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Association studies and direct DNA sequencing implicate genetic susceptibility loci in the etiology of nonsyndromic orofacial clefts in sub-Saharan African populations
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نویسنده
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gowans l.j.j. ,adeyemo w.l. ,eshete m. ,mossey p.a. ,busch t. ,aregbesola b. ,donkor p. ,arthur f.k.n. ,bello s.a. ,martinez a. ,li m. ,augustine-akpan e.a. ,deressa w. ,twumasi p. ,olutayo j. ,deribew m. ,agbenorku p. ,oti a.a. ,braimah r. ,plange-rhule g. ,gesses m. ,obiri-yeboah s. ,oseni g.o. ,olaitan p.b. ,abdur-rahman l. ,abate f. ,hailu t. ,gravem p. ,ogunlewe m.o. ,buxó c.j. ,marazita m.l. ,adeyemo a.a. ,murray j.c. ,butali a.
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منبع
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journal of dental research - 2016 - دوره : 95 - شماره : 11 - صفحه:1245 -1256
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چکیده
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Orofacial clefts (ofcs) are congenital dysmorphologies of the human face and oral cavity,with a global incidence of 1 per 700 live births. these anomalies exhibit a multifactorial pattern of inheritance,with genetic and environmental factors both playing crucial roles. many loci have been implicated in the etiology of nonsyndromic cleft lip with or without cleft palate (nscl/p) in populations of asian and european ancestries,through genome-wide association studies and candidate gene studies. however,few populations of african descent have been studied to date. here,the authors show evidence of an association of some loci with nscl/p and nonsyndromic cleft palate only (nscpo) in cohorts from africa (ghana,ethiopia,and nigeria). the authors genotyped 48 single-nucleotide polymorphisms that were selected from previous genome-wide association studies and candidate gene studies. these markers were successfully genotyped on 701 nscl/p and 163 nscpo cases,1,070 unaffected relatives,and 1,078 unrelated controls. the authors also directly sequenced 7 genes in 184 nonsyndromic ofc (nsofc) cases and 96 controls from ghana. population-specific associations were observed in the case-control analyses of the subpopulations,with west african subpopulations (ghana and nigeria) showing a similar pattern of associations. in meta-analyses of the case-control cohort,pax7 (rs742071,p = 5.10 × 10-3),8q24 (rs987525,p = 1.22 × 10-3),and vax1 (rs7078160,p = 0.04) were nominally associated with nscl/p,and msx1 (rs115200552,p = 0.01),tulp4 (rs651333,p = 0.04),crispld2 (rs4783099,p = 0.02),and nog1 (rs17760296,p = 0.04) were nominally associated with nscpo. moreover,7 loci exhibited evidence of threshold overtransmission in nsofc cases through the transmission disequilibrium test and through analyses of the family-based association for disease traits. through dna sequencing,the authors also identified 2 novel,rare,potentially pathogenic variants (p.asn323asp and p.lys426ilefster6) in arhgap29. in conclusion,the authors have shown evidence for the association of many loci with nscl/p and nscpo. to the best of this knowledge,this study is the first to demonstrate any of these association signals in any african population. © international & american associations for dental research 2016.
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کلیدواژه
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candidate genes; craniofacial genetics; genetic heterogeneity; genome-wide association studies (GWAS); population genetics; rare variants
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آدرس
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department of biochemistry and biotechnology,kwame nkrumah university of science and technology,kumasi,ghana,cleft clinic,komfo anokye teaching hospital,kumasi,ghana,department of pediatrics,university of iowa,iowa city,ia,united states,department of oral pathology,radiology and medicine,dows institute for dental research,college of dentistry,university of iowa,butali laboratory,ml2198,500 newton road,iowa city,ia, United States, college of medicine,university of lagos,lagos, Nigeria, addis ababa university,addis ababa, Ethiopia, department of orthodontics,university of dundee,dundee, United Kingdom, department of oral pathology,radiology and medicine,dows institute for dental research,college of dentistry,university of iowa,butali laboratory,ml2198,500 newton road,iowa city,ia, United States, obafemi awolowo university teaching hospital,ile-ife, Nigeria, cleft clinic,komfo anokye teaching hospital,kumasi,ghana,department of surgery,school of medical sciences,kwame nkrumah university of science and technology,kumasi, Ghana, department of biochemistry and biotechnology,kwame nkrumah university of science and technology,kumasi, Ghana, department of oral and maxillofacial surgery,state house hospital,abuja, Nigeria, department of oral pathology,radiology and medicine,dows institute for dental research,college of dentistry,university of iowa,butali laboratory,ml2198,500 newton road,iowa city,ia, United States, department of oral pathology,radiology and medicine,dows institute for dental research,college of dentistry,university of iowa,butali laboratory,ml2198,500 newton road,iowa city,ia, United States, department of oral pathology,radiology and medicine,dows institute for dental research,college of dentistry,university of iowa,butali laboratory,ml2198,500 newton road,iowa city,ia, United States, addis ababa university,addis ababa, Ethiopia, department of biochemistry and biotechnology,kwame nkrumah university of science and technology,kumasi, Ghana, college of medicine,university of lagos,lagos, Nigeria, addis ababa university,addis ababa, Ethiopia, cleft clinic,komfo anokye teaching hospital,kumasi,ghana,department of surgery,school of medical sciences,kwame nkrumah university of science and technology,kumasi, Ghana, cleft clinic,komfo anokye teaching hospital,kumasi,ghana,department of surgery,school of medical sciences,kwame nkrumah university of science and technology,kumasi, Ghana, obafemi awolowo university teaching hospital,ile-ife, Nigeria, cleft clinic,komfo anokye teaching hospital,kumasi, Ghana, yekatit 12 hospital medical college,addis ababa, Ethiopia, cleft clinic,komfo anokye teaching hospital,kumasi,ghana,department of surgery,school of medical sciences,kwame nkrumah university of science and technology,kumasi, Ghana, department of burns and plastic surgery,ladoke akintola university of technology teaching hospital,osogbo, Nigeria, department of burns and plastic surgery,ladoke akintola university of technology teaching hospital,osogbo, Nigeria, division of pediatric surgery,department of surgery,university of ilorin,ilorin, Nigeria, yekatit 12 hospital medical college,addis ababa, Ethiopia, yekatit 12 hospital medical college,addis ababa, Ethiopia, haukeland university hospital bergen,bergen, Norway, department of burns and plastic surgery,ladoke akintola university of technology teaching hospital,osogbo, Nigeria, school of dental medicine,university of puerto rico medical science campus,san juan, Puerto Rico, department of oral biology,university of pittsburgh,pittsburgh,pa, United States, center for research on genomics and global health,national human genome research institute,national institutes of health,bethesda,md, United States, department of pediatrics,university of iowa,iowa city,ia, United States, department of oral pathology,radiology and medicine,dows institute for dental research,college of dentistry,university of iowa,butali laboratory,ml2198,500 newton road,iowa city,ia, United States
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Authors
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