Abstract The presence of Native Americans, Europeans, and Africans has led to the development of a multi-ethnic, admixed population in Chile. This study aimed to contribute to the characterization of the uniparental genetic structure of three Chilean regions. Newborns from seven hospitals in Independencia, Providencia, Santiago, Curicó, Cauquenes, Valdívia, and Puerto Montt communes, belonging to the Chilean regions of Santiago, Maule, and Los Lagos, were studied. The presence of Native American mitochondrial DNA (mtDNA) haplogroups and two markers present in the non-recombinant region of the Y chromosome, DYS199 and DYS287, indicative of Native American and African ancestry, respectively, was determined. A high Native American matrilineal contribution and a low Native American and African patrilineal contributions were found in all three studied regions. As previously found in Chilean admixed populations, the Native American matrilineal contribution was lower in Santiago than in the other studied regions. However, there was an unexpectedly higher contribution of Native American ancestry in one of the studied communes in Santiago, probably due to the high rate of immigration from other regions of the country. The population genetic sub-structure we detected in Santiago using few uniparental markers requires further confirmation, owing to possible stratification for autosomal and X-chromosome markers.

Holoprosencephaly (HPE) is a spectrum of brain and facial malformations primarily reflecting genetic factors, such as chromosomal abnormalities and gene mutations. Here, we present a clinical and molecular analysis of 195 probands with HPE or microforms; approximately 72% of the patients were derived from the Latin American Collaborative Study of Congenital Malformations (ECLAMC), and 82% of the patients were newborns. Alobar HPE was the predominant brain defect in almost all facial defect categories, except for patients without oral cleft and median or lateral oral clefts. Ethmocephaly, cebocephaly, and premaxillary agenesis were primarily observed among female patients. Premaxillary agenesis occurred in six of the nine diabetic mothers. Recurrence of HPE or microform was approximately 19%. The frequency of microdeletions, detected using Multiplex Ligation-dependant Probe Amplification (MLPA) was 17% in patients with a normal karyotype. Cytogenetics or QF-PCR analyses revealed chromosomal anomalies in 27% of the probands. Mutational analyses in genes SHH, ZIC2, SIX3 and TGIF were performed in 119 patients, revealing eight mutations in SHH, two mutations in SIX3 and two mutations in ZIC2. Thus, a detailed clinical description of new HPE cases with identified genetic anomalies might establish genotypic and phenotypic correlations and contribute to the development of additional strategies for the analysis of new cases.

Os estudos sobre fendas lábio-palatinas (FL/P) demonstram existir uma maior incidência do defeito nas famílias de afetados, mas seu modo de herança permanece indefinido. Esse trabalho apresenta os resultados de uma análise de segregação complexa realizada em 1.792 famílias sul-americanas que possuíam um recém-nascido com FL/P. Essas crianças foram registradas entre 1967 e 1997 e os nascimentos foram consecutivos. Um modelo sem um locus principal foi o que melhor se adequou às famílias de FL/P estudadas. Esse resultado está de acordo com estudos anteriores que mostraram uma significativa associação entre vários loci de suscetibilidade e FL/P, indicando que os genes relacionados com FL/P, isoladamente, contribuem pouco para o risco desse defeito.

Although several studies have demonstrated familial aggregation of nonsyndromic cleft lip with or without cleft palate (CL/P), its model of inheritance remains uncertain. We report the results of complex segregation analysis performed in South American families with a newborn affected with CL/P. Families of 1,792 consecutive newborns affected with CL/P and registered during the period 1967 to 1997 were studied. A model that did not include a major locus was the best-fitting model for CL/P families. This result is in agreement with previous studies which showed a significant association of several putative susceptibility loci and CL/P, indicating that the genes involved in CL/P are likely to have only a very modest impact on disease risk.