Biology subjects

Bolla, M.

Publications and source records attributed to Bolla, M..

3 recordsLinked to original sources

bioRxiv2020

Mosaic expression of X-linked PCDH19 Protein by in Utero Electroporation in Rats Replicates Human Cortical and Hippocampal Developmental Abnormalities, Associated Core Behaviors Related to Autism, and Cognitive Impairment.

PCDH19 gene-related epilepsy or epileptic encephalopathy, early infantile, 9 (EIEE9) is an infantile onset epilepsy syndrome characterized by psychiatric (including autistic) sensory and cognitive impairment of varying degrees. EIEE9 is caused by X-linked PCDH19 protein loss of function. Due to random X-chromosome inactivation, EIEE9-affected females present a mosaic population of healthy and Pcdh19-mutant cells. Unfortunately, no mouse models recapitulate to date both the brain histological and behavioural deficits present in people with EIEE9. Thus, the search for a proper understanding of the disease, and possible future treatment is hampered. By inducing a focal mosaicism of Pcdh19 expression using in utero electroporation in rat, we found here that Pcdh19 signaling in specific brain areas is implicated in neuronal migration, as well as in core behaviors related to autism and cognitive function.

neuroscience↗

bioRxiv2019

Fine-mapping of 150 breast cancer risk regions identifies 178 high confidence target genes

Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants (CCVs) in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium, and enriched genomic features to determine variants with high posterior probabilities (HPPs) of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of potentially causal variants, using gene expression (eQTL), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways, were over-represented among the 178 highest confidence target genes.

genetics↗

bioRxiv2018

Shared heritability and functional enrichment across six solid cancers

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg=0.57, p=4.6x10-8), breast and ovarian cancer (rg=0.24, p=7x10-5), breast and lung cancer (rg=0.18, p=1.5x10-6) and breast and colorectal cancer (rg=0.15, p=1.1x10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.

genomics↗