posted 23 January 2005 02:18 AM            

• Blood group phenotypes and the origin of sickle cell hemoglobin in Sicilians.

  Sandler SG, Schiliro G, Russo A, Musumeci S, Rachmilewitz EA.

  "As an approach to investigating the origin of sickle cell hemoglobin (hemoglobin S) in white persons of Sicilian ancestry, two groups of native Sicilians were tested for blood group evidence of African admixture. Among 100 unrelated Sicilians, the phenotypes cDe(Rho) and Fy(a-b-), and the antigens V(hrv) and Jsa, which are considered to be African genetic markers, were detected in 12 individuals. Among 64 individuals from 21 families with at least one known hemoglobin S carrier, African blood group markers were detected in 7 (11%). These findings indicate that hemoglobin S is only one of multiple African genes present in contemporary Sicilian populations. The occurrence of hemoglobin S in white persons of Sicilian ancestry is considered to be a manifestation of the continuing dissemination of the original African mutation."

  
  

• Sickle cell disease in Sicily.

  Roth EF Jr, Schiliro G, Russo A, Musumeci S, Rachmilewitz E, Neske V, Nagel R.

  "The chemical and physical properties of haemoglobin S derived from homozygotes for this haemoglobin in Sicily were examined, as well as some erythrocytic characteristics. Sicilian Hb S was identical to that found in USA black patients in electrophoretic mobility on both starch and citrate agar media, solubility, mechanical precipitation rate of oxyhaemoglobins, and minimum gelling concentration, as well as by peptide mapping and amino-acid analysis of all beta-chain peptides. Taken together with the presence in Sicily of African blood group markers and certain historical considerations, it seems clear that the source of Hb S in Sicily is Africa. While the clinical severity in nine Sicilian children did not seem remarkably different from the disease in the USA, the most severe and fatal complications were not seen. Mean Hb F Was 10.5% and 2,3-diphosphoglycerate (2,3-DPG) values were higher in Sicilian homozygotes than in black USA counterparts (21.79 mumol/g Hb vs 15.16). Red cell AT values were also slightly higher in Sicilian patients. The presence of concomitant thalassaemia was excluded by both family studies and globin chain synthetic ratios. In conclusion, haemoglobin S in Sicilian homozygotes is identical to Hb S found in USA blacks. Although the severity of the disease seems quite similar in both groups of patients, other erythrocytic properties were found to be different. Whether these factors influence severity remains to be elucidated."

  Source:Med Genet. 1980 Feb;17(1):34-8.

• Sickle cell anemia and S-thalassemia in Sicilian children

  Giovanna Russo and Gino Schiliro
  Division of pediatric Hematology and Oncology, University of Catania, Catania,

  "HbS is endemic in Sicily area for and this anomaly has been described in Sicilians and in people of Sicilian ancestry (3). For thousands of years the Mediterranean basin has been the crossroad for trade, races, ideas, and art. The geographical position of Sicily at the center of the Mediterranean made it a natural stopover on these journeys. Phoenicians, Greeks, Carthaginians, Byzantines, Saracens, Normans, Spaniards, Arabs, Jews, and mercenaries from allover the world came to Sicily in large numbers to settle. In contrast with the past, there has been almost no immigration during the last few centuries. The genetic structure of the Sicilians is clearly not due to recent additions. The consensus is that the gene was introduced into Sicily and Southern Italy from Northern Africa through the trans-Saharan trade routes, or, alternatively, by means of the Greek colonisation, although the introduction of the gene into Sicily during the Muslim invasion cannot be excluded."

  Source: http://www.sicklecellsociety.org/information/resrep/res14.htm

  
  

• HbS Benin Haplotype:

  "The Benin haplotype accounts for HbS associated chromosomes in Sicily, 4 Northern Greece,10 Southern Turkey,11 and South West Saudi Arabia,6,7 suggesting that these genes had their origin in West Africa. The Asian haplotype is rarely encountered outside its geographic origin because there have been few large population movements and Indian emigrants have been predominantly from non HbS containing populations. However, it is of interest that the Asian haplotype was first described among descendants of Indian indentured laborers in Jamaica.12 The disease now occurs against diverse genetic and environmental backgrounds, which provide experimental models for investigating the mechanisms of the clinical and hematological variability of the disease."

  Source: http://www.kfshrc.edu.sa/annals/143/rev9239.html

• PET-CT fusion imaging in differentiating physiologic from pathologic FDG uptake.-RadioGraphics 2004

  "On the basis of the different prototypes of restriction enzyme locations, four different DNA configurations--the beta globin haplotypes associated with the sickle cell gene that designate the independent occurrences of the sickle cell mutation--have been recognized. They are named after the places where they were originally described (1,2).

  I. Senegal haplotype, on the Atlantic coast of West Africa.

  II. Bantu or Central African Republic haplotype, in Zaire, the Central African Republic, Angola, and Kenya.

  III. Benin haplotype, in central West Africa, especially Ghana, Nigeria, Ivory Coast, and southwestern Saudi Arabia.

  IV. Asian haplotype, in the eastern province of Saudi Arabia (2,3) and central India.

  The Benin haplotype, with the gene of origin in West Africa, spread along the slave trading routes to North America and the Caribbean region and through migration to the Mediterranean region (Sicily, northern Greece, and southern Turkey) and to southwestern Saudi Arabia. Thus, two diverse forms of sickle cell disease exist in Saudi Arabia: the Benin haplotype in the southwestern region, apparently imported from Africa, and the Asian haplotype in the eastern province, possibly representing an independent local occurrence of the sickle cell mutation…However, the significantly lower mortality rate of end-stage sickle cell nephropathy patients in eastern Saudi Arabia (Asian haplotype) compared with that of African American patients (largely Benin haplotype) may conceivably be an additional difference in the survival of sickle cell disease patients receiving hemodialysis. For that reason, Saudi Arabia provides a unique opportunity for studying the clinical effects of the two different haplotypes within similar environments (3). -Dr Kostakoglu

  source: Kostakoglu L, Hardoff R, Mirtcheva R, Goldsmith SJ. PET-CT fusion imaging in differentiating physiologic from pathologic FDG uptake. RadioGraphics 2004; 24:1411-1431)
  http://radiographics.rsnajnls.org/cgi/eletters?lookup=by_date&days=710

• S.O.Y. Keita
  American Journal of Human Biology 16:679-689 (2004)

  "Populations should be viewed processually as dynamic entities over time and not "static" entities. The prescence of M35/215 lineages and the Benin sickle cell variant in southern Europe illustrates this well."

  "The consideration of the results of this analysis, with the observation that the African peoples of the PN2 clade are tremendously diverse in skin color, body build, facial conformation, hair form, etc. forces a reexamination of the ideas about the relationship of craniofacial similarity to descent group in Africa."

• Haplotypes of the beta-globin gene as prognostic factors in sickle-cell disease.

  el-Hazmi MA, Warsy AS, Bashir N, Beshlawi A, Hussain IR, Temtamy S, Qubaili F.

  Medical Biochemistry Department, World Health Organization Collaborating Centre for Haemoglobinopathies, Thalassaemias and Enzymopathies, College of Medicine, King Khalid University Hospital, Riyadh, Saudi Arabia.

  "We collaborated with researchers from Egypt, Syrian Arab Republic and Jordan in a study of patients with sickle-cell disease from those countries, and from various parts of Saudi Arabia, in order to investigate the influence of genetics on the clinical presentation of the disease, and to attempt to determine the **origin** of the sickle-cell gene in Arabs. Our results suggest that beta-globin gene haplotypes influence the clinical presentation of sickle-cell disease, and that there are at least two major foci for the origin of the sickle-cell gene, one in the eastern part of Saudi Arabia, and the other in the populations of North Africa and the north-western part of the Arabian peninsula…The Benin haplotype was found in patients with severe disease, either as homozygous or in combination with another haplotype. The majority of Syrians and Jordanians had the Benin haplotype, and severe disease. However, one in three Syrians and one in five Jordanians had a milder disease, and the Saudi-Indian haplotype was identified. All Saudi patients from south-western and north-western areas, where the disease is generally severe, had the Benin haplotype in the homozygous or heterozygous state. Of the Saudi patients from the eastern area, where a mild form of SCD exists, only 9% had the Benin haplotype. The remainder had the Saudi-Indian haplotype, either in its homozygous or heterozygous state…Restriction endonuclease restriction sites have provided a useful insight into the normal polymorphic variations in the DNA surrounding various gene loci, where a combination of two or more polymorphic sites has led to the identification of specific haplotype patterns [13,14]. This has been of significance in the study of the regions surrounding the b-globin gene (i.e. the b-globin gene cluster), where several polymorphic sites have been identified, and population differences have been found on analysis of the haplotype pattern [9]. An interesting observation is that the sickle-cell mutation has occurred on chromosomes carrying different polymorphic sites and different b-globin gene haplotypes, and this seems to play a role in the clinical expression of SCD [9].
  We compared the haplotype pattern of SCD patients from different Arabic-speaking countries. Benin haplotype was the major haplotype in all countries with a severe presentation of SCD and it was present in both the homozygous and heterozygous state. This was true for those SCD patients from south-western and north-western areas of Saudi Arabia, and for those from Egypt, Jordan and Syrian Arab Republic. On the other hand, patients from the eastern part of Saudi Arabia, who present with a significantly milder clinical picture, carried the Saudi-Indian b-globin gene haplotype either in its homozygous or heterozygous state."
  
  Source: East Mediterr Health J. 1999 Nov;5(6):1154-8 http://www.emro.who.int/Publications/EMHJ/0506/10.htm

  
  

• (Courtesy of Thought2):

  "Les surprises de l'ADN ancien" de E. Crubezy et al. publié dans le magazine de vulgarisation scientifique La Recherche n°353 de Mai 2002."

  quote:

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  Thought Writes:

  has anyone read this study on the finding of the Benin Sickle Cell haplotype in pre-dynastic Egyptain remains?

  ---

  "Use of the amplification refractory mutation system (ARMS) in the study of HbS in predynastic Egyptian remains. Marin A, Cerutti N, Massa ER. publié dans Boll. Soc. Ital. Biol. Sper. 1999 May-Jun ;75(5-6):27-30"

• Bottom Line:
  I think it is safe to say from these references, that HbS is much more than what some people make it out to be. It is not only region-specific related hereditary disease, but origins can also be traced!
  

posted 24 January 2005 07:39 AM            

• Presence of an African Beta-globin Gene Cluster Haplotype in Normal Chromosomes in Sicily

  Ragusa et al. Am J Hematol, 1992; 40:313-315

  "African admixture in Sicily has been long suspected because of the presence of the sickle gene. Nevertheless, the degree of African admixture cannot be derived from the study of HbS frequency, since this gene was most likely expanded by the selective pressure of malaria, for a long time endemic to the region. We have examined 142 individuals from the Sicilian town of Butera (12% sickle trait) to search for other markers of the globin gene cluster less likely to be selected for by malaria. The TaqI polymorphism in the intervening sequences between the two gamma genes is informative. We have found only two instances of this African marker (TaqI(-)) among 267 normal chromosomes, demonstrating that the admixture occurred at a much lower level than previously thought."

And this corollary information:

• Romano et al. (2003) have detected sub-Saharan (Negroid) mtDNA sequences at a rate of 0.65% in a sample of 465 Sicilians, which is comparable to admixture levels for Western and Northern Europe. No Y-chromosomes of sub-Saharan origin have ever been observed in Sicilians.

  [Autosomal microsatellite and mtDNA genetic analysis in Sicily (Italy). Ann Hum Genet; 67:42-53]

posted 24 January 2005 08:09 AM            

quote:

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No Y-chromosomes of sub-Saharan origin have ever been observed in Sicilians.

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It has been proposed that E3b originated in sub-saharan Africa and expanded into the Near EAst Northern Africa and Sourthern Europe. E3b - E-M78 was observed over a wide area including:
East Africa (21.5%) North Africa (18.5%) and Europe (7.2%), the Balkans (20-32%), and Sicily (7.4%) - Y Chromosomes reveal multiple migratory events within and out of AFrica Cruciani, et al.

posted 24 January 2005 11:27 AM            

quote:

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Originally posted by Evil Euro:
You forgot the most important one:

• [b]Presence of an African Beta-globin Gene Cluster Haplotype in Normal Chromosomes in Sicily

  Ragusa et al. Am J Hematol, 1992; 40:313-315

  "African admixture in Sicily has been long suspected because of the presence of the sickle gene. Nevertheless, the degree of African admixture cannot be derived from the study of HbS frequency, since this gene was most likely expanded by the selective pressure of malaria, for a long time endemic to the region. We have examined 142 individuals from the Sicilian town of Butera (12% sickle trait) to search for other markers of the globin gene cluster less likely to be selected for by malaria. The TaqI polymorphism in the intervening sequences between the two gamma genes is informative. We have found only two instances of this African marker (TaqI(-)) among 267 normal chromosomes, demonstrating that the admixture occurred at a much lower level than previously thought."

And this corollary information:

• Romano et al. (2003) have detected sub-Saharan (Negroid) mtDNA sequences at a rate of 0.65% in a sample of 465 Sicilians, which is comparable to admixture levels for Western and Northern Europe. No Y-chromosomes of sub-Saharan origin have ever been observed in Sicilians.

  [Autosomal microsatellite and mtDNA genetic analysis in Sicily (Italy). Ann Hum Genet; 67:42-53]

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posted 24 January 2005 12:11 PM            

quote:

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[Ragusa et al. Am J Hematol, 1992; 40:313-315

"African admixture in Sicily has been long suspected because of the presence of the sickle gene. Nevertheless, the degree of African admixture cannot be derived from the study of HbS frequency, since this gene was most likely expanded by the selective pressure of malaria, for a long time endemic to the region.

[quote]Evil Euro, this doesn't say anything about the sick cell type not being African in origin. Sickle Cells can and have been traced back to their origins. The Benin type is predominant in Mediterranean populations. It's origins are obviously in Sub-Saharan Africa. It basically states that the "amount" of sub-saharan admixture in Sicilians can't be determined from sickle disease alone.

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