2005 Prague - European Society of Human Genetics
2005 Prague - European Society of Human Genetics 2005 Prague - European Society of Human Genetics
Normal variation, population genetics, genetic epidemiology P1185. Cystic Fibrosis is not a frequent disease in Cyprus except for a village with founder effect and very high carrier frequency of 1/14 V. Neocleous 1 , P. Yiallouros 2 , M. Zeniou 2 , M. Tzetis 3 , E. Kanavakis 3,1 , C. Deltas 4 ; 1 The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus, 2 Makarios Hospital, Nicosia, Cyprus, 3 Athens University, Athens, Greece, 4 University of Cyprus, Nicosia, Cyprus. Cystic Fibrosis is a common autosomal recessive condition in Caucasians, with average carrier frequency of 1/25. In the Greek- Cypriot population of about 650000 we diagnosed during the past 12 years, 27 patients, 24 of whom are alive. Thus, about 1/83 people is a carrier of a CF mutation. The most frequent mutation is F508del, accounting for 43.8% of mutant alleles. The second most frequent is L346P (12.5%), carried by 6 patients in heterozygosity. Apparently this is a Cypriot mutation, as it has not been reported in other populations, to our knowledge. It is found in compound heterozygosity with other severe mutations, and we reckon it is a mild mutation dominating over the severe one, since all patients carrying it have milder phenotypes. Other mutations are: 1677delTA (6.2%), 3849+10kbC>T, (4.2%), S549N (4.2%), N1303K (4.2%), M348K (2.1%), 2789+5G>A (2.1%), W1282X (4.2%), G542X (2.1%), Unknown (12.5%). Interestingly, in Athienou, a village of 4500 people, we located a large family with two affected siblings, presently deceased. In an epidemiological study involving more than 800 people, 1/14 was a carrier of F508del, most probably as a result of founder effect, dating back to the times that the Ottomans conquered Cyprus. The legend has it that after the Ottomans conquered Famagusta at the Southeast coast, some noble Francs who escaped the massacre, moved to a region close to Athienou. Interestingly, most of our patients, >70%, presented with dehydration and electrolytic disturbance during summer months. During the past years we performed 8 prenatal diagnoses. P1186. Y-chromosome bi-allelic and STR markers in the three main ethnic groups of modern Bosnia-Herzegovina D. /. Marjanovic1 , S. Fornarino2 , N. Bakal1 , S. Montagna2 , R. Hadziselimovic1 , D. Primorac3 , S. Vidovic4 , N. Pojskic1 , V. Battaglia2 , A. Achilli2 , A. Torroni2 , S. Andjelinovic5 , K. Drobnic6 , A. Santachiara-Benerecetti2 , O. Semino2 ; 1Institute for genetic engineering and biotechnology, Sarajevo, Bosnia and Herzegovina, 2Dipartimento di Genetica e Microbiologia “A Buzzati-Traverso”, Università di Pavia, Pavia, Italy, 3Medical School at Split University,, Split, Croatia, 4Faculty of Medicine, University of Banjaluka, Banjaluka, Bosnia and Herzegovina, 5Medical School at Split University, Split, Croatia, 6Forensic Laboratory and Research Center, Ministry of the Interior, Ljubljana, Slovenia. The variation at 28 Y-chromosome bi-allelic markers was analysed in 256 males (90 Croats, 81 Serbs and 85 Bosniacs-Muslims) from Bosnia-Herzegovina. In addition, 100 individuals (35 Bosniacs, 31 Serbs, 34 Croats) have been also analyzed at twelve Y-chromosomal short tandem repeats loci. An important shared feature between the three ethnic groups is the high frequency of the “Palaeolithic” Europeanspecific haplogroup (Hg) I, a likely signature of a Balkan population reexpansion after the Last Glacial Maximum. This haplogroup is almost completely represented by the sub-haplogroup I-P37 whose frequency is higher in the Croats (~71%) than in Bosniacs (~44%) and Serbs (~31%). Other rather frequent haplogroups are E (~15%) and J (~7%), together with R-M17 (~14%). Hg E, almost exclusively represented by its subclade E-M78, is more common in the Serbs than in Bosniacs and Croats; Hg J observed in only one Croat, encompasses ~9% of the Serbs and ~12% of the Bosniacs, where, it shows its highest differentiation. Differently, Hg R-M17 harbours similar frequencies in all three groups. Overall, the three main Bosnia-Herzegovina groups, in spite of some quantitative differences, share a large fraction of the same ancient gene pool. At the STR analyses, 81 different Y-STR haplotypes were detected, 69 of them were unique. Six of twelve not singleton haplotypes were shared by different population groups: two of them by Croats and Bosniacs, two by Bosniacs and Serbs and the last two by Serbs and Croats, thus testifying recent gene flows between groups. 339 P1187. The epidemiology of Leber hereditary optic neuropathy (LHON) in Finland A. Puomila1,2 , S. Kivioja1 , M. Savontaus1 , E. Nikoskelainen1 , K. Huoponen1 ; 1 2 University of Turku, Turku, Finland, Turku Graduate School of Biomedical Sciences, Turku, Finland. Leber hereditary optic neuropathy (LHON) has been estimated to be one of the most common mitochondrial disorders, with a prevalence of 3.22 of 100 000. In Finland, among a population of 5.2 million individuals, we have identified 36 genealogically unrelated LHON families with at least one affected family member. During the 25-year research period, we have identified large families, collecting information mainly by going through Finnish parish records. The three primary mutations in the mitochondrial DNA (mtDNA) and mtDNA haplogroups were determined in all families; in addition, entire mitochondrial genomes were sequenced in some patients. Heteroplasmy was detected in 14% (5/36) of the families. Penetrance values were determined for all pedigrees separately and combined; and for instance, for different primary mutations and genders. The total penetrance of LHON was notably higher among males (32%) than among females (10%). The male-female ratio was 3.2:1 which is in accordance with previous studies. A combined penetrance value calculated for all families varied only slightly between different primary mutations. P1188. Sao Miguel: the genetic history of an Azorean island described by HLA Class I and Class II genes P. R. Pacheco1,2 , C. C. Branco1,2 , A. Lismond1 , L. de Fez1,2 , R. Cabral1,2 , B. R. Peixoto1,2 , L. Mota-Vieira1,2 ; 1 2 Hospital Divino Espirito Santo, Azores, Portugal, Instituto Gulbenkian de Ciência, Oeiras, Portugal. Sao Miguel is the biggest and most populated island (131,609 inhabitants) of the Azores archipelago (Portugal). Here, we present the frequencies of alleles and haplotypes for Class I (A, B and Cw) and II (DRB1, DQB1, DPA1 and DPB1) at the DNA level in Sao Miguel. Blood samples were taken, after informed consent, from 106 unrelated blood donors, whose parents were born in the same locality. HLA typing was carried out using PCR-SSP from Olerup SSP. Statistical analysis was performed with Arlequin v.2.0. and phylogenetic trees were constructed by using the genetic distances between populations (DA) with the DISPAN software. Our data shows that the gene diversity at the seven loci is high (0.9997) and that all genotype frequencies are in Hardy-Weinberg equilibrium. We identified 16 HLA-A alleles, 24 HLA-B alleles, 13 HLA-C alleles, 6 HLA-DPA1 alleles, 22 HLA- DPB1 alleles, 5 HLA-DQB1 alleles and 13 HLA-DRB1 alleles, of which the most frequent are, respectively, A*02 (GF=0.2500), B*44 (GF=0.1557), Cw*07 (GF=0.3113), DPA1*01 (GF=0.4623), DPB1*0401 (GF=0.3161), DQB1*03 (GF=0.3208) and DRB1*07 (GF=0.1698). The most frequent three-locus haplotype in S. Miguel is of West European origin, HLA-A*01-B*08-DRB1*03 (HF=0.0802). We also found the Iberian-North African haplotype HLA-A*30-B*18- DRB1*03 (HF=0.0047), the Iberian-Berbers haplotype HLA-A*02- B*51-DRB1*13 (HF=0.0047) and a Mongol haplotype HLA-A*02-B*44- DRB1*04 (HF=0.0142). These observations suggest an important mixture of alleles from geographically distinct areas, which agree with the history of settlement and molecular data from Y-chromosome. The HLA data presented here will be useful to study the molecular basis of autoimmune diseases in Azores. (paularpacheco@hdes.pt) Funded by DRCT-Azores. P1189. Demographic and baseline clinical data of 638 patients with Fabry disease: latest analysis from FOS - the Fabry Outcome Survey A. Mehta1 , M. Beck2 , G. Sunder-Plassmann3 , U. Widmer4 ; 1 2 Royal Free Hospital, London, United Kingdom, University of Mainz, Mainz, Germany, 3Medical University, Vienna, Austria, 4University of Zurich, Zurich, Switzerland. Background: Fabry disease is an X-linked lysosomal storage disorder caused by deficient activity of the lysosomal enzyme αgalactosidase A. Progressive accumulation of the enzyme substrate in cells throughout the body leads to organ failure and premature death. Treatment for this disease has recently become available in the form of enzyme replacement therapy (ERT). To determine the efficacy and
Normal variation, population genetics, genetic epidemiology safety of ERT with agalsidase alfa, FOS - the Fabry Outcome Survey - was established. The present analysis of the FOS database aims to provide demographic information and baseline data on the natural history of Fabry disease. Methods: The FOS database was analysed in terms of patient demography and baseline manifestations of Fabry disease. Results: As of November 2004, 638 patients (387 receiving agalsidase alfa and 251 currently untreated) were enrolled in FOS from 11 European countries. For the first time since FOS was initiated in 2001, there are more female patients (n=324) than males (n=314); 59 of the female and 48 of the male patients are under 18 years of age. Approximately one-third of these children have significant signs and symptoms before 10 years of age. A severity score, based on the Mainz Severity Score Index, confirms the progressive nature of Fabry disease with age in both male (r=0.53; p
- Page 289 and 290: Molecular and biochemical basis of
- Page 291 and 292: Molecular and biochemical basis of
- Page 293 and 294: Molecular and biochemical basis of
- Page 295 and 296: Molecular and biochemical basis of
- Page 297 and 298: Molecular and biochemical basis of
- Page 299 and 300: Genetic analysis, linkage, and asso
- Page 301 and 302: Genetic analysis, linkage, and asso
- Page 303 and 304: Genetic analysis, linkage, and asso
- Page 305 and 306: Genetic analysis, linkage, and asso
- Page 307 and 308: Genetic analysis, linkage, and asso
- Page 309 and 310: Genetic analysis, linkage, and asso
- Page 311 and 312: Genetic analysis, linkage, and asso
- Page 313 and 314: Genetic analysis, linkage, and asso
- Page 315 and 316: Genetic analysis, linkage, and asso
- Page 317 and 318: Genetic analysis, linkage, and asso
- Page 319 and 320: Genetic analysis, linkage, and asso
- Page 321 and 322: Genetic analysis, linkage, and asso
- Page 323 and 324: Genetic analysis, linkage, and asso
- Page 325 and 326: Genetic analysis, linkage, and asso
- Page 327 and 328: Genetic analysis, linkage, and asso
- Page 329 and 330: Genetic analysis, linkage, and asso
- Page 331 and 332: Genetic analysis, linkage, and asso
- Page 333 and 334: Genetic analysis, linkage, and asso
- Page 335 and 336: Genetic analysis, linkage, and asso
- Page 337 and 338: Genetic analysis, linkage, and asso
- Page 339: Normal variation, population geneti
- Page 343 and 344: Normal variation, population geneti
- Page 345 and 346: Normal variation, population geneti
- Page 347 and 348: Normal variation, population geneti
- Page 349 and 350: Normal variation, population geneti
- Page 351 and 352: Normal variation, population geneti
- Page 353 and 354: Normal variation, population geneti
- Page 355 and 356: Normal variation, population geneti
- Page 357 and 358: Normal variation, population geneti
- Page 359 and 360: Genomics, technology, gene function
- Page 361 and 362: Genomics, technology, gene function
- Page 363 and 364: Genomics, technology, gene function
- Page 365 and 366: Genomics, technology, gene function
- Page 367 and 368: Genomics, technology, gene function
- Page 369 and 370: Genomics, technology, gene function
- Page 371 and 372: Genomics, technology, gene function
- Page 373 and 374: Genetic counselling, education, gen
- Page 375 and 376: Genetic counselling, education, gen
- Page 377 and 378: Genetic counselling, education, gen
- Page 379 and 380: Genetic counselling, education, gen
- Page 381 and 382: Genetic counselling, education, gen
- Page 383 and 384: Genetic counselling, education, gen
- Page 385 and 386: Therapy for genetic disease This wa
- Page 387 and 388: Therapy for genetic disease P1403.
- Page 389 and 390: Author Index A A.D.H. French Res. N
Normal variation, population genetics, genetic epidemiology<br />
safety <strong>of</strong> ERT with agalsidase alfa, FOS - the Fabry Outcome Survey<br />
- was established. The present analysis <strong>of</strong> the FOS database aims<br />
to provide demographic information and baseline data on the natural<br />
history <strong>of</strong> Fabry disease.<br />
Methods: The FOS database was analysed in terms <strong>of</strong> patient<br />
demography and baseline manifestations <strong>of</strong> Fabry disease.<br />
Results: As <strong>of</strong> November 2004, 638 patients (387 receiving<br />
agalsidase alfa and 251 currently untreated) were enrolled in FOS<br />
from 11 <strong>European</strong> countries. For the first time since FOS was initiated<br />
in 2001, there are more female patients (n=324) than males (n=314);<br />
59 <strong>of</strong> the female and 48 <strong>of</strong> the male patients are under 18 years <strong>of</strong><br />
age. Approximately one-third <strong>of</strong> these children have significant signs<br />
and symptoms before 10 years <strong>of</strong> age. A severity score, based on the<br />
Mainz Severity Score Index, confirms the progressive nature <strong>of</strong> Fabry<br />
disease with age in both male (r=0.53; p
Change language