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Transfus Med Hemother. 2009 August; 36(4): 244–245.
PMCID: PMC2941828

The ‘Whole Genome Age’

The development and application of highly parallel molecular assay technologies started almost 20 years ago. The first microarray systems were developed for the complex analysis of gene expression with several hundred parameters in one assay [1]. Within a few years the complexity of the array systems was significantly increased so that all known and unknown (hypothetical) genes of the human genome could be analyzed in one single assay. This represented the basis for the first whole-genome analysis at the level of gene expression (mRNA). Nowadays, a whole-genome RNA profile includes about 40,000 parameters (e.g. Whole Human Genome Microarrays; Agilent Technologies, Böblingen, Germany), and the use of such microarrays has become standard in molecular genetic investigation in almost all fields of biological research.

Only few years ago the development of assay systems for highly parallel whole-genome genotyping started, and the first systems were also based on the microarray technology [2]. The aim was the analysis of a maximum number of genomic polymorphisms within one assay. Genomic polymorphisms can be found dispersed throughout the entire genome, and the most abundant and probably most important types of polymorphisms are i) single nucleotide polymorphisms (SNPs) [3] and ii) copy number variations (CNVs) [4]. The whole-genome assay systems for the highly parallel genotyping are mostly focused on these types of polymorphisms, and current microarray-based platforms enable the parallel genotyping of almost 2 million markers (about 1 million SNPs and 1 million CNVs) dispersed throughout the human genome (Genomewide Human SNP Array 6.0; Affymetrix, Santa Clara, CA, USA). Such technologies opened up the chance for so-called Genomewide association studies (GWAS) in which the genomic profiles of patients and healthy control individuals are compared in order to identify new genetic markers associated with the development of a complex multifactorial disease. Recently, GWAS led to the identification of novel risk genes for cardiovascular disease and myocardial infarction [5, 6]. The SNP array technology also offers new possibilities in the Genomewide detection of CNVs such as loss of heterozygosity or uniparental disomy. In this issue of TRANSFUSION MEDICINE AND HEMOTHERAPY the article by Nowak and colleagues [7] describes the scope of SNP array-based whole-genome analysis for detection of such abnormalities.

In addition to the SNP array technology, other assay systems suitable for whole-genome genotyping were developed. The so-called next-generation sequencing technologies are based on different principles and are used for de novo sequencing and re-sequencing of an entire genome or to analyze gene expression by measuring RNA abundance [8, 9]. Furthermore, the adaptation of mass spectrometry, especially matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), to molecular DNA analysis provided another powerful tool for high-throughput genotyping. However, current platforms were rather conceived for high sample throughput than for high complexity of parameters. The principles and applications of MALDI-TOF MS in genome research and diagnostic applications are summarized in two articles in the present issue [10, 11]. Current and future diagnostic applications of MALDI-TOF MS also include genotyping for blood cell antigens, such as leukocyte antigens (HLA) [12] or platelet antigens (HPA) [13]. Finally, new technologies based on the use of color-coded microbeads (Luminex™ technology; Luminex Corporation, Austin, TX, USA) were introduced and also enable a highly parallel analysis of different parameters. The bead technology appears to be suitable not only for genetic testing but also for antibody characterization. In the article by Heinemann [14] the combination of the two approaches on the same platform for Histocompatibility testing is described.

The introduction of whole-genome assay systems heralded the ‘whole genome age’, at least in biomedical research. However, when thinking about the use of whole-genome approaches in diagnostic medicine a number of ethical and legal aspects arise:

  • – Mutation scanning of a patient's genome based on a certain clinical indication may additionally identify susceptibility genes for other diseases. Is it the doctor's responsibility to inform the patient about such genetic risk factors, or is it the patient's right not to be upset by such information?
  • – The knowledge about genetic risk factors for certain diseases is of great interest especially to health insurances or employers. How can the abuse of personal genetic data be avoided?
  • – Informed written consent of the patient is an important prerequisite to perform genetic testing. Is a truly informed consent of laymen possible?

On April 24, 2009 the German government passed a new law about genetic diagnosis (Gendiagnostikgesetz; GenDG). The law strengthens the rights of patients to decide about being or not being informed about genetic risk factors. Among other things the GenDG i) bans discrimination because of genetic traits, ii) defines informed written consent of the patient as a mandatory prerequisite to perform genetic testing, iii) ascertains that the information of genetic data is understandably explained to patients, and iv) defines rules for the storage and elimination of biological material and genetic data. Against the background of the German law and similar laws in other countries, the application of whole-genome genetic testing in diagnostic medicine seems rather challenging. Doctors, human geneticists, and patients may hardly evaluate the impact of each genetic marker detectable by a Genomewide approach. Whether whole-genome genetic testing in diagnostic medicine is a chance for improved personalized diagnosis and treatment or provides too much information for doctors and patients need to be discussed in detail (see commentary by Henn [15] in this issue).


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Articles from Transfusion Medicine and Hemotherapy are provided here courtesy of Karger Publishers