Advertisement

Genetic and Epigenetic Basis of Development and Disease

  • Peter A. KaubEmail author
  • Christopher P. Barnett

Abstract

This chapter aims to give an overview of the basis, forms, and output of genetic testing. It is intended to be a quick introductory reference and primer to more detailed sources, such as the references (predominantly reviews) and many online sources cited. Divided into two parts, the first section aims to outline genetic structures and their modes of inheritance to explain the genetic basis of disease. The second section gives an overview of the main technologies currently available for genetic testing, outlining the basic concepts underpinning each test, simple laboratory considerations, plus some commentary on result interpretation and limitations. Useful if read in its entirety, this chapter is also designed to allow easy reference and jumping between sections if only after a definition, refresher of theory, or specific details of a test, technology, or online database.

Keywords

Human genome Genetic structures Deoxyribonucleic acid (DNA) Ribonucleic acid (RNA) Chromosome Ploidy Cytogenetics Karyotype Mutation Nomenclature Databases Mendelian inheritance Next-generation sequencing Sex-linked inheritance Epigenetics Epigenome 

References

  1. 1.
    HGNC. HUGO Gene Nomenclature Committee; Available from http://www.genenames.org/.
  2. 2.
    Anonymous. DNA replication: how genetic information is passed on, 3d animation with narration. The Cold Spring Harbor Laboratory. Available from www.dnalc.org/view/15530-DNA-replication-how-genetic-information-is-passed-on-3D-animation-with-narration.html.
  3. 3.
    Anonymous. Codons and amino acids. Hum Genome Var Soc. Available from www.hgvs.org/mutnomen/codon.html. 4 Jan 2015.
  4. 4.
    Ward AJ, Cooper TA. The pathobiology of splicing. J Pathol. 2010;220:152–63.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Trent RJ. Molecular medicine: genomics to personalized healthcare. 4th ed. Amsterdam: Elsevier/AP; 2012.Google Scholar
  6. 6.
    Anonymous. Genbank. National Institutes of Health. Available from ncbi.nlm.nih.gov/genbank. 4 Jan 2015.
  7. 7.
    Anonymous. Ensembl European Molecular Biology Laboratory. Available from www.ensembl.org. 4 Jan 2015.
  8. 8.
    Anonymous. DNA Databank of Japan. Available from www.ddbj.nig.ac.jp. 4 Jan 2015.
  9. 9.
    Anonymous. International Nucleotide Sequence Database Collaboration. Available from www.insdc.org. 4 Jan 2015.
  10. 10.
    Anonymous. Ucsc Genome Bioinformatics. University of California, Santa Cruz. Available from http://genome.ucsc.edu. 4 Jan 2015.
  11. 11.
    Anonymous. Vega genome browser. Wellcome Trust Sanger Institute. Available from http://vega.sanger.ac.uk/index.html. 4 Jan 2015.
  12. 12.
    Anonymous. The Atlas For Genetics and Cytogenetics in Oncology and Haematology. Available from http://atlasgeneticsoncology.org/Educ/NomMutID30067ES.html. 4 Jan 2015.
  13. 13.
    Wain HMBE, Lovering RC, Lush MJ, Wright MW, Povey S, HUGO Gene Nomenclature Committee. Guidelines for human gene nomenclature. Genomics. 2002;79:464–70.CrossRefGoogle Scholar
  14. 14.
    Anonymous. Quick reference – simple examples description of sequence changes. Hum Genome Var Soc. Available from www.hgvs.org/mutnomen/quickref.html. Updated Jan 2011, 4 Jan 2015.
  15. 15.
    Anonymous. Recommendations for the description of sequence variants. Hum Genome Var Soc. Available from www.hgvs.org/mutnomen/recs.html. Updated 8 Jul 2013, 4 Jan 2015.
  16. 16.
    Anonymous. dbsnp short genetic variations. NCBI. Available from www.ncbi.nlm.nih.gov/projects/SNP. 4 Jan 2015.
  17. 17.
    Anonymous. Online Mendelian Inheritance in Man® (OMIM). An online catalog of human genes and genetic disorders OMIM. Available from www.omim.org. 4 Jan 2015.
  18. 18.
    Anonymous. dbgap. National Center for Biotechnology Information (NCBI). Available from www.ncbi.nlm.nih.gov/gap. 4 Jan 2015.
  19. 19.
    Köhler SDS, Mungall CJ, Bauer S, Firth HV, Bailleul-Forestier I, et al. The human phenotype ontology project: linking molecular biology and disease through phenotype data. 2014. Available from: www.human-phenotype-ontology.org. 4 Jan 2015.
  20. 20.
    Groth P KI, Kirov I, Traikov B, Leser U, Weiss B. PhenomicDB. Available from: www.phenomicdb.de. Updated 19 Sept 2014, 4 Jan 2015.
  21. 21.
    Anonymous. Enzyme nomenclature database. International Union of Biochemistry and Molecular Biology (IUBMB) Nomenclature. Available from http://expasy.org/enzyme. 4 Jan 2015.
  22. 22.
    Anonymous. Roadmap Epigenomics Project. NIH Roadmap Epigenomics Mapping Consortium. Available from www.roadmapepigenomics.org/overview. 4 Jan 2015.
  23. 23.
    KEGG: Kyoto Encyclopedia of Genes and Genomes. Kanehisa Laboratories; a useful compilation of biochemical pathways and biological basis of drug interactions. Available from: www.genome.jp/kegg.4 Jan 2015.
  24. 24.
    Wright MW. A short guide to long non-coding RNA gene nomenclature. Hum Genomics. 2014;8:7.CrossRefGoogle Scholar
  25. 25.
    Anonymous. Catalogue of somatic mutations in cancer (cosmic). Wellcome Trust Sanger Institute. Available from http://cancer.sanger.ac.uk/cosmic. 4 Jan 2015.
  26. 26.
    International Standing Committee on Human Cytogenetic Nomenclature, Shaffer LG, McGowan-Jordan J, Schmid M. ISCN 2013: an international system for human cytogenetic nomenclature (2013). Basel: Karger; 2013.Google Scholar
  27. 27.
    Anonymous. Genetics Home Reference. U.S. National Library of Medicine. Available from http://ghr.nlm.nih.gov. Updated 12 Jan 2015, 15 Jan 2015.
  28. 28.
    Anonymous. Scitable. Nat Educ. Available from www.nature.com/scitable. 4 Jan 2015.
  29. 29.
    Anonymous. Fact sheets about genetic and genomic science. National Human Genome Research Institute (NHGRI). Available from www.genome.gov/10000202. Updated 7 Aug 2014, 4 Jan 2015.
  30. 30.
    Castillo-Fernandez JE, Spector TD, Bell JT. Epigenetics of discordant monozygotic twins: implications for disease. Genome Med [Rev]. 2014;6:60.CrossRefGoogle Scholar
  31. 31.
    Lee JT, Bartolomei MS. X-inactivation, imprinting, and long noncoding RNAs in health and disease. Cell. 2013;152:1308–23.CrossRefGoogle Scholar
  32. 32.
    Kalish JM, Jiang C, Bartolomei MS. Epigenetics and imprinting in human disease. Int J Dev Biol. 2014;58:291–8.CrossRefGoogle Scholar
  33. 33.
    Anonymous. Video animation: RNA interference. Nature Publishing Group; animation of RNAi mechanism. Available from www.nature.com/nrg/multimedia/rnai/animation/index.html. 4 Jan 2015.
  34. 34.
    Barlow DP, Bartolomei MS. Genomic imprinting in mammals. Cold Spring Harb Perspect Biol. 2014;6.pii: a018382.Google Scholar
  35. 35.
    Anonymous. Long Noncoding Rna Database v2.0: the reference database for functional long noncoding RNAs. Garvan Institute. Available from www.lncrnadb.org. Updated 3 Sept 2014, 4 Jan 2015.
  36. 36.
    Anonymous. International Human Epigenome Consortium. Available from www.ihec-epigenomes.org. 4 Jan 2015.
  37. 37.
    Anonymous. Hep: Human Epigenome Project. Available from www.epigenome.org. 4 Jan 2015.
  38. 38.
    Bae JB. Perspectives of international human epigenome consortium. Genomics Inf. 2013;11:7–14.CrossRefGoogle Scholar
  39. 39.
    Schmidt EE PO, Buhlmann S, Kerr G, Horn T, Boutros M. Genomernai: a database for cell-based and in vivo rnai phenotypes. Available from www.genomernai.org. 4 Jan 2015.
  40. 40.
    Eijk-Van Os PG, Schouten JP. Multiplex ligation-dependent probe amplification (mlpa®) for the detection of copy number variation in genomic sequences. Methods Mol Biol. 2011;688:97–126.CrossRefGoogle Scholar
  41. 41.
    Sørensen KM, Agergaard P, Olesen C, Andersen PS, Larsen LA, Ostergaard JR, et al. Detecting 22q11.2 deletions by use of multiplex ligation-dependent probe amplification on DNA from neonatal dried blood spot samples. J Mol Diagn. 2010;12:147–51.CrossRefGoogle Scholar
  42. 42.
    Sørensen KM, El-Segaier M, Fernlund E, Errami A, Bouvagnet P, Nehme N, et al. Screening of congenital heart disease patients using multiplex ligation-dependent probe amplification: early diagnosis of syndromic patients. Am J Med Genet A. 2012;158A:720–5.CrossRefGoogle Scholar
  43. 43.
    Furtado LV, Paxton CN, Jama MA, Tripp SR, Wilson AR, Lyon E, et al. Diagnostic utility of microsatellite genotyping for molar pregnancy testing. Arch Pathol Lab Med. 2013;137:55–63.CrossRefGoogle Scholar
  44. 44.
    Manning M, Hudgins L, Professional Practice and Guidelines Committee. Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genet Med. 2010;12:742–5.CrossRefGoogle Scholar
  45. 45.
    Bianchi DW, Parker RL, Wentworth J, Madankumar R, Saffer C, Das AF, et al. DNA sequencing versus standard prenatal aneuploidy screening. N Engl J Med. 2014;370:799–808.CrossRefGoogle Scholar
  46. 46.
    Hudecova I, Sahota D, Heung MM, Jin Y, Lee WS, Leung TY, et al. Maternal plasma fetal DNA fractions in pregnancies with low and high risks for fetal chromosomal aneuploidies. PLoS One. 2014;9:e88484.CrossRefGoogle Scholar
  47. 47.
    Liao C, Yin AH, Peng CF, Fu F, Yang JX, Li R, et al. Noninvasive prenatal diagnosis of common aneuploidies by semiconductor sequencing. Proc Natl Acad Sci U S A. 2014;111:7415–20.CrossRefGoogle Scholar
  48. 48.
    Wang JC, Sahoo T, Schonberg S, Kopita KA, Ross L, Patek K, et al. Discordant noninvasive prenatal testing and cytogenetic results: a study of 109 consecutive cases. 2015;17:234–6.Google Scholar
  49. 49.
    Anonymous. Genome Analysis Toolkit (gatk). The Broad Institute. Available from www.broadinstitute.org/gatk. 4 Jan 2015.
  50. 50.
    Wallis YPS, McAnulty C, Bodmer D, Sistermans E, Robertson K, Moore D, et al. Practice guidelines for the evaluation of pathogenicity and the reporting of sequence variants in clinical molecular medicine. Association for Clinical Genetic Science (ACGS), Dutch Society of Clinical Laboratory Specialists (VKGL) http://www.acgs.uk.com/media/774853/evaluation_and_reporting_of_sequence_variants_bpgs_june_2013_-_finalpdf.pdf. 2013.
  51. 51.
    Anonymous. 1000 Genomes A Deep Catalog of Human Genetic Variation. The 1000 Genomes Project. Available from www.1000genomes.org. 4 Jan 2015.
  52. 52.
    Anonymous. 1000 genomes browser. National Center for Biotechnology Information (NCBI). Available from www.ncbi.nlm.nih.gov/variation/tools/1000genomes. 4 Jan 2015.
  53. 53.
    Anonymous. International HapMap project. Available from http://hapmap.ncbi.nlm.nih.gov. 4 Jan 2015.
  54. 54.
    Anonymous. Exome Variant Server. NHLBI Exome Sequencing Project (ESP). Available from http://evs.gs.washington.edu/EVS. 4 Jan 2015.
  55. 55.
    Anonymous. SnpEff. Available from http://snpeff.sourceforge.net/SnpEff_manual.html. 4 Jan 2015.
  56. 56.
    Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. Polyphen-2 prediction of functional effects of human nsSNPs. Harvard; Available from http://genetics.bwh.harvard.edu/pph2. 4 Jan 2015.
  57. 57.
    Anonymous. Sift. J. Craig Venter Institute. Available from http://sift.jcvi.org. 4 Jan 2015.
  58. 58.
    Anonymous. The Human Gene Mutation Database. The Institute of Medical Genetics in Cardiff. Available from www.hgmd.cf.ac.uk. 4 Jan 2015.
  59. 59.
    Anonymous. GeneTests™. Available from www.genetests.org. Updated 15 Jan 2015, 4 Jan 2015.
  60. 60.
    Jamuar SS, Lam AT, Kircher M, D’Gama AM, Wang J, Barry BJ, et al. Somatic mutations in cerebral cortical malformations. N Engl J Med. 2014;371:733–43.CrossRefGoogle Scholar
  61. 61.
    Reid JG, Carroll A, Veeraraghavan N, Dahdouli M, Sundquist A, English A, et al. Launching genomics into the cloud: deployment of mercury, a next generation sequence analysis pipeline. BMC Bioinf. 2014;15:30.Google Scholar
  62. 62.
    Lohmann K, Klein C. Next generation sequencing and the future of genetic diagnosis. Neurother: J Am Soc Exp NeuroTher. 2014;11:699–707.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing 2015

Authors and Affiliations

  1. 1.Genetics and Molecular Pathology, SA PathologyWomen’s and Children’s Hospital, Royal Adelaide Hospital and University of AdelaideAdelaideAustralia
  2. 2.Paediatric and Reproductive Genetics UnitWomen’s and Children’s HospitalNorth AdelaideAustralia

Personalised recommendations