Jul 032017

Thursday, July 6, 2017 – 14:30, room U3-07, Building U3

Giuliana Giannuzzi, PhD, Center for Integrative Genomics, University of Lausanne, Switzerland

Segmental and gene duplications in the human genome are important for human genetic variation, disease and evolution. They represent human genome trade-offs between the potential adaptive function of duplicated genes mapping to these segments and their potential priming of pathogenic rearrangements.

One example is the 16p11.2 locus, where recurrent copy number variation (CNV) is mediated by a complex set of segmental duplications. The deletion and duplication are associated with autism, schizophrenia, and reciprocal defects in head size and body weight. We reconstructed the evolutionary history of the locus and discovered that it had been dramatically reorganized during hominid evolution. This series of genomic changes includes the Homo sapiens-specific duplication of a 95 kbp segment containing the BOLA2 (BolA family member 2) gene, a gene involved in iron homeostasis, approximately 282 thousand years ago. This duplication that predisposes our species to the recurrent pathogenic 16p11.2 CNV, is absent from the genomes of our extinct relatives Neanderthal and Denisovan. It is apparently under selection (P<0.0097) and nearly fixed in the human lineage.

This region exemplifies that in the future we should comprehensively study and understand the role of structurally composite and repetitive regions of the human genome in disease, complex traits and human-specific features. To this aim it will be crucial to extend the study to other relevant regions that predispose to pathogenic rearrangements while embedding human-specific genes, such as the 1q21, 2q13 and 10q11 cytobands. These complex loci are usually overlooked in genome-wide studies due to analytical issues, requiring dedicated efforts to their investigation.

Host: Prof. Luca De Gioia

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