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Sports Cardiology Essentials pp 85–100Cite as

Role of Genetic Testing for Sudden Death Predisposing Heart Conditions in Athletes

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Abstract

Sudden death in a young competitive athlete occurs with a prevalence of approximately 1 per 100,000 athletes per year [2, 3]. Despite its rarity, the sudden death of an athlete is devastating to both the family and community.

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Notes

  1. 1.

    1 Dr. Ackerman is a consultant for Boston Scientific, Medtronic, PGxHealth, and St. Jude Medical, Inc. and chairs PGxHealth’s Scientific Advisory Board with respect to their FAMILIONTM genetic tests for heritable channelopathies and cardiomyopathies. There is a royalty relationship between PGxHealth and Mayo Clinic Health Solutions with respect to genetic testing for long QT syndrome and catecholaminergic polymorphic ventricular tachycardia.

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Author information

Authors and Affiliations

  1. Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA

    Andrew P. Landstrom

  2. Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA

    Andrew P. Landstrom

  3. Division of Pediatric Cardiology, Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, USA

    Andrew P. Landstrom

Authors
  1. Andrew P. Landstrom
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  2. David J. Tester
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  3. Michael J. Ackerman
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Editor information

Editors and Affiliations

  1. Sports Cardiology Consultants, LLC, Chicago, 60654, Illinois, USA

    Christine E. Lawless

Glossary

Dideoxy DNA sequencing

To directly determine a DNA sequence, a primer binds to the region of interest on the sample DNA and initiates polymerization of DNA which is terminated in small amounts after each nucleotide addition. Each resulting oligonucleotide is labeled with a fluorescent tag identifying the sequence of the final nucleotide. The collection of fluorescent products is separated based on size, where the smallest fragment represents the first sequenced nucleotide, and the sequence is determined by the order of the nucleotide-specific fluorescent signals. Generally, this can yield a DNA sequence up to 800 nucleotides per reaction.

Exon

DNA sequence of a gene that is present in the mature mRNA after splicing removal of introns. Generally, the exonic DNA sequence ultimately codes for the corresponding amino acid sequence of the protein. There is exonic sequence at the termini of the mature mRNA of variable lengths which do not code for protein in this manner and remain untranslated (5′ and 3′ untranslated regions).

Gene

The basic hereditary unit of life which, in humans, is composed of a DNA sequence traditionally containing “coding” exonic sequence that is ultimately transcribed into mRNA and translated into protein as well as intervening “noncoding” intronic sequences which are removed during transcription and do not code for protein.

Genome

The hereditary information of an organism encoded by nucleic acid including all chromosomes. In humans, there are two complete homologous sets of DNA – one paternal and one maternal – and are thus considered diploid genomes.

Germline

The cells within an organism that pass genetic information to progeny. In humans, this refers to sperm and egg cells specifically.

Intron

A gene’s DNA sequence that is removed during splicing of the mature mRNA and does not ultimately code for protein during translation.

Mutation

Changes in the DNA sequence of an organism. In humans, mutations can generally be described as synonymous (does not ultimately alter the coding protein sequence) or nonsynonymous (does ultimately alter the original coding sequence). Nonsynonymous mutations include missense (altering a single amino acid), nonsense (changes an amino acid to a stop codon which truncates the protein), and insertion/deletion (addition or subtraction of DNA which often shifts the open reading frame of the gene resulting in an altered, “frame-shifted,” protein sequence after that point and usually an early truncation of the protein). For the hypertrophic cardiomyopathy-associated missense mutation, TNNT2-R92W, for example, the DNA mutation has changed an arginine amino acid (R) to a tryptophan (W) at position 92 of the protein troponin T which is encoded by TNNT2.

Next-generation DNA sequencing

A conglomeration of recently developed DNA sequencing methodologies capable of sequencing over 20 × 109 nucleotides per reaction depending on the platform [1].

Oligonucleotide hybridization mutation detection

Sample (patient) DNA is fluorescently labeled and exposed to a microarray chip containing thousands of short sequences of DNA (oligonucleotides) corresponding to mutated sequences of the genes of interest. If a mutation is present in the patient, it will bind (hybridize) to the known oligonucleotide on the chip and deliver an identifiable fluorescent signal.

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Landstrom, A.P., Tester, D.J., Ackerman, M.J. (2011). Role of Genetic Testing for Sudden Death Predisposing Heart Conditions in Athletes. In: Lawless, C. (eds) Sports Cardiology Essentials. Springer, New York, NY. https://doi.org/10.1007/978-0-387-92775-6_5

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  • DOI: https://doi.org/10.1007/978-0-387-92775-6_5

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