DOCSLIB.ORG

PDE1A Polymorphism Contributes to the Susceptibility

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
PDE1A Polymorphism Contributes to the Susceptibility Yang et al. BMC Genomics (2017) 18:982 DOI 10.1186/s12864-017-4247-8 RESEARCHARTICLE Open Access PDE1A polymorphism contributes to the susceptibility of nephrolithiasis Zhenxing Yang1†, Tao Zhou1†, Bishao Sun1, Qingqing Wang1, Xingyou Dong1, Xiaoyan Hu1, Jiangfan Zhong1,3, Bo Song2 and Longkun Li1,3* Abstract Background: Previous studies have confirmed a family risk of nephrolithiasis (NL), but only 15% of all cases are associated with an identified monogenic factor. In clinical practice, our group encountered a patient with NL combined with cystic kidney disease that had 3 affected family members. No known mutations association with NL was detected in this family, and thus further investigation of the molecular cause of NL was deemed to be necessary. Results: Quality analysis from the sequencing stage showed a more than 80-fold average depth and 95% coverage for each sample, and six mutations within six genes were chosen as candidate variants for further validation. Genotyping of rs182089527in the phosphodiesterase 1A (PDE1A) gene in the validation cohort indicated that the alternative allele was present in 15 patients with heterozygosity and in 1 patient with homozygosity, and exhibited significant enrichment in NL patients (Fisher’s exact test, adjusted p = 0.0042) and kidney cystic patients (Fisher’s exact test, adjusted p = 0.067) compared to controls. In addition, function analysis displayed a significant decrease in the protein and mRNA expression levels resulting from the rs182089527 mutant sequence compared with the wild-type sequence. Moreover, patients with this mutation displayed a high level of creatinine and urea in urinalysis. Conclusions: Our study provides genetic evidence that the rs182089527 mutation in PDE1A is involved in the development of NL and kidney cysts, which should help to improve personalized medicine for diagnosis and treatment. Keywords: PDE1A, Nephrolithiasis, Polymorphism Background different between northern (4.1%) and southern Nephrolithiasis (NL), also known as kidney stones, is regions (4.0%) [2]. Both genetic and environmental a common disease associated with major morbidity factors contribute to the risk of NL. In a genetic because of colicky pain, the necessity of surgical pro- epidemiology follow-up investigation of a cohort of cedures, and even acute renal failure [1]. The esti- 37,999 male participants, the relative risk of the mated life time prevalence of NL is about 1–15% incidence of stone formation in men with a positive worldwide, which varies according to age, gender, family history was 2.75 (95% confidence inter- race, and geographic location. In China, the overall val = 2.19–3.12) [3].A twin study in Vietnam indi- prevalence rate was estimated to be 4.0% (4.8% in cated that the proband concordance rate in men and 3.0% in women), and the prevalence was monozygotic twins (32.4%) was significantly greater than the rate in dizygotic twins (17.3%), and the estimated heritability of the risk for NL was 56%. * Correspondence: [email protected] †Equal contributors The genetic cause of NL is complicated, ranging from the 1Department of Urology, Second Affiliated Hospital, Third Military Medical rare monogenic to the more common polygenic forms. To University, Chongqing, People’s Republic of China date, at least 30 genes have been reported to be associated 3Ostrow School of Dentistry and Department of Pediatrics, School of Medicine, University of Southern California, Los Angeles, CA, USA with Mendelian forms of NL or nephrocalcinosis by Full list of author information is available at the end of the article autosomal-recessive, autosomal-dominant, or X-linked © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Yang et al. BMC Genomics (2017) 18:982 Page 2 of 8 transmission [4, 5].Several renal calcium stone-related Therefore, to further explore the potential causal disorders are known to be monogenic, such as Dent disease genes, we employed whole-exome sequencing technol- (Online Mendelian Inheritance in Man [OMIM 300009]), ogy of blood samples from 10 family members (4 af- Bartter’s syndrome, idiopathic hypercalciuria, primary distal fected and 6 unaffected) and 2307 validation samples renal tubular acidosis, hypophosphatemic rickets with hyper- (including 993 NL patients and 1314 controls, 328 calciuria, familial hypomagnesemia with hypercalciuria and kidney cystic patients and 622 controls) to investigate nephrocalcinosis, primary hyperoxaluria, cystinuria, renal the causal mutations, and postulated that NL may be hypouricemia, and hypocalciurichypercalcemia [6], but only a monogenic disease. Following functional validation about 15% of 272 genetically unrelated individuals were was conducted using RT-PCR and western blot. shown to have single-gene disease which have mentioned above [7]. With the development of microarray technology, Methods genome-wide association studies have also been employed to Sample collection investigate the susceptibility genes of NL. One such study Proband and nephrolithiasis family description conducted by Gudmar et al. [8] identified common, syn- A elder man presented with post-polio syndrome of onymous variants in the CLDN14 gene that were associated right foot claudication,20 years history of renal calculi, with kidney stones, and homozygous carriers of the single repeated bilateral back pain, urgent micturition, nucleotide polymorphism (SNP) rs219780[C] in CLDN14 hematuria and dysuria. The patient suffered from hyper- were estimated to have a 1.64-times greater risk of develop- tension almost 10 years, admitted oral antihypertensive ing the disease compared to non-carriers. Another study drugs, and also complained with intermittent voiding conducted in Japan found three novel loci for NL and stones in urine 3 times, but was not treated. He had revealed the association of SNP rs11746443 (upstream of the noticed with aggravation of back pain and voiding stones SLC34A1 gene) with the reduction of estimated glomerular in urine again 1 month ago, which make them admitted filtration rate [9]. Although dozens of susceptibility genes to our Urology Department. Physical examination have been reported, in-depth analysis of the monogenic revealed a temperature of 36.3 °C, pulse of 102, blood causes of NL is still necessary. pressure (BP) of 109/88 mmHg, left flank tenderness With the advent of next-generation sequencing, the and a palpable left kidney but was otherwise normal. mutation analysis of Mendelian genes has not only Laboratory testing indicated that creatinine concentra- become technically available but is also cost-effective. In tion was 89.9 umol/L, the serum calcium was clinical practice, our group encountered a family affected 2.26 mmol/L, uric acid was357 umol/L, serum by NL (Fig. 1), with four family members affected. phosphorus was 1.06 mmol/L, and serum magnesium Proband DNA samples were collected and sequenced was 0.78 mmol/L. The serum electrolytes were within initially, but no known association mutation of NL was normal limits. Urinalysis showed specific gravity of 1.02, detected. PH 6.5, no protein, and 6 to 10 white blood cells and red In addition, renal cysts are extremely common and blood cells (RBCs) per high-power field without casts or are present in more than one third of NL patients crystals. Abdominal ultrasound showed multiple cystic older than 50 years. More importantly, NL shows a dark areas with the maximum diameter of 2.2 cm, clear common complication of kidney cyst development. boundaries and regular morphology. Ultrasonography and Fig. 1 A pedigree of nephrolithiasis family with affected patients (blackened symbols) and PDE1A gene mutation which located in chr2:183,106,640. Symbols with question mark denote family members who are probably affected. Circles represent female family members, squares represent male family members,and crosses represent dead family members. Wilde-type and mutant-type are marked by a plus sign (+) and a minus sign (−). Arrows indicate probands Yang et al. BMC Genomics (2017) 18:982 Page 3 of 8 computed tomography (CT) of left kidney demon- product. The size selectedproduct was PCR amplified, strated hydronephrosis, no marked parenchymal and the final product was validated using the Agilent atrophy, and multiple stones in therenal pelvis. There Bioanalyzer. Two steps of hybridization and wash were was a cystic dark area, diameter of 1.1 cm, in right needed for construction. PCR was used in order to amp- kidney with regular morphology and clear boundary lify the enriched DNA library for sequencing. PCR was (Additional file 1: Figure S1).The patient has endured performed with the same PCR primer cocktail used in family history of nephrolithiasis (Fig. 1). TruSeq DNA Sample Preparation. Axeq Technologies performs procedures for quality control analysis on the Cohort samples sample library and quantification of the DNA library Nine hundred ninety three cases of nephrolithiasis templates. Illumina utilizes a unique “bridged” amplifica- (NL) and 1314
Load more

Recommended publications
  • Genome Wide Association Study of Response to Interval and Continuous Exercise Training: the Predict‑HIIT Study Camilla J
    Williams et al. J Biomed Sci (2021) 28:37 https://doi.org/10.1186/s12929-021-00733-7 RESEARCH Open Access Genome wide association study of response to interval and continuous exercise training: the Predict-HIIT study Camilla J. Williams1†, Zhixiu Li2†, Nicholas Harvey3,4†, Rodney A. Lea4, Brendon J. Gurd5, Jacob T. Bonafglia5, Ioannis Papadimitriou6, Macsue Jacques6, Ilaria Croci1,7,20, Dorthe Stensvold7, Ulrik Wislof1,7, Jenna L. Taylor1, Trishan Gajanand1, Emily R. Cox1, Joyce S. Ramos1,8, Robert G. Fassett1, Jonathan P. Little9, Monique E. Francois9, Christopher M. Hearon Jr10, Satyam Sarma10, Sylvan L. J. E. Janssen10,11, Emeline M. Van Craenenbroeck12, Paul Beckers12, Véronique A. Cornelissen13, Erin J. Howden14, Shelley E. Keating1, Xu Yan6,15, David J. Bishop6,16, Anja Bye7,17, Larisa M. Haupt4, Lyn R. Grifths4, Kevin J. Ashton3, Matthew A. Brown18, Luciana Torquati19, Nir Eynon6 and Jef S. Coombes1* Abstract Background: Low cardiorespiratory ftness (V̇O2peak) is highly associated with chronic disease and mortality from all causes. Whilst exercise training is recommended in health guidelines to improve V̇O2peak, there is considerable inter-individual variability in the V̇O2peak response to the same dose of exercise. Understanding how genetic factors contribute to V̇O2peak training response may improve personalisation of exercise programs. The aim of this study was to identify genetic variants that are associated with the magnitude of V̇O2peak response following exercise training. Methods: Participant change in objectively measured V̇O2peak from 18 diferent interventions was obtained from a multi-centre study (Predict-HIIT). A genome-wide association study was completed (n 507), and a polygenic predictor score (PPS) was developed using alleles from single nucleotide polymorphisms= (SNPs) signifcantly associ- –5 ated (P < 1 ­10 ) with the magnitude of V̇O2peak response.
    [Show full text]
  • Supplementary Table 1: Adhesion Genes Data Set
    Supplementary Table 1: Adhesion genes data set PROBE Entrez Gene ID Celera Gene ID Gene_Symbol Gene_Name 160832 1 hCG201364.3 A1BG alpha-1-B glycoprotein 223658 1 hCG201364.3 A1BG alpha-1-B glycoprotein 212988 102 hCG40040.3 ADAM10 ADAM metallopeptidase domain 10 133411 4185 hCG28232.2 ADAM11 ADAM metallopeptidase domain 11 110695 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 195222 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 165344 8751 hCG20021.3 ADAM15 ADAM metallopeptidase domain 15 (metargidin) 189065 6868 null ADAM17 ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) 108119 8728 hCG15398.4 ADAM19 ADAM metallopeptidase domain 19 (meltrin beta) 117763 8748 hCG20675.3 ADAM20 ADAM metallopeptidase domain 20 126448 8747 hCG1785634.2 ADAM21 ADAM metallopeptidase domain 21 208981 8747 hCG1785634.2|hCG2042897 ADAM21 ADAM metallopeptidase domain 21 180903 53616 hCG17212.4 ADAM22 ADAM metallopeptidase domain 22 177272 8745 hCG1811623.1 ADAM23 ADAM metallopeptidase domain 23 102384 10863 hCG1818505.1 ADAM28 ADAM metallopeptidase domain 28 119968 11086 hCG1786734.2 ADAM29 ADAM metallopeptidase domain 29 205542 11085 hCG1997196.1 ADAM30 ADAM metallopeptidase domain 30 148417 80332 hCG39255.4 ADAM33 ADAM metallopeptidase domain 33 140492 8756 hCG1789002.2 ADAM7 ADAM metallopeptidase domain 7 122603 101 hCG1816947.1 ADAM8 ADAM metallopeptidase domain 8 183965 8754 hCG1996391 ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma) 129974 27299 hCG15447.3 ADAMDEC1 ADAM-like,
    [Show full text]
  • Supp Material.Pdf
    Simon et al. Supplementary information: Table of contents p.1 Supplementary material and methods p.2-4 • PoIy(I)-poly(C) Treatment • Flow Cytometry and Immunohistochemistry • Western Blotting • Quantitative RT-PCR • Fluorescence In Situ Hybridization • RNA-Seq • Exome capture • Sequencing Supplementary Figures and Tables Suppl. items Description pages Figure 1 Inactivation of Ezh2 affects normal thymocyte development 5 Figure 2 Ezh2 mouse leukemias express cell surface T cell receptor 6 Figure 3 Expression of EZH2 and Hox genes in T-ALL 7 Figure 4 Additional mutation et deletion of chromatin modifiers in T-ALL 8 Figure 5 PRC2 expression and activity in human lymphoproliferative disease 9 Figure 6 PRC2 regulatory network (String analysis) 10 Table 1 Primers and probes for detection of PRC2 genes 11 Table 2 Patient and T-ALL characteristics 12 Table 3 Statistics of RNA and DNA sequencing 13 Table 4 Mutations found in human T-ALLs (see Fig. 3D and Suppl. Fig. 4) 14 Table 5 SNP populations in analyzed human T-ALL samples 15 Table 6 List of altered genes in T-ALL for DAVID analysis 20 Table 7 List of David functional clusters 31 Table 8 List of acquired SNP tested in normal non leukemic DNA 32 1 Simon et al. Supplementary Material and Methods PoIy(I)-poly(C) Treatment. pIpC (GE Healthcare Lifesciences) was dissolved in endotoxin-free D-PBS (Gibco) at a concentration of 2 mg/ml. Mice received four consecutive injections of 150 μg pIpC every other day. The day of the last pIpC injection was designated as day 0 of experiment.
    [Show full text]
  • Supplementary Materials
    Supplementary materials Supplementary Table S1: MGNC compound library Ingredien Molecule Caco- Mol ID MW AlogP OB (%) BBB DL FASA- HL t Name Name 2 shengdi MOL012254 campesterol 400.8 7.63 37.58 1.34 0.98 0.7 0.21 20.2 shengdi MOL000519 coniferin 314.4 3.16 31.11 0.42 -0.2 0.3 0.27 74.6 beta- shengdi MOL000359 414.8 8.08 36.91 1.32 0.99 0.8 0.23 20.2 sitosterol pachymic shengdi MOL000289 528.9 6.54 33.63 0.1 -0.6 0.8 0 9.27 acid Poricoic acid shengdi MOL000291 484.7 5.64 30.52 -0.08 -0.9 0.8 0 8.67 B Chrysanthem shengdi MOL004492 585 8.24 38.72 0.51 -1 0.6 0.3 17.5 axanthin 20- shengdi MOL011455 Hexadecano 418.6 1.91 32.7 -0.24 -0.4 0.7 0.29 104 ylingenol huanglian MOL001454 berberine 336.4 3.45 36.86 1.24 0.57 0.8 0.19 6.57 huanglian MOL013352 Obacunone 454.6 2.68 43.29 0.01 -0.4 0.8 0.31 -13 huanglian MOL002894 berberrubine 322.4 3.2 35.74 1.07 0.17 0.7 0.24 6.46 huanglian MOL002897 epiberberine 336.4 3.45 43.09 1.17 0.4 0.8 0.19 6.1 huanglian MOL002903 (R)-Canadine 339.4 3.4 55.37 1.04 0.57 0.8 0.2 6.41 huanglian MOL002904 Berlambine 351.4 2.49 36.68 0.97 0.17 0.8 0.28 7.33 Corchorosid huanglian MOL002907 404.6 1.34 105 -0.91 -1.3 0.8 0.29 6.68 e A_qt Magnogrand huanglian MOL000622 266.4 1.18 63.71 0.02 -0.2 0.2 0.3 3.17 iolide huanglian MOL000762 Palmidin A 510.5 4.52 35.36 -0.38 -1.5 0.7 0.39 33.2 huanglian MOL000785 palmatine 352.4 3.65 64.6 1.33 0.37 0.7 0.13 2.25 huanglian MOL000098 quercetin 302.3 1.5 46.43 0.05 -0.8 0.3 0.38 14.4 huanglian MOL001458 coptisine 320.3 3.25 30.67 1.21 0.32 0.9 0.26 9.33 huanglian MOL002668 Worenine
    [Show full text]
  • A Common Variant in CLDN14 Is Associated with Primary Biliary
    www.nature.com/scientificreports OPEN A Common Variant in CLDN14 is Associated with Primary Biliary Cirrhosis and Bone Mineral Density Received: 13 October 2015 Ruqi Tang1,*, Yiran Wei1,*, Zhiqiang Li2,*, Haoyan Chen1, Qi Miao1, Zhaolian Bian1, Accepted: 16 December 2015 Haiyan Zhang1, Qixia Wang1, Zhaoyue Wang1, Min Lian1, Fan Yang1, Xiang Jiang1, Yue Yang1, Published: 04 February 2016 Enling Li1, Michael F. Seldin3,4, M. Eric Gershwin4, Wilson Liao5, Yongyong Shi3 & Xiong Ma1 Primary biliary cirrhosis (PBC), a chronic autoimmune liver disease, has been associated with increased incidence of osteoporosis. Intriguingly, two PBC susceptibility loci identified through genome-wide association studies are also involved in bone mineral density (BMD). These observations led us to investigate the genetic variants shared between PBC and BMD. We evaluated 72 genome-wide significant BMD SNPs for association with PBC using two European GWAS data sets (n = 8392), with replication of significant findings in a Chinese cohort (685 cases, 1152 controls). Our analysis identified a novel variant in the intron of the CLDN14 gene (rs170183, Pfdr = 0.015) after multiple testing correction. The three associated variants were followed-up in the Chinese cohort; one SNP rs170183 demonstrated −5 consistent evidence of association in diverse ethnic populations (Pcombined = 2.43 × 10 ). Notably, expression quantitative trait loci (eQTL) data revealed that rs170183 was correlated with a decline in CLDN14 expression in both lymphoblastoid cell lines and T cells (Padj = 0.003 and 0.016, respectively). In conclusion, our study identified a novel PBC susceptibility variant that has been shown to be strongly associated with BMD, highlighting the potential of pleiotropy to improve gene discovery.
    [Show full text]
  • 1 Integrative Omics Analyses Reveal Epigenetic Memory in Diabetic Renal
    Page 1 of 53 Diabetes Integrative Omics analyses reveal epigenetic memory in diabetic renal cells regulating genes associated with kidney dysfunction. Anita Bansal1, Sreeram Balasubramanian2, Sangeeta Dhawan3, Amy Leung1, Zhen Chen1, Rama Natarajan*1. 1Department of Diabetes Complications and Metabolism, Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, 2 Division of Biology and Biological Engineering, California Institute of Technology, 1200 E California Blvd, Pasadena, CA 91125, 3Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010. Correspondence to * Rama Natarajan. Email: [email protected] 626-218-2289 Keywords Diabetic kidney disease, tubular epithelial cells, metabolic memory, epigenomics Running title: Epigenetic memory in diabetic renal tubular cells Word count: 4949 Number of Figures: 6 1 Diabetes Publish Ahead of Print, published online August 3, 2020 Diabetes Page 2 of 53 Abstract Diabetic kidney disease (DKD) is a major complication of diabetes and the leading cause of end- stage renal failure. Epigenetics has been associated with metabolic memory, in which prior periods of hyperglycemia enhance the future risk of developing DKD despite subsequent glycemic control. To understand the mechanistic role of such epigenetic memory in human DKD and identify new therapeutic targets, we profiled gene expression, DNA methylation, and chromatin accessibility in kidney proximal tubule epithelial cells (PTECs) derived from non-diabetic and Type-2 diabetic (T2D) subjects. T2D-PTECs displayed persistent gene expression and epigenetic changes with and without TGFβ1 treatment, even after culturing in vitro under similar conditions as non-diabetic PTECs, signified by deregulation of fibrotic and transport associated genes (TAGs).
    [Show full text]
  • Whole Genome Sequencing of Familial Non-Medullary Thyroid Cancer Identifies Germline Alterations in MAPK/ERK and PI3K/AKT Signaling Pathways
    biomolecules Article Whole Genome Sequencing of Familial Non-Medullary Thyroid Cancer Identifies Germline Alterations in MAPK/ERK and PI3K/AKT Signaling Pathways Aayushi Srivastava 1,2,3,4 , Abhishek Kumar 1,5,6 , Sara Giangiobbe 1, Elena Bonora 7, Kari Hemminki 1, Asta Försti 1,2,3 and Obul Reddy Bandapalli 1,2,3,* 1 Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany; [email protected] (A.S.); [email protected] (A.K.); [email protected] (S.G.); [email protected] (K.H.); [email protected] (A.F.) 2 Hopp Children’s Cancer Center (KiTZ), D-69120 Heidelberg, Germany 3 Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), D-69120 Heidelberg, Germany 4 Medical Faculty, Heidelberg University, D-69120 Heidelberg, Germany 5 Institute of Bioinformatics, International Technology Park, Bangalore 560066, India 6 Manipal Academy of Higher Education (MAHE), Manipal, Karnataka 576104, India 7 S.Orsola-Malphigi Hospital, Unit of Medical Genetics, 40138 Bologna, Italy; [email protected] * Correspondence: [email protected]; Tel.: +49-6221-42-1709 Received: 29 August 2019; Accepted: 10 October 2019; Published: 13 October 2019 Abstract: Evidence of familial inheritance in non-medullary thyroid cancer (NMTC) has accumulated over the last few decades. However, known variants account for a very small percentage of the genetic burden. Here, we focused on the identification of common pathways and networks enriched in NMTC families to better understand its pathogenesis with the final aim of identifying one novel high/moderate-penetrance germline predisposition variant segregating with the disease in each studied family.
    [Show full text]
  • Application of Microarray-Based Comparative Genomic Hybridization in Prenatal and Postnatal Settings: Three Case Reports
    SAGE-Hindawi Access to Research Genetics Research International Volume 2011, Article ID 976398, 9 pages doi:10.4061/2011/976398 Case Report Application of Microarray-Based Comparative Genomic Hybridization in Prenatal and Postnatal Settings: Three Case Reports Jing Liu, Francois Bernier, Julie Lauzon, R. Brian Lowry, and Judy Chernos Department of Medical Genetics, University of Calgary, 2888 Shaganappi Trail NW, Calgary, AB, Canada T3B 6A8 Correspondence should be addressed to Judy Chernos, [email protected] Received 16 February 2011; Revised 20 April 2011; Accepted 20 May 2011 Academic Editor: Reha Toydemir Copyright © 2011 Jing Liu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Microarray-based comparative genomic hybridization (array CGH) is a newly emerged molecular cytogenetic technique for rapid evaluation of the entire genome with sub-megabase resolution. It allows for the comprehensive investigation of thousands and millions of genomic loci at once and therefore enables the efficient detection of DNA copy number variations (a.k.a, cryptic genomic imbalances). The development and the clinical application of array CGH have revolutionized the diagnostic process in patients and has provided a clue to many unidentified or unexplained diseases which are suspected to have a genetic cause. In this paper, we present three clinical cases in both prenatal and postnatal settings. Among all, array CGH played a major discovery role to reveal the cryptic and/or complex nature of chromosome arrangements. By identifying the genetic causes responsible for the clinical observation in patients, array CGH has provided accurate diagnosis and appropriate clinical management in a timely and efficient manner.
    [Show full text]
  • Chromosome 21 Leading Edge Gene Set
    Chromosome 21 Leading Edge Gene Set Genes from chr21q22 that are part of the GSEA leading edge set identifying differences between trisomic and euploid samples. Multiple probe set IDs corresponding to a single gene symbol are combined as part of the GSEA analysis. Gene Symbol Probe Set IDs Gene Title 203865_s_at, 207999_s_at, 209979_at, adenosine deaminase, RNA-specific, B1 ADARB1 234539_at, 234799_at (RED1 homolog rat) UDP-Gal:betaGlcNAc beta 1,3- B3GALT5 206947_at galactosyltransferase, polypeptide 5 BACE2 217867_x_at, 222446_s_at beta-site APP-cleaving enzyme 2 1553227_s_at, 214820_at, 219280_at, 225446_at, 231860_at, 231960_at, bromodomain and WD repeat domain BRWD1 244622_at containing 1 C21orf121 240809_at chromosome 21 open reading frame 121 C21orf130 240068_at chromosome 21 open reading frame 130 C21orf22 1560881_a_at chromosome 21 open reading frame 22 C21orf29 1552570_at, 1555048_at_at, 1555049_at chromosome 21 open reading frame 29 C21orf33 202217_at, 210667_s_at chromosome 21 open reading frame 33 C21orf45 219004_s_at, 228597_at, 229671_s_at chromosome 21 open reading frame 45 C21orf51 1554430_at, 1554432_x_at, 228239_at chromosome 21 open reading frame 51 C21orf56 223360_at chromosome 21 open reading frame 56 C21orf59 218123_at, 244369_at chromosome 21 open reading frame 59 C21orf66 1555125_at, 218515_at, 221158_at chromosome 21 open reading frame 66 C21orf7 221211_s_at chromosome 21 open reading frame 7 C21orf77 220826_at chromosome 21 open reading frame 77 C21orf84 239968_at, 240589_at chromosome 21 open reading frame 84
    [Show full text]
  • Human Social Genomics in the Multi-Ethnic Study of Atherosclerosis
    Getting “Under the Skin”: Human Social Genomics in the Multi-Ethnic Study of Atherosclerosis by Kristen Monét Brown A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Epidemiological Science) in the University of Michigan 2017 Doctoral Committee: Professor Ana V. Diez-Roux, Co-Chair, Drexel University Professor Sharon R. Kardia, Co-Chair Professor Bhramar Mukherjee Assistant Professor Belinda Needham Assistant Professor Jennifer A. Smith © Kristen Monét Brown, 2017 [email protected] ORCID iD: 0000-0002-9955-0568 Dedication I dedicate this dissertation to my grandmother, Gertrude Delores Hampton. Nanny, no one wanted to see me become “Dr. Brown” more than you. I know that you are standing over the bannister of heaven smiling and beaming with pride. I love you more than my words could ever fully express. ii Acknowledgements First, I give honor to God, who is the head of my life. Truly, without Him, none of this would be possible. Countless times throughout this doctoral journey I have relied my favorite scripture, “And we know that all things work together for good, to them that love God, to them who are called according to His purpose (Romans 8:28).” Secondly, I acknowledge my parents, James and Marilyn Brown. From an early age, you two instilled in me the value of education and have been my biggest cheerleaders throughout my entire life. I thank you for your unconditional love, encouragement, sacrifices, and support. I would not be here today without you. I truly thank God that out of the all of the people in the world that He could have chosen to be my parents, that He chose the two of you.
    [Show full text]
  • Zimmer Cell Calcium 2013 Mammalian S100 Evolution.Pdf
    Cell Calcium 53 (2013) 170–179 Contents lists available at SciVerse ScienceDirect Cell Calcium jo urnal homepage: www.elsevier.com/locate/ceca Evolution of the S100 family of calcium sensor proteins a,∗ b b,1 b Danna B. Zimmer , Jeannine O. Eubanks , Dhivya Ramakrishnan , Michael F. Criscitiello a Center for Biomolecular Therapeutics and Department of Biochemistry & Molecular Biology, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD 20102, United States b Comparative Immunogenetics Laboratory, Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843-4467, United States a r t i c l e i n f o a b s t r a c t 2+ Article history: The S100s are a large group of Ca sensors found exclusively in vertebrates. Transcriptomic and genomic Received 4 October 2012 data from the major radiations of mammals were used to derive the evolution of the mammalian Received in revised form 1 November 2012 S100s genes. In human and mouse, S100s and S100 fused-type proteins are in a separate clade from Accepted 3 November 2012 2+ other Ca sensor proteins, indicating that an ancient bifurcation between these two gene lineages Available online 14 December 2012 has occurred. Furthermore, the five genomic loci containing S100 genes have remained largely intact during the past 165 million years since the shared ancestor of egg-laying and placental mammals. Keywords: Nonetheless, interesting births and deaths of S100 genes have occurred during mammalian evolution. Mammals The S100A7 loci exhibited the most plasticity and phylogenetic analyses clarified relationships between Phylogenetic analyses the S100A7 proteins encoded in the various mammalian genomes.
    [Show full text]
  • E. M. G. Campbell, D. Nonneman and G. A. Rohrer Chromosome 8 Fine Mapping a Quantitative Trait Locus Affecting Ovulation Rate In
    Fine mapping a quantitative trait locus affecting ovulation rate in swine on chromosome 8 E. M. G. Campbell, D. Nonneman and G. A. Rohrer J Anim Sci 2003. 81:1706-1714. The online version of this article, along with updated information and services, is located on the World Wide Web at: http://jas.fass.org/cgi/content/full/81/7/1706 www.asas.org Downloaded from jas.fass.org by on February 3, 2011. Fine mapping a quantitative trait locus affecting ovulation rate in swine on chromosome 81 E. M. G. Campbell2, D. Nonneman, and G. A. Rohrer3 USDA, ARS, U.S. Meat Animal Research Center, Clay Center, NE 68933 ABSTRACT: Ovulation rate is an integral compo- least 3 Mb in the human genome was detected; all other nent of litter size in swine, but is difficult to directly differences could be explained by resolution of mapping select for in commercial swine production. Because a techniques used. Fourteen of the most informative mi- QTL has been detected for ovulation rate at the termi- crosatellite markers in the first 27 cM of the map were nal end of chromosome 8p, genetic markers for this genotyped across the entire MARC swine resource pop- QTL would enable direct selection for ovulation rate ulation, increasing the number of markers typed from in both males and females. Eleven genes from human 2 to 14 and more than doubling the number of genotyped chromosome 4p16-p15, as well as one physiological can- animals with ovulation rate data (295 to 600). Results didate gene, were genetically mapped in the pig.
    [Show full text]