Scott Bio

Dr. Scott is a member of The Laboratory for Clinical Biochemistry Research (LCBR). The laboratory is studying a large kindred with type I protein C deficiency and inherited thrombophilia. Investigation is based upon the observation that although a number of family members with protein C deficiency have deep vein thrombosis (DVT) at an early age, many of their protein C deficient relatives never have a DVT episode. Segregation analysis of DVT and protein C deficiency within the family suggests that inheritance of a second prothrombotic abnormality in conjunction with protein C deficiency is responsible for the pattern of DVT occurrence. The focus of the laboratory is to test the second gene hypothesis and identify the putative second prothrombotic gene in this family. To this end, molecular genetic and quantitative serological traits are scored for family members and utilized in segregation analysis.

The search for the second gene centers on testing candidate genes selected either because of their key position in hemostasis or because they were identified as co-segregating loci from whole genome micro-satellite short tandem repeat (STR) marker scans. STR marker scans, obtained from analyzing family members' DNA, are used in conjunction with medical history data to detect potential disease loci within the genome. Refined genetic mapping of potential second gene loci is used to identify candidate genes and direct discovery and testing for novel DNA polymorphisms. Data from DNA sequencing, polymerase chain reaction based restriction fragment length polymorphism (RFLP), single nucleotide polymorphisms (SNP), and STR marker analysis are used to test novel and known risk factor genes for a prothrombotic interaction with protein C deficiency.

In parallel to genomic studies, serological testing of coagulation factor levels provides a quantitative coagulation related phenotype measure that is useful in disease association analysis. In conjunction with the genome scan data, the serological data may also be used to identify genetic loci that affect the levels of the factors themselves.

The laboratory's research efforts are part of a collaborative study of inherited type I protein C deficiency headed by Dr. Bovill and is currently re-sampling and expanding the number of participants from the kindred which will enhance the power of the study. Collaborative institutions include the University of Laval, Quebec, Canada, Univesity of Paris, Paris, France and University of Leiden, Netherlands. Mathematical modeling and statistical analysis of inheritance are performed by Dr. S. Hasstedt, Department of Human Genetics, University of Utah.