Day 1 :
- Human Genetics
Ben-Gurion University of the Negev, Beer-Sheva, Israel
I'm Maram26 years old, completed my master degree at the age of 23 years, in Ben Gurion University in Israel. Now i'm at the third year of my PhD in Genetics at Ben Gurion University in Israel. I puplished two papers, and presnting 3 posters in different conference.
Introduction: Infertility is defined as a failure of conception after 12 months of having unprotected intercourse, and male infertility accounts for 30–55% of infertile couples. Azoospermia, is diagnosed when sperm is completely absent in the ejaculate even after centrifugation.
Materials and Methods: Genotyping was done on four azoospermic individuals of a consanguineous Bedouin family and their parents. Exome sequencing was performed on the DNA of one patient.
Results: Assuming homozygosity of a recessive founder mutation as the likely cause of the disorder, we have genotyped 4 patients and their parents. We identified 5 shared homozygous regions larger than 2 cM, encompassing a total of 13.8Mbp on the autosomal chromosomes. In these regions only one homozygous variant with allele frequencies of less than 1% in the public databases (ExAc browser, 1000 Genomes and dbSNP) was identified. This variant segregated as expected in the family, with a calculated Lod score of 3.42. The variation was not present in 620 Bedouin controls.
The variation is a frameshift mutation in a gene encoding a protein demonstrated to be essential for silencing of Line-1 retrotransposon in the male germline. Using a commercial antibody to the N-terminus of the encoded protein, immunofluorescent studies demonstrated it is produced in patients' testes, especially in spermatogonial cells (mainly in the cytoplasm) and in spermatocysts/round spermatids (mainly in the nucleus).
Discussion: The identification of the mutation causing azoospermia enables accurate diagnosis in the enlarged family and demonstrates the importance of repressing retrotransposon activation in the male germline in human.
- Diabetes and Obesity
Universidad de los Andes, Bogotá, Colombia
Diana Carolina Polania Villanueva has completed her Master's degree in Biological Sciences at Universidad de Los Andes. She is pursuing her PhD in Biology at the same university. She is currently conducting a research on the characterization of the DNA demethylation pathway using as biological models Diabetes and Cancer. Her research fields include Epigenetics, Genetics of Human Coagulopathies such as Hemophilia and von Willebrand disease, and Molecular Epidemiology of Cancer.
Type 2 Diabetes Mellitus (T2DM) is characterized by hyperglycemia and increased oxidative stress that could lead to chronic micro and macro-vascular complications. We hypothesized that part of the target organ damage is mediated by involving the epigenetic mechanism of DNA demethylation. It is currently believed that this process is catalyzed by the TET enzyme family; however, we explore another pathway mediated by high cellular oxidative environment, like the one present in diabetes. We measured glycated hemoglobin (HbA1C %) and global DNA methylation and hydroxymethylation in peripheral blood cells in 79 subjects: 19 well-controlled and 25 poorly controlled patients with T2DM, and 35 healthy controls. We also analyzed microarrays of DNA methylation and gene expression of other important tissues in the context of diabetes from the GEO database repository. According to the results, levels of DNA methylation and DNA hydroxymethylation were increased in poorly controlled patients compared to well controlled and healthy individuals (p=0.0039 for 5 mC, and p=0.0034 for 5 hmC). The analysis of methylation microarrays of the same tissue was concordant since levels of 5 mC were increased in T2DM blood as compared to controls. However, the levels of DNA methylation and hydroxymethylation in peripheral blood cells were contrary to the ones observed in other tissues such as pancreas, adipose tissue and skeletal muscle. Analysis of gene expression associated with DNA demethylation indicates that the TET-mediated enzymatic demethylation pathway is not sufficient to explain the changes found, and therefore there is a new and non-enzymatic pathway mediated by oxidative stress.