only ~7 grams. We use evolutionary genetics and next generation sequencing approaches to show that positive selection has acted on the TP53 locus across bats, and two recently duplicated TP53 gene copies in the little brown bat are both highly conserved and expressed, suggesting they are functional. We also report an extraordinary genomic copy number expansion of the tumor suppressor gene FBXO31 in the common ancestor of vesper bats which accelerated in the Myotis lineage, leading to 34\u201457 copies and the expression of 20 functional FBXO31 homologs in Brandt's bat. As FBXO31 directs the degradation of MDM2, which is a negative regulator of TP53, we suggest that increased expression of both FBXO31 and TP53 may be related to an enhanced DNA-damage response to genotoxic stress brought on by long lifespans and rapid metabolic rates in bats.

Contributors

Agent

Created

Date Created
2018-12

Career Options for Students Seeking a Degree in the School of Life Sciences

Description

This project was designed to develop resources to highlight diverse career options for students achieving a degree within the School of Life Sciences. Many students have a very narrow view of what careers their degree prepares them for. In addition,

This project was designed to develop resources to highlight diverse career options for students achieving a degree within the School of Life Sciences. Many students have a very narrow view of what careers their degree prepares them for. In addition, if they have a career in mind, they have difficulty selecting an appropriate degree that will prepare them for their intended career. The goal of this project was to provide a broader view of career options, as well as illustrate the requirements each student would need to meet in order to pursue these careers. This was done by interviewing five career professionals and developing a major map that corresponds to the specific requirements of that career.

Contributors

Created

Date Created
2018-05

Building Diverse Resources for Exploratory School of Life Sciences Students

Description

This creative thesis project aimed to create career development resources that School of Life Sciences majors could use to enhance their college experience, expand the breadth of relevant career options for School of Life Sciences majors, and confront and divert

This creative thesis project aimed to create career development resources that School of Life Sciences majors could use to enhance their college experience, expand the breadth of relevant career options for School of Life Sciences majors, and confront and divert career problems through the implementation of these career development resources. Students encounter career problems when their intention and action diverge. These career problems may cause a student to stop their pursuit of a given career, change majors, or even stop schooling completely. It is the objective of this project to help resolve these career problems by introducing a career development resource flyer that educates the student about a given career, provides coursework to guide a student towards this career path, familiarize students with extracurricular efforts necessary for this position, propose valuable resources that the student can utilize to learn more about the career, and offer a question and answer portion for further career and professional understanding. In order to create these career development resource flyers a variety of professionals, both with and without relationships with Arizona State University were contacted and interviewed. The answers gathered from these interviews were then utilized to create the career flyers. The project was successful in creating five distinct career development resource flyers, as well as a blank template with instructions to be used in the future by the School of Life Sciences. The career development resource flyers will be utilized by the School of Life Sciences advising staff for future exploratory majors, but is not limited to just these students. Aspirations are set to create an expansive reservoir of these resources for future generations of students to access in hopes that they will be better suited to find a career path that they are passionate about and be better prepared to attain.

Contributors

Agent

Created

Date Created
2017-05

134552-Thumbnail Image.png

Standard mapping protocols misestimate sex-biased gene expression

Description

There are several challenges to accurately inferring levels of transcription using RNA-sequencing (RNA-seq) data, including detecting and correcting for reference genome mapping bias. One potential confounder of RNA-seq analysis results from the application of a standardized pipeline to samples of

There are several challenges to accurately inferring levels of transcription using RNA-sequencing (RNA-seq) data, including detecting and correcting for reference genome mapping bias. One potential confounder of RNA-seq analysis results from the application of a standardized pipeline to samples of different sexes in species with chromosomal sex determination. The homology between the human X and Y chromosomes will routinely cause mismapping to occur, artificially biasing estimates of sex-biased gene transcription. For this reason we tested sex-specific mapping scenarios in humans on RNA-seq samples from the brains of 5 genetic females and 5 genetic males to assess how inferences of differential gene expression patterns change depending on the reference genome. We first applied a mapping protocol where we mapped all individuals to the entire human reference genome (complete), including the X and Y chromosomes, and computed differential expression between the set of genetic male and genetic female samples. We next mapped the genetic female samples (46,XX) to the human reference genome with the Y chromosome removed (Y-excluded) and the genetic male samples (46, XY) to the human reference genome (including the Y chromosome), but with the pseudoautosomal regions of the Y chromosome hard-masked (YPARs-masked) for the two sex-specific mappings. Using the complete and sex-specific mapping protocols, we compared the differential expression measurements of genetic males and genetic females from cuffDiff outputs. The second strategy called 33 additional genes as being differentially expressed between the two sexes when compared to the complete mapping protocol. This research provides a framework for a new standard of reference genome mappings to correct for sex-biased gene expression estimates that can be used in future studies.

Contributors

Agent

Created

Date Created
2017-05

134524-Thumbnail Image.png

An Analysis of the Benchmark Test lzbench for Open-Source Compressors

Description

With the rising data output and falling costs of Next Generation Sequencing technologies, research into data compression is crucial to maintaining storage efficiency and costs. High throughput sequencers such as the HiSeqX Ten can produce up to 1.8 terabases of

With the rising data output and falling costs of Next Generation Sequencing technologies, research into data compression is crucial to maintaining storage efficiency and costs. High throughput sequencers such as the HiSeqX Ten can produce up to 1.8 terabases of data per run, and such large storage demands are even more important to consider for institutions that rely on their own servers rather than large data centers (cloud storage)1. Compression algorithms aim to reduce the amount of space taken up by large genomic datasets by encoding the most frequently occurring symbols with the shortest bit codewords and by changing the order of the data to make it easier to encode. Depending on the probability distribution of the symbols in the dataset or the structure of the data, choosing the wrong algorithm could result in a compressed file larger than the original or a poorly compressed file that results in a waste of time and space2. To test efficiency among compression algorithms for each file type, 37 open-source compression algorithms were used to compress six types of genomic datasets (FASTA, VCF, BCF, GFF, GTF, and SAM) and evaluated on compression speed, decompression speed, compression ratio, and file size using the benchmark test lzbench. Compressors that outpreformed the popular bioinformatics compressor Gzip (zlib -6) were evaluated against one another by ratio and speed for each file type and across the geometric means of all file types. Compressors that exhibited fast compression and decompression speeds were also evaluated by transmission time through variable speed internet pipes in scenarios where the file was compressed only once or compressed multiple times.

Contributors

Agent

Created

Date Created
2017-05

132980-Thumbnail Image.png

Beginning to investigate Lactase Persistence in Turkana

Description

Lactase persistence is the ability of adults to digest lactose in milk (Segurel & Bon, 2017). Mammals are generally distinguished by their mammary glands which gives females the ability to produce milk and feed their newborn children. The new born

Lactase persistence is the ability of adults to digest lactose in milk (Segurel & Bon, 2017). Mammals are generally distinguished by their mammary glands which gives females the ability to produce milk and feed their newborn children. The new born therefore requires the ability to breakdown the lactose in the milk to ensure its proper digestion (Segurel & Bon, 2017). Generally, humans lose the expression of lactase after weaning, which prevents them being able to breakdown lactose from dairy (Flatz, 1987).
My research is focused on the people of Turkana, a human pastoral population inhabiting Northwest Kenya. The people of Turkana are Nilotic people that are native to the Turkana district. There are currently no conclusive studies done on evidence for genetic lactase persistence in Turkana. Therefore, my research will be on the evolution of lactase persistence in the people of Turkana. The goal of this project is to investigate the evolutionary history of two genes with known involvement in lactase persistence, LCT and MCM6, in the Turkana. Variants in these genes have previously been identified to result in the ability to digest lactose post-weaning age. Furthermore, an additional study found that a closely related population to the Turkana, the Massai, showed stronger signals of recent selection for lactase persistence than Europeans in these genes. My goal is to characterize known variants associated with lactase persistence by calculating their allele frequencies in the Turkana and conduct selection scans to determine if LCT/MCM6 show signatures of positive selection. In doing this, we conducted a pilot study consisting of 10 female Turkana individuals and 10 females from four different populations from the 1000 genomes project namely: the Yoruba in Ibadan, Nigeria (YRI); Luhya in Webuye, Kenya; Utah Residents with Northern and Western European Ancestry (CEU); and the Southern Han Chinese. The allele frequency calculation suggested that the CEU (Utah Residents with Northern and Western European Ancestry) population had a higher lactase persistence associated allele frequency than all the other populations analyzed here, including the Turkana population. Our Tajima’s D calculations and analysis suggested that both the Turkana population and the four haplotype map populations shows signatures of positive selection in the same region. The iHS selection scans we conducted to detect signatures of positive selection on all five populations showed that the Southern Han Chinese (CHS), the LWK (Luhya in Webuye, Kenya) and the YRI (Yoruba in Ibadan, Nigeria) populations had stronger signatures of positive selection than the Turkana population. The LWK (Luhya in Webuye, Kenya) and the YRI (Yoruba in Ibadan, Nigeria) populations showed the strongest signatures of positive selection in this region. This project serves as a first step in the investigation of lactase persistence in the Turkana population and its evolution over time.

Contributors

Agent

Created

Date Created
2019-05