With a new examination method, scientists of the Charité – Universitätsmedizin Berlin and the Max-Planck-Institute for Molecular Genetics Berlin have deciphered the cause of a special form of congenital malformation of the skull and fingers. The genetic cause for this disease lies in a region of the human genome, which is loosely referred to as "gene desert". Its function is still largely unknown, because this part of the genome has no protein-coding properties, that is, no blueprints for proteins. The results of the research group of Dr. Eva Klopocki and Prof. Stefan Mundlos, Director, Institute of Medical Genetics and Human Genetics at the Charité, are published in the current issue of the "American Journal of Human Genetics"*.They show important functions performed by this part of the human genome
The object of their research was a rare, inheritable disease which is transmitted with a likelihood of 50 percent by affected parents to their offspring. In this disease, the so-called “Philadelphia type craniosynostosis”, in addition to the premature closure of cranial sutures, a fusion of individual fingers is also observed. By means of a special method the scientists could show that a specific gene is not responsible for the formation of this defect; but a changed "enhancer" element, a regulator, which lies in the non-protein-coding part of the genome and faultily controls the relevant gene during embryonic development. This so-called "gene chip diagnostics“, makes it possible to detect very small chromosomal changes which are not visible in conventional chromosome analysis.
„We know now where we must put forth therapies for this hereditary disease“, explained Prof. Mundlos. "The really fascinating thing is the insight we gained into the complex interaction of the protein-coding and non-coding part of the genome. The so-called 'gene desert' contains regulators which must switch genes and proteins on and off during embryonic development at precisely the right time and place in order to create complex structures, such as hands and skulls. "Here lies a treasure trove for future research."
*Klopocki E. et al. Copy-Number Variations Involving the IHH Locus Are Associated with Syndactyly and Craniosynostosis. American Journal of Human Genetics. 2011 Jan 7;88(1):70-5. doi:10.1016/j.ajhg.2010.11.006
Prof. Stefan Mundlos
Institut für Medizinische Genetik und Humangenetik
t: +49 30 450 569 121
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