Professor, dr.med., Professor
Institut for Cellulær og Molekylær Medicin
Blegdamsvej 3, Bygning: 22.4.28
2200 2200 København N
Medical Genetics Program
2200 København N.
Mapping of balanced chromosomal rearrangements (BCR) to identify and characterize novel disease and phenotype genes, regulatory domains (Topological Associating Domains (TADs) of disease genes and novel genetic mecahnisms. Characterization of germline chromothripsis. Functional studies of non-coding RNA genes.
The first study of long-term risk of prenatally diagnosed de novo BCRs increases the risk from 7% to appr. 20% and lead to new guidelines (Am J Hum Genet 2018;102:1090-1103); the multiple breakpoints in germline chromothripsis may predispose to complex multigenic disorders (Hum Mutat 2019;40:1057-62); haploinsufficiency of ARHGAP42 leads to age-dependent hypertension (Eur J Hum Genet 2019;27:1296-1303). The latter study also provides support for an obesity locus in the CELF4 regulatory domain on chromosome 18.
- Coordination of International Breakpoint Mapping Consortium (2014-), involving >100 diagnostic cytogenetic laboratories from >50 countries/6 continents.
- In the so far largest study of the effect of chromosomal breakpoints which also include the first control cohort we define >300 high-risk TADs for long-range-position effects (18% of the genome). This window into the developmental regulome establish links to multiple disorders, incl. intellectual disability, autism, epilepsy, narcolepsy, speech defects and congenital brain malformations.
- Studies of germline chromothripsis associated with complex translocations/inversions, and in cellular model systems.
- Linking anatomical variation to genetic variation.
- Development of methods for visualization of nuclear genome organization.