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Tools for genetics and genomics: Cytogenetics and molecular genetics

Authors
Iris Schrijver, MD
James L Zehnder, MD
Athena M Cherry, PhD
Section Editor
Benjamin A Raby, MD, MPH
Deputy Editor
Jennifer S Tirnauer, MD

INTRODUCTION

Intense genetic research has exponentially increased our knowledge of the genetic code of humans and other organisms, leading to the development of numerous methods that facilitate our understanding of normal and abnormal genetic processes. Many of these methods and related techniques are now routinely used in the molecular diagnosis of both inherited disorders and diseases that result from somatic mutations, such as the hematologic malignancies. Molecular genetic and cytogenetic diagnostics are invaluable additions to laboratory testing and clinical evaluation, providing diagnostic, therapeutic, and prognostic information. (See "Genetic abnormalities in hematologic and lymphoid malignancies".)

Although the advent of improved and faster molecular methods has transformed the traditional diagnostic process, keeping current with the most recent advances is daunting [1]. A conceptual approach to a selection of the most common standard and novel diagnostic tools will be applied to this review. An outline of the advantages and limitations of each of the techniques is included, as well as some examples of their applications. A brief introduction to the terms required to properly understand these applications is provided separately. (See "Principles of molecular genetics".)

Three general categories of testing can be distinguished.

Mutation detection of known sequence changes can be performed. This type of testing is targeted and typically limited to a predefined number of sequence changes, selected in advance. Selection is generally based on association with clinical phenotypes. Sequence changes may be located within a single gene or across multiple genes. Depending on the testing method used, the number of included sequence changes can range from a single mutation to thousands of mutations.

Cytogenetic studies of large structural variants are typically performed when the phenotype does not seem limited to point mutations and relatively small deletions and duplications. Such studies are helpful in syndromic phenotypes and for constellations of symptoms typically associated with abnormalities on the scale of chromosomes rather than single exons or genes.

                   

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Literature review current through: Nov 2016. | This topic last updated: Wed Mar 16 00:00:00 GMT 2016.
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References
Top
  1. Zamicnikova A. Genetic testing methods in myelodysplastic syndromes and leukemias: A review. Clin Leukemia 2007; 1:331.
  2. Haliassos A, Chomel JC, Grandjouan S, et al. Detection of minority point mutations by modified PCR technique: a new approach for a sensitive diagnosis of tumor-progression markers. Nucleic Acids Res 1989; 17:8093.
  3. Newton CR, Graham A, Heptinstall LE, et al. Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucleic Acids Res 1989; 17:2503.
  4. Schrijver I, Liu W, Francke U. The pathogenicity of the Pro1148Ala substitution in the FBN1 gene: causing or predisposing to Marfan syndrome and aortic aneurysm, or clinically innocent? Hum Genet 1997; 99:607.
  5. Shaughnessy J, Tian E, Sawyer J, et al. High incidence of chromosome 13 deletion in multiple myeloma detected by multiprobe interphase FISH. Blood 2000; 96:1505.
  6. van Ommen GJ, Breuning MH, Raap AK. FISH in genome research and molecular diagnostics. Curr Opin Genet Dev 1995; 5:304.
  7. Haralambieva E, Banham AH, Bastard C, et al. Detection by the fluorescence in situ hybridization technique of MYC translocations in paraffin-embedded lymphoma biopsy samples. Br J Haematol 2003; 121:49.
  8. Schröck E, Veldman T, Padilla-Nash H, et al. Spectral karyotyping refines cytogenetic diagnostics of constitutional chromosomal abnormalities. Hum Genet 1997; 101:255.
  9. Jalal SM, Law ME, Stamberg J, et al. Detection of diagnostically critical, often hidden, anomalies in complex karyotypes of haematological disorders using multicolour fluorescence in situ hybridization. Br J Haematol 2001; 112:975.
  10. Hilgenfeld E, Padilla-Nash H, McNeil N, et al. Spectral karyotyping and fluorescence in situ hybridization detect novel chromosomal aberrations, a recurring involvement of chromosome 21 and amplification of the MYC oncogene in acute myeloid leukaemia M2. Br J Haematol 2001; 113:305.
  11. Kallioniemi A, Kallioniemi OP, Sudar D, et al. Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 1992; 258:818.
  12. Aradhya S, Cherry AM. Array-based comparative genomic hybridization: clinical contexts for targeted and whole-genome designs. Genet Med 2007; 9:553.
  13. Papenhausen P, Schwartz S, Risheg H, et al. UPD detection using homozygosity profiling with a SNP genotyping microarray. Am J Med Genet A 2011; 155A:757.
  14. Nagamine CM, Chan K, Lau YF. A PCR artifact: generation of heteroduplexes. Am J Hum Genet 1989; 45:337.
  15. Hayashi K. PCR-SSCP: a method for detection of mutations. Genet Anal Tech Appl 1992; 9:73.
  16. Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 1975; 98:503.