Wednesday, 13th December, 2017, 12:00 - 13.00

Genetic linkage analysis of heritable pulmonary arterial hypertension in a large pedigree identifies candidate modulators of reduced penetrance

Large-scale genetic profiling and clinical sequencing are revealing an increasing number of carriers of disease-causing mutations who do not develop the disease phenotype. This characteristic is clinically reported as a genetic disorder of reduced or incomplete penetrance. Several mechanisms have been proposed to explain reduced penetrance, such as the molecular context of mutations, patient characteristics, such as age or sex, as well as specific environmental conditions that delay or trigger the disease onset. The phenomenon of reduced penetrance constitutes a major challenge in the field of genetic diagnosis and counselling because phenotypes no longer unambiguously exhibit underlying genotypes. Nevertheless, its existence also provides new opportunities to learn how genotypes shape phenotypes. In this talk, I will describe our efforts using linkage analysis to find a genetic modifier that explains the reduced penetrance in a particular genetic disorder: heritable pulmonary arterial hypertension. The results from linkage will be further discussed regarding evidence on haplotype prediction, functional enrichment tests as well other functional genomics tools. These steps are required to narrow down the list of potential candidates mapping the modifier and eventually to hypothesize about a particular genetic mechanism underlying reduced penetrance.

Speaker: Pau Puigdevall, Functional Genomics, GRIB (UPF)

Room Aula 473.10 (PRBB, 4th floor)