Istituto di Genetica Molecolare “Luigi Luca Cavalli-Sforza”
Via Abbiategrasso, 207 – 27100 PAVIA
tel: +39 0382 546361
fax: +39 0382 546370
Curriculum e pubblicazioni
Attività di Ricerca:
- Analisi statistica di sequenze molecolari
- Studi di Genetica di Popolazioni
- Analisi epidemiologiche e statistiche di dati biomedici
- Sviluppo di strumenti bioinformatici per la gestione e l’analisi di dati “genome-wide”
Abou Alezz M; Celli L; Belotti G; Lisa A; Bione S
In: Frontiers in Genetics - RNA, 11 , pp. 488-502, 2020.
Long non-coding RNAs (lncRNAs) are recognized as an important class of regulatory molecules involved in a variety of biological functions. However, the regulatory mechanisms of long non-coding genes expression are still poorly understood. The characterization of the genomic features of lncRNAs is crucial to get insight into their function. In this study, we exploited recent annotations by GENCODE to characterize the genomic and splicing features of long non-coding genes in comparison with protein-coding ones, both in human and mouse. Our analysis highlighted differences between the two classes of genes in terms of their gene architecture. Significant differences in the splice sites usage were observed between long non-coding and protein-coding genes (PCG). While the frequency of non-canonical GC-AG splice junctions represents about 0.8% of total splice sites in PCGs, we identified a significant enrichment of the GC-AG splice sites in long non-coding genes, both in human (3.0%) and mouse (1.9%). In addition, we found a positional bias of GC-AG splice sites being enriched in the first intron in both classes of genes. Moreover, a significant shorter length and weaker donor and acceptor sites were found comparing GC-AG introns to GT-AG introns. Genes containing at least one GC-AG intron were found conserved in many species, more prone to alternative splicing and a functional analysis pointed toward their enrichment in specific biological processes such as DNA repair. Our study shows for the first time that GC-AG introns are mainly associated with lncRNAs and are preferentially located in the first intron. Additionally, we discovered their regulatory potential indicating the existence of a new mechanism of non-coding and PCGs expression regulation.
Bavagnoli L; Campanini G; Forte M; Ceccotti G; Percivalle E; Bione S; Lisa A; Baldanti F; Maga G
In: Antiviral research, 171 , pp. 104593, 2019.
The influenza A virus (IAV) NS1 protein is one of the major regulators of pathogenicity, being able to suppress innate immune response and host protein synthesis. In this study we identified the human micro RNA hsa-miR-1307-3p as a novel potent suppressor of NS1 expression and influenza virus replication. Transcriptomic analysis indicates that hsa-miR-1307-3p also negatively regulates apoptosis and promotes cell proliferation. In addition, we identified a novel mutation in the NS1 gene of A(H1N1)pdm09 strains circulating in Italy in the 2010-11 season, which enabled the virus to escape the hsa-miR-1307-3p inhibition, conferring replicative advantage to the virus in human cells. To the best of our knowledge, this is the first validation of suppression of IAV H1N1 NS1 by a human micro RNA and the first example of an escape mutation from micro RNA-mediated antiviral response for the A(H1N1)pdm09 virus.
Grugni V; Raveane A; Colombo G; Nici C; Crobu F; Ongaro L; Battaglia V; Sanna D; Al-Zahery N; Fiorani O; Lisa A; Ferretti L; Achilli A; Olivieri A; Francalacci P; Piazza A; Torroni A; Semino O
In: International journal of molecular sciences, 20 (22), pp. e5763, 2019.
Many anthropological, linguistic, genetic and genomic analyses have been carried out to evaluate the potential impact that evolutionary forces had in shaping the present-day Sardinian gene pool, the main outlier in the genetic landscape of Europe. However, due to the homogenizing effect of internal movements, which have intensified over the past fifty years, only partial information has been obtained about the main demographic events. To overcome this limitation, we analyzed the male-specific region of the Y chromosome in three population samples obtained by reallocating a large number of Sardinian subjects to the place of origin of their monophyletic surnames, which are paternally transmitted through generations in most of the populations, much like the Y chromosome. Three Y-chromosome founding lineages, G2-L91, I2-M26 and R1b-V88, were identified as strongly contributing to the definition of the outlying position of Sardinians in the European genetic context and marking a significant differentiation within the island. The present distribution of these lineages does not always mirror that detected in ancient DNAs. Our results show that the analysis of the Y-chromosome gene pool coupled with a sampling method based on the origin of the family name, is an efficient approach to unravelling past heterogeneity, often hidden by recent movements, in the gene pool of modern populations. Furthermore, the reconstruction and comparison of past genetic isolates represent a starting point to better assess the genetic information deriving from the increasing number of available ancient DNA samples.
Boattini A; Sarno S; Fiorani O; Lisa A; Luiselli D; Pettener D
In: Annals of Human Biology, 45 (1), pp. 57-65, 2018.
Southern Italy and Sicily played a key role in the peopling history of the Mediterranean. While genetic research showed the remarkable homogeneity of these regions, surname-based studies instead suggested low population mobility, hence potential structuring. AIM: In order to better understand these different patterns, this study (1) thoroughly analysed the surname structure of Sicily and Southern Italy and (2) tested its relationships with a wide set of molecular markers. SUBJECTS AND METHODS: Surname data were collected from 1213 municipalities and compared to uniparental and autosomal genetic markers typed in about 300 individuals from 8-10 populations. Surname analyses were performed using different multivariate methods, while comparisons with genetic data relied on correlation tests. RESULTS: Surnames were clearly structured according to regional geographic patterns, which likely emerged because of recent isolation-by-distance-like population dynamics. In general, genetic markers, hinting at a pervasive homogeneity, did not correlate with surname distribution. However, long autosomal haplotypes (>5 cM) that compared to genotypic (SNPs) data identify more "recent" relatedness, showing a clear association with surname patterns. CONCLUSION: The apparent contradiction between surname structure and genetic homogeneity was resolved by figuring surnames as recent "ripples" deposited on a vast and ancient homogeneous genetic "surface".
Manni M; Guglielmino CR; Scolari F; Vega-Rúa A; Failloux AB; Somboon P; Lisa A; Savini G; Bonizzoni M; Gomulski LM; Malacrida AR; Gasperi G
In: PLoS neglected tropical diseases, 11 (1), pp. e0005332, 2017.
BACKGROUND: Invasive species represent a global concern for their rapid spread and the possibility of infectious disease transmission. This is the case of the global invader Aedes albopictus, the Asian tiger mosquito. This species is a vector of medically important arboviruses, notably chikungunya (CHIKV), dengue (DENV) and Zika (ZIKV). The reconstruction of the complex colonization pattern of this mosquito has great potential for mitigating its spread and, consequently, disease risks.
METHODOLOGY/PRINCIPAL FINDINGS: Classical population genetics analyses and Approximate Bayesian Computation (ABC) approaches were combined to disentangle the demographic history of Aedes albopictus populations from representative countries in the Southeast Asian native range and in the recent and more recently colonized areas. In Southeast Asia, the low differentiation and the high co-ancestry values identified among China, Thailand and Japan indicate that, in the native range, these populations maintain high genetic connectivity, revealing their ancestral common origin. China appears to be the oldest population. Outside Southeast Asia, the invasion process in La Réunion, America and the Mediterranean Basin is primarily supported by a chaotic propagule distribution, which cooperates in maintaining a relatively high genetic diversity within the adventive populations. CONCLUSIONS/SIGNIFICANCE:
From our data, it appears that independent and also trans-continental introductions of Ae. albopictus may have facilitated the rapid establishment of adventive populations through admixture of unrelated genomes. As a consequence, a great amount of intra-population variability has been detected, and it is likely that this variability may extend to the genetic mechanisms controlling vector competence. Thus, in the context of the invasion process of this mosquito, it is possible that both population ancestry and admixture contribute to create the conditions for the efficient transmission of arboviruses and for outbreak establishment.
Cremaschi P; Carriero R; Astrologo S; Colì C; Lisa A; Parolo S; Bione S
In: Biomed Research International, 2015 , pp. 146250, 2015.
In the past few years, the role of long noncoding RNAs (lncRNAs) in tumor development and progression has been disclosed although their mechanisms of action remain to be elucidated. An important contribution to the comprehension of lncRNAs biology in cancer could be obtained through the integrated analysis of multiple expression datasets. However, the growing availability of public datasets requires new data mining techniques to integrate and describe relationship among data. In this perspective, we explored the powerness of the Association Rule Mining (ARM) approach in gene expression data analysis. By the ARM method, we performed a meta-analysis of cancer-related microarray data which allowed us to identify and characterize a set of ten lncRNAs simultaneously altered in different brain tumor datasets. The expression profiles of the ten lncRNAs appeared to be sufficient to distinguish between cancer and normal tissues. A further characterization of this lncRNAs signature through a comodulation expression analysis suggested that biological processes specific of the nervous system could be compromised.
Parolo S; Lisa A; Gentilini D; Di Blasio AM; Barlera S; Nicolis EB; Boncoraglio GB; Parati EA; Bione S
In: BMC Genetics, 16 , pp. 132, 2015.
BACKGROUND: The genetic structure of human populations is the outcome of the combined action of different processes such as demographic dynamics and natural selection. Several efforts toward the characterization of population genetic architectures and the identification of adaptation signatures were recently made. In this study, we provide a genome-wide depiction of the Italian population structure and the analysis of the major determinants of the current existing genetic variation. RESULTS: We defined and characterized 210 genomic loci associated with the first Principal Component calculated on the Italian genotypic data and correlated to the North-south genetic gradient. Using a gene-enrichment approach we identified the immune function as primarily involved in the Italian population differentiation and we described a locus on chromosome 13 showing combined evidence of North-south diversification in allele frequencies and signs of recent positive selection. In this region our bioinformatics analysis pinpointed an uncharacterized long intergenic non-coding (lincRNA), whose expression appeared specific for immune-related tissues suggesting its relevance for the immune function. CONCLUSIONS:
Our study, combining population genetic analyses with biological insights provides a description of the Italian genetic structure that in future could contribute to the evaluation of complex diseases risk in the population context.
Lisa A; Astolfi P; Zei G; Tentoni S
In: Annals of Human Genetics, 79 (1), pp. 37-45, 2015.
The role of consanguinity on human complex traits is an important and controversial issue. In this work we focused on the Sardinian population and examined the effect of consanguineous unions on late female fertility. During the last century the island has been characterized by a high incidence of marriages between relatives, favoured by socio economic conditions and geographical isolation, and by high fertility despite a widespread tendency to delay reproduction. Through spatial analysis techniques, we explored the geographical heterogeneity of consanguinity and late fertility, and identified in Central-Eastern Sardinia a common area with an excess of both traits, where the traits are positively associated. We found that their association did not significantly affect women's fertility in the area, despite the expected negative role of both traits. Intriguingly, this critical zone corresponds well to areas reported by previous studies as being peculiar for a high frequency of centenarians and for lower risk in pregnancy outcome. The proposed approach can be generally exploited to identify target populations on which socioeconomic, biodemographic and genetic data can be collected at the individual level, and deeper analyses carried out to disentangle the determinants of complex biological traits and to investigate their association. 2014 John Wiley & Sons Ltd/University College London.