Browsing by Subject "SNP"

Now showing 1 - 4 of 4
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    Associations between traits (blood pressure and body height growth) and reproductive timing related genetic variants from genome-wide association studies
    (2017-07-18) Mo, Daojun; He, Chunyan; Tu, Wanzhu; Song, Yiqing; Stone, Cynthia S.
    Recent genome-wide association studies (GWAS) have identified many common genetic variants that are associated with women’s reproductive timing characteristics including ages at menarche and at natural menopause. However, the associations of these variants with other human health related phenotypes such as blood pressure, cancer, diabetes, obesity, and body height growth have not been well studied. No published studies to our knowledge have directly assessed the genetic influence of reproductive timing related variants on the aforementioned common traits. A better understanding of pleiotropic effects of these variants is important because it will help elucidate the precise mechanisms of common traits/diseases such as hypertension which have not been fully understood so far, and give clues for developing better solutions for disease prevention and treatment. We, therefore, conducted three studies to explore genetic variant effects on blood pressure and body height growth. In the first study, we analyzed data from a local cohort of 601 healthy adolescents from Indianapolis schools. Mixed effect model analysis revealed that 11 reproductive related single nucleotide polymorphisms (SNPs) were significantly associated with blood pressure in the study subjects. In order to assess if these genetic effects extended to the adult blood pressure, we performed the second study to investigate the genetic effect on blood pressure in adults. We used the summary statistics obtained from the two large international GWAS consortia, the Blood Pressure Consortium and the ReproGen Consortium. Bivariate analyses showed that more than 100 SNPs were associated with both blood pressure and reproductive timing. As the blood pressure development is closely related to somatic growth, we conducted the third study to exam the genetic effect of reproductive-timing related variants on the linear growth from the aforementioned local cohort. We identified 8 genetic variants significantly associated with the catch-up of linear growth in the study subjects. In conclusion, these three studies collectively provided evidence in support of the pleiotropic effects of the reproductive timing variants, suggesting the common genetic basis underlying the correlated traits. Future research is needed to validate the findings.
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    DNA Testing Reveals the Putative Identity of JB55, a 19th Century Vampire Buried in Griswold, Connecticut
    (MDPI, 2019-08-22) Daniels-Higginbotham, Jennifer; Gorden, Erin M.; Farmer, Stephanie K.; Spatola, Brian; Damann, Franklin; Bellantoni, Nicholas; Gagnon, Katie S.; de la Puente, Maria; Xavier, Catarina; Walsh, Susan; Parson, Walther; McMahon, Timothy P.; Marshall, Charla; Biology, School of Science
    In 1990 in Griswold, Connecticut, archaeologists excavated a burial found in a "skull and crossbones" orientation. The lid of the 19th century coffin had brass tacks that spelled "JB55", the initials of the person lying there and age at death. JB55 had evidence of chronic pulmonary infection, perhaps tuberculosis. It is possible that JB55 was deemed a vampire due to his disease, and therefore had to be "killed" by mutilating his corpse. In an attempt to reveal the identity of JB55, DNA testing was performed. Ancestry informative single nucleotide polymorphism (SNP) analysis using the Precision ID Ancestry Panel indicated European ancestry. A full Y-chromosomal short tandem repeat (Y-STR) profile was obtained, belonging to haplogroup R1b. When the Y-STR profile was searched in the publicly accessible FamilyTreeDNA R1b Project website, the two closest matches had the surname "Barber". A search of historical records led to a death notice mentioning John Barber, whose son Nathan Barber was buried in Griswold in 1826. The description of Nathan Barber closely fits the burial of "NB13," found near JB55. By applying modern forensic DNA tools to a historical mystery, the identity of JB55 as John Barber, the 19th century Connecticut vampire, has been revealed.
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    Elucidating the mechanisms or interactions involved in differing hair color follicles
    (2016) Muralidharan, Charanya; Walsh, Susan
    Forensic DNA phenotyping is an up and coming area in forensic DNA analyses that enables the prediction of physical appearance of an individual from DNA left at a crime scene. At present, there has been substantial work performed in understanding what genes/markers are required to produce a reliable prediction of categorical eye and hair color from the DNA of an individual of interest. These pigmentation markers (variants from HERC2, OCA2, TYR, SLC24A4, SLC45A2, IRF4 to name a few) are at the core of several prediction systems for eye and hair color such as IrisPlex, HIrisPlex, and the Snipper 2.5 suite. The contribution of these markers towards prediction in most cases however, only factors in an independent effect and do not take into account potential interactions or epistasis in the production of the final phenotypic color. Epistasis is a phenomenon that occurs when a gene’s effect relies on the presence of ‘modifier genes’, and can display different effects (enhance/repress a particular color) in genotype combinations rather than individually. In an effort to detect such epistatic interactions and their influence on hair color prediction models, for this current study, 872 individuals were genotyped at 61 associative and predictive pigmentation markers from several diverse population subsets. Individuals were phenotypically evaluated for eye and hair color by three separate independent assessments. Several analyses were performed using statistical approaches such as multifactor dimensionality reduction (MDR) for example, in an effort to detect if there are any SNP- SNP epistatic interactions present that could potentially enhance eye and hair color prediction model performances. The ultimate goal of this study was to assess what SNP-SNP combinations amongst these known pigmentation genes should be included as an additional variable in future prediction models and how much they can potentially enhance overall pigmentation prediction model performance. The second part of the project involved the analyses of several differentially expressed candidate genes between different hair color follicles of the same individual using quantitative Real Time PCR. We looked at 26 different genes identified through a concurrent non-human primate study being performed in the laboratory. The purpose of this study was to gain more insight on the level of differentially expressed mRNA between different hair color follicles within the same human individual. Data generated from this part of the project will act as a pilot study or ‘proof of principle’ on the mRNA expression of several pigmentation associated genes on individual beard hair of varying phenotypic colors. This analysis gives a first glimpse at expression levels that remain constant or differentiate between hairs of the same individual, therefore limiting the contribution of individual variation.
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    PASSPORT-seq: A Novel High-Throughput Bioassay to Functionally Test Polymorphisms in Micro-RNA Target Sites
    (Frontiers Media, 2018-06-15) Ipe, Joseph; Collins, Kimberly S.; Hao, Yangyang; Gao, Hongyu; Bhatia, Puja; Gaedigk, Andrea; Liu, Yunlong; Skaar, Todd C.; Pharmacology and Toxicology, School of Medicine
    Next-generation sequencing (NGS) studies have identified large numbers of genetic variants that are predicted to alter miRNA-mRNA interactions. We developed a novel high-throughput bioassay, PASSPORT-seq, that can functionally test in parallel 100s of these variants in miRNA binding sites (mirSNPs). The results are highly reproducible across both technical and biological replicates. The utility of the bioassay was demonstrated by testing 100 mirSNPs in HEK293, HepG2, and HeLa cells. The results of several of the variants were validated in all three cell lines using traditional individual luciferase assays. Fifty-five mirSNPs were functional in at least one of three cell lines (FDR ≤ 0.05); 11, 36, and 27 of them were functional in HEK293, HepG2, and HeLa cells, respectively. Only four of the variants were functional in all three cell lines, which demonstrates the cell-type specific effects of mirSNPs and the importance of testing the mirSNPs in multiple cell lines. Using PASSPORT-seq, we functionally tested 111 variants in the 3' UTR of 17 pharmacogenes that are predicted to alter miRNA regulation. Thirty-three of the variants tested were functional in at least one cell line.