Giuseppina Casu
Technician
Area of interest:
Giuseppina Casu obtained her degree of Biomedical Laboratory Technician at the University of Sassari in 1994, at present she works as technical assistant at the IRGB-CNR since 1996. Her research has almost always focused on the study of multifactorial diseases (kidney stones, hypertension) in isolated Sardinian Populations. Since 2008 to 2018, following an agreement between the IRGB and the Veterinary Physiology Institute of the University of Sassari, she participated in the project concerning the enhancement and conservation of the goat heritage in Sardinia. Furthermore, in the meantime she also collaborated to a study focusing on thalassemia in Vietnam.
Her activities were based on the application of the main molecular biology techniques, such as: DNA extraction, with the saline method and with the Qiagen Kit, amplification of DNA with PCR, DNA sequencing with the ABI PRISM 3130 XL Genetic Analyzer automatic sequencer and DNA fragmentation with restriction endonucleases.
Since 2020 she works on the detection and quantization of genetic mutations of DNA extracted from paraffin-embedded tumor tissue of cholangiocarcinoma and thyroid patients using the technique of Pyrosequencing with the PyroMark Q24 Qiagen version 2.0.6.
Most significant publications:
2017
Doro, Maria G.; Casu, Giuseppina; Frogheri, Laura; Persico, Ivana; Triet, Le Phan Minh; Hoa, Phan Thi Thuy; Hoang, Nguyen Huy; Pirastru, Monica; Mereu, Paolo; Cucca, Francesco; Masala, Bruno
Molecular Characterization of beta-Thalassemia Mutations in Central Vietnam. Journal Article
In: Hemoglobin, 41 (2), pp. 96–99, 2017, ISSN: 1532-432X 0363-0269.
@article{doro_molecular_2017,
title = {Molecular Characterization of beta-Thalassemia Mutations in Central Vietnam.},
author = {Doro, Maria G. and Casu, Giuseppina and Frogheri, Laura and Persico, Ivana and Triet, Le Phan Minh and Hoa, Phan Thi Thuy and Hoang, Nguyen Huy and Pirastru, Monica and Mereu, Paolo and Cucca, Francesco and Masala, Bruno},
doi = {10.1080/03630269.2017.1321013},
issn = {1532-432X 0363-0269},
year = {2017},
date = {2017-03-01},
journal = {Hemoglobin},
volume = {41},
number = {2},
pages = {96--99},
abstract = {The molecular basis of beta-thalassemia (beta-thal) mutations in North and in South Vietnam have been described during the past 15 years, whereas limited data were available concerning the central area of the country. In this study, we describe the molecular characterization and frequency of beta-globin gene mutations in the Thua Thien Hue Province of Central Vietnam as the result of a first survey conducted in 22 transfusion-dependent patients, and four unrelated heterozygotes. Nine different known mutations were identified (seven of the beta(0) and two of the beta(+) type) in a total of 48 chromosomes. The most common was codon 26 (GtextgreaterA) or Hb E (HBB: c.79 GtextgreaterA) accounting for 29.2% of the total studied chromosomes, followed by codon 17 (AtextgreaterT) (HBB: c.52 AtextgreaterT) (25.0%), and codons 41/42 (-TTCT) (HBB: c.126_129delCTTT) (18.8%). Other mutations with appreciable frequencies (6.3-8.3%) were IVS-I-1 (GtextgreaterT) (HBB: c.92+1 GtextgreaterT), codon 26 (GtextgreaterT) (HBB: c.79 GtextgreaterT) and codons 71/72 (+A) (HBB: c.216_217insA). Relatively rarer (2.0%) were the promoter -28 (AtextgreaterG) (HBB: c.78 AtextgreaterG) mutation, the codon 95 (+A) (HBB: c.287_288insA), which is reported only in the Vietnamese, and the codons 14/15 (+G) (HBB: c.45_46insG) mutation, thus far observed only in Thailand. Results are relevant for implementing appropriate measures for beta-thal prevention and control in the region as well as in the whole country.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The molecular basis of beta-thalassemia (beta-thal) mutations in North and in South Vietnam have been described during the past 15 years, whereas limited data were available concerning the central area of the country. In this study, we describe the molecular characterization and frequency of beta-globin gene mutations in the Thua Thien Hue Province of Central Vietnam as the result of a first survey conducted in 22 transfusion-dependent patients, and four unrelated heterozygotes. Nine different known mutations were identified (seven of the beta(0) and two of the beta(+) type) in a total of 48 chromosomes. The most common was codon 26 (GtextgreaterA) or Hb E (HBB: c.79 GtextgreaterA) accounting for 29.2% of the total studied chromosomes, followed by codon 17 (AtextgreaterT) (HBB: c.52 AtextgreaterT) (25.0%), and codons 41/42 (-TTCT) (HBB: c.126_129delCTTT) (18.8%). Other mutations with appreciable frequencies (6.3-8.3%) were IVS-I-1 (GtextgreaterT) (HBB: c.92+1 GtextgreaterT), codon 26 (GtextgreaterT) (HBB: c.79 GtextgreaterT) and codons 71/72 (+A) (HBB: c.216_217insA). Relatively rarer (2.0%) were the promoter -28 (AtextgreaterG) (HBB: c.78 AtextgreaterG) mutation, the codon 95 (+A) (HBB: c.287_288insA), which is reported only in the Vietnamese, and the codons 14/15 (+G) (HBB: c.45_46insG) mutation, thus far observed only in Thailand. Results are relevant for implementing appropriate measures for beta-thal prevention and control in the region as well as in the whole country.
2014
Doro, Maria Grazia; Piras, Daniela; Leoni, Giovanni Giuseppe; Casu, Giuseppina; Vaccargiu, Simona; Parracciani, Debora; Naitana, Salvatore; Pirastu, Mario; Novelletto, Andrea
Phylogeny and patterns of diversity of goat mtDNA haplogroup A revealed by resequencing complete mitogenomes Journal Article
In: PloS One, 9 (4), pp. e95969, 2014, ISSN: 1932-6203.
@article{doro_phylogeny_2014,
title = {Phylogeny and patterns of diversity of goat mtDNA haplogroup A revealed by resequencing complete mitogenomes},
author = {Maria Grazia Doro and Daniela Piras and Giovanni Giuseppe Leoni and Giuseppina Casu and Simona Vaccargiu and Debora Parracciani and Salvatore Naitana and Mario Pirastu and Andrea Novelletto},
doi = {10.1371/journal.pone.0095969},
issn = {1932-6203},
year = {2014},
date = {2014-01-01},
journal = {PloS One},
volume = {9},
number = {4},
pages = {e95969},
abstract = {We sequenced to near completion the entire mtDNA of 28 Sardinian goats, selected to represent the widest possible diversity of the most widespread mitochondrial evolutionary lineage, haplogroup (Hg) A. These specimens were reporters of the diversity in the island but also elsewhere, as inferred from their affiliation to each of 11 clades defined by D-loop variation. Two reference sequences completed the dataset. Overall, 206 variations were found in the full set of 30 sequences, of which 23 were protein-coding non-synonymous single nucleotide substitutions. Many polymorphic sites within Hg A were informative for the reconstruction of its internal phylogeny. Bayesian and network clustering revealed a general similarity over the entire molecule of sequences previously assigned to the same D-loop clade, indicating evolutionarily meaningful lineages. Two major sister groupings emerged within Hg A, which parallel distinct geographical distributions of D-loop clades in extant stocks. The pattern of variation in protein-coding genes revealed an overwhelming role of purifying selection, with the quota of surviving variants approaching neutrality. However, a simple model of relaxation of selection for the bulk of variants here reported should be rejected. Non-synonymous diversity of Hg's A, B and C denoted that a proportion of variants not greater than that allowed in the wild was given the opportunity to spread into domesticated stocks. Our results also confirmed that a remarkable proportion of pre-existing Hg A diversity became incorporated into domestic stocks. Our results confirm clade A11 as a well differentiated and ancient lineage peculiar of Sardinia.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We sequenced to near completion the entire mtDNA of 28 Sardinian goats, selected to represent the widest possible diversity of the most widespread mitochondrial evolutionary lineage, haplogroup (Hg) A. These specimens were reporters of the diversity in the island but also elsewhere, as inferred from their affiliation to each of 11 clades defined by D-loop variation. Two reference sequences completed the dataset. Overall, 206 variations were found in the full set of 30 sequences, of which 23 were protein-coding non-synonymous single nucleotide substitutions. Many polymorphic sites within Hg A were informative for the reconstruction of its internal phylogeny. Bayesian and network clustering revealed a general similarity over the entire molecule of sequences previously assigned to the same D-loop clade, indicating evolutionarily meaningful lineages. Two major sister groupings emerged within Hg A, which parallel distinct geographical distributions of D-loop clades in extant stocks. The pattern of variation in protein-coding genes revealed an overwhelming role of purifying selection, with the quota of surviving variants approaching neutrality. However, a simple model of relaxation of selection for the bulk of variants here reported should be rejected. Non-synonymous diversity of Hg's A, B and C denoted that a proportion of variants not greater than that allowed in the wild was given the opportunity to spread into domesticated stocks. Our results also confirmed that a remarkable proportion of pre-existing Hg A diversity became incorporated into domestic stocks. Our results confirm clade A11 as a well differentiated and ancient lineage peculiar of Sardinia.
2012
Piras, Daniela; Doro, Maria Grazia; Casu, Giuseppina; Melis, Paola Maria; Vaccargiu, Simona; Piras, Ignazio; Parracciani, Debora; Stradoni, Roberta; Frongia, Bruno; Lai, Graziano; Sale, Salvatore; Cattari, Walter; Piras, Roberto; Querci, Ombretta; Demuro, Piergiorgio; Cui, Sandro; Atzori, Franco; Mancosu, Marco; Marchiori, Francesca; Cammelli, Rossana; Spiga, Alessandra; Loddo, Pier Paolo; Pili, Gianfranco; Boi, Roberto; Argiolas, Giuseppe; Mereu, Paolo; Leoni, Giovanni Giuseppe; Naitana, Salvatore; Pirastu, Mario; Novelletto, Andrea
Haplotype affinities resolve a major component of goat (Capra hircus) MtDNA D-loop diversity and reveal specific features of the Sardinian stock Journal Article
In: PloS One, 7 (2), pp. e30785, 2012, ISSN: 1932-6203.
@article{piras_haplotype_2012,
title = {Haplotype affinities resolve a major component of goat (Capra hircus) MtDNA D-loop diversity and reveal specific features of the Sardinian stock},
author = {Daniela Piras and Maria Grazia Doro and Giuseppina Casu and Paola Maria Melis and Simona Vaccargiu and Ignazio Piras and Debora Parracciani and Roberta Stradoni and Bruno Frongia and Graziano Lai and Salvatore Sale and Walter Cattari and Roberto Piras and Ombretta Querci and Piergiorgio Demuro and Sandro Cui and Franco Atzori and Marco Mancosu and Francesca Marchiori and Rossana Cammelli and Alessandra Spiga and Pier Paolo Loddo and Gianfranco Pili and Roberto Boi and Giuseppe Argiolas and Paolo Mereu and Giovanni Giuseppe Leoni and Salvatore Naitana and Mario Pirastu and Andrea Novelletto},
doi = {10.1371/journal.pone.0030785},
issn = {1932-6203},
year = {2012},
date = {2012-01-01},
journal = {PloS One},
volume = {7},
number = {2},
pages = {e30785},
abstract = {Goat mtDNA haplogroup A is a poorly resolved lineage absorbing most of the overall diversity and is found in locations as distant as Eastern Asia and Southern Africa. Its phylogenetic dissection would cast light on an important portion of the spread of goat breeding. The aims of this work were 1) to provide an operational definition of meaningful mtDNA units within haplogroup A, 2) to investigate the mechanisms underlying the maintenance of diversity by considering the modes of selection operated by breeders and 3) to identify the peculiarities of Sardinian mtDNA types. We sequenced the mtDNA D-loop in a large sample of animals (1,591) which represents a non-trivial quota of the entire goat population of Sardinia. We found that Sardinia mirrors a large quota of mtDNA diversity of Western Eurasia in the number of variable sites, their mutational pattern and allele frequency. By using bayesian analysis, a distance-based tree and a network analysis, we recognized demographically coherent groups of sequences identified by particular subsets of the variable positions. The results showed that this assignment system could be reproduced in other studies, capturing the greatest part of haplotype diversity.We identified haplotype groups overrepresented in Sardinian goats as a result of founder effects. We found that breeders maintain diversity of matrilines most likely through equalization of the reproductive potential. Moreover, the relevant amount of inter-farm mtDNA diversity found does not increase proportionally with distance. Our results illustrate the effects of breeding practices on the composition of maternal gene pool and identify mtDNA types that may be considered in projects aimed at retrieving the maternal component of the oldest breeds of Sardinia.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Goat mtDNA haplogroup A is a poorly resolved lineage absorbing most of the overall diversity and is found in locations as distant as Eastern Asia and Southern Africa. Its phylogenetic dissection would cast light on an important portion of the spread of goat breeding. The aims of this work were 1) to provide an operational definition of meaningful mtDNA units within haplogroup A, 2) to investigate the mechanisms underlying the maintenance of diversity by considering the modes of selection operated by breeders and 3) to identify the peculiarities of Sardinian mtDNA types. We sequenced the mtDNA D-loop in a large sample of animals (1,591) which represents a non-trivial quota of the entire goat population of Sardinia. We found that Sardinia mirrors a large quota of mtDNA diversity of Western Eurasia in the number of variable sites, their mutational pattern and allele frequency. By using bayesian analysis, a distance-based tree and a network analysis, we recognized demographically coherent groups of sequences identified by particular subsets of the variable positions. The results showed that this assignment system could be reproduced in other studies, capturing the greatest part of haplotype diversity.We identified haplotype groups overrepresented in Sardinian goats as a result of founder effects. We found that breeders maintain diversity of matrilines most likely through equalization of the reproductive potential. Moreover, the relevant amount of inter-farm mtDNA diversity found does not increase proportionally with distance. Our results illustrate the effects of breeding practices on the composition of maternal gene pool and identify mtDNA types that may be considered in projects aimed at retrieving the maternal component of the oldest breeds of Sardinia.
2011
Tore, S.; Casula, S.; Casu, G.; Concas, M. P.; Pistidda, P.; Persico, I.; Sassu, A.; Maestrale, G. B.; Mele, C.; Caruso, M. R.; Bonerba, B.; Usai, P.; Deiana, I.; Thornton, T.; Pirastu, M.; Forabosco, P.
Application of a new method for GWAS in a related case/control sample with known pedigree structure: identification of new loci for nephrolithiasis Journal Article
In: PLoS Genet, 7 (1), pp. e1001281, 2011.
@article{pmid21283782,
title = {Application of a new method for GWAS in a related case/control sample with known pedigree structure: identification of new loci for nephrolithiasis},
author = {Tore, S. and Casula, S. and Casu, G. and Concas, M. P. and Pistidda, P. and Persico, I. and Sassu, A. and Maestrale, G. B. and Mele, C. and Caruso, M. R. and Bonerba, B. and Usai, P. and Deiana, I. and Thornton, T. and Pirastu, M. and Forabosco, P.},
year = {2011},
date = {2011-01-01},
journal = {PLoS Genet},
volume = {7},
number = {1},
pages = {e1001281},
abstract = {In contrast to large GWA studies based on thousands of individuals and large meta-analyses combining GWAS results, we analyzed a small case/control sample for uric acid nephrolithiasis. Our cohort of closely related individuals is derived from a small, genetically isolated village in Sardinia, with well-characterized genealogical data linking the extant population up to the 16(th) century. It is expected that the number of risk alleles involved in complex disorders is smaller in isolated founder populations than in more diverse populations, and the power to detect association with complex traits may be increased when related, homogeneous affected individuals are selected, as they are more likely to be enriched with and share specific risk variants than are unrelated, affected individuals from the general population. When related individuals are included in an association study, correlations among relatives must be accurately taken into account to ensure validity of the results. A recently proposed association method uses an empirical genotypic covariance matrix estimated from genome-screen data to allow for additional population structure and cryptic relatedness that may not be captured by the genealogical data. We apply the method to our data, and we also investigate the properties of the method, as well as other association methods, in our highly inbred population, as previous applications were to outbred samples. The more promising regions identified in our initial study in the genetic isolate were then further investigated in an independent sample collected from the Italian population. Among the loci that showed association in this study, we observed evidence of a possible involvement of the region encompassing the gene LRRC16A, already associated to serum uric acid levels in a large meta-analysis of 14 GWAS, suggesting that this locus might lead a pathway for uric acid metabolism that may be involved in gout as well as in nephrolithiasis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In contrast to large GWA studies based on thousands of individuals and large meta-analyses combining GWAS results, we analyzed a small case/control sample for uric acid nephrolithiasis. Our cohort of closely related individuals is derived from a small, genetically isolated village in Sardinia, with well-characterized genealogical data linking the extant population up to the 16(th) century. It is expected that the number of risk alleles involved in complex disorders is smaller in isolated founder populations than in more diverse populations, and the power to detect association with complex traits may be increased when related, homogeneous affected individuals are selected, as they are more likely to be enriched with and share specific risk variants than are unrelated, affected individuals from the general population. When related individuals are included in an association study, correlations among relatives must be accurately taken into account to ensure validity of the results. A recently proposed association method uses an empirical genotypic covariance matrix estimated from genome-screen data to allow for additional population structure and cryptic relatedness that may not be captured by the genealogical data. We apply the method to our data, and we also investigate the properties of the method, as well as other association methods, in our highly inbred population, as previous applications were to outbred samples. The more promising regions identified in our initial study in the genetic isolate were then further investigated in an independent sample collected from the Italian population. Among the loci that showed association in this study, we observed evidence of a possible involvement of the region encompassing the gene LRRC16A, already associated to serum uric acid levels in a large meta-analysis of 14 GWAS, suggesting that this locus might lead a pathway for uric acid metabolism that may be involved in gout as well as in nephrolithiasis.
2001
Archival, demographic and genetic studies define a Sardinian sub-isolate as a suitable model for mapping complex traits Journal Article
In: Hum Genet, 109 (2), pp. 198–209, 2001.
@article{pmid11511926,
title = {Archival, demographic and genetic studies define a Sardinian sub-isolate as a suitable model for mapping complex traits},
year = {2001},
date = {2001-01-01},
journal = {Hum Genet},
volume = {109},
number = {2},
pages = {198--209},
abstract = {Genetic isolates represent exceptional resources for the mapping of complex traits but not all isolates are similar. We have selected a genetic and cultural isolate, the village of Talana from an isolated area of Sardinia, and propose that this population is suitable for the mapping of complex traits. A wealth of historical and archive data allowed the reconstruction of the demographic and genealogical history of the village. Key features of the population, which has grown slowly with no significant immigration, were defined by using a combination of historical, demographic and genetic studies. The genealogy of each Talana inhabitant was reconstructed and the main maternal and paternal lineages of the village were defined. Haplotype and phylogenetic analyses of the Y chromosome and characterisation of mitochondrial DNA haplogroups were used to determine the number of ancestral village founders. The extent of linkage disequilibrium (LD) was evaluated by the analysis of several microsatellites in chromosomal region Xq13.3, which was previously used to asses the extension of LD. Genealogical reconstructions were confirmed and reinforced by the genetic analyses, since some lineages were found to have merged prior to the beginning of the archival records, suggesting an even smaller number of founders than initially predicted. About 80% of the present-day population appears to derive from eight paternal and eleven maternal ancestral lineages. LD was found to span, on average, a 5-Mb region in Xq13.3. This suggests the possibility of identifying identical-by-descent regions associated with complex traits in a genome-wide search by using a low-density marker map. The present study emphasises the importance of combining genetic studies with genealogical and historical information.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Genetic isolates represent exceptional resources for the mapping of complex traits but not all isolates are similar. We have selected a genetic and cultural isolate, the village of Talana from an isolated area of Sardinia, and propose that this population is suitable for the mapping of complex traits. A wealth of historical and archive data allowed the reconstruction of the demographic and genealogical history of the village. Key features of the population, which has grown slowly with no significant immigration, were defined by using a combination of historical, demographic and genetic studies. The genealogy of each Talana inhabitant was reconstructed and the main maternal and paternal lineages of the village were defined. Haplotype and phylogenetic analyses of the Y chromosome and characterisation of mitochondrial DNA haplogroups were used to determine the number of ancestral village founders. The extent of linkage disequilibrium (LD) was evaluated by the analysis of several microsatellites in chromosomal region Xq13.3, which was previously used to asses the extension of LD. Genealogical reconstructions were confirmed and reinforced by the genetic analyses, since some lineages were found to have merged prior to the beginning of the archival records, suggesting an even smaller number of founders than initially predicted. About 80% of the present-day population appears to derive from eight paternal and eleven maternal ancestral lineages. LD was found to span, on average, a 5-Mb region in Xq13.3. This suggests the possibility of identifying identical-by-descent regions associated with complex traits in a genome-wide search by using a low-density marker map. The present study emphasises the importance of combining genetic studies with genealogical and historical information.
- Sassari – Li Punti
- 079 2841307
