Francesca Crobu

@article{pala_population-_2017,

title = {Population- and individual-specific regulatory variation in Sardinia},

author = {Mauro Pala and Zachary Zappala and Mara Marongiu and Xin Li and Joe R Davis and Roberto Cusano and Francesca Crobu and Kimberly R Kukurba and Michael J Gloudemans and Frederic Reinier and Riccardo Berutti and Maria G Piras and Antonella Mulas and Magdalena Zoledziewska and Michele Marongiu and Elena P Sorokin and Gaelen T Hess and Kevin S Smith and Fabio Busonero and Andrea Maschio and Maristella Steri and Carlo Sidore and Serena Sanna and Edoardo Fiorillo and Michael C Bassik and Stephen J Sawcer and Alexis Battle and John Novembre and Chris Jones and Andrea Angius and Gon{ç}alo R Abecasis and David Schlessinger and Francesco Cucca and Stephen B Montgomery},

doi = {10.1038/ng.3840},

issn = {1546-1718},

year  = {2017},

date = {2017-05-01},

journal = {Nature Genetics},

volume = {49},

number = {5},

pages = {700--707},

abstract = {Genetic studies of complex traits have mainly identified associations with noncoding variants. To further determine the contribution of regulatory variation, we combined whole-genome and transcriptome data for 624 individuals from Sardinia to identify common and rare variants that influence gene expression and splicing. We identified 21,183 expression quantitative trait loci (eQTLs) and 6,768 splicing quantitative trait loci (sQTLs), including 619 new QTLs. We identified high-frequency QTLs and found evidence of selection near genes involved in malarial resistance and increased multiple sclerosis risk, reflecting the epidemiological history of Sardinia. Using family relationships, we identified 809 segregating expression outliers (median z score of 2.97), averaging 13.3 genes per individual. Outlier genes were enriched for proximal rare variants, providing a new approach to study large-effect regulatory variants and their relevance to traits. Our results provide insight into the effects of regulatory variants and their relationship to population history and individual genetic risk.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{marongiu_novel_2016,

title = {Novel action of FOXL2 as mediator of Col1a2 gene autoregulation},

author = {Mara Marongiu and Manila Deiana and Loredana Marcia and Andrea Sbardellati and Isadora Asunis and Alessandra Meloni and Andrea Angius and Roberto Cusano and Angela Loi and Francesca Crobu and Giorgio Fotia and Francesco Cucca and David Schlessinger and Laura Crisponi},

doi = {10.1016/j.ydbio.2016.05.022},

issn = {1095-564X},

year  = {2016},

date = {2016-08-01},

journal = {Developmental Biology},

volume = {416},

number = {1},

pages = {200--211},

abstract = {FOXL2 belongs to the evolutionarily conserved forkhead box (FOX) superfamily and is a master transcription factor in a spectrum of developmental pathways, including ovarian and eyelid development and bone, cartilage and uterine maturation. To analyse its action, we searched for proteins that interact with FOXL2. We found that FOXL2 interacts with specific C-terminal propeptides of several fibrillary collagens. Because these propeptides can participate in feedback regulation of collagen biosynthesis, we inferred that FOXL2 could thereby affect the transcription of the cognate collagen genes. Focusing on COL1A2, we found that FOXL2 indeed affects collagen synthesis, by binding to a DNA response element located about 65Kb upstream of this gene. According to our hypothesis we found that in Foxl2(-/-) mouse ovaries, Col1a2 was elevated from birth to adulthood. The extracellular matrix (ECM) compartmentalizes the ovary during folliculogenesis, (with type I, type III and type IV collagens as primary components), and ECM composition changes during the reproductive lifespan. In Foxl2(-/-) mouse ovaries, in addition to up-regulation of Col1a2, Col3a1, Col4a1 and fibronectin were also upregulated, while laminin expression was reduced. Thus, by regulating levels of extracellular matrix components, FOXL2 may contribute to both ovarian histogenesis and the fibrosis attendant on depletion of the follicle reserve during reproductive aging and menopause.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{rootsi_distinguishing_2012,

title = {Distinguishing the co-ancestries of haplogroup G Y-chromosomes in the populations of Europe and the Caucasus},

author = {Siiri Rootsi and Natalie M Myres and Alice A Lin and Mari J{ä}rve and Roy J King and Ildus Kutuev and Vicente M Cabrera and Elza K Khusnutdinova and K{ä}rt Varendi and Hovhannes Sahakyan and Doron M Behar and Rita Khusainova and Oleg Balanovsky and Elena Balanovska and Pavao Rudan and Levon Yepiskoposyan and Ardeshir Bahmanimehr and Shirin Farjadian and Alena Kushniarevich and Rene J Herrera and Viola Grugni and Vincenza Battaglia and Carmela Nici and Francesca Crobu and Sena Karachanak and Baharak {Hooshiar Kashani} and Massoud Houshmand and Mohammad H Sanati and Draga Toncheva and Antonella Lisa and Ornella Semino and Jacques Chiaroni and Julie {Di Cristofaro} and Richard Villems and Toomas Kivisild and Peter A Underhill},

doi = {10.1038/ejhg.2012.86},

issn = {1476-5438},

year  = {2012},

date = {2012-12-01},

journal = {European journal of human genetics: EJHG},

volume = {20},

number = {12},

pages = {1275--1282},

abstract = {Haplogroup G, together with J2 clades, has been associated with the spread of agriculture, especially in the European context. However, interpretations based on simple haplogroup frequency clines do not recognize underlying patterns of genetic diversification. Although progress has been recently made in resolving the haplogroup G phylogeny, a comprehensive survey of the geographic distribution patterns of the significant sub-clades of this haplogroup has not been conducted yet. Here we present the haplogroup frequency distribution and STR variation of 16 informative G sub-clades by evaluating 1472 haplogroup G chromosomes belonging to 98 populations ranging from Europe to Pakistan. Although no basal G-M201* chromosomes were detected in our data set, the homeland of this haplogroup has been estimated to be somewhere nearby eastern Anatolia, Armenia or western Iran, the only areas characterized by the co-presence of deep basal branches as well as the occurrence of high sub-haplogroup diversity. The P303 SNP defines the most frequent and widespread G sub-haplogroup. However, its sub-clades have more localized distribution with the U1-defined branch largely restricted to Near/Middle Eastern and the Caucasus, whereas L497 lineages essentially occur in Europe where they likely originated. In contrast, the only U1 representative in Europe is the G-M527 lineage whose distribution pattern is consistent with regions of Greek colonization. No clinal patterns were detected suggesting that the distributions are rather indicative of isolation by distance and demographic complexities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{crobu_differentiation_2012,

title = {Differentiation of single cell derived human mesenchymal stem cells into cells with a neuronal phenotype: RNA and microRNA expression profile},

author = {Francesca Crobu and Veronica Latini and Maria Franca Marongiu and Valeria Sogos and Franca Scintu and Susanna Porcu and Carla Casu and Manuela Badiali and Adele Sanna and Maria Francesca Manchinu and Maria Serafina Ristaldi},

doi = {10.1007/s11033-011-1180-9},

issn = {1573-4978},

year  = {2012},

date = {2012-04-01},

journal = {Molecular Biology Reports},

volume = {39},

number = {4},

pages = {3995--4007},

abstract = {The adult bone marrow contains a subset of non-haematopoietic cells referred to as bone marrow mesenchymal stem cells (BMSCs). Mesenchymal stem cells (MSCs) have attracted immense research interest in the field of regenerative medicine due to their ability to be cultured for successive passages and multi-lineage differentiation. The molecular mechanisms governing the self-renewal and differentiation of MSCs remain largely unknown. In a previous paper we demonstrated the ability to induce human clonal MSCs to differentiate into cells with a neuronal phenotype (DMSCs). In the present study we evaluated gene expression profiles by Sequential Analysis of Gene Expression (SAGE) and microRNA expression profiles before and after the neuronal differentiation process. Various tissue-specific genes were weakly expressed in MSCs, including those of non-mesodermal origin, suggesting multiple potential tissue-specific differentiation, as well as stemness markers. Expression of OCT4, KLF4 and c-Myc cell reprogramming factors, which are modulated during the differentiation process, was also observed. Many peculiar nervous tissue genes were expressed at a high level in DMSCs, along with genes related to apoptosis. MicroRNA profiling and correlation with mRNA expression profiles allowed us to identify putative important genes and microRNAs involved in the differentiation of MSCs into neuronal-like cells. The profound difference in gene and microRNA expression patterns between MSCs and DMSCs indicates a real functional change during differentiation from MSCs to DMSCs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}