Genetic contribution for non‐syndromic cleft lip with or without cleft palate (NS CL/P) in different regions of Brazil and implications for association studies

American Journal of Medical Genetics, Part A - Tập 155 Số 7 - Trang 1581-1587 - 2011
Luciano Abreu Brito1, Lucas Alvizi Cruz1, Kátia M. Rocha1, Lígia Kobayashi Bárbara1, Camila B.F. Silva1, Daniela Franco Bueno1, Meire Aguena1, Débora Romeo Bertola2,1, Diogo Franco3, André Monteiro Costa4, Nivaldo Alonso5, Paulo Alberto Otto1, Maria Rita Passos‐Bueno1
1Human Genome Research Center, Institute of Biosciences, University of São Paulo, São Paulo, Brazil
2Genetics Unit, Department of Pediatrics, Children Institute, School of Medicine, University of São Paulo, São Paulo, Brazil
3Department of Plastic Surgery, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
4Division of Plastic Surgery, University of Health Sciences of Alagoas, Maceió, Brazil
5Division of Plastic Surgery, Department of Surgery, School of Medicine of São Paulo University, São Paulo, Brazil

Tóm tắt

AbstractNon‐syndromic cleft lip with or without cleft palate (NS CL/P) is a complex disease in which heritability estimates vary widely depending on the population studied. To evaluate the importance of genetic contribution to NS CL/P in the Brazilian population, we conducted a study with 1,042 families from five different locations (Santarém, Fortaleza, Barbalha, Maceió, and Rio de Janeiro). We also evaluated the role of consanguinity and ethnic background. The proportion of familial cases varied significantly across locations, with the highest values found in Santarém (44%) and the lowest in Maceió (23%). Heritability estimates showed a higher genetic contribution to NS CL/P in Barbalha (85%), followed by Santarém (71%), Rio de Janeiro (70%), Fortaleza (64%), and Maceió (45%). Ancestry was not correlated with the occurrence of NS CL/P or with the variability in heritability. Only in Rio de Janeiro was the coefficient of inbreeding significantly larger in NS CL/P families than in the local population. Recurrence risk for the total sample was approximately 1.5–1.6%, varying according to the location studied (0.6–0.7% in Maceió to 2.2–2.8% in Barbalha). Our findings show that the degree of genetic contribution to NS CL/P varies according to the geographic region studied, and this difference cannot be attributed to consanguinity or ancestry. These findings suggest that Barbalha is a promising region for genetic studies. The data presented here will be useful in interpreting results from molecular analyses and show that care must be taken when pooling samples from different populations for association studies. © 2011 Wiley‐Liss, Inc.

Từ khóa


Tài liệu tham khảo

10.1111/j.1469-1809.2006.00287.x

10.1038/ng.580

10.1111/j.1600-0722.2009.00680.x

10.1038/ng.333

10.1002/tera.1420380603

10.1016/j.ijporl.2007.06.007

Cavalli‐Sforza LL, 1971, The genetics of human populations, 966

10.1002/ajmg.1320470620

Emery AEH, 1986, Methodology in medical genetics, 198

Fraser FC, 1974, Updating the genetics of cleft lip and palate, Birth Defects Orig Artic Ser, 10, 107

Gorlin RJ, 2001, Syndromes of the head and neck, 1283, 10.1093/oso/9780195118612.001.0001

10.1136/jmg.2009.069385

10.1093/aje/kwi214

Hedrick PW, 1986, Average inbreeding or equilibrium inbreeding?, Am J Hum Genet, 38, 965

Hu DN, 1982, Genetics of cleft lip and cleft palate in China, Am J Hum Genet, 34, 999

10.1038/ejhg.2009.228

10.1002/ajmg.a.32849

10.1111/j.1601-0825.2009.01577.x

10.1056/NEJM199407073310101

Lin YC, 1999, Cleft of the lip and palate in twins, Changgeng Yi Xue Za Zhi, 22, 61

10.1590/S0034-89102001000600011

10.1038/ng.506

10.1002/ajmg.1320420104

10.1597/1545-1569(1991)028<0373:EOOCIA>2.3.CO;2

10.1136/jmg.28.2.110

10.1093/hmg/ddp444

10.1597/1545-1569(1996)033<0340:CTSIF>2.3.CO;2

10.1073/pnas.0126614100

10.1590/S0100-879X2009005000026

10.1111/j.1365-294X.2004.02396.x

10.1038/ng.242

Salzano FM, 1967, Populações brasileiras, 178

10.1002/humu.21159

10.1093/hmg/8.10.1853

10.1136/bmj.39458.563611.AE

10.1136/jmg.28.5.325

10.1097/FPC.0b013e3281c10e52

10.1136/jmg.25.4.243

10.1056/NEJMoa032909

Thông tin
Thông tin xuất bản

American Journal of Medical Genetics, Part A

Tập 155 Số 7

1581-1587

Thông tin tác giả