ABSTRACT
Family, twin and adoption studies suggest that genetics plays an important role in the etiology of many psychiatric disorders. It has been proposed that the dopaminergic brain system could be affected in schizophrenia, substance abuse and attention deficit hyperactivity disorder. The most studied genes are two VNTR polymorphic systems; one located in the exon 3 of the dopamine D4 receptor (DRD4) gene, and the other in the 3' untranslated region of the dopamine transporter (DAT1 or SCLA6A3) gene. It has been reported that allele frequencies of these polymorphisms varied between populations and this could affect the results in the association studies. Due to the previous findings, the objective of the present study was to determine the allele frequencies of DRD4 and DAT1 in an epidemiological sample of the adolescent population of México City. We found that the frequencies presented in our study were in between those reported for Caucasians and those reported for the American Indigenous population, this result are consistent with Euro-Indigenous inbreeding that has occurred in Mexico. Moreover, the results presented in the present study could explain the lack of consistency in the association analysis and make necessary to develop these investigations in our population.
Existe evidencia fehaciente de la influencia genética en los trastornos psiquiátricos y se ha propuesto que el sistema dopáminergico cerebral puede ser uno de los afectados en diversos trastornos como la esquizofrenia, el abuso de sustancias y el trastorno por déficit de atención e hiperactividad. En este sentido, los sistemas genéticos más estudiados son 2 VNTRs; uno localizado en el exón 3 del gen del Receptor a dopamina D4 (DRD4) y el otro en la región 3' no traducida del transportador a dopamina (DAT1 o SCL6A3). Se ha reportado que las frecuencias alélicas de estos polimorfismos difieren significativamente entre poblaciones y que esto puede afectar los resultados en los estudios de asociación. Debido a lo anterior, el objetivo del presente trabajo fue determinar las frecuencias alélicas del DRD4 y del DAT1 a partir de una muestra epidemiológica de la población adolescente de la Ciudad de México. Las frecuencias alélicas reportadas en el presente estudio son intermedias a las reportadas en caucásicos y poblaciones indígenas de América, lo que concuerda con la historia de mestizaje ocurrida en México. Estás diferencias pueden ayudar a explicar la falta de consistencia en diferentes estudios de asociación y hacen necesario realizarlos en población mexicana.
ABSTRACT
GENDISCAN study (Gene Discovery for Complex traits in Asian population of Northeast area) was designed to incorporate methodologies which enhance the power to identify genetic variations underlying complex disorders. Use of population isolates as the target population is a unique feather of this study. However, population isolates may have hidden inbreeding structures which can affect the validity of the study. To understand how this issue may affect results of GENDISCAN, we estimated inbreeding coefficients in two study populations in Mongolia. We analyzed the status of Hardy-Weinberg Equilibrium (HWE), polymorphism information contents (PIC), heterozygosity, allelic diversity, and inbreeding coefficients, using 317 and 1,044 STR (short tandem repeat) markers in Orkhontuul and Dashbalbar populations. HWE assumptions were generally met in most markers (88.6% and 94.2% respectively), and single marker PIC ranged between 0.2 and 0.9. Inbreeding coefficients were estimated to be 0.0023 and 0.0021, which are small enough to assure that conventional genetic analysis would work without any specific modification. We concluded that the population isolates used in GENDISCAN study would not present significant inflation of type I errors from inbreeding effects in its gene discovery analysis.
Subject(s)
Animals , Humans , Asian People , Feathers , Genetic Association Studies , Genetic Variation , Health Services Needs and Demand , Inbreeding , Inflation, Economic , MongoliaABSTRACT
GENDISCAN study (Gene Discovery for Complex traits in Asian population of Northeast area) was designed to incorporate methodologies which enhance the power to identify genetic variations underlying complex disorders. Use of population isolates as the target population is a unique feather of this study. However, population isolates may have hidden inbreeding structures which can affect the validity of the study. To understand how this issue may affect results of GENDISCAN, we estimated inbreeding coefficients in two study populations in Mongolia. We analyzed the status of Hardy-Weinberg Equilibrium (HWE), polymorphism information contents (PIC), heterozygosity, allelic diversity, and inbreeding coefficients, using 317 and 1,044 STR (short tandem repeat) markers in Orkhontuul and Dashbalbar populations. HWE assumptions were generally met in most markers (88.6% and 94.2% respectively), and single marker PIC ranged between 0.2 and 0.9. Inbreeding coefficients were estimated to be 0.0023 and 0.0021, which are small enough to assure that conventional genetic analysis would work without any specific modification. We concluded that the population isolates used in GENDISCAN study would not present significant inflation of type I errors from inbreeding effects in its gene discovery analysis.