ة مجلة إبن الھیثم للعلوم الصرفة و التطبیقی 2012 السنة 25 المجلد 1 العدد Ibn A l-Hai tham Journal f or Pure and Applied Science No. 1 Vol. 25 Year 2012 Diversity of Heamatogenetic Markers in Kirkuk Population S. M.AI-Taei, M. ,I.Nader Genetic engineering and Biotechnology for Postgraduate Studies, Unive rsity of Baghdad Received in: 3 October 2010 Accepte d in: 18 April 2011 Abstract Immuno-haematological genetic markers st udy was carried out to understand the genetic background variations among Kirkuk (Iraq) indigenous p op ulation. A cross-sectional st udy of 179 p atients with thalassemia major was conducted in Kirkuk. A detailed review was undertaken to define the relationship s between ethnic origins, p henoty p e and immuno-genetic markers uniformity in relation to genetic isolation and interethnic admixture. A total of 179 thalassemia major p atients were subjected to analysis in the hereditary blood diseases centre, including (18(10.05 %)) of intermarriages between different ethnic group s origin, whereas the overall consanguinity marriage rate was estimated at (161 (89.9%)) including (63(35.1%)) for first cousin marriages origin. Out of the 161 cases, 63(39.1%), 52(32.2%) and 46(28.5%) represent Kurdish, Arab and Turkmen ethnic group s, resp ectively. The distribution of thalassemia major cases within ethnic group s relatively differs (d.f.2, P< 0.2). Arab, (46 (28.5%)) represents the lowest disease (thalassemia) sufferer group because of its relative high rate of outbreeding (14, 77.7%).Blood group s (ABO) and Rhesus (D) genetic marker show no significant differences among the triethnic sample group s (thalassemia p atients) of Kirkuk with a p reponderance of blood group O. No app arent relationship was found between ABO or Rhesus blood group s and the frequencies of t halassemia major cases. The st udy showed a relative genetic heterogeneity and diversity with resp ect to the immuno-hematological genetic markers. Furt her, all ethnic p op ulations from Kirkuk were found to harbor thalassemia major genetic marker. ، ABO blood group s ،Inbreeding ، genetic isolation ، Key Words: Thalassemia, reproductive isolation, gentic variation Introduction Thalassemia is the most common, inherited single gene disorder in the world [1] among the several hereditary hemoglobinop athies. Thalassemia major occurs when a p erson inherits two thalassemia genes, one from each p arent. Both p arents must have thalassemia minor. When two individuals who have thalassemia minor marry , there is a chance that p regnancy may result in a child with thalassemia M ajor. As the frequency of thalassemia is increased by the consanguinity mating, it may be assumed that the net effect has been the creation of multiple genetic and reproductive isolates, accentuation of certain recessive alleles. However, ة مجلة إبن الھیثم للعلوم الصرفة و التطبیقی 2012 السنة 25 المجلد 1 العدد Ibn A l-Hai tham Journal f or Pure and Applied Science No. 1 Vol. 25 Year 2012 this clinical consequence of this highly comp lex differentiation, leads to p op ulation heterogeneity and genetic diversity [2].M oreover, various evolutionary forces such as waves of p eople of different ethnic st ocks, cultures and languages who either invaded Kirkuk or migrated to Kirkuk from different directions and contributed significantly to the p resent-day gene p ool. These p eople not only settled in Kirkuk but also gradually merged and mingled with the original local pop ulations [3]. Ethnic origin and migrations are factors that affect p op ulation genetics which focus on relative dist ribution of genes or inherited traits (genetic markers) [4]. Hence this st udy aims at st udy ing genetic marker p olymorphism (hemoglobinop athies and ABO blood group s) to determine the genetic similarity of different ethnic group s of Kirkuk community ,whether these markers are exp ressed as clinical phenoty p e or not. [5,6] Materials and Methods The st udy was conducted in the M edical Centre of Hereditary Blood Disorder, main Kirkuk hosp ital, (All p atients were visiting this centre for regular follow-up and blood transfusion at fixed monthly intervals). The st udy was carried out during a 6-month p eriod between October 2006 and M arch 2007. The st udy includes 179 subjects with thalassemia major who att end the Kirkuk hosp ital from all over Kirkuk for follow up and blood transfusion. Quest ioner was introduced to each p atient to characterize the age, sex, ethnic origins and hematological features of all included blood transfusion dependent thalassemia major p atients. Patient data were based on a medical-record review sup p lemented by p atient interview. Control group The ABO blood group s distribution of the 1901 blood donors from the Central Blood Bank in Kirkuk was used as a control group for ABO blood group s dist ribution of the study sample group . S tatistical anal ysis Statist ical analysis was p erformed using the SPSS 7.5 st atist ical soft ware p ackage. Continuous variables were exp ressed as mean ± SD. Chi square test was used to comp are variables between p atients and controls or between p atient group s, and (P<0.05) was considered statist ically significant. Results One handred seventy nine p atients with thalassemia major were eligible for the st udy . Patient's data were obtained from medical records, and not all the required data were available for some patients. All p atients (179) belonged to three ethnic origins (Turkmen, Arab, and Kurdish) excep t eighteen p atients who had a mixed ethnic background. Consanguineous marriage has been a historically longst anding p ractice among the different ethnic classes of Iraq. Hereditary diseases like thalassemia major can p revail in epidemic p rop ortions in areas characterized by high p ercentage of marriages between relatives [8] that is a common practice in the Kirkuk regions. ة مجلة إبن الھیثم للعلوم الصرفة و التطبیقی 2012 السنة 25 المجلد 1 العدد Ibn A l-Hai tham Journal f or Pure and Applied Science No. 1 Vol. 25 Year 2012 The overall consanguinity marriage rate was estimated at (161, 89.9%) including (63, 35.1%) for first cousin marriages origin, While only (18, 10.05 %) have intermarriages origin between different ethnic group s. Arab versus Turkmen, Arab versus Kurdish and Turkmen versus Kurdish, intermarriages were 14(77.7%), 3(16.6%) and 1(5.5%), resp ectively. Out of the 161 cases, 63(39.1%), 52(32.2%) and 46(28.5%), represent Kurdish, Arab and Turkmen st udied ethnic group s resp ectively. But the difference out breeding and inbreeding was relatively significant at (d.f.2, P< 0.2). However, this result confirms a fact that high rate out breeding group s disp lay less disease suffer(Arab 46; 28.5%). Although the disease is p revalent mainly among mediterranean peoples, [9] countries such as Iraq disp lay a large increase of thalassemia p atients due to lack of genetic counseling and screening and breeding the people in the local p op ulation. The mean age (mean ± st andard deviation [SD]) at diagnosis of all the st udied cases (179) was l.7± 2.2 y ears (median 1.0). While the mean age (at st udy time) was 11.6 ± 6.8 y ears (median 10.0). These results indicate that the mean p eriod of treatment by regular blood transfusion accomp anied by good resp onse and survival was 9.7± 6.34 y ears (median 9.0).However, two p atients died at t he ages of 3.6 and 13 years, resp ectively. Actually, st able p op ulations show more uniform distribution of ages, but in this study , age distribution of thalassemia major p atients among different ethnic group s shows that most of the sample group p op ulation was y oungs; fewer p eople were beyond the reproductive age (comp ared to die age distribution of a growing p op ulation), and there were no app arent significant differences (d.f.6, PO.05) between different ethnic group s (T able 1). Any p op ulation with many y oung (p re-rep roductive) individuals and few p eople beyond reproductive age will increase because many p eople will enter the p rime reproductive age group and few will reach the end of their lifesp an. [10]. This ty p e of demographic momentum usually serves as an examp le of how p op ulation growt h can be p redicted from current age st ructure; but in the p resent st udy , the age-related p rofiles of the sample (thalassemia major p atients) have been showed that fewer p eople are beyond the reproductive age which is most likely due to death before reaching the reproductive ages or due to loss of p eople or due to high inflow of immigrants. Eventually, blood indices results of the samp le group revealed that the mean values of PCV and hemoglobin levels were 22.52±5.8 and 7.5±6.4, resp ectively. Distribution of AB O Blood Groups The p henoty p es and genoty p es of ABO blood group s, become more uniform in high degree intermingled p op ulation (Nepali GS, 1965). A p art of t he raw data and results of this st udy was p erformed to "p enetrate the essence of the racial traits (ABO & Rh blood group s) sp eciation of thalassemia major patients of Kirkuk p op ulations based on the p otential degree of genetic isolation and intermingling. Phenoty p e frequency of the four ABO blood group s and the three corresp onding allele frequencies of the sample group along with data from control group s are shown in Tables 2 & 3. In the combined data of thalassemia major p atients ,the most frequently occurring blood group is O (40.9%), followed by A (30.4%), B (21.1%) and AB (7.4%). Rhesus blood group ings revealed that the majority of cases (157 (97.5%)) were Rh p ositive (Rhesus p ositive), but only 4 cases (2.4%) were represented as Rh negative". Chi square test ة مجلة إبن الھیثم للعلوم الصرفة و التطبیقی 2012 السنة 25 المجلد 1 العدد Ibn A l-Hai tham Journal f or Pure and Applied Science No. 1 Vol. 25 Year 2012 (d.f.2,P<0.05) revealed that there were no significant differences between the triethnic group s in A,B & O blood group s. Comparison of ABO blood group s dist ribution sequences within the st udied tri-ethnic group s of thalassemia major p atients with those of the studied control group , revealed that there were significant differences (d.f.l,P<0.05) in AB blood group distribution only. A similar frequency distribution of the ABO blood group s of the control group has been reported in several other scheduled p op ulations of Asian, such as, I long Kong, China, where frequency of blood group O & B showed preponderance over that of the other blood group s. (T able 2).(1) The most st riking feature that emerged from the p resent st udy was the relative genetic isolation in almost all the genetic p arameters (sero-haematological) which were st udied here among Kirkuk ethnicities. This genetic isolation may be due to reproductive isolation which is a category of the mechanisms that p revent two or more p op ulations from exchanging genes. [12]. The sep aration of the gene p ools of p op ulations, under some conditions, can lead to t he genesis of dist inct diversity [13]. Various factors of p op ulation structure - such as p op ulation size, density , mating p att ern, and micro-evolutionary forces like differential selection, migration, etc., considerably contribute to the diversity within the p op ulation. The p resent analysis indicates t hat in addition to gene flow and selection, the genetic st ructure of the ethnic p op ulations of Kirkuk is highly influenced by socio-cultural adap tation and inbreeding. The present analy sis strongly suggests that the infrast ructure of these ethnic p op ulations is highly influenced by the local inbreeding within each ethnical pop ulation. Thus, the st udy suggested that the Kirkuk ethnic group s should intermarry more with each other in order to reduce the heterogeneity and the number of recessive genes alleles. However, the st udy also recommends p ublic education, p op ulation screening, genetic counseling and p renatal diagnosis as successful p rograms for genetic p revention. Re ferences 1.Piomelli, S,and Lowe,T. (1991): M anagement of thalassemia major (Cooley 's anemia). Hematol. Oncol. Clin. Nort h. Am. 5: 557-69. 2. Cao, A. and Galanello, R. (2002): Effect of consanguinity on screening for thalassemia. N. Engl. J. M ed., 347: 1200-1202. 3. http ://en.wikipedia.org/wiki/Kirkuk 4. Conrad, DF.and Hurels, M E, (2007):.The pop ulation genetics of structural variation. Nature Genetics, 39: S30-S31. 5. Risch, N. and M erikanges. (1996): The future of genetic st udies of comp lex human diseases. Science, 273:1516-1517. 6. Weatherall, DJ. (1998):Thalassemia, in the next millennium. Ann NY Acad. ScL, 850: 1-9. 7.M inich,V.; NA-Nakorn, S.; Chongcharoensuk, S. and Kochaseni,S. (1954): M editerranean anemia: A study of thirty -two cases in Thailand. Blood, 9: 1-23. 8. Smith, C.A.B. (1974): M easures of homozy gosity and inbreeding in p op ulations. Ann, Hum. Genet, 37: 377-391. 9. Leung,N.T .; Lau,T.K. and Chung, T.k (2005): 'Thalassemia screening in p regnancy ". Curr Op inion in Ob Gy n, 17: 129-34. ة مجلة إبن الھیثم للعلوم الصرفة و التطبیقی 2012 السنة 25 المجلد 1 العدد Ibn A l-Hai tham Journal f or Pure and Applied Science No. 1 Vol. 25 Year 2012 10. Lee,Ronald (1994):The formal Demography Life Cy cle, in Linda M artin and Samuel Prest on,eds., The Demography of Aging ( National Academy Press, Washington, DC).8-49. 11. http ://en.wikipedia.org/wiki/Blood_ ty p e. 12. Wu, C.I.; and Davis, A.W. (1993): Evolution of p ost mating reproductive isolation: the comp osite nature of Haldane's rule and its genetic bases. Am. Nat., 142: 187-212. 13. Race, Ethnicity and genetic working group , National Human Genome Research Inst itut e, Bethesda (2005) : The Use of Racial, Ethnic, and Ancestral Categories in Human Genetics Research The American Journal of Human Genetics, 77: 519-525 Table (1): Age distribution of thalasse mia major patients among the three diffe rent ethnic groups Ethnic group 1-7 y ears 8- 14 y ears 15-21 y ears 22-28 y ears Total Turkmen 16 17 7 6 46 Arab 13 _ 24 10 5 52 Kurdish 19 27 11 6 63 Total 48 (29.8%) 68(42.2%) 28(17.3%) 17(10.7%) 161(100%) Table (2): Distribution of ABO blood groups among e thni c groups Blood group Turkmen No % Arab No % Kurdish No % Total No % A 15 32.6 18 34.6 16 25.3 49 30.4 B 13 28.2 8 15.3 13 20.6 34 21.1 AB 3 6.5 4 7.6 5 7.9 12 7.4 0 15 32.6 22 42.3 29 46.0 66 40.9 total 46 100 52 100 63 100 161 100 ة مجلة إبن الھیثم للعلوم الصرفة و التطبیقی 2012 السنة 25 المجلد 1 العدد Ibn A l-Hai tham Journal f or Pure and Applied Science No. 1 Vol. 25 Year 2012 Table (3): Distribution of ABO blood groups among a control group Blood group Turkmen No % Arab No % Kurdish No % Total No % A 236 23.1 138 21.9 38 15.2 412 21.6 B 295 28.8 117 18.6 78 31.2 490 25.7 AB 176 17.2 157 24.9 19 7.6 352 18.5 O 315 30.8 217 34.4 115 46 647 34 total 1022 100 629 100 250 100 1901 100 ة مجلة إبن الھیثم للعلوم الصرفة و التطبیقی 2012 السنة 25 المجلد 1 العدد Ibn A l-Hai tham Journal f or Pure and Applied Science No. 1 Vol. 25 Year 2012 تباین المؤشرات الجینیة المناعیة الدمویة في كركوك محمد ابراھیم نادر ، صفاء منعثر الطائي معھد الھندسة الوراثیة للدراسات العلیا ، جامعة بغداد 2011 نیسان 18: قبل البحث في2010 تشرین االول 3: استلم البحث في الخالصة ع محافظـة درست المؤشرات الجینیة للعالمات المناعیـة الدمویـة لتقـدیر خلفیـة بعـض التغیـرات الجینیـة فـي مجتـم ى . كركوك ض179اذ أجریت الدراسـة عـل ین المجـامیع . بالثالسـمیا ًا مرـی ى العالقـة ـب رف عـل وتمـت مراجعـة تنقیحیـة للتـع ین المجـامیع اإلثنیـة اإلثنیة والنشأة األنموطیة وتوحد المؤشرات المناعیة ي واالخـتالف ـب زال الجیـن . الجینیة على خلفیـة االنـع وك) مریضا179(اخضع المرضى المشمولین بالدراسة ي كرـك دم الوراثیـة ـف كـان . للفحوصات للدراسة في مركز أمراض اـل سبة زواج األقـارب )%10.05( من المرضى18 ن )%89.9( 161 كانوا نتاج لتزاوج بین أقلیات مختلفة حیث كانت ـن وـم ــم )%35.1( 63ضــمنھم ـــ . زواج أوالد الع ــریض كـــان 161مـــن ال )%28.5( 46 و )%32.2( 52 و )%39.1( 63 م وأن توزیـع مرضـى الثالسـمیا المتعـاظم فـي مجمـوع األقلیـات كـان . یمثلون أقلیات األكراد والعرب والتركمان علـى التـوالي ف d.f.2,p(ًنسبیا مختـل سبة )0.05> ر العـرب أدنـى ـن ن )%28.5( 46 اد أظـھ سبة العالیـة ـم سبب الـن ك ـب ن المرضـى وذـل ـم دم . التزاوج خارج األقارب )ABO&Rh(وأظھرت الدراسة عدم وجود فروق ذي داللة إحصائیة في توزیع مجامیع اـل دم ــة اـل سبة مجموع ادة ـن ي كركـوك مـع زـی ف األقلیـات ـف م وجـود عالقـة مـا بــین وعـد. علـى بقیـة المجـامیع Oمـا بـین مختـل ي المؤشـرات .مجموعات الدم وتكرار مرض الثالسمیا المتعاظم ن التغـایر واالخـتالف ـف سبة ـم ى وجـود ـن خلصت الدراسـة إـل . ًفضال عن وجدت الدراسة أن جمیع األقلیات یكمن فیھم مرض الثالسمیا المتعاظم . المدروسة داخلیة ، تلالسیمیا ، االننعزال الوراثي ، والتغایر ممجامیع الدم ، التزاوجات ال: كلمات المفتاحیة ة مجلة إبن الھیثم للعلوم الصرفة و التطبیقی 2012 السنة 25 المجلد 1 العدد Ibn A l-Hai tham Journal f or Pure and Applied Science No. 1 Vol. 25 Year 2012 ة مجلة إبن الھیثم للعلوم الصرفة و التطبیقی 2012 السنة 25 المجلد 1 العدد Ibn A l-Hai tham Journal f or Pure and Applied Science No. 1 Vol. 25 Year 2012 ة مجلة إبن الھیثم للعلوم الصرفة و التطبیقی 2012 السنة 25 المجلد 1 العدد Ibn A l-Hai tham Journal f or Pure and Applied Science No. 1 Vol. 25 Year 2012