Copy number variations (CNVs) in the assessment of stroke susceptibility in patients with sickle cell anemia

Author(s)

Pedro Rodrigues Sousa da Cruz

• Document type: Doctoral Thesis
• Institution: Universidade Estadual de Campinas, Instituto de Biologia
• Defense date: 2016
• Advisor: Mônica Barbosa de Melo

Abstract

Although sickle cell anemia results from homozygosity for a single mutation at position 6 of gamma-hemoglobin locus, this disease presents high heterogenity in phenotype, so that different patients may have significantly different clinical outcomes. Virtually all organs may be affected by vascular occlusion, with emphasis on the Central Nervous System (CNS), where are observed transient ischemic attacks, stroke and cerebral hemorrhage, which affect approximately 25% of patients with SCA. Neurological complications are serious and can be fatal in up to 15% of cases. Early identification of patients with sickle cell anemia, susceptible to stroke (CVA) could reduce the risk, possibly preventing the recurrence of heart attacks and potentially reduce their incidence. Therefore, studies aimed at identifying new risk groups for development of stroke in sickle cell patients would be essential to optimize the clinical management of this disease, one of these pathways the molecular approach of this group of patients. Thus, we propose to investigate the presence of copy number variation in allele or "Copy Number Variation" (CNV), using high density microarray in order to identify genomic regions potentially involved in the increased risk of stroke in sickle cell patients. The present work also proposes to assess the Brazilian population genetic aspects. It is highly desirable in human genetics to unveil the manifestation of a given phenotype in distinct populations, as well as whether an association identified on a specific population may hold to other populations. Sickle cell anemia provides a model for this purpose, and may be extrapolated to complex diseases given its well known geographical region, and for being a classic case of balanced selection in humans, the first disease to have its molecular mechanism unraveled, and a Mendelian trait. Ancestral components markedly differ in Brazilian SCA patients compared to the United States subjects on both the genomic landscape and the local ancestry on chromosome 11. Here we present a list of CNV events potentially associated to stroke on both populations (AU)

• FAPESP's process: 12/06438-5 - HIGH-DENSITY MICROARRAY TECHNIQUE IN THE ASSESSMENT OF STROKE SUSCEPTIBILITY IN PATIENTS WITH SICKLE CELL ANEMIA
• Grantee: Pedro Rodrigues Sousa da Cruz
• Support type: Scholarships in Brazil - Doctorate