Video LectureDeconvoluting the Most Clinically Relevant Region of the Human Genome

The MHC, a segment of 4Mb, is recognized to be the genomic region in the Human Genome associated with the highest number of diseases. Its significance calls for its detailed and thorough characterization. Our recent attempts to characterize the 4Mb of the MHC for heterozygote samples using long sequencing reads (3-10kb) and de novo (not reference-based) assembly is presented. Our eventual objective is the generation of MHC haplotypes, if possible for the whole MHC or any other sizeable sub-segment of interest. Most recently, within the MHC we have identified genomic elements, (like miRNAs) playing important biological role by controlling the expression of many other genes in the cell. Through computational means we have identified a likely large number of miRNAs encoded by the MHC. Could the presence of these elements explain the high density of SNPs, within the MHC, associated with many diseases? Alternative approaches combining NGS/Genetics and Complexity Theory/Physics provide new insights in the relationships of the different genomic sequences (exons/introns/intergenic sequences) and suggest that these sequences encode for elements forming a continuum of information throughout the MHC. We are in the process of identifying both the information and the interactive relationships of the different subsegments of the MHC.

Originally published on December 5, 2018



Lecture Presenter

Dimitri S. Monos, PhD

Dimitri S. Monos, PhD

Director, Immunogenetics Laboratory
Children's Hospital of Philidelphia
Professor of Pathology and Laboratory Medicine
Perelman School of Medicine at the University of Pennsylvania

Dr. Monos is the Director of Immunogenetics laboratory at The Children's Hospital of Philadelphia and Professor of Pathology and Lab Medicine at Perelman School of Medicine, University of Pennsylvania. He received his bachelor of science in biology from the University of Patras, Greece, and his PhD in Biochemistry/Immunology from Georgetown University in Washington, DC. Dr. Monos was a visiting fellow in Laboratory of Tumor Immunology and Biology at the National Cancer Institute, NIH, Bethesda, MD. Additionally he was an immunopathology fellow in the Department of Pathology and Laboratory Medicine at the University of Pennsylvania, School of Medicine.

Dr. Monos has the following faculty appoints: Research Associate in Immunology, Department of Pathology and Laboratory Medicine, University of Pennsylvania, School of Medicine; Visiting Scholar Department of Biochemistry and Molecular Biology, Harvard University; Assistant Professor to Professor, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania.

Dr. Monos’s research interests cover a wide spectrum of HLA-related topics. His lab has pioneered the DNA-based methodologies for HLA typing and more recently the introduction of Next Generation Sequencing in the field of Immunogenetics. He has worked on a number of structure/function relationships of HLAs, contributed in identifying the exact structural elements on the different HLA molecules associated with several autoimmune diseases and through genome-wide association studies identify additional genomic regions associated with autoimmunity. Most recently, his lab has identified miRNAs encoded by the HLA genes and miRNAs targeting the HLA genes. These new findings identify a new functional role for the HLA genes potentially influencing a large number of cellular pathways that may explain the significant associations of these genes with many diseases. His work has been funded by: NIH, ADA, JDF, University of Pennsylvania, The Children’s Hospital of Philadelphia, Diabetes Research and Education Foundation, National Marrow Donor Program and other foundations. He has authored more than 100 original publications in international journals (including Nature and Νature Genetics). He served on the editorial boards of several journals and as ad hoc reviewer in 20 journals (including NEJM and Nature). Dr. Monos has been invited to present his work at different Universities, National and International meetings. He has also participated in Study Sections reviewing grants for NIH, NMDP, University of Pennsylvania and The Children’s Hospital of Philadelphia.



Objectives

After this presentation, participants will be able to:

  • Recognize the significance of the MHC for many human diseases.
  • List recent attempts to characterize the 4Mb of the MHC for heterozygote samples using long sequencing reads (3-10kb) and de novo (not reference-based) assembly referencing the generation of MHC haplotypes if possible for the whole MHC or any other sizeable sub-segment of interest.
  • Explain how the genomic characterization of the MHC is relevant to the identification of genomic elements, like miRNAs, and elaborate on the biological role of these miRNAs. Expand on the possible presence of miRNAs within the MHC using computational approaches.
  • Discuss alternative approaches combining NGS/Genetics and Complexity Theory/Physics that provide totally new insights in the relationships of different genomic sequences (exons/introns/intergenic sequences) and their possible interdependences by computational means.

Sponsored by:

University of Utah School of Medicine, Department of Pathology, and ARUP Laboratories