Search for founder effects and cellular characterization of cells from brazilian patients with the DNA repair-deficient Xeroderma Pigmentosum disease

Abstract

Human genetic syndromes deficient in the Nucleotide Excision Repair (NER) pathway are known to display photosensitivity and neurological problems, such as xeroderma pigmentosum (XP). In Brazil, a few case-reports had described patients with these phenotypes, but genetic and molecular characterization data are scarce. In the current post-doc project, we are identifying mutations from Brazilian XP patients. We observed a high frequency of patients from different states with the same mutation, as well as patients with mutations already reported abroad. We plan to investigate the origins of three mutations and their ancestrality by the haplotype analysis from an SNP-array assay that we already performed. In this 3-month period (April to June 2019), we are proposing a collaboration to analyze the haplotypes with a group from France. This connection will provide us training and the tools to analyze the data on the origins of these variants. We expect to gain knowledge of the history of some of these mutations, identifying founder effects and, consequently, some of the migration histories of these XP patients and our population. We also propose to perform cellular characterization of cells from four Brazilian patients under the supervision of Dr. Alain Sarasin. This 3-month period in France will be enough for me to learn the bioinformatics pipeline for the SNP-array analysis, as well as to provide an excellent flux of knowledge from the Centre d'Etudes du Polymorphisme Humain (CEPH) and Institut Gustave Roussy (IGR) groups. (AU)