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Molekulare Karyotypisierung in der klinischen Anwendung

Molecular karyotyping in the clinical setting

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medizinische genetik

Zusammenfassung

In den vergangenen Jahren hat sich die Anwendung der Mikroarraytechnologie für die Detektion von putativ pathologischen submikroskopischen Copy-Number-Variationen (CNV) einen festen Platz in der molekularen Zytogenetik erobert. Neben der Identifikation somatischer CNV in der onkologischen Diagnostik wird diese Technologie nunmehr für die Analyse von konstitutionellen CNV bei Patienten mit mentaler Retardierung genutzt. Arraybasierte genomische Hybridisierungen zeigen eine deutliche Verbesserung zu der bereits seit Jahren angewendeten komparativen genomischen Hybridisierung (CGH). Insbesondere weisen die dazugehörigen Technologien eine verbesserte Auflösung von weniger als 100 kb für Deletionen und Duplikationen auf und haben damit eine deutlich bessere Aufklärungsrate von Krankheiten mit Behinderungen ungeklärter Ursache. In einigen Zentren gehört die Arraytechnologie daher bereits zur Routinetechnologie der Syndromabklärung. Im vorliegenden Beitrag soll deshalb auch auf die Gemeinsamkeiten bzw. Unterschiede der verschiedenen Basistechnologien der Arraytechnik eingegangen werden.

Abstract

Microarray technology for the detection of putative pathological submicroscopic copy number variants (CNV) has become a standard tool in the field of molecular cytogenetics in recent years. In addition to the identification of somatic CNVs in tumour genetics this technology is increasingly used for the analysis of constitutional CNVs in patients with developmental delay. Array-based genomic hybridisation increases sensitivity in comparison to more conventional technologies such as comparative genomic hybridisation (CGH). Recent developments now allow a genome-wide detection of submicroscopic chromosomal alterations, deletions and duplications smaller than 100 Kb, thus significantly increasing the detection rate of chromosomal aberrations in patients suffering from idiopathic mental retardation. Several centers are already using array technology in their routine setting in the diagnostic approach to syndromes. Therefore, this overview focuses on the similarities, as well as the differences, of several basic array techniques.

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Abbreviations

BAC:

„bacterial artificial chromosome“

CGH:

Komparative genomische Hybridisierung

CNAG:

„Copy number analyser for GeneChip®“

CNP:

Copy-Number-Polymorphismus

CNV:

Copy-Number-Variation

DNA:

Desoxyribonukleinsäure

FISH:

Fluoreszenz-in-situ-Hybridisierung

LOH:

„loss of heterocygosity“

MLPA:

„multiplex ligation-dependent probe amplification“

OMIM :

„online mendelian inheritance in man“

PAC:

„P1 artificial chromosome“

PCR:

Polymerasekettenreaktion

qPCR:

Quantitative Polymerasekettenreaktion

qRT-PCR:

Quantitative Real-Time-Polymerasekettenreaktion

SNP:

„single nucleotide polymorphism“

TAR:

„thrombocytopenia-absent radius syndrome“

UPD:

Uniparentale Disomie

YAC:

„yeast artificial chromosome“

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  1. Abteilung Medizinische Genetik, Universität Tübingen, Calwer Straße 7, 72076, Tübingen, Deutschland

    A. Dufke, O. Riess & M. Bonin

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  1. A. Dufke
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  2. O. Riess
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  3. M. Bonin
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Correspondence to A. Dufke.

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Dufke, A., Riess, O. & Bonin, M. Molekulare Karyotypisierung in der klinischen Anwendung. medgen 20, 419–431 (2008). https://doi.org/10.1007/s11825-008-0112-0

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  • DOI: https://doi.org/10.1007/s11825-008-0112-0

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