ABSTRACT INVIATO ED ACCETTATO per una presentazione al
29th International Congress of the IALP 25-29 August 2013, Turin
A screening on Specific Learning Disabilities in a high genetic homogeneity area.
Claudia Cappa*, Fabrizio Meloni° ,
Sara Giulivi**,Carlo Muzio*, Antonino Schilirò°
* ISAC-CNR Turin Italy, °Servizio di NPI ASL 4 di Lanusei, Italy
**SUPSI Locarno, Switzerland
Abstract
The present research is about the prevalence of Specific Learning Disabilities in a specific area of
Italy, Ogliastra (Sardinia). This region has experienced centuries of isolation, which led to high
genetic homogeneity and made the area particularly interesting for studies on different kinds of
pathologies.
Here we are going to describe the results of a screening carried out in 23 second grade classes in the
Ogliastra region, for a total of 285 pupils. The tool used for the screening was “RSR-DSA.
Questionnaire for the detection of learning difficulties and disorders”, for first and second grade.
The tool is made up of two checklists, one for parents and one for teachers, in order to collect
information about the child not only in relation to the school context, but also with regard to the
home context. The checklists items cover 9 areas of competence: reading, writing, calculation
abilities, language, memory and attention, motor-praxic area, visual perceptual area, behavioural
area, emotional and affective area.
The RSR-DSA questionnaire detected 34/285 cases at risk. Due to possible discrepancies between
teachers’ and parents’ responses, regarding the same aspects of the child’s profile, it was considered
necessary to analyse the questionnaire results in combination with the overall achievement of the
pupils’ classes. This led to exclude 5 cases out of the above mentioned 34, and to reintroduce
further 17 cases out of the original 285.
On the whole, 46 pupils (29+17) were considered in need of further examinations.
This first epidemiological investigation allowed to detect 5,26% of children with SLD. Among
them, 13.33% (0,70% on the total) were cases of SLD in comorbidity with ADHD and another
13.33% were in comorbidity with a language disorder. The prevalence result obtained by the first
national epidemiological investigation was 3,1-3,2%, which is much lower than the percentage
obtained in the present. Considering the characteristics of the area where the study was carried out,
this discrepancy may further confirm the genetic basis of SLD. Further investigation in the territory
would be desirable.
Summary of proposals
The present study concerns the estimate of prevalence of Specific Learning Disabilities (dyslexia,
dysortography, dysgraphia and dyscalculia) in a specific area of Italy, Ogliastra.
For centuries, Ogliastra has experienced isolation, it has been subject to little influence from outside
and has undergone little change. As a consequence, Ogliastra is a region of high genetic
homogeneity and this is the reason why, for years, it has been the setting of numerous studies on a
variety of pathologies. For the same reason the data collected for the present study in this same area
can lead to considerably relevant results.
Articoli isolamaento ogliastra
Se escludiamo le zone costiere, la Sardegna e sempre stata, per cultura, ostile ai contatti con diverse
popolazioni, nonostante gli innumerevoli tentativi di colonizzazione subiti nei secoli.
In Ogliastra è un territorio dove non si sono registrati fenomeni di immigrazione, se non in tempi
recenti
-This region has experienced centuries of isolation, which led to high genetic homogeneity and made
the area particularly interesting for studies on different kinds of pathologies.
l’intera Ogliastra, ma forse come tutta la Sardegna, è un serbatoio ricchissimo per chi, come noi,
cerca nei geni le cause di malattie legate alla senilità. L’isolamento della nostra terra ha determinato
quello che per noi oggi è un campo di studi particolarmente favorevole.
Genome-wide scan with nearly 700 000 SNPs in two Sardinian sub-populations suggests some
regions as candidate targets for positive selection
Ignazio Stefano Piras*,1, Antonella De Montis2, Carla Maria Calo`1, Monica Marini2, Manuela
Atzori2,
Laura Corrias1, Marco Sazzini3, Alessio Boattini3,4, Giuseppe Vona1,4 and Licinio Contu2,4
European Journal of Human Genetics (2012) 20, 1155–1161 & 2012 Macmillan Publishers Limited
All rights reserved 1018-4813/12
Zei G.., Lisa A., Fiorani O., Magri C, Quintana-Murci L., Semino O and Santachiara-Benerecetti
S., From surnames to the history
of Y chromosomes: the Sardinian population as a paradigm European Journal of Human
Genetics (2003) 11, 802–807.
La ragione secondo l'esperto sarebbe dovuto a un isolamento sia geografico sia riproduttivo degli
abitanti dell'Ogliastra (Guido Barbujani dell'universita' di Ferrara)
Così come l'Islanda si è rivelata essere una terra ideale per uno studio genetico capillare dell'intera
sua popolazione, anche l'Ogliastra con le sue peculiari caratteristiche geo-morfologiche e
demografiche, un territorio dove non si sono registrati fenomeni di immigrazione, se non in tempi
recenti e dove l'endogamia (la percentuale di matrimoni tra individui della stessa comunità) arriva a
toccare percentuali altissime, sino a picchi del 95%, si è dimostrata, sin dai primi studi preliminari
da noi effettuati, un luogo ideale per lo sviluppo della ricerca genetica sul territorio.
1)Sardinian populations are undoubtedly of particular interest owing to their genetic background
and elevated degree of isolation.
Cavalli-Sforza LL, Menozzi P, Piazza A: The History and Geography of Human Genes. Princeton,
NJ: Princeton University Press, 1994.
2) These characteristics have made them suitable models for studies on monogenic diseases, such as
G6PD deficiency,20 Thalassemia21 and Wilson disease.22 Moreover, as the Sardinian population is
considered a founder population, the dissection of its genetic variation is also useful for association
studies on complex diseases, in particular on autoimmune diseases, such as Type-I Diabetes and
Multiple Sclerosis, which are highly represented on the island.23, 24
- 20 Siniscalco M, Bernini L, Latte B, Motulsky AG: Favism and thalassæmia in sardinia and their
relationship to malaria. Nature 1961; 190: 1179–1180. | Article | ISI |
http://www.readcube.com/articles/10.1038/1901179a0
- 21 Rosatelli MC, Dozy A, Faa V et al. Molecular characterization of β-thalassemia in the
Sardinian population. Am J Hum Genet 1992; 50: 422–426. | PubMed | ISI | CAS |
- 22 Loudianos G, Dessi V, Lovicu M et al. Molecular characterization of wilson disease in the
Sardinian population–evidence of a founder effect. Hum Mutat 1999; 14: 294–
303. | Article | PubMed | CAS |
23- Karvonen M, Tuomilehto J, Libman I, La Porte R: A review of the recent epidemiological data
on the worldwide incidence of type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1993; 36:
883–892. | Article | PubMed | ISI | CAS |
24 - Pugliatti M, Rosati G, Carton H et al. The epidemiology of multiple sclerosis in Europe. Eur J
Neurol 2006; 13: 700–722. | Article | PubMed | ISI | CAS |
“l primo sotto-popolazione comprende tutti i campioni di Ogliastra, una delle regioni più
isolate, 25 , 26 , 27 , 28della Sardegna
25 -Cappello N, Rendine S, Griffo R et al. Genetic analysis of Sardinia: I. data on 12
polymorphisms in 21 linguistic domains. Ann Hum Genet 60: 125–141. | PubMed |
Angius A, Melis PM, Morelli L et al. Archival, demographic and genetic studies define a Sardinian
sub-isolate as a suitable model for mapping complex traits. Hum Genet 2001; 109: 198–
209. | Article | PubMed | ISI | CAS |
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 genomewide search by using a low-density marker map. The present study emphasises the importance of
combining genetic studies with genealogical and historical information.
26 - Angius A, Bebbere D, Petretto E et al. Not all isolates are equal: linkage disequilibrium
analysis on Xq13.3 reveals different patterns in Sardinian sub-populations. Hum Genet 2002; 111:
9–15. | Article | PubMed | ISI | CAS |
Abstract.
Recent studies indicate that, whereas the Sardinian population as a whole is comparable to outbred
populations for linkage disequilibrium (LD) mapping of common variants, LD in Sardinian subisolates is more extended, making these populations particularly suitable for this approach. To
evaluate the extent of LD between microsatellite markers, we compared different sub-populations
within Sardinia selected on the basis of their geographical position and isolation: two small isolated
villages (Talana, Urzulei), two larger but remote areas (Ogliastra, Nuoro province) and a cohort of
samples representing the wider Sardinian population. LD analysis was carried out by using six
microsatellite markers that are located on Xq13.3 and that have been extensively studied in different
populations. We found different extents and patterns of LD in the sub-population samples
depending on their degree of isolation and demographic history. All LD measurements and
haplotype analyses indicate that there is a decreasing trend from Talana (the most inbred
population, LD up to 9.5–11.5 Mb) to the more outbred Sardinian population (LD only for intervals
<2 Mb). In one village (Talana), five haplotype classes accounting for 80% of the entire sample
perfectly matched five Ogliastra clusters, supporting the origin of the village from the Ogliastra
genetic pool. In contrast, the other village (Urzulei) showed a different pattern of haplotypes with a
closer relationship to the Nuoro region sub-population. LD analyses therefore show that even
neighbouring isolate villages may differ in their genetic background. Here, we highlight the
importance of selecting appropriate populations and/or sub-populations for the analysis of complex
traits. Isolated sub-populations showing different extents of LD can provide a powerful method for
mapping complex traits by LD scanning at relatively low marker density.
27 - Fraumene C, Petretto E, Angius A, Pirastu M: Striking differentiation of sub-populations
within a genetically homogeneous isolate (Ogliastra) in Sardinia as revealed by mtDNA
analysis. Hum Genet 2003; 114: 1–10. | Article | PubMed | ISI | CAS |
Estratto
In quanto la ridotta diversità genetica presente negli isolati dovrebbe semplificare lo studio dei
caratteri complessi, analisi dei modelli di omogeneità all'interno delle popolazioni sono di
particolare interesse. Abbiamo analizzato gli aplogruppi del mtDNA ed io (HVS-I) sequenze di 475
persone provenienti da una zona geograficamente limitata e isolata (Ogliastra) segmento
ipervariabile all'interno Sardegna, comprendendo 175 campioni casuali da 20 su 23 villaggi. I
rimanenti 300 soggetti sono stati scelti dagli altri tre villaggi, Talana, Urzulei e Perdasdefogu,
campionando tutti i lignaggi materni. Il confronto con le altre popolazioni europee rivela che
colloca Ogliastra tra la popolazione più geneticamente omogenea e che è stato piccolo e isolato tutta
la sua storia. La mancanza di variazione e l'elevata omogeneità genetica indicano che un importante
evento fondatore e una espansione demografica ha avuto luogo durante il Neolitico (~ 7700 anni
prima di oggi) nel pool genetico del DNA mitocondriale di Ogliastra. Presentiamo reti filogenetici
altamente risolti per Ogliastra e per i tre sotto-isolati. MtDNA differenziazione delle subpopolazioni contro Ogliastra è rivelato da una forte demarcazione nelle loro piscine genetiche causa
di effetti fondatore distintivi e la deriva genetica. Abbiamo scoperto che l'omogeneità genetica
dipende strettamente da un fattore di scala in termini di dimensioni della popolazione e sulla
metodologia di campionamento.L'omogeneità eccezionale e il ridotto pool genetico femminile
osservata in Ogliastra, nel contesto europeo, nascondono estremamente marcata differenziazione in
sub-isolati originati dalla stessa popolazione arcaica. Sebbene Ogliastra può essere considerato un
geneticamente omogenea isolare, divergenti storie genetiche piccoli villaggi "sottolineano
l'importanza di un'analisi più sistematica delle variazioni del DNA tra e all'interno delle
popolazioni.
Abstract
Since the reduced genetic diversity found in isolates should simplify the study of complex traits,
analyses of patterns of homogeneity within populations are of particular interest. We analysed the
mtDNA haplogroups and hypervariable segment I (HVS-I) sequences of 475 individuals from a
geographically restricted and isolated area (Ogliastra) within Sardinia, comprehending 175 random
samples from 20 out of 23 villages. The remaining 300 subjects were chosen from the other three
villages, Talana, Urzulei and Perdasdefogu, by sampling all maternal lineages. A comparison with
other European populations reveals that Ogliastra ranks among the most genetically homogenous
population and that it has been small and isolated throughout its history. The lack of variation and
the high genetic homogeneity indicate that an important founder event and a demographic
expansion took place during the Neolithic (~ 7,700 years before present) in Ogliastra's mtDNA gene
pool. We present highly resolved phylogenetic networks for Ogliastra and for the three sub-isolates.
MtDNA differentiation in the sub-populations versus Ogliastra is revealed by a strong demarcation
in their genetic pools due to distinctive founder effects and genetic drift. We found that genetic
homogeneity strictly depends on a scale factor in population size and on sampling methodology.
The outstanding homogeneity and the reduced female gene pool observed in Ogliastra, in the
European context, hide an extremely marked differentiation in sub-isolates originated from the
same archaic population. Although Ogliastra can be considered a genetically homogeneous isolate,
small villages' divergent genetic histories underline the importance of more systematic analysis of
DNA variation between and within populations.
http://mbe.oxfordjournals.org/content/23/11/2101.long
---------------
Per questa sua caratteristica è luogo di diversi studi sulla longevità, malattie genetiche ( talassemia,
e morbo di Wilson), malattie autoimmuni (sclerosi multipla), malattie cosiddette multifattoriali
(ipertensione, obesità, calcolosi renali etc.)
Alla base della piramide si trovano infine le fondamenta genetiche, responsabili dello sviluppo
delle cellule del nostro organismo in interazione con l’ambiente di vita. Oggi sappiamo che non
esiste un singolo “gene della dislessia”. Nelle ricerche sulla famigliarità di questo disturbo, sono
stati individuati più loci genetici (E. Grigorenko 2005). La pluralità dei loci coinvolti determina la
variabilità dei deficit neuropsicologici riscontrati; di conseguenza i sottotipi di DSA si possono
rivelare come manifestazioni comportamentali di diversi fenotipi.
fattori “AMBIENTALI” giocano un ruolo
fondamentale nella comparsa di un fenotipo
Morbo di Wilson
Il morbo di Wilson è una rara malattia ereditaria causata da un difetto nel metabolismo
che porta ad un’eccessivo accumulo di rame nel fegato e in altri tessuti (soprattutto il cervello e
il sistema nervoso centrale).
This region has experienced centuries of isolation, which led to high genetic homogeneity and made
the area particularly interesting for studies on different kinds of pathologies.
l’intera Ogliastra, ma forse come tutta la Sardegna, è un serbatoio ricchissimo per chi, come noi,
cerca nei geni le cause di malattie legate alla senilità. L’isolamento della nostra terra ha determinato
quello che per noi oggi è un campo di studi particolarmente favorevole. Se escludiamo le zone
costiere, la Sardegna e sempre stata, per cultura, ostile ai contatti con diverse popolazioni,
nonostante gli innumerevoli tentativi di colonizzazione subiti nei secoli.
Genome-wide scan with nearly 700 000 SNPs in two Sardinian sub-populations suggests some
regions as candidate targets for positive selection
Ignazio Stefano Piras*,1, Antonella De Montis2, Carla Maria Calo`1, Monica Marini2, Manuela
Atzori2,
Laura Corrias1, Marco Sazzini3, Alessio Boattini3,4, Giuseppe Vona1,4 and Licinio Contu2,4
European Journal of Human Genetics (2012) 20, 1155–1161 & 2012 Macmillan Publishers Limited
All rights reserved 1018-4813/12
Zei G.., Lisa A., Fiorani O., Magri C, Quintana-Murci L., Semino O and Santachiara-Benerecetti
S., From surnames to the history
of Y chromosomes: the Sardinian population as a paradigm European Journal of Human
Genetics (2003) 11, 802–807.
La ragione secondo l'esperto sarebbe dovuto a un isolamento sia geografico sia riproduttivo degli
abitanti dell'Ogliastra (Guido Barbujani dell'universita' di Ferrara)
1)Sardinian populations are undoubtedly of particular interest owing to their genetic background
and elevated degree of isolation.
Cavalli-Sforza LL, Menozzi P, Piazza A: The History and Geography of Human Genes. Princeton,
NJ: Princeton University Press, 1994.
2) These characteristics have made them suitable models for studies on monogenic diseases, such as
G6PD deficiency,20 Thalassemia21 and Wilson disease.22 Moreover, as the Sardinian population is
considered a founder population, the dissection of its genetic variation is also useful for association
studies on complex diseases, in particular on autoimmune diseases, such as Type-I Diabetes and
Multiple Sclerosis, which are highly represented on the island.23, 24
- 20 Siniscalco M, Bernini L, Latte B, Motulsky AG: Favism and thalassæmia in sardinia and their
relationship to malaria. Nature 1961; 190: 1179–1180. | Article | ISI |
http://www.readcube.com/articles/10.1038/1901179a0
- 21 Rosatelli MC, Dozy A, Faa V et al. Molecular characterization of β-thalassemia in the
Sardinian population. Am J Hum Genet 1992; 50: 422–426. | PubMed | ISI | CAS |
- 22 Loudianos G, Dessi V, Lovicu M et al. Molecular characterization of wilson disease in the
Sardinian population–evidence of a founder effect. Hum Mutat 1999; 14: 294–
303. | Article | PubMed | CAS |
23- Karvonen M, Tuomilehto J, Libman I, La Porte R: A review of the recent epidemiological data
on the worldwide incidence of type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1993; 36:
883–892. | Article | PubMed | ISI | CAS |
24 - Pugliatti M, Rosati G, Carton H et al. The epidemiology of multiple sclerosis in Europe. Eur J
Neurol 2006; 13: 700–722. | Article | PubMed | ISI | CAS |
“l primo sotto-popolazione comprende tutti i campioni di Ogliastra, una delle regioni più
isolate, 25 , 26 , 27 , 28della Sardegna
25 -Cappello N, Rendine S, Griffo R et al. Genetic analysis of Sardinia: I. data on 12
polymorphisms in 21 linguistic domains. Ann Hum Genet 60: 125–141. | PubMed |
Angius A, Melis PM, Morelli L et al. Archival, demographic and genetic studies define a Sardinian
sub-isolate as a suitable model for mapping complex traits. Hum Genet 2001; 109: 198–
209. | Article | PubMed | ISI | CAS |
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 genomewide search by using a low-density marker map. The present study emphasises the importance of
combining genetic studies with genealogical and historical information.
26 - Angius A, Bebbere D, Petretto E et al. Not all isolates are equal: linkage disequilibrium
analysis on Xq13.3 reveals different patterns in Sardinian sub-populations. Hum Genet 2002; 111:
9–15. | Article | PubMed | ISI | CAS |
Abstract.
Recent studies indicate that, whereas the Sardinian population as a whole is comparable to outbred
populations for linkage disequilibrium (LD) mapping of common variants, LD in Sardinian subisolates is more extended, making these populations particularly suitable for this approach. To
evaluate the extent of LD between microsatellite markers, we compared different sub-populations
within Sardinia selected on the basis of their geographical position and isolation: two small isolated
villages (Talana, Urzulei), two larger but remote areas (Ogliastra, Nuoro province) and a cohort of
samples representing the wider Sardinian population. LD analysis was carried out by using six
microsatellite markers that are located on Xq13.3 and that have been extensively studied in different
populations. We found different extents and patterns of LD in the sub-population samples
depending on their degree of isolation and demographic history. All LD measurements and
haplotype analyses indicate that there is a decreasing trend from Talana (the most inbred
population, LD up to 9.5–11.5 Mb) to the more outbred Sardinian population (LD only for intervals
<2 Mb). In one village (Talana), five haplotype classes accounting for 80% of the entire sample
perfectly matched five Ogliastra clusters, supporting the origin of the village from the Ogliastra
genetic pool. In contrast, the other village (Urzulei) showed a different pattern of haplotypes with a
closer relationship to the Nuoro region sub-population. LD analyses therefore show that even
neighbouring isolate villages may differ in their genetic background. Here, we highlight the
importance of selecting appropriate populations and/or sub-populations for the analysis of complex
traits. Isolated sub-populations showing different extents of LD can provide a powerful method for
mapping complex traits by LD scanning at relatively low marker density.
27 - Fraumene C, Petretto E, Angius A, Pirastu M: Striking differentiation of sub-populations
within a genetically homogeneous isolate (Ogliastra) in Sardinia as revealed by mtDNA
analysis. Hum Genet 2003; 114: 1–10. | Article | PubMed | ISI | CAS |
Estratto
In quanto la ridotta diversità genetica presente negli isolati dovrebbe semplificare lo studio dei
caratteri complessi, analisi dei modelli di omogeneità all'interno delle popolazioni sono di
particolare interesse. Abbiamo analizzato gli aplogruppi del mtDNA ed io (HVS-I) sequenze di 475
persone provenienti da una zona geograficamente limitata e isolata (Ogliastra) segmento
ipervariabile all'interno Sardegna, comprendendo 175 campioni casuali da 20 su 23 villaggi. I
rimanenti 300 soggetti sono stati scelti dagli altri tre villaggi, Talana, Urzulei e Perdasdefogu,
campionando tutti i lignaggi materni. Il confronto con le altre popolazioni europee rivela che
colloca Ogliastra tra la popolazione più geneticamente omogenea e che è stato piccolo e isolato tutta
la sua storia. La mancanza di variazione e l'elevata omogeneità genetica indicano che un importante
evento fondatore e una espansione demografica ha avuto luogo durante il Neolitico (~ 7700 anni
prima di oggi) nel pool genetico del DNA mitocondriale di Ogliastra. Presentiamo reti filogenetici
altamente risolti per Ogliastra e per i tre sotto-isolati. MtDNA differenziazione delle subpopolazioni contro Ogliastra è rivelato da una forte demarcazione nelle loro piscine genetiche causa
di effetti fondatore distintivi e la deriva genetica. Abbiamo scoperto che l'omogeneità genetica
dipende strettamente da un fattore di scala in termini di dimensioni della popolazione e sulla
metodologia di campionamento.L'omogeneità eccezionale e il ridotto pool genetico femminile
osservata in Ogliastra, nel contesto europeo, nascondono estremamente marcata differenziazione in
sub-isolati originati dalla stessa popolazione arcaica. Sebbene Ogliastra può essere considerato un
geneticamente omogenea isolare, divergenti storie genetiche piccoli villaggi "sottolineano
l'importanza di un'analisi più sistematica delle variazioni del DNA tra e all'interno delle
popolazioni.
Abstract
Since the reduced genetic diversity found in isolates should simplify the study of complex traits,
analyses of patterns of homogeneity within populations are of particular interest. We analysed the
mtDNA haplogroups and hypervariable segment I (HVS-I) sequences of 475 individuals from a
geographically restricted and isolated area (Ogliastra) within Sardinia, comprehending 175 random
samples from 20 out of 23 villages. The remaining 300 subjects were chosen from the other three
villages, Talana, Urzulei and Perdasdefogu, by sampling all maternal lineages. A comparison with
other European populations reveals that Ogliastra ranks among the most genetically homogenous
population and that it has been small and isolated throughout its history. The lack of variation and
the high genetic homogeneity indicate that an important founder event and a demographic
expansion took place during the Neolithic (~ 7,700 years before present) in Ogliastra's mtDNA gene
pool. We present highly resolved phylogenetic networks for Ogliastra and for the three sub-isolates.
MtDNA differentiation in the sub-populations versus Ogliastra is revealed by a strong demarcation
in their genetic pools due to distinctive founder effects and genetic drift. We found that genetic
homogeneity strictly depends on a scale factor in population size and on sampling methodology.
The outstanding homogeneity and the reduced female gene pool observed in Ogliastra, in the
European context, hide an extremely marked differentiation in sub-isolates originated from the
same archaic population. Although Ogliastra can be considered a genetically homogeneous isolate,
small villages' divergent genetic histories underline the importance of more systematic analysis of
DNA variation between and within populations.
http://mbe.oxfordjournals.org/content/23/11/2101.long
Alla base della piramide si trovano infine le fondamenta genetiche, responsabili dello sviluppo
delle cellule del nostro organismo in interazione con l’ambiente di vita. Oggi sappiamo che non
esiste un singolo “gene della dislessia”. Nelle ricerche sulla famigliarità di questo disturbo, sono
stati individuati più loci genetici (E. Grigorenko 2005). La pluralità dei loci coinvolti determina la
variabilità dei deficit neuropsicologici riscontrati; di conseguenza i sottotipi di DSA si possono
rivelare come manifestazioni comportamentali di diversi fenotipi.
fattori “AMBIENTALI” giocano un ruolo
fondamentale nella comparsa di un fenotipo
Morbo di Wilson
Il morbo di Wilson è una rara malattia ereditaria causata da un difetto nel metabolismo
che porta ad un’eccessivo accumulo di rame nel fegato e in altri tessuti (soprattutto il cervello e
il sistema nervoso centrale).
This region has experienced centuries of isolation, which led to high genetic homogeneity and made
the area particularly interesting for studies on different kinds of pathologies.
l’intera Ogliastra, ma forse come tutta la Sardegna, è un serbatoio ricchissimo per chi, come noi,
cerca nei geni le cause di malattie legate alla senilità. L’isolamento della nostra terra ha determinato
quello che per noi oggi è un campo di studi particolarmente favorevole. Se escludiamo le zone
costiere, la Sardegna e sempre stata, per cultura, ostile ai contatti con diverse popolazioni,
nonostante gli innumerevoli tentativi di colonizzazione subiti nei secoli.
Genome-wide scan with nearly 700 000 SNPs in two Sardinian sub-populations suggests some
regions as candidate targets for positive selection
Ignazio Stefano Piras*,1, Antonella De Montis2, Carla Maria Calo`1, Monica Marini2, Manuela
Atzori2,
Laura Corrias1, Marco Sazzini3, Alessio Boattini3,4, Giuseppe Vona1,4 and Licinio Contu2,4
European Journal of Human Genetics (2012) 20, 1155–1161 & 2012 Macmillan Publishers Limited
All rights reserved 1018-4813/12
Zei G.., Lisa A., Fiorani O., Magri C, Quintana-Murci L., Semino O and Santachiara-Benerecetti
S., From surnames to the history
of Y chromosomes: the Sardinian population as a paradigm European Journal of Human
Genetics (2003) 11, 802–807.
La ragione secondo l'esperto sarebbe dovuto a un isolamento sia geografico sia riproduttivo degli
abitanti dell'Ogliastra (Guido Barbujani dell'universita' di Ferrara)
1)Sardinian populations are undoubtedly of particular interest owing to their genetic background
and elevated degree of isolation.
Cavalli-Sforza LL, Menozzi P, Piazza A: The History and Geography of Human Genes. Princeton,
NJ: Princeton University Press, 1994.
2) These characteristics have made them suitable models for studies on monogenic diseases, such as
G6PD deficiency,20 Thalassemia21 and Wilson disease.22 Moreover, as the Sardinian population is
considered a founder population, the dissection of its genetic variation is also useful for association
studies on complex diseases, in particular on autoimmune diseases, such as Type-I Diabetes and
Multiple Sclerosis, which are highly represented on the island.23, 24
- 20 Siniscalco M, Bernini L, Latte B, Motulsky AG: Favism and thalassæmia in sardinia and their
relationship to malaria. Nature 1961; 190: 1179–1180. | Article | ISI |
http://www.readcube.com/articles/10.1038/1901179a0
- 21 Rosatelli MC, Dozy A, Faa V et al. Molecular characterization of β-thalassemia in the
Sardinian population. Am J Hum Genet 1992; 50: 422–426. | PubMed | ISI | CAS |
- 22 Loudianos G, Dessi V, Lovicu M et al. Molecular characterization of wilson disease in the
Sardinian population–evidence of a founder effect. Hum Mutat 1999; 14: 294–
303. | Article | PubMed | CAS |
23- Karvonen M, Tuomilehto J, Libman I, La Porte R: A review of the recent epidemiological data
on the worldwide incidence of type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1993; 36:
883–892. | Article | PubMed | ISI | CAS |
24 - Pugliatti M, Rosati G, Carton H et al. The epidemiology of multiple sclerosis in Europe. Eur J
Neurol 2006; 13: 700–722. | Article | PubMed | ISI | CAS |
“l primo sotto-popolazione comprende tutti i campioni di Ogliastra, una delle regioni più
isolate, 25 , 26 , 27 , 28della Sardegna
25 -Cappello N, Rendine S, Griffo R et al. Genetic analysis of Sardinia: I. data on 12
polymorphisms in 21 linguistic domains. Ann Hum Genet 60: 125–141. | PubMed |
Angius A, Melis PM, Morelli L et al. Archival, demographic and genetic studies define a Sardinian
sub-isolate as a suitable model for mapping complex traits. Hum Genet 2001; 109: 198–
209. | Article | PubMed | ISI | CAS |
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 genomewide search by using a low-density marker map. The present study emphasises the importance of
combining genetic studies with genealogical and historical information.
26 - Angius A, Bebbere D, Petretto E et al. Not all isolates are equal: linkage disequilibrium
analysis on Xq13.3 reveals different patterns in Sardinian sub-populations. Hum Genet 2002; 111:
9–15. | Article | PubMed | ISI | CAS |
Abstract.
Recent studies indicate that, whereas the Sardinian population as a whole is comparable to outbred
populations for linkage disequilibrium (LD) mapping of common variants, LD in Sardinian subisolates is more extended, making these populations particularly suitable for this approach. To
evaluate the extent of LD between microsatellite markers, we compared different sub-populations
within Sardinia selected on the basis of their geographical position and isolation: two small isolated
villages (Talana, Urzulei), two larger but remote areas (Ogliastra, Nuoro province) and a cohort of
samples representing the wider Sardinian population. LD analysis was carried out by using six
microsatellite markers that are located on Xq13.3 and that have been extensively studied in different
populations. We found different extents and patterns of LD in the sub-population samples
depending on their degree of isolation and demographic history. All LD measurements and
haplotype analyses indicate that there is a decreasing trend from Talana (the most inbred
population, LD up to 9.5–11.5 Mb) to the more outbred Sardinian population (LD only for intervals
<2 Mb). In one village (Talana), five haplotype classes accounting for 80% of the entire sample
perfectly matched five Ogliastra clusters, supporting the origin of the village from the Ogliastra
genetic pool. In contrast, the other village (Urzulei) showed a different pattern of haplotypes with a
closer relationship to the Nuoro region sub-population. LD analyses therefore show that even
neighbouring isolate villages may differ in their genetic background. Here, we highlight the
importance of selecting appropriate populations and/or sub-populations for the analysis of complex
traits. Isolated sub-populations showing different extents of LD can provide a powerful method for
mapping complex traits by LD scanning at relatively low marker density.
27 - Fraumene C, Petretto E, Angius A, Pirastu M: Striking differentiation of sub-populations
within a genetically homogeneous isolate (Ogliastra) in Sardinia as revealed by mtDNA
analysis. Hum Genet 2003; 114: 1–10. | Article | PubMed | ISI | CAS |
Estratto
In quanto la ridotta diversità genetica presente negli isolati dovrebbe semplificare lo studio dei
caratteri complessi, analisi dei modelli di omogeneità all'interno delle popolazioni sono di
particolare interesse. Abbiamo analizzato gli aplogruppi del mtDNA ed io (HVS-I) sequenze di 475
persone provenienti da una zona geograficamente limitata e isolata (Ogliastra) segmento
ipervariabile all'interno Sardegna, comprendendo 175 campioni casuali da 20 su 23 villaggi. I
rimanenti 300 soggetti sono stati scelti dagli altri tre villaggi, Talana, Urzulei e Perdasdefogu,
campionando tutti i lignaggi materni. Il confronto con le altre popolazioni europee rivela che
colloca Ogliastra tra la popolazione più geneticamente omogenea e che è stato piccolo e isolato tutta
la sua storia. La mancanza di variazione e l'elevata omogeneità genetica indicano che un importante
evento fondatore e una espansione demografica ha avuto luogo durante il Neolitico (~ 7700 anni
prima di oggi) nel pool genetico del DNA mitocondriale di Ogliastra. Presentiamo reti filogenetici
altamente risolti per Ogliastra e per i tre sotto-isolati. MtDNA differenziazione delle subpopolazioni contro Ogliastra è rivelato da una forte demarcazione nelle loro piscine genetiche causa
di effetti fondatore distintivi e la deriva genetica. Abbiamo scoperto che l'omogeneità genetica
dipende strettamente da un fattore di scala in termini di dimensioni della popolazione e sulla
metodologia di campionamento.L'omogeneità eccezionale e il ridotto pool genetico femminile
osservata in Ogliastra, nel contesto europeo, nascondono estremamente marcata differenziazione in
sub-isolati originati dalla stessa popolazione arcaica. Sebbene Ogliastra può essere considerato un
geneticamente omogenea isolare, divergenti storie genetiche piccoli villaggi "sottolineano
l'importanza di un'analisi più sistematica delle variazioni del DNA tra e all'interno delle
popolazioni.
Abstract
Since the reduced genetic diversity found in isolates should simplify the study of complex traits,
analyses of patterns of homogeneity within populations are of particular interest. We analysed the
mtDNA haplogroups and hypervariable segment I (HVS-I) sequences of 475 individuals from a
geographically restricted and isolated area (Ogliastra) within Sardinia, comprehending 175 random
samples from 20 out of 23 villages. The remaining 300 subjects were chosen from the other three
villages, Talana, Urzulei and Perdasdefogu, by sampling all maternal lineages. A comparison with
other European populations reveals that Ogliastra ranks among the most genetically homogenous
population and that it has been small and isolated throughout its history. The lack of variation and
the high genetic homogeneity indicate that an important founder event and a demographic
expansion took place during the Neolithic (~ 7,700 years before present) in Ogliastra's mtDNA gene
pool. We present highly resolved phylogenetic networks for Ogliastra and for the three sub-isolates.
MtDNA differentiation in the sub-populations versus Ogliastra is revealed by a strong demarcation
in their genetic pools due to distinctive founder effects and genetic drift. We found that genetic
homogeneity strictly depends on a scale factor in population size and on sampling methodology.
The outstanding homogeneity and the reduced female gene pool observed in Ogliastra, in the
European context, hide an extremely marked differentiation in sub-isolates originated from the
same archaic population. Although Ogliastra can be considered a genetically homogeneous isolate,
small villages' divergent genetic histories underline the importance of more systematic analysis of
DNA variation between and within populations.
http://mbe.oxfordjournals.org/content/23/11/2101.long
OBIETTIVI RICERCA
MATERIALI E METODI
Inserire presentazione daa e stum di screening a genitori e insegnantii
Rest risultati questionari a marzo
Restituzione ai gen da parte asl singolarmente
Autorizzazione ai genitotori a comunicare l’esito agli insegnanti in modo che ancje gòi ins possano
lavora suòle aree dficitarie
Èoteziamento svolto inizialmente dal servzio come counceling
Alcuni vengono tenuti in Asl altri servizi educativi di comuni e cooperative sociao educatove
Cosa cambia la dde dalla dde-2?????
La batteria è composta di 12 prove, di cui 9 per l'analisi del processo di lettura e 3 per l'analisi del
processo di scrittura.
Inoltre è incluso uno spazio per confrontare i risultati della prova MT, che permette un confronto
diretto con la lettura di brano.
Le prove 1 e 2 servono per valutare la conversione grafema-fonema;
la 1-b per verificare l'efficienza nel recupero di informazioni verbali;
la 3 per valutare il lessico posseduto;
la 4 per il processo di lettura senza contesto sintattico e semantico;
la 5 per valutare l'efficienza del modo di lettura indiretto;
la 6 per la lettura di parole accentate irregolarmente;
la 7, la 8, la 9 servono a valutare lo sviluppo del modo diretto di lettura.
la 10 valuta l'efficienza ortografica in genere
la 11 serve per valutare il modo indiretto di scrittura
la 12 per valutare il modo diretto
Per la valutazione delle prove dalla 1 alla 6 si osservano sia tempi di lettura, sia numero di errori;
per le altre, solo il numero di errori.
BREVE DESCRIZIONE rsr-dsa
The research project described here involved 23 second grade classes in 23 districts under the
Healthcare Service of Lanusei. These cover the whole Ogliastra region.
A screening was carried out using the validated questionnaire “RSR-DSA. Questionnaire for the
detection of learning difficulties and disorders”, for first and second grade. The questionnaire is
highly reliable ( Cronbach teachers questionnaire = 0.97,  Cronbach parents questionnaire =
0.92) and is made up of a double checklist, one for parents and one for teachers. This allows to
integrate information from both types of respondents, to obtain a wide detailed picture of the child’s
difficulties and to describe his/her behaviours in the school context as well as at home.
The questionnaire items are grouped into 9 areas of competence, that allow a description of the
subject’s skills in school activities (1. reading, 2. writing, 3. calculation abilities), the collection of
information regarding some of the neuropsychological abilities of the child (4. language, 5. memory
and attention, 6. motor-praxic area, 7. visual perceptual area), his/her behaviour (8. behavioural
area) and his/her affective experience related to school learning (9. emotional and affective area).
The RSR-DSA questionnaire allows to obtain a snap-shot of the subject’s abilities in the
investigated areas. Obviously, the more thorough the observation, the more useful the information
that can be obtained.
The research was carried out in 2012 and involved all schools in the district of Lanusei, for a total
of 285 pupils (143 females and 142 males). Two children were excluded from the study, due to a
certification of mental retardation (according to the Italian Law 104/92). In January 2013, the
research broadened to further 350 pupils. Questionnaires were collected and are in the process of
being analysed.
Among the 285 pupils, the RSR-DSA tool detected 34 cases at risk.
Since the questionnaire is based on observation, a discrepancy between parents’ and teachers’ views
can emerge. An overestimation or underestimation of the child’s difficulties is also possible. For
this reason, in selecting the children who may need further examinations, the Healthcare Services
took into consideration not only the questionnaire results, but also the overall achievements of the
whole class. This led to excluding 5 cases, for whom further testing was considered unnecessary.
Therefore 29 out of 34 cases went through further examinations. Among these 29 children, 3 have
been certified according to the legislation in force (Law n.°104/92), 8 have gone through an
enhancement program, after which their questionnaire scores were within normal parameters, 18
obtained a diagnosis. Among the latter 18 children, 10 were diagnosed with SLD, 2 were diagnosed
with SLD in comorbidity with Attention Deficit and Hyperactivity Disorder (ADHD), 2 were
diagnosed with SLD in comorbidity with a language disorder , 1 was diagnosed with ADHD, and 3
with an unspecified developmental disorder of scholastic skills.
Looking at the overall achievements of the classes along with teachers’ and parents’ responses led
the Healthcare Service to decide to examine 17 further cases besides the 29 described above.
Among these 17 cases, none had resulted at risk of SLD according to the RSR-DSA questionnaire,
however
-
-
-
4 had resulted at risk of difficulties in other areas, not related to school learning. Among
them, 2 obtained a diagnosis of ADHD and one is currently receiving support for
behavioural difficulties, that are about to be overcome, 1 was not diagnosed with any
specific disorder/difficulty.
5 had resulted at risk of school difficulties. Among them, 1 was diagnosed with mild
dyslexia and dysortography, 4 went through an enhancement program, after which their
questionnaire scores were within normal parameters.
8 had resulted as at no risk, according to the RSR-DSA questionnaire. Among them 7 did
not receive any kind of diagnosis, 1 was diagnosed with a mild mental retardation (the RSRDSA questionnaire is not designed for subjects with this kind of disorder. As already
mentioned, subjects with mental retardation need to be excluded from RSR-DSA
screenings).
This first epidemiological investigation allowed to detect 5,26% of children with SLD. Among
them, 13.33% (0,70% on the total) were cases of SLD in comorbidity with ADHD and another
13.33% were in comorbidity with a language disorder. The investigation also highlighted a greater
incidence of SLD in males than in females (2:1).
The prevalence result obtained within the present research (5,26%) is greater than that obtained by
the first national epidemiological investigation (3,1-3,2%). Considering the characteristics of the
area where the study was carried out, these preliminary results may further confirm the genetic basis
of SLD. For this reason, further investigation in the territory would be desirable.
RISULTATI 1 ANNO
Financial disclosure statement
Financial disclosure: no funding, nor financial relationship to disclose
Conflict of interest: none