DOCSLIB.ORG

Subchromosomal Anomalies in Small for Gestational-Age Fetuses And

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Subchromosomal Anomalies in Small for Gestational-Age Fetuses And Archives of Gynecology and Obstetrics (2019) 300:633–639 https://doi.org/10.1007/s00404-019-05235-4 MATERNAL-FETAL MEDICINE Subchromosomal anomalies in small for gestational‑age fetuses and newborns Ying Ma1 · Yan Pei1 · Chenghong Yin2 · Yuxin Jiang3 · Jingjing Wang4 · Xiaofei Li4 · Lin Li5 · Karl Oliver Kagan6 · Qingqing Wu4 Received: 9 January 2019 / Accepted: 27 June 2019 / Published online: 4 July 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Purpose To analyze copy number variants (CNVs) in subjects with small for gestational age (SGA) in China. Methods A total of 85 cases with estimated fetal weight (EFW) or birth weight below the 10th percentile for gestational age were recruited, including SGA associated with structural anomalies (Group A, n = 20) and isolated SGA (Group B, n = 65). In all cases, cytogenetic karyotyping and infection screening were normal. We examined DNA from fetuses (amniocentesis or cordocentesis) and newborns (cord blood) to detect CNVs using a single nucleotide polymorphism (SNP, n = 75) array or low-pass whole-genome sequencing (WGS, n = 10). Results Of 85 total cases, 3 (4%) carried pathogenic chromosomal abnormalities, including 2 cases with pathological CNVs and 1 case with upd(22)pat. In Group A, the mean gestational age at the time of diagnosis was 26.8 (SD 4.1) weeks and mean EFW/birth weight was 907.2 (SD 567.8) g. In Group B, the mean gestational age at the time of diagnosis was 34.1 (SD 5.8) weeks. Mean EFW/birth weight was 1879.2 (SD 714.5) g. The pathologic detection rate was 10% (2/20) in Group A and 2% (1/65) in Group B. It was inclined that the lower the EFW percentile, the more frequent the occurrence of CNVs. Conclusions Pathological subchromosomal anomalies were detected by CMA or low-pass WGS in 10% and 2% of SGA subjects with and without malformation, respectively. SGA fetuses with structural anomalies presented with higher pathologi- cal subchromosomal anomalies. The molecular genetic analysis is not recommended for isolated SGA pregnancies without other abnormal fndings. Keywords Copy number variations · Small for gestational age · Single-nucleotide polymorphism array · Whole-genome sequencing Introduction * Qingqing Wu [email protected] The association of small-for-gestational-age (SGA) fetuses 1 Department of Obstetrics, Beijing Obstetrics with chromosomal abnormalities, especially trisomy 18 is and Gynecology Hospital, Capital Medical University, well established [1, 2]. However, there is still an ongoing Beijing 100026, China debate regarding whether copy number variants (CNVs) 2 Beijing Obstetrics and Gynecology Hospital, Capital Medical detected by molecular genetic tests such as chromosomal University, Beijing 100026, China microarray analysis (CMA) are more common in fetuses 3 Department of Ultrasound, Peking Union Medical College with SGA. Biron-Shental et al. [3] used single-nucleotide Hospital, Chinese Academy of Medical Sciences and Peking polymorphism (SNP) arrays to detect CNVs in placentas Union Medical College, Beijing 100730, China from small fetuses with normal anomaly scans and karyo- 4 Department of Ultrasound, Beijing Obstetrics types and healthy neonates. The authors identifed signif- and Gynecology Hospital, Capital Medical University, 251 cantly more genomic alterations in small fetal group and a Yaojia Yuan Road, Chaoyang District, Beijing 100026, China signifcant correlation between the size of the CNVs and the 5 Central Laboratory, Beijing Obstetrics and Gynecology severity of growth restriction [3]. Borrell et al. [4] exam- Hospital, Capital Medical University, Beijing 100026, China ined fetuses with isolated fetal growth below the 3rd cen- 6 Department of Women’S Health, University of Tuebingen, tile and with a normal cytogenetic karyotype, pathological Tübingen, Germany Vol.:(0123456789)1 3 634 Archives of Gynecology and Obstetrics (2019) 300:633–639 genomic imbalances were found in 4% of the cases. This Maternal and pregnancy characteristics and the results of rate was increased to 10% in those small fetuses’ cases with the antenatal examinations are entered into a digital data- additional defects [4]. A multicenter study revealed that base (Excel 2007, Microsoft, Richmond, USA). Data of after exclusion of aneuploides, in fetuses with early growth pregnancy outcome were followed up and were added after retardation (estimated fetal weight below the 3rd percen- delivery. tile before 32 weeks of pregnancy), pathogenic CNVs were The study cohort includes women with SGA pregnancies detected in 4.8%, 10%, and 10.5% of subjects having isolated between 2014 and 2016 where frst, cytogenetic karyotyping SGA, SGA with minor congenital anomalies and SGA with and infection screening were uneventful, second, where a major congenital anomalies, respectively [5]. CMA or a low-pass WGS was done and third, who agreed Ongoing research is focused on the extension of molecu- to participate in the study. lar genetic testing to whole-exome and -genome sequenc- ing. To date, experience with these methods is still limited, Molecular genetic follow-up examinations but in approximately 23–50% of cases with normal cytoge- netic and CMA results, whole-exome sequencing revealed From 2014 to 2015, CMA technology was used. To detect a chromosomal abnormality [6, 7]. Others have reported a CNVs the CytoScan™ 750D array (Afymetrix Inc., Santa 16% incremental CNVs yield by genome-wide screening in Clara, CA, USA) was used in combination with the CytoS- infants with prenatal and postnatal growth retardation asso- can™ 750D Reagent Kit. One array was used for each sam- ciated with dysmorphic features and/or developmental delay ple. The results were analyzed with Chromosome Analysis [8]. However, the high cost of WES and WGS limits their Suite (ChAS) software (Afymetrix, USA) using annotations wide use in clinical practice. CNVs is still one of screening of the genome version GRCH37 (hg19). The array detects methods with reasonable cost-efect. the sample at the resolution level of 50 kb/50 marker dele- In this study, we examined the proportion of pathogenic tion and 100 kb/50 marker repeat. subchromosomal anomalies in pregnancies with SGA fetuses In cases in which CNVs were detected in fetal or neonatal with and without structural defects, to investigate clinical DNA, DNA from the parents (peripheral blood) was exam- value of CNVs screening in both groups of SGA fetuses. ined using the same CytoScan™ 750D array to detect CNVs and establish whether the CNVs were de novo or inherited. In 2016, CNVs were detected by NGS technique, named low-pass whole genome sequencing (WGS). The DNA Methods library was prepared and subjected to deep sequencing using a NextSeq CN500 high-throughput sequencer. The detection Patients sensitivity of low-pass WGS is 100 kb. If Uniparental disomy (UPD) was detected, then link- Outpatient and inpatient singleton pregnant women treated age analysis by polymerase chain reaction (PCR)-based at Beijing Obstetrics and Gynecology Hospital of Capital Sequence-Tagged Site (STS) marker showed which one the Medical University between 2014 and 2016 were selected segmental isodisomy was of parental origin. for this study. Gestational age (GA) was assessed accord- The URLs for data presented herein are as follows: ing to the last menstrual period and the crown-rump length at 11–13 + 6 weeks. All these cases underwent a detailed • Database of Chromosomal Imbalance and Phenotype in ultrasound examination according to the practice guidelines Humans using Ensembl Resources (DECIPHER), https of the International Society of Ultrasound in Obstetrics and ://decip her.sange r.ac.uk/appli catio n/. Gynecology to detect structural anomalies. Fetal weight was • Database of Genomic Variants (DGV), https ://proje cts. estimated (EFW) according to the Hadlock II formula [9]. tcag.ca/varia tion/. An EFW or birth weight below the 10th percentile for GA • Database of Genotype and Phenotype, dbGaP, https :// was defned as SGA [10, 11]. An assessment of the maternal www.ncbi.nlm.nih.gov/gap. infection status (standard TORCH serology including Parvo • Database of Structural Variation, dbVAR, https ://www. virus B19) was performed in all cases. Furthermore, inva- ncbi.nlm.nih.gov/dbvar /. sive testing including cytogenetic karyotyping and CNVs • International Standard Cytogenomic Array Consortium, detection was recommended prenatally. In cases the parents https ://isca.genet ics.emory .edu. opted against invasive testing, above genetic examinations • Online Mendelian Inheritance in Man (OMIM), https :// were carried out after birth if requested. CNVs was detected www.ncbi.nlm.nih.gov/Omim. using CMA from 2014 to 2015, whereas in 2016 they were identifed by new generation sequencing (NGS), named low- All analysis results of CNVs and genes in this study pass whole genome sequencing(WGS). were interpreted by professionally certified clinical 1 3 Archives of Gynecology and Obstetrics (2019) 300:633–639 635 molecular geneticists or genetic experts. Pathological Results CNVs were assessed if they met the following criteria: gene content, overlap with genomic coordinates for a Clinical features known genomic imbalance syndrome, and overlap with a CNVs previously identified in FGR or short stature The study enrolled 85 pregnancies. There were 20 cases subjects. with a fetal defect (Group A) whereas in 65 cases, there was CNVs were classified according to the recommenda- isolated SGA (Group B). All families were of nonconsan- tion of the American College of Medical
Load more

Recommended publications
  • PARSANA-DISSERTATION-2020.Pdf
    DECIPHERING TRANSCRIPTIONAL PATTERNS OF GENE REGULATION: A COMPUTATIONAL APPROACH by Princy Parsana A dissertation submitted to The Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland July, 2020 © 2020 Princy Parsana All rights reserved Abstract With rapid advancements in sequencing technology, we now have the ability to sequence the entire human genome, and to quantify expression of tens of thousands of genes from hundreds of individuals. This provides an extraordinary opportunity to learn phenotype relevant genomic patterns that can improve our understanding of molecular and cellular processes underlying a trait. The high dimensional nature of genomic data presents a range of computational and statistical challenges. This dissertation presents a compilation of projects that were driven by the motivation to efficiently capture gene regulatory patterns in the human transcriptome, while addressing statistical and computational challenges that accompany this data. We attempt to address two major difficulties in this domain: a) artifacts and noise in transcriptomic data, andb) limited statistical power. First, we present our work on investigating the effect of artifactual variation in gene expression data and its impact on trans-eQTL discovery. Here we performed an in-depth analysis of diverse pre-recorded covariates and latent confounders to understand their contribution to heterogeneity in gene expression measurements. Next, we discovered 673 trans-eQTLs across 16 human tissues using v6 data from the Genotype Tissue Expression (GTEx) project. Finally, we characterized two trait-associated trans-eQTLs; one in Skeletal Muscle and another in Thyroid. Second, we present a principal component based residualization method to correct gene expression measurements prior to reconstruction of co-expression networks.
    [Show full text]
  • HOOK3 Is a Scaffold for the Opposite-Polarity Microtubule-Based
    bioRxiv preprint doi: https://doi.org/10.1101/508887; this version posted December 31, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. HOOK3 is a scaffold for the opposite-polarity microtubule-based motors cytoplasmic dynein and KIF1C Agnieszka A. Kendrick1, William B. Redwine1,2†, Phuoc Tien Tran1‡, Laura Pontano Vaites2, Monika Dzieciatkowska4, J. Wade Harper2, and Samara L. Reck-Peterson1,3,5 1Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 92093. 2 Department of Cell Biology, Harvard Medical School, Boston, MA 02115. 3Section of Cell and Developmental Biology, Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093. 4Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, CO 80045. 5Howard Hughes Medical Institute †Present address: Stowers Institute for Medical Research, Kansas City, MO 64110 ‡Present address: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138. *Correspondence to: Samara Reck-Peterson 9500 Gilman Drive, Leichtag 482 La Jolla CA, 92093 [email protected]; https://orcid.org/0000-0002-1553-465X 1 bioRxiv preprint doi: https://doi.org/10.1101/508887; this version posted December 31, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license.
    [Show full text]
  • Environmental Influences on Endothelial Gene Expression
    ENDOTHELIAL CELL GENE EXPRESSION John Matthew Jeff Herbert Supervisors: Prof. Roy Bicknell and Dr. Victoria Heath PhD thesis University of Birmingham August 2012 University of Birmingham Research Archive e-theses repository This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. ABSTRACT Tumour angiogenesis is a vital process in the pathology of tumour development and metastasis. Targeting markers of tumour endothelium provide a means of targeted destruction of a tumours oxygen and nutrient supply via destruction of tumour vasculature, which in turn ultimately leads to beneficial consequences to patients. Although current anti -angiogenic and vascular targeting strategies help patients, more potently in combination with chemo therapy, there is still a need for more tumour endothelial marker discoveries as current treatments have cardiovascular and other side effects. For the first time, the analyses of in-vivo biotinylation of an embryonic system is performed to obtain putative vascular targets. Also for the first time, deep sequencing is applied to freshly isolated tumour and normal endothelial cells from lung, colon and bladder tissues for the identification of pan-vascular-targets. Integration of the proteomic, deep sequencing, public cDNA libraries and microarrays, delivers 5,892 putative vascular targets to the science community.
    [Show full text]
  • Open Dogan Phdthesis Final.Pdf
    The Pennsylvania State University The Graduate School Eberly College of Science ELUCIDATING BIOLOGICAL FUNCTION OF GENOMIC DNA WITH ROBUST SIGNALS OF BIOCHEMICAL ACTIVITY: INTEGRATIVE GENOME-WIDE STUDIES OF ENHANCERS A Dissertation in Biochemistry, Microbiology and Molecular Biology by Nergiz Dogan © 2014 Nergiz Dogan Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy August 2014 ii The dissertation of Nergiz Dogan was reviewed and approved* by the following: Ross C. Hardison T. Ming Chu Professor of Biochemistry and Molecular Biology Dissertation Advisor Chair of Committee David S. Gilmour Professor of Molecular and Cell Biology Anton Nekrutenko Professor of Biochemistry and Molecular Biology Robert F. Paulson Professor of Veterinary and Biomedical Sciences Philip Reno Assistant Professor of Antropology Scott B. Selleck Professor and Head of the Department of Biochemistry and Molecular Biology *Signatures are on file in the Graduate School iii ABSTRACT Genome-wide measurements of epigenetic features such as histone modifications, occupancy by transcription factors and coactivators provide the opportunity to understand more globally how genes are regulated. While much effort is being put into integrating the marks from various combinations of features, the contribution of each feature to accuracy of enhancer prediction is not known. We began with predictions of 4,915 candidate erythroid enhancers based on genomic occupancy by TAL1, a key hematopoietic transcription factor that is strongly associated with gene induction in erythroid cells. Seventy of these DNA segments occupied by TAL1 (TAL1 OSs) were tested by transient transfections of cultured hematopoietic cells, and 56% of these were active as enhancers. Sixty-six TAL1 OSs were evaluated in transgenic mouse embryos, and 65% of these were active enhancers in various tissues.
    [Show full text]
  • Evidence for Differential Alternative Splicing in Blood of Young Boys With
    Stamova et al. Molecular Autism 2013, 4:30 http://www.molecularautism.com/content/4/1/30 RESEARCH Open Access Evidence for differential alternative splicing in blood of young boys with autism spectrum disorders Boryana S Stamova1,2,5*, Yingfang Tian1,2,4, Christine W Nordahl1,3, Mark D Shen1,3, Sally Rogers1,3, David G Amaral1,3 and Frank R Sharp1,2 Abstract Background: Since RNA expression differences have been reported in autism spectrum disorder (ASD) for blood and brain, and differential alternative splicing (DAS) has been reported in ASD brains, we determined if there was DAS in blood mRNA of ASD subjects compared to typically developing (TD) controls, as well as in ASD subgroups related to cerebral volume. Methods: RNA from blood was processed on whole genome exon arrays for 2-4–year-old ASD and TD boys. An ANCOVA with age and batch as covariates was used to predict DAS for ALL ASD (n=30), ASD with normal total cerebral volumes (NTCV), and ASD with large total cerebral volumes (LTCV) compared to TD controls (n=20). Results: A total of 53 genes were predicted to have DAS for ALL ASD versus TD, 169 genes for ASD_NTCV versus TD, 1 gene for ASD_LTCV versus TD, and 27 genes for ASD_LTCV versus ASD_NTCV. These differences were significant at P <0.05 after false discovery rate corrections for multiple comparisons (FDR <5% false positives). A number of the genes predicted to have DAS in ASD are known to regulate DAS (SFPQ, SRPK1, SRSF11, SRSF2IP, FUS, LSM14A). In addition, a number of genes with predicted DAS are involved in pathways implicated in previous ASD studies, such as ROS monocyte/macrophage, Natural Killer Cell, mTOR, and NGF signaling.
    [Show full text]
  • Identifying Glaucoma Susceptibility Genes in Extended Families
    Identifying Glaucoma Susceptibility Genes in Extended Families by Patricia Stacey Graham BSc(Hons), GradDipEd Menzies Institute for Medical Research | College of Health and Medicine Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy (Medical Studies) University of Tasmania, March 2020 Declaration of Originality This thesis contains no material which has been accepted for a degree or diploma by the University or any other institution, except by way of background information and duly acknowledged in the thesis, and to the best of my knowledge and belief no material previously published or written by another person except where due acknowledgement is made in the text of the thesis, nor does the thesis contain any material that infringes copyright. 13/3/2020 i Authority of access This thesis may be made available for loan and limited copying and communication in accordance with the Copyright Act 1968. 13/3/2020 ii Statement of ethical conduct The research associated with this thesis abides by the international and Australian codes on human experimentation and the guidelines and the rulings of the Ethics Committee of the University. Ethics Approval Numbers: University of Tasmania Human Research Ethics Committee H0014085 Oregon Health and Science University Institutional Review Board #1306 13/3/2020 iii Dedication To my parents Susie and Micky Lowry Who instilled in me the love of learning and who would have been so proud iv Acknowledgements What a rollercoaster the last four years have been …. it’s been an amazing ride. Rollercoasters are no fun alone, and I would sincerely like to thank the following people who kept the ride rolling and to those who sat with me in the carriage and didn’t let me fall out.
    [Show full text]
  • Evolution of the DAN Gene Family in Vertebrates
    bioRxiv preprint doi: https://doi.org/10.1101/794404; this version posted June 29, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. RESEARCH ARTICLE Evolution of the DAN gene family in vertebrates Juan C. Opazo1,2,3, Federico G. Hoffmann4,5, Kattina Zavala1, Scott V. Edwards6 1Instituto de Ciencias Ambientales y Evolutivas, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile. 2David Rockefeller Center for Latin American Studies, Harvard University, Cambridge, MA 02138, USA. 3Millennium Nucleus of Ion Channels-Associated Diseases (MiNICAD). 4 Department of Biochemistry, Molecular Biology, Entomology, and Plant Pathology, Mississippi State University, Mississippi State, 39762, USA. Cite as: Opazo JC, Hoffmann FG, 5 Zavala K, Edwards SV (2020) Institute for Genomics, Biocomputing, and Biotechnology, Mississippi State Evolution of the DAN gene family in University, Mississippi State, 39762, USA. vertebrates. bioRxiv, 794404, ver. 3 peer-reviewed and recommended by 6 PCI Evolutionary Biology. doi: Department of Organismic and Evolutionary Biology, Harvard University, 10.1101/794404 Cambridge, MA 02138, USA. This article has been peer-reviewed and recommended by Peer Community in Evolutionary Biology Posted: 29 June 2020 doi: 10.24072/pci.evolbiol.100104 ABSTRACT Recommender: Kateryna Makova The DAN gene family (DAN, Differential screening-selected gene Aberrant in Neuroblastoma) is a group of genes that is expressed during development and plays fundamental roles in limb bud formation and digitation, kidney formation and morphogenesis and left-right axis specification.
    [Show full text]
  • 1 Supporting Information for a Microrna Network Regulates
    Supporting Information for A microRNA Network Regulates Expression and Biosynthesis of CFTR and CFTR-ΔF508 Shyam Ramachandrana,b, Philip H. Karpc, Peng Jiangc, Lynda S. Ostedgaardc, Amy E. Walza, John T. Fishere, Shaf Keshavjeeh, Kim A. Lennoxi, Ashley M. Jacobii, Scott D. Rosei, Mark A. Behlkei, Michael J. Welshb,c,d,g, Yi Xingb,c,f, Paul B. McCray Jr.a,b,c Author Affiliations: Department of Pediatricsa, Interdisciplinary Program in Geneticsb, Departments of Internal Medicinec, Molecular Physiology and Biophysicsd, Anatomy and Cell Biologye, Biomedical Engineeringf, Howard Hughes Medical Instituteg, Carver College of Medicine, University of Iowa, Iowa City, IA-52242 Division of Thoracic Surgeryh, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada-M5G 2C4 Integrated DNA Technologiesi, Coralville, IA-52241 To whom correspondence should be addressed: Email: [email protected] (M.J.W.); yi- [email protected] (Y.X.); Email: [email protected] (P.B.M.) This PDF file includes: Materials and Methods References Fig. S1. miR-138 regulates SIN3A in a dose-dependent and site-specific manner. Fig. S2. miR-138 regulates endogenous SIN3A protein expression. Fig. S3. miR-138 regulates endogenous CFTR protein expression in Calu-3 cells. Fig. S4. miR-138 regulates endogenous CFTR protein expression in primary human airway epithelia. Fig. S5. miR-138 regulates CFTR expression in HeLa cells. Fig. S6. miR-138 regulates CFTR expression in HEK293T cells. Fig. S7. HeLa cells exhibit CFTR channel activity. Fig. S8. miR-138 improves CFTR processing. Fig. S9. miR-138 improves CFTR-ΔF508 processing. Fig. S10. SIN3A inhibition yields partial rescue of Cl- transport in CF epithelia.
    [Show full text]
  • Variation in Protein Coding Genes Identifies Information
    bioRxiv preprint doi: https://doi.org/10.1101/679456; this version posted June 21, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Animal complexity and information flow 1 1 2 3 4 5 Variation in protein coding genes identifies information flow as a contributor to 6 animal complexity 7 8 Jack Dean, Daniela Lopes Cardoso and Colin Sharpe* 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Institute of Biological and Biomedical Sciences 25 School of Biological Science 26 University of Portsmouth, 27 Portsmouth, UK 28 PO16 7YH 29 30 * Author for correspondence 31 [email protected] 32 33 Orcid numbers: 34 DLC: 0000-0003-2683-1745 35 CS: 0000-0002-5022-0840 36 37 38 39 40 41 42 43 44 45 46 47 48 49 Abstract bioRxiv preprint doi: https://doi.org/10.1101/679456; this version posted June 21, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Animal complexity and information flow 2 1 Across the metazoans there is a trend towards greater organismal complexity. How 2 complexity is generated, however, is uncertain. Since C.elegans and humans have 3 approximately the same number of genes, the explanation will depend on how genes are 4 used, rather than their absolute number.
    [Show full text]
  • Snps Detection in DHPS-WDR83 Overlapping Genes Mapping On
    Zambonelli et al. BMC Genetics 2013, 14:99 http://www.biomedcentral.com/1471-2156/14/99 RESEARCH ARTICLE Open Access SNPs detection in DHPS-WDR83 overlapping genes mapping on porcine chromosome 2 in a QTL region for meat pH Paolo Zambonelli1*, Roberta Davoli1, Mila Bigi1, Silvia Braglia1, Luigi Francesco De Paolis1, Luca Buttazzoni2,3, Maurizio Gallo3 and Vincenzo Russo1 Abstract Background: The pH is an important parameter influencing technological quality of pig meat, a trait affected by environmental and genetic factors. Several quantitative trait loci associated to meat pH are described on PigQTL database but only two genes influencing this parameter have been so far detected: Ryanodine receptor 1 and Protein kinase, AMP-activated, gamma 3 non-catalytic subunit. To search for genes influencing meat pH we analyzed genomic regions with quantitative effect on this trait in order to detect SNPs to use for an association study. Results: The expressed sequences mapping on porcine chromosomes 1, 2, 3 in regions associated to pork pH were searched in silico to find SNPs. 356 out of 617 detected SNPs were used to genotype Italian Large White pigs and to perform an association analysis with meat pH values recorded in semimembranosus muscle at about 1 hour (pH1) and 24 hours (pHu) post mortem. The results of the analysis showed that 5 markers mapping on chromosomes 1 or 3 were associated with pH1 and 10 markers mapping on chromosomes 1 or 2 were associated with pHu. After False Discovery Rate correction only one SNP mapping on chromosome 2 was confirmed to be associated to pHu.
    [Show full text]
  • Maternal Diabetes and Obesity Influence the Fetal Epigenome in a Largely Hispanic Population Heather E
    Rizzo et al. Clinical Epigenetics (2020) 12:34 https://doi.org/10.1186/s13148-020-0824-9 RESEARCH Open Access Maternal diabetes and obesity influence the fetal epigenome in a largely Hispanic population Heather E. Rizzo1, Elia N. Escaname2,3, Nicholas B. Alana1,3, Elizabeth Lavender2,3, Jonathan Gelfond3 , Roman Fernandez3, Matthew A. Hibbs1, Jonathan M. King1*, Nicholas R. Carr4 and Cynthia L. Blanco2,3 Abstract Background: Obesity and diabetes mellitus are directly implicated in many adverse health consequences in adults as well as in the offspring of obese and diabetic mothers. Hispanic Americans are particularly at risk for obesity, diabetes, and end-stage renal disease. Maternal obesity and/or diabetes through prenatal programming may alter the fetal epigenome increasing the risk of metabolic disease in their offspring. The aims of this study were to determine if maternal obesity or diabetes mellitus during pregnancy results in a change in infant methylation of CpG islands adjacent to targeted genes specific for obesity or diabetes disease pathways in a largely Hispanic population. Methods: Methylation levels in the cord blood of 69 newborns were determined using the Illumina Infinium MethylationEPIC BeadChip. Over 850,000 different probe sites were analyzed to determine whether maternal obesity and/or diabetes mellitus directly attributed to differential methylation; epigenome-wide and regional analyses were performed for significant CpG sites. Results: Following quality control, agranular leukocyte samples from 69 newborns (23 normal term (NT), 14 diabetes (DM), 23 obese (OB), 9 DM/OB) were analyzed for over 850,000 different probe sites. Contrasts between the NT, DM, OB, and DM/OB were considered.
    [Show full text]
  • Breakpoint Characterization of the Der(19)T(11;19)(Q13;P13) in the Ovarian Cancer Cell Line SKOV-3
    GENES, CHROMOSOMES & CANCER 52:512–522 (2013) Breakpoint Characterization of the der(19)t(11;19)(q13;p13) in the Ovarian Cancer Cell Line SKOV-3 Wiebke Onkes,1 Regina Fredrik,1 Francesca Micci,2,3 Benjamin J Scho¨nbeck,4 Jose I Martin-Subero,5 Reinhard Ullmann,6 Felix Hilpert,1 Karen Bra¨utigam,7 Ottmar Janssen,4 Nicolai Maass,7 Reiner Siebert,8 Sverre Heim,2,3 Norbert Arnold,1 and Jo¨rg Weimer1* 1Department of Obstetrics and Gynaecology,University Medical Center Schleswig-Holstein, Christian-Albrechts University,Kiel, Germany 2Section for Cancer Cytogenetics, Institute for Medical Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway 3Centre for Cancer Biomedicine, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Norway 4Molecular Immunology,Institute of Immunology,University Medical Center Schleswig-Holstein, Kiel,Germany 5Department of Anatomic Pathology,Pharmacology and Microbiology,University of Barcelona, Barcelona, Spain 6Department Human Molecular Genetics, Max Planck Institute for Molecular Genetics,14195 Berlin, Germany 7Department of Gynecology and Obstetrics, University Medical Center RWTH, Aachen, Germany 8Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel/ University Kiel,Germany About 20% of ovarian carcinomas show alterations of 19p13 and/or 19q13 in the form of added extra material whose ori- gin often is from chromosome 11. Based on earlier spectral karyotype analysis of the ovarian cancer cell line SKOV-3, which shows an unbalanced translocation der(19)t(11;19), the aim of this study was to determine the precise breakpoints of that derivative chromosome. After rough delimitation of the breakpoints of microdissected derivative chromosomes by array analysis, we designed a matrix of primers spanning 11q13.2 and 19p13.2 detecting multiple amplicons on genomic and cDNA.
    [Show full text]