scholarly journals Associations between forensic loci and neighboring gene expression levels may compromise medical privacy

2021 ◽  
Author(s):  
Mayra M Banuelos ◽  
Jhony A Zavaleta ◽  
Alennie Roldan ◽  
Rochelle-Jan Reyes ◽  
Miguel Guardado ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tandem Repeats ◽  
Medical Information ◽  
The United States ◽  
Neighboring Gene ◽  
Putative Gene ◽  
Expression Levels ◽  
Expression Variation ◽  
Genetic Profiles ◽  
Forensic Genetic

A set of 20 short tandem repeats (STRs) is used by the United States criminal justice system to identify suspects, and to maintain a database of genetic profiles for individuals who have been previously convicted or arrested. Some of these STRs were identified in the 1990s, with a preference for markers in putative gene deserts to avoid forensic profiles revealing protected medical information. We revisit that assumption, investigating whether forensic genetic profiles reveal information about gene expression variation, or potential medical information. We find six significant correlations (FDR = 0.23) between the forensic STRs and the expression levels of neighboring genes in lymphoblastoid cell lines. We explore possible mechanisms for these associations, with evidence compatible with forensic STRs causing expression variation, or being in LD with a causal locus in three cases, and weaker or potentially spurious associations in the other three cases. Together, these results suggest that forensic genetic loci may reveal expression level and, perhaps, medical information.

scholarly journals Abundant contribution of short tandem repeats to gene expression variation in humans

2015 ◽  
Vol 48 (1) ◽  
pp. 22-29 ◽  
Author(s):  
Melissa Gymrek ◽  
Thomas Willems ◽  
Audrey Guilmatre ◽  
Haoyang Zeng ◽  
Barak Markus ◽  
...  
Keyword(s):  
Gene Expression ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Gene Expression Variation ◽  
Expression Variation ◽  
Short Tandem

scholarly journals The Genetic Architecture of Gene Expression Levels in Wild Baboons

2014 ◽  
Author(s):  
Jenny Tung ◽  
Xiang Zhou ◽  
Susan C Alberts ◽  
Matthew Stephens ◽  
Yoav Gilad
Keyword(s):  
Gene Expression ◽  
Genetic Architecture ◽  
Nonhuman Primates ◽  
Rna Seq ◽  
Gene Expression Variation ◽  
Data Set ◽  
Expression Levels ◽  
Expression Variation ◽  
Wild Baboons ◽  
Gene Expression Levels

Gene expression variation is well documented in human populations and its genetic architecture has been extensively explored. However, we still know little about the genetic architecture of gene expression variation in other species, particularly our closest living relatives, the nonhuman primates. To address this gap, we performed an RNA sequencing (RNA-seq)-based study of 63 wild baboons, members of the intensively studied Amboseli baboon population in Kenya. Our study design allowed us to measure gene expression levels and identify genetic variants using the same data set, enabling us to perform complementary mapping of putative cis-acting expression quantitative trait loci (eQTL) and measurements of allele-specific expression (ASE) levels. We discovered substantial evidence for genetic effects on gene expression levels in this population. Surprisingly, we found more power to detect individual eQTL in the baboons relative to a HapMap human data set of comparable size, probably as a result of greater genetic variation, enrichment of SNPs with high minor allele frequencies, and longer-range linkage disequilibrium in the baboons. eQTL were most likely to be identified for lineage-specific, rapidly evolving genes. Interestingly, genes with eQTL significantly overlapped between the baboon and human data sets, suggesting that some genes may tolerate more genetic perturbation than others, and that this property may be conserved across species. Finally, we used a Bayesian sparse linear mixed model to partition genetic, demographic, and early environmental contributions to variation in gene expression levels. We found a strong genetic contribution to gene expression levels for almost all genes, while individual demographic and environmental effects tended to be more modest. Together, our results establish the feasibility of eQTL mapping using RNA-seq data alone, and act as an important first step towards understanding the genetic architecture of gene expression variation in nonhuman primates.

scholarly journals N-MYC Downstream Regulated Gene 4 (NDRG4), a Frequent Downregulated Gene through DNA Hypermethylation, plays a Tumor Suppressive Role in Esophageal Adenocarcinoma

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2573 ◽  
Author(s):  
Longlong Cao ◽  
Tianling Hu ◽  
Heng Lu ◽  
Dunfa Peng
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Tumor Cell ◽  
Esophageal Adenocarcinoma ◽  
The United States ◽  
The Cancer Genome Atlas ◽  
Downregulated Gene ◽  
Tissue Samples ◽  
Expression Levels ◽  
Gene 4

The incidence of esophageal adenocarcinoma (EAC) has been rising dramatically in the past few decades in the United States and Western world. The N-myc downregulated gene 4 (NDRG4) belongs to the human NDRG family. In this study, we aimed to identify the expression levels, regulation, and functions of NDRG4 in EAC. Using an integrative epigenetic approach, we identified genes showing significant downregulation in EAC and displaying upregulation after 5-Aza-deoxycitidine. Among these genes, likely to be regulated by DNA methylation, NDRG4 was among the top 10 candidate genes. Analyses of TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) data sets and EAC tissue samples demonstrated that NDRG4 was significantly downregulated in EAC (p < 0.05). Using Pyrosequencing technology for quantification of DNA methylation, we detected that NDRG4 promoter methylation level was significantly higher in EAC tissue samples, as compared to normal esophagus samples (p < 0.01). A strong inverse correlation between NDRG4 methylation and its gene expression levels (r = −0.4, p < 0.01) was observed. Treatment with 5-Aza restored the NDRG4 expression, confirming that hypermethylation is a driving force for NDRG4 silencing in EAC. Pathway and gene set enrichment analyses of TCGA data suggested that NDRG4 is strongly associated with genes related to cell cycle regulation. Western blotting analysis showed significant downregulation of Cyclin D1, CDK4 and CDK6 in EAC cells after overexpression of NDRG4. Functionally, we found that the reconstitution of NDRG4 resulted in a significant reduction in tumor cell growth in two-dimensional (2D) and three-dimensional (3D) organotypic culture models and inhibited tumor cell proliferation as indicated by the EdU (5-ethynyl-2′-deoxyuridine) proliferation assay.

Gene expression profiles and tumor locations in colorectal cancer (left vs. right vs. rectum).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3527-3527 ◽  
Author(s):  
Martin K. H. Maus ◽  
Diana L. Hanna ◽  
Craig Stephens ◽  
Peter Philipp Grimminger ◽  
Melinda Epstein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Expression Profiles ◽  
Tumor Biology ◽  
Tumor Location ◽  
Genetic Profile ◽  
Mrna Levels ◽  
Mutation Status ◽  
Expression Levels ◽  
Genetic Profiles

3527 Background: Recent data suggests that CRC from different locations show distinct genetic profiles. Right-sided tumors have a worse prognosis and may have less benefit from targeted therapies. We investigated the tumor locations and genetic profiles (KRAS and BRAF mutation status and ERCC1, TS, EGFR and VEGFR2 mRNA expression) in 580 CRC tumors. Methods: FFPE tumor specimen from 580 patients with advanced CRC adenocarcinoma were microdissected and DNA and RNA were extracted. Specifically designed primers and probes were used to detect 7 different base substitutions in codon 12 and 13 of KRAS, V600E mutations in BRAF and the mRNA expression levels of ERCC1, TS, EGFR and VEGFR2 by RT-PCR. These values were analyzed according to tumor location (left vs. right vs. rectum). Results: BRAF mutations were significantly more common in the right colon (15%), followed by rectum (3.8%) and left colon (2.5%). KRAS mutations occurred at similar frequencies throughout the colon. Gene expression of ERCC1 was significantly higher in right-sided than left-sided colon tumors in KRAS wild-type colon cancers. The highest expression levels for all genes were seen in rectum. These differences reached significant levels for ERCC1 (rectum vs. right and rectum vs. left, p<0.001), TS (rectum vs. left, p<0.036) and VEGFR2 (rectum vs. right and rectum vs. left, p<0.001). Conclusions: Tumor location in CRC is associated with specific mutation and expression profiles. Differences in chemosensitivity may be explained by mutation status and mRNA levels in right vs. left CRC. Rectum cancers showed a distinct genetic profile when compared to colon which indicates different tumor biology and may be related to differences in the microflora.

scholarly journals Analysis of Patterns of Gene Expression Variation within and between Ethnic Populations in Pediatric B-ALL

2013 ◽  
Vol 12 ◽  
pp. CIN.S11831 ◽  
Author(s):  
Chindo Hicks ◽  
Lucio Miele ◽  
Tejaswi Koganti ◽  
LaFarra Young-Gaylor ◽  
Deidre Rogers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Networks ◽  
Lymphoblastic Leukemia ◽  
The United States ◽  
Expression Data ◽  
Expression Levels ◽  
Ethnic Populations ◽  
Racial Ethnic ◽  
Key Pathways ◽  
Gene Expression Levels

B-Precursor acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer. Although 80% of B-ALL patients are able to be cured, significant challenges persist. Significant disparities in clinical outcomes and mortality rates exist between racial/ ethnic populations. The objective of this study was to determine whether gene expression levels significantly differ between ethnic populations. We compared gene expression levels between four ethnic populations (Whites, Blacks, Hispanics, and Asians) in the United States. Additionally, we performed network and pathway analysis to identify gene networks and pathways. Gene expression data involved 198 samples distributed as follows: 126 Whites, 51 Hispanics, 13 Blacks, and 8 Asians. We identified 300 highly significantly ( P < 0.001) differentially expressed genes between the four ethnic populations. Among the identified genes included the genes PHF6, BRD3, CRLF2, and RNF135 which have been implicated in pediatric B-ALL. We identified key pathways implicated in B-ALL including the PDGF, PI3/AKT, ERBB2-ERBB3, and IL-15 signaling pathways.

scholarly journals Measurement of selective constraint on human gene expression

2018 ◽  
Author(s):  
Emily C Glassberg ◽  
Ziyue Gao ◽  
Arbel Harpak ◽  
Xun Lant ◽  
Jonathan K Pritchard
Keyword(s):  
Gene Expression ◽  
Genetic Variation ◽  
Complex Traits ◽  
Stabilizing Selection ◽  
Common Variants ◽  
Loss Of Function ◽  
Specific Expression ◽  
Expression Levels ◽  
Expression Variation ◽  
Regulatory Variants

Gene expression variation is a major contributor to phenotypic variation in human complex traits. Selection on complex traits may therefore be reflected in constraint on gene expression levels. Here, we explore the effects of stabilizing selection on cis-regulatory genetic variation in humans. We analyze patterns of expression variation at copy number variants and find evidence for selection against large increases in gene expression. Using allele-specific expression (ASE) data, we further show evidence of selection against smaller-effect variants. We estimate that, across all genes, singletons in a sample of 122 individuals have approximately 2.5 × greater effects on expression variance than common variants. Despite their increased effect sizes relative to common variants, we estimate that singletons in the sample studied explain, on average, only 5% of the heritability of gene expression from cis-regulatory variants. Finally, we show that genes depleted for loss-of-function variants are also depleted for cis-eQTLs and have low levels of allelic imbalance, confirming tighter constraint on the expression levels of these genes. We conclude that constraint on gene expression is present, but has relatively weak effects on most cis-regulatory variants, thus permitting high levels of gene-regulatory genetic variation.

Gene expression analysis of metabolic markers during bone regeneration in a rat model

2014 ◽  
Vol 23 (03) ◽  
pp. 207-211
Author(s):  
C. Kasch ◽  
A. Osterberg ◽  
Thordis Granitzka ◽  
T. Lindner ◽  
M. Haenle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Analysis ◽  
Saline Solution ◽  
Female Rats ◽  
Synthesis Rate ◽  
Metabolic Markers ◽  
Expression Levels ◽  
Fibrotic Tissue ◽  
Intermittent Pth ◽  
Lower Expression

SummaryThe RANK/RANKL/OPG system plays an important role in the regulation of bone metabolism and bony integration around implants. The aim of this study was to analyse gene expression of OPG, RANK, and RANKL in regenerating bone during implant integration. Additionally, the effect of intermittent para - thyroid hormone (PTH) treatment was analysed. A titanium chamber was implanted in the proximal tibiae of 48 female rats. The animals received either human PTH or saline solution (NaCl). After 21 and 42 days, RNA was isolated from tissue adjacent to the implant and expression of RANK, RANKL, and OPG was analysed. After 21 days, very low expression levels of all genes were shown. In contrast, increased gene expression after 42 days was determined. Expression of RANK and RANKL was lower than that for OPG. The lower expression levels after 21 days might be due to still ossifying, fibrotic tissue around the titanium chamber. An increased OPG synthesis rate associated with decreased RANKL expression after 42 days revealed bone-forming processes. Despite significant differences in gene expression between the time points, only slight differences were observed between application of intermittent PTH and NaCl after a period of 42 days.

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