Lucia Perseu
Technician
Area of interest:
Definition of molecular defect, regulatory genes and globin expression modifiers in the thalassemic population and knock-out and transgenic mice. I participate in the activity of the institute in the use of mouse models for malaria studies. Techniques acquired: DNA and RNA extraction, PCR, qPCR DNA sequencing, hematological analysis, FACS, iron extraction and dosing in the organs, maintenance of murine knock-out and transgenic lines, biological material removal
Most significant publications:
2015
Danjou, Fabrice; Zoledziewska, Magdalena; Sidore, Carlo; Steri, Maristella; Busonero, Fabio; Maschio, Andrea; Mulas, Antonella; Perseu, Lucia; Barella, Susanna; Porcu, Eleonora; Pistis, Giorgio; Pitzalis, Maristella; Pala, Mauro; Menzel, Stephan; Metrustry, Sarah; Spector, Timothy D; Leoni, Lidia; Angius, Andrea; Uda, Manuela; Moi, Paolo; Thein, Swee Lay; Galanello, Renzo; Abecasis, Gonçalo R; Schlessinger, David; Sanna, Serena; Cucca, Francesco
Genome-wide association analyses based on whole-genome sequencing in Sardinia provide insights into regulation of hemoglobin levels Journal Article
In: Nature Genetics, 47 (11), pp. 1264–1271, 2015, ISSN: 1546-1718.
@article{danjou_genome-wide_2015,
title = {Genome-wide association analyses based on whole-genome sequencing in Sardinia provide insights into regulation of hemoglobin levels},
author = {Fabrice Danjou and Magdalena Zoledziewska and Carlo Sidore and Maristella Steri and Fabio Busonero and Andrea Maschio and Antonella Mulas and Lucia Perseu and Susanna Barella and Eleonora Porcu and Giorgio Pistis and Maristella Pitzalis and Mauro Pala and Stephan Menzel and Sarah Metrustry and Timothy D Spector and Lidia Leoni and Andrea Angius and Manuela Uda and Paolo Moi and Swee Lay Thein and Renzo Galanello and Gon{ç}alo R Abecasis and David Schlessinger and Serena Sanna and Francesco Cucca},
doi = {10.1038/ng.3307},
issn = {1546-1718},
year = {2015},
date = {2015-11-01},
journal = {Nature Genetics},
volume = {47},
number = {11},
pages = {1264--1271},
abstract = {We report genome-wide association study results for the levels of A1, A2 and fetal hemoglobins, analyzed for the first time concurrently. Integrating high-density array genotyping and whole-genome sequencing in a large general population cohort from Sardinia, we detected 23 associations at 10 loci. Five signals are due to variants at previously undetected loci: MPHOSPH9, PLTP-PCIF1, ZFPM1 (FOG1), NFIX and CCND3. Among the signals at known loci, ten are new lead variants and four are new independent signals. Half of all variants also showed pleiotropic associations with different hemoglobins, which further corroborated some of the detected associations and identified features of coordinated hemoglobin species production.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We report genome-wide association study results for the levels of A1, A2 and fetal hemoglobins, analyzed for the first time concurrently. Integrating high-density array genotyping and whole-genome sequencing in a large general population cohort from Sardinia, we detected 23 associations at 10 loci. Five signals are due to variants at previously undetected loci: MPHOSPH9, PLTP-PCIF1, ZFPM1 (FOG1), NFIX and CCND3. Among the signals at known loci, ten are new lead variants and four are new independent signals. Half of all variants also showed pleiotropic associations with different hemoglobins, which further corroborated some of the detected associations and identified features of coordinated hemoglobin species production.
2012
van der Harst, Pim; Zhang, Weihua; Mateo Leach, Irene; Rendon, Augusto; Verweij, Niek; Sehmi, Joban; Paul, Dirk S; Elling, Ulrich; Allayee, Hooman; Li, Xinzhong; Radhakrishnan, Aparna; Tan, Sian-Tsung; ...,; Sanna, Serena; Uda, Manuela; Hicks, Andrew A; Penninger, Josef Martin; Gieger, Christian; Kooner, Jaspal S; Ouwehand, Willem H; Soranzo, Nicole; Chambers, John C
Seventy-five genetic loci influencing the human red blood cell Journal Article
In: Nature, 492 (7429), pp. 369–375, 2012, ISSN: 1476-4687.
@article{van_der_harst_seventy-five_2012,
title = {Seventy-five genetic loci influencing the human red blood cell},
author = {van der Harst, Pim and Zhang, Weihua and {Mateo Leach}, Irene and Rendon, Augusto and Verweij, Niek and Sehmi, Joban and Paul, Dirk S and Elling, Ulrich and Allayee, Hooman and Li, Xinzhong and Radhakrishnan, Aparna and Tan, Sian-Tsung and ... and Sanna, Serena and Uda, Manuela and Hicks, Andrew A and Penninger, Josef Martin and Gieger, Christian and Kooner, Jaspal S and Ouwehand, Willem H and Soranzo, Nicole and Chambers, John C},
doi = {10.1038/nature11677},
issn = {1476-4687},
year = {2012},
date = {2012-12-01},
journal = {Nature},
volume = {492},
number = {7429},
pages = {369--375},
abstract = {Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
Danjou, Fabrice; Anni, Franco; Perseu, Lucia; Satta, Stefania; Dessì, Carlo; Lai, Maria Eliana; Fortina, Paolo; Devoto, Marcella; Galanello, Renzo
Genetic modifiers of β-thalassemia and clinical severity as assessed by age at first transfusion Journal Article
In: Haematologica, 97 (7), pp. 989–993, 2012, ISSN: 1592-8721.
@article{danjou_genetic_2012,
title = {Genetic modifiers of β-thalassemia and clinical severity as assessed by age at first transfusion},
author = {Fabrice Danjou and Franco Anni and Lucia Perseu and Stefania Satta and Carlo Dess{ì} and Maria Eliana Lai and Paolo Fortina and Marcella Devoto and Renzo Galanello},
doi = {10.3324/haematol.2011.053504},
issn = {1592-8721},
year = {2012},
date = {2012-07-01},
journal = {Haematologica},
volume = {97},
number = {7},
pages = {989--993},
abstract = {BACKGROUND: The clinical and hematologic features of β-thalassemia are modulated by different factors, resulting in a wide range of clinical severity. The main factors are the type of disease-causing mutation and the ability to produce α-globin and γ-globin chains. In the present study we investigated the respective contributions of known modifiers to the prediction of the clinical severity of β-thalassemia as assessed by the patients' age at first transfusion.
DESIGN AND METHODS: We studied the effect of seven loci in a cohort of 316 Sardinian patients with β(0)-thalassemia. In addition to characterizing the β-globin gene mutations, α-globin gene defects and HBG2:g.-158C>T polymorphism, we genotyped two different markers in the BCL11A gene and three in the HBS1L-MYB intergenic region using single nucleotide polymorphism microarrays, imputation and direct genotyping. We performed Cox proportional hazard analysis of the time to first transfusion. RESULTS: According to the resulting model, we were able to explain phenotypic severity to a large extent (Harrell's concordance index=0.72; Cox & Snell R(2)=0.394) and demonstrated that most of the model's discriminatory ability is attributable to the genetic variants affecting fetal hemoglobin production (HBG2:g.-158C>T, BCL11A and HBS1L-MYB loci: C-index=0.68, R(2)=0.272), while the remaining is due to α-globin gene defects and gender. Consequently, significantly distinct survival curves can be described in our population.
CONCLUSIONS: This detailed analysis clarifies the impact of genetic modifiers on the clinical severity of the disease, measured by time to first transfusion, by determining their relative contributions in a homogeneous cohort of β(0)-thalassemia patients. It may also support clinical decisions regarding the beginning of transfusion therapy in patients with β-thalassemia.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: The clinical and hematologic features of β-thalassemia are modulated by different factors, resulting in a wide range of clinical severity. The main factors are the type of disease-causing mutation and the ability to produce α-globin and γ-globin chains. In the present study we investigated the respective contributions of known modifiers to the prediction of the clinical severity of β-thalassemia as assessed by the patients' age at first transfusion.
DESIGN AND METHODS: We studied the effect of seven loci in a cohort of 316 Sardinian patients with β(0)-thalassemia. In addition to characterizing the β-globin gene mutations, α-globin gene defects and HBG2:g.-158C>T polymorphism, we genotyped two different markers in the BCL11A gene and three in the HBS1L-MYB intergenic region using single nucleotide polymorphism microarrays, imputation and direct genotyping. We performed Cox proportional hazard analysis of the time to first transfusion. RESULTS: According to the resulting model, we were able to explain phenotypic severity to a large extent (Harrell's concordance index=0.72; Cox & Snell R(2)=0.394) and demonstrated that most of the model's discriminatory ability is attributable to the genetic variants affecting fetal hemoglobin production (HBG2:g.-158C>T, BCL11A and HBS1L-MYB loci: C-index=0.68, R(2)=0.272), while the remaining is due to α-globin gene defects and gender. Consequently, significantly distinct survival curves can be described in our population.
CONCLUSIONS: This detailed analysis clarifies the impact of genetic modifiers on the clinical severity of the disease, measured by time to first transfusion, by determining their relative contributions in a homogeneous cohort of β(0)-thalassemia patients. It may also support clinical decisions regarding the beginning of transfusion therapy in patients with β-thalassemia.
DESIGN AND METHODS: We studied the effect of seven loci in a cohort of 316 Sardinian patients with β(0)-thalassemia. In addition to characterizing the β-globin gene mutations, α-globin gene defects and HBG2:g.-158C>T polymorphism, we genotyped two different markers in the BCL11A gene and three in the HBS1L-MYB intergenic region using single nucleotide polymorphism microarrays, imputation and direct genotyping. We performed Cox proportional hazard analysis of the time to first transfusion. RESULTS: According to the resulting model, we were able to explain phenotypic severity to a large extent (Harrell's concordance index=0.72; Cox & Snell R(2)=0.394) and demonstrated that most of the model's discriminatory ability is attributable to the genetic variants affecting fetal hemoglobin production (HBG2:g.-158C>T, BCL11A and HBS1L-MYB loci: C-index=0.68, R(2)=0.272), while the remaining is due to α-globin gene defects and gender. Consequently, significantly distinct survival curves can be described in our population.
CONCLUSIONS: This detailed analysis clarifies the impact of genetic modifiers on the clinical severity of the disease, measured by time to first transfusion, by determining their relative contributions in a homogeneous cohort of β(0)-thalassemia patients. It may also support clinical decisions regarding the beginning of transfusion therapy in patients with β-thalassemia.
Satta, Stefania; Perseu, Lucia; Maccioni, Liliana; Giagu, Nicolina; Galanello, Renzo
Delayed fetal hemoglobin switching in subjects with KLF1 gene mutation Journal Article
In: Blood Cells, Molecules & Diseases, 48 (1), pp. 22–24, 2012, ISSN: 1096-0961.
@article{satta_delayed_2012,
title = {Delayed fetal hemoglobin switching in subjects with KLF1 gene mutation},
author = {Stefania Satta and Lucia Perseu and Liliana Maccioni and Nicolina Giagu and Renzo Galanello},
doi = {10.1016/j.bcmd.2011.10.003},
issn = {1096-0961},
year = {2012},
date = {2012-01-01},
journal = {Blood Cells, Molecules & Diseases},
volume = {48},
number = {1},
pages = {22--24},
abstract = {Variations at the KLF1 gene have been associated with a series of human erythroid phenotypes including the In-(Lu) phenotype, hereditary persistence of fetal hemoglobin, congenital dyserythropoietic anemia, borderline HbA(2) and increased red blood cell protoporphyrin. Natural mutations have shown that KLF1 regulates gamma globin gene expression and its role in the switching from fetal to adult globin expression has been suggested by experimental studies. In this paper we report that subjects with S270X KLF1 mutations show a decrease of HbF levels with increasing age, supporting in vivo the role of KLF1 in hemoglobin switching in humans.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Variations at the KLF1 gene have been associated with a series of human erythroid phenotypes including the In-(Lu) phenotype, hereditary persistence of fetal hemoglobin, congenital dyserythropoietic anemia, borderline HbA(2) and increased red blood cell protoporphyrin. Natural mutations have shown that KLF1 regulates gamma globin gene expression and its role in the switching from fetal to adult globin expression has been suggested by experimental studies. In this paper we report that subjects with S270X KLF1 mutations show a decrease of HbF levels with increasing age, supporting in vivo the role of KLF1 in hemoglobin switching in humans.
- Monserrato
- 320 1183583