Constitutional chromosomal rearrangements and late onset disorders
My research interest is to identify disease genes and mechanisms for late onset disorders by studying germline chromosomal rearrangements in carriers collected as part of my research employment at Department of Cellular and Molecular Medicine from 2001 and as part of my clinical employment at the Department of Clinical Genetics, Rigshospitalet from 2009.
Mapping of germline chromosomal rearrangements in patients with congenital diseases is a classical strategy to identify disease genes and their regulatory elements. This strategy has only sporadically been used for studying genes and mechanisms involved in later onset disorders because knowledge about a germline chromosomal rearrangement and a later onset disorder are seldom present at the same time. We have therefore re-examined all Danish carriers of a constitutional chromosomal rearrangement by questionnaires and registries. The cohort is continuously supplemented with new carriers resulting in a patient-database of currently 6345 carriers. This cohort has been important for several research projects e.g. for describing a new X-linked syndrome, defining risk and guidelines for carriers of a prenatally detected de novo chromosomal rearrangement, identifying an intact chromosome 1 as critical for male fertility, showing the variable phenotype associated with a mutation in TAB2 and the variable penetrance of mutations in CNTNAP2.
Current Project Areas
My research projects include studies on hypertension, obesity, cancer and reproductive difficulties and they are carried out in collaboration with colleagues at the clinical departments as well as at the university taking advantage of my dual employment. In the hypertension and obesity projects, I collaborate with the Novo Nordisk Foundation Center for Basic Metabolic Research: we have found that a specific gene is associated with hypertension and identified several candidate loci for obesity by studying carriers of chromosomal rearrangements. In collaboration with several medical doctors within oncology and cancer genetics at Rigshospitalet I study cancer patients with germline chromosomal rearrangements to search for candidate genes and regulatory elements. Furthermore, I am mapping chromosomal rearrangements of carriers with infertility to define critical regions for male infertility and to estimate reproductive risks for subgroups.
- Basilicata MF, Bruel AL, Semplicio G, Valsecchi CIK, … Bache I et al. De novo mutations in MSL3 cause an X-linked syndrome marked by impaired histone H4 lysine 16 acetylation. Nat Genet 2018.
- Halgren C, Nielsen NM, Nazaryan-Petersen L, Silahtaroglu A… Bache I. Risks and Recommendations in Prenatally Detected De Novo Balanced Chromosomal Rearrangements from Assessment of Long-Term Outcomes. Am J Hum Genet. 2018:102:1090-1103.
- Rudolf G, Lesca G, Mehrjouy MM, Labalme A, Salmi M, Bache I et al. Loss of function of the retinoid-related nuclear receptor (RORB) gene and epilepsy. Eur J Hum Genet. 2016:24:1761-70.
- Thienpont B, Zhang L, Postma AV, Breckpot J, … Bache I et al. Haploinsufficiency of TAB2 causes congenital heart defects in humans. Am J Hum Genet 2010:86:839-49.
- Belloso JM, Bache I, Guitart M, Caballin MR, Halgren C et al. Disruption of the CNTNAP2 gene in a t(7;15) translocation family without symptoms of Gilles de la Tourette syndrome. Eur J Hum Genet. 2007:15:711-3.
- Bache I, Nielsen NM, Rostgaard K, Tommerup N, Frisch M. Autoimmune diseases in a Danish cohort of 4,866 carriers of constitutional structural chromosomal rearrangements. Arthritis Rheum. 2007:56:2402-9.
- Bache I, Hjorth M, Bugge M, Holstebroe S, Hilden J et al. Systematic re-examination of carriers of balanced reciprocal translocations: a strategy to search for candidate regions for common and complex diseases. Eur J Hum Genet. 2006:14:410-7.
- Bache I, Hasle H, Tommerup N, Olsen JH. Population-based study of cancer among carriers of a constitutional structural chromosomal rearrangement. Genes Chromosomes Cancer. 2006:45:231-46.
- Bache I, Assche EV, Cingoz S, Bugge M, Tümer Z et al. An excess of chromosome 1 breakpoints in male infertility. Eur J Hum Genet. 2004:12:993-1000.