Familial Relative Risks and Complex Segregation Analysis of Isolated Cleft Lip with or without Cleft Palate in a high-prevalence cluster of South America.

FERNANDO A. POLETTA; EDUARDO E. CASTILLA; IEDA M. ORIOLI; JUAN C. MEREB; JUAN A. GILI; BELEN COMAS; HUGO KRUPITZKI; JORGE S. LOPEZ-CAMELO

Heidelberg

Congreso; Congreso; 20th ANNUAL IGES (International Genetic Epidemiology Society) CONFERENCE; 2011; 2011

International Genetic Epidemiology Society

The genetic contribution to the etiology of cleft lip and cleft palate (CL/P) is complex and heterogeneous. An area with high prevalence of CL/P was previously identified in Argentine Patagonia, probably associated with Amerindian ancestry and low socioeconomic status.The aim of this work was to estimate the mode of inheritance and the number of loci involved in CL/P families from Patagonia prior to planned for linkage/association studies.The sample included 117 extended pedigrees (2,835 total people) ascertained from CL/P probands registered by ECLAMC hospitals in Patagonia. Family Risk Ratios (FRR) were estimated for first-, second-, and third-degree relatives of CL/P probands, and Complex Segregation Analyses (CSA) were conducted using Pointer and SAGE software.CSA excluded the Sporadic, Environmental and Multifactorial threshold models, and provided evidence that CL/P is most likely determined by a dominant major gene with incomplete penetrance and with residual familial effects on affection status. Furthermore, FRR for relatives equate well with a major gene (or multiple additive or independent loci). One or two loci interacting epistatically with an poligenic background was also shown to be a plausible alternative.