Professor Dr. Hans-Hilger Ropers
Emeritus Scientific Member
Hans-Hilger Ropers studied medicine in Freiburg and Munich. From 1984 to 1997, he headed the Institute for Human Genetics at the University of Nijmegen, The Netherlands, and in 1994, he became Director at the Max Planck Institute for Molecular Genetics (MPIMG) and Professor for Human Genetics at the Free University in Berlin, Germany. From 2008 and 2014, he also served as Secretary of the Biomedical Class of the (former Prussian) Berlin-Brandenburg Academy of Science (BBAW). Since 2014 he is Director emeritus (active) at the MPIMG as well as Clinical Geneticist and Senior Adviser at the Institute of Human Genetics, University of Mainz, Germany.
As MD and first-generation Board-Certified Clinical Geneticist, Hans-Hilger Ropers has a long-standing interest in the molecular elucidation, diagnosis, prevention and treatment of genetic disorders. In the 1980ies, he was an active member of the Gene Mapping Community, acting as Chromosome Chair and Co-Chair at all Human Genome Mapping Conferences between 1985 and 1993, and from 2003 to 2011, he served as Council and Program Committee member of the Human Genome Organization (HUGO).
In the early 1990ies, he and his coworkers were among the first to employ positional cloning strategies for systematically identifying the molecular causes of Mendelian disorders, with a focus on X-linked blindness, deafness and mental retardation. As members of the European X-linked Mental Retardation Consortium (*1995), they made seminal contributions to the elucidation and diagnosis of X-linked intellectual disability (XLID). Together with N. Tommerup (Copenhagen), they were also involved in the first systematic effort to characterize disease-associated balanced chromosome rearrangements; moreover, they were among the first to describe copy number variants in complex disorders other than ID. In 2004, when XLID turned out to be less common than previously thought, Hans-Hilger Ropers and his partner H. Najmabadi (Tehran) set out to study autosomal recessive forms of ID (ARID) in a systematic manner. By pioneering the use of SNP arrays for large-scale autozygosity mapping in consanguineous ARID families, they demonstrated that ARID is extremely heterogeneous. Another milestone was the early adoption of Next Generation Sequencing (NGS) techniques in 2007, which added a new dimension to the molecular elucidation of X-linked and autosomal ID.
Hans-Hilger Ropers was an early critic of the world-wide search for common genetic markers of complex diseases, which he characterized as futile and ‘a waste of time’ (FAZ, 2001). He was among the first to point out that for the vast majority of complex diseases, common genetic markers are unlikely to exist (Am. J. Hum. Genet. 2007), and he argued that genome research should focus on monogenic diseases instead (Dialogues in Clin. Neurosci. 2010; Max-Planck-Jahrbuch 2011). Later on, he repeatedly urged the German government to emulate the Genomics England project that had started in 2012 (BBAW 2013) and to implement next generation sequencing techniques into genetic health care (Ropers, Konrad-Adenauer-Stiftung (KAS) 2018; Arnold et al, KAS 2019).
Hans-Hilger Ropers is member of the Royal Dutch Academy of Sciences (since 2002) and the BBAW (since 2003), Honorary Member of the German Society of Human Genetics and recipient of its Medal of Honor (2009). In 2014 he received the Scientific Award of the European Organization for Rare Diseases (EURORDIS), and in 2015 he was awarded an honorary PhD by the University of Social Welfare and Rehabilitation, Tehran.
Selected original articles
Effect of inbreeding on intellectual disability revisited by trio sequencing
Clin Genet 2019 Jan;95(1):151-159. Epub 2018 Nov 19.
Genetics of intellectual disability in consanguineous families.
Mol Psychiatry. 2019 Jul;24(7):1027-1039. Epub 2018 Jan 4.
X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes.
Mol Psychiatry. 2016 Jan;21(1):133-48. Epub 2015 Feb 3.
Penetrance of pathogenic mutations in haploinsufficient genes for intellectual disability and related disorders.
Eur J Med Genet. 2015 Dec;58(12):715-8. Epub 2015 Oct 24.
Integrated sequence analysis pipeline provides one-stop solution for identifying disease-causing mutations.
Hum Mutat. 2014 Dec;35(12):1427-35.
De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndrome.
Genome Med. 2013 Feb 5;5(2):11. eCollection 2013.
Mutations in NSUN2 cause autosomal-recessive intellectual disability.
Am J Hum Genet. 2012 May 4;90(5):847-55. Epub 2012 Apr 26.
Deep sequencing reveals 50 novel genes for recessive cognitive disorders.
Nature 2011 Sep 21;478(7367):57-63.
A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation.
Nat Genet. 2009 May; 41(5):535-43. Epub 2009 Apr 19.
High frequency of submicroscopic genomic aberrations detected by tiling path array comparative genome hybridisation in patients with isolated congenital heart disease.
J Med Genet. 2008 Nov; 45(11):704-9. Epub 2008 Aug 19.
Mapping translocation breakpoints by next-generation sequencing.
Genome Research 2008 Jul;18(7):1143-9
A defect in the TUSC3 gene is associated with autosomal recessive mental retardation.
Am J Hum Genet. 2008 May;82(5):1158-64. Epub 2008 May 1.
Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia.
Hum Mol Genet. 2008 Feb 1;17(3):458-65. Epub 2007 Nov 6.
A defect in the ionotropic glutamate receptor 6 gene (GRIK2) is associated with autosomal recessive mental retardation.
Am J Hum Genet. 2007 Oct;81(4):792-8. Epub 2007 Aug 31.
Array CGH identifies reciprocal 16p13.1 duplications and deletions that predispose to autism and/or mental retardation.
Hum Mutat. 2007 Jul;28(7):674-82.
Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci.
Hum Genet. 2007 Mar;121(1):43-8. Epub 2006 Nov 21.
CGHPRO -- a comprehensive data analysis tool for array CGH.
BMC Bioinformatics. 2005 Apr 5;6:85.
Mutations in the JARID1C gene, which is involved in transcriptional regulation and chromatin remodeling, cause X-linked mental retardation.
Am J Hum Genet. 2005 Feb;76(2):227-36. Epub 2004 Dec 7.
Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation.
Nat Genet. 2003 Dec;35(4):313-5. Epub 2003 Nov 23.
A new gene involved in X-linked mental retardation identified by analysis of an X;2 balanced translocation.
Nat Genet. 2000 Feb;24(2):167-70.
A new member of the IL-1 receptor family highly expressed in hippocampus and involved in X-linked mental retardation.
Nat Genet. 1999 Sep;23(1):25-31.
The Opitz syndrome gene product, MID1, associates with microtubules.
Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2794-9.
Positional cloning of the gene for X-linked retinitis pigmentosa 2.
Nat Genet. 1998 Aug;19(4):327-32.
Positional cloning of the gene for X-linked retinitis pigmentosa 3: homology with the guanine-nucleotide-exchange factor RCC1.
Hum Mol Genet. 1996 Jul;5(7):1035-41.
Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4.
Science. 1995 Feb 3;267(5198):685-8.
Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A.
Science. 1993 Oct 22;262(5133):578-80.
Isolation of a candidate gene for Norrie disease by positional cloning.
Nat Genet. 1992 Jun;1(3):199-203.
Cloning of a gene that is rearranged in patients with choroideraemia.
Nature. 1990 Oct 18;347(6294):674-7.
Selected review articles
Genetics of recessive cognitive disorders.
Trends Genet. 2014 Jan;30(1):32-9. Epub 2013 Oct 28.
Genetics of early onset cognitive impairment.
Annu Rev Genomics Hum Genet. 2010;11:161-87.
Genetics of intellectual disability.
Curr Opin Genet Dev. 2008 Jun;18(3):241-50. Epub 2008 Aug 28.
X-linked mental retardation.
Nat Rev Genet. 2005 Jan;6(1):46-57.
Selected opinion papers and perspectives
Medizinische Genomsequenzierung: Bedeutung für die Krankenversorgung und Genomforschung.
Konrad-Adenauer-Stiftung e.V., Wissenschaftsnetzwerk, 12. Juli 2019
Medizinische Genomsequenzierung: Warum Deutschland nicht länger abseits stehen darf.
Konrad-Adenauer-Stiftung e.V., Analysen und Argumente Nr. 324 / November 2018
Wer hat Deutungshoheit über das Genom?
F.A.Z. Frankfurter Allgemeine Zeitung vom 22.11.2013, S. 007 / Seitenüberschrift: Bildungswelten Ressort: Politik
Neue Sequenzierungstechniken und Konsequenzen für die genetische Krankenversorgung.
Berlin-Brandenburgische Akademie der Wissenschaften, 2013. ISBN: 978-3-939818-38-0
On the future of genetic risk assessment.
J Community Genet. 2012 Jul; 3(3): 229–236. Published online 2012 Apr 1.
Späte Einsicht: Die Genomforschung wendet sich seltenen Krankheiten zu
Jahrbuch der Max-Planck-Gesellschaft 2011
Single gene disorders come into focus - again.
Dialogues Clin Neurosci. 2010 Mar; 12(1): 95–102.
New perspectives for the elucidation of genetic disorders.
Am J Hum Genet. 2007 Aug;81(2):199-207. Epub 2007 Jun 29.
In der Genomforschung macht Schröder einen Riesenfehler.
Frankfurter Allgemeine Zeitung, 26. Januar 2001