Alleles of the D2 dopamine receptor (DRD2) and the alcohol dehydrogenase 2 (ADH2) genes were determined in 69 French Polynesian alcoholic patients and 57 controls matched for racial origin. Three racial groups were studied: pure Polynesians (PP), Polynesians mixed with Caucasian (PCA) ancestry and Polynesians mixed with Chinese (PCH) ancestry. DRD2 A1 allele frequencies in the alcoholics compared to their controls in these groups were: PP,.26 vs .32 (P = .69); PCA, .44 vs .35 (P = .46); PCH, .40 vs 0.39 (P = .88). ADH2 1 allele frequencies in alcoholics compared to their controls groups were: PP, .56 vs .62 (P = .66); PCA, .75 vs .56 (P = .09); PCH, .78 vs .32 (P = .009). In the PCA group, the combination of the DRD2 A1 genotypes and the ADH2 1 homozygotes was strongly associated with alcoholism (P = .0027). This preliminary study shows the importance of ascertaining racial ancestry in molecular genetic association studies. Moreover, it suggests that a combination of genes are involved in susceptibility to the development of alcoholism.

Many genetic disorders are caused by mutations in single genes (monogenic diseases), and the inheritance pattern of these diseases follows simple rules. If a mutation in both copies of the gene on both chromosome homologues is necessary to cause the disease, the inheritance pattern is recessive, and a patient is the offspring of two clinically unaffected carriers. However, if a mutation in a single homologue is sufficient, the inheritance pattern is dominant and the disease is transmitted from generation to generation. Monogenic diseases are responsible for only a small fraction of all patients with genetic diseases. Many common diseases, including cancer, heart disease, diabetes and several psychiatric diseases, are the results of a complex interaction between genetic and environmental factors. However, these diseases can have important genetic components and can therefore still be considered genetic diseases. The identification of genes involved in complex genetic diseases can be very important for the understanding and treatment of these diseases. Over the last 15 years, much progress has been made in the identification of genes responsible for monogenic diseases, but the identification of genes involved in complex diseases has been more difficult, and at this moment little is known about the genes involved in most common diseases.

Behavioral genetic research has been conducted at the University of Warsaw for the past 20 years. The work done at the University focuses primarily on the origins of individual differences in temperament and other personality traits. In particular, research is directed toward the traits postulated in the Regulative Theory of Temperament. We also focused on the heritability of socio-political attitudes, risk factors for human health, and post-traumatic stress disorder. The majority of the research that has been carried out is grounded in twin and family studies, although recent work based on molecular techniques has also been developed. This article reviews the most important directions and findings of behavioral genetics research at the University of Warsaw.

In the mammary gland, Wnt signals are strongly implicated in initial development of the mammary rudiments and in the ductal branching and alveolar morphogenesis that occurs during pregnancy. Previously, we identified two Wnt signaling pathway-implicated genes, PPP3CA and MARK4, as having a role in more aggressive and potentially metastatic breast tumors. In this study, we examined two SNPs within PPP3CA and MARK4 in an Australian case-control study population for a potential role in human breast cancers. 182 cases and 180 controls were successfully genotyped for the PPP3CA SNP (rs2850328) and 182 cases and 177 controls were successfully genotyped for the MARK4 SNP (rs2395) using High Resolution Melt (HRM) analysis. Genotypes of randomly selected samples for both SNPs were validated by dye terminator sequencing. Chi-square tests were performed to determine any significant differences in the genotype and allele frequencies between the cases and controls. Chi-square analysis showed no statistically significant difference (ρ > .05) for genotype frequencies between cases and controls for rs2850328 (χ2 = 1.2, p = .5476) or rs2395 (χ2 = .3, p = .8608). Similarly, no statistical difference was observed for allele frequencies for rs2850328 (χ2 = .68, p = .4108) or rs2395 (χ2 = .02, p = .893). Even though an association of the polymorphisms rs2850328 and rs2395 and breast cancer was not detected in our case-control study population, other variants within the PPP3CA and MARK4 genes may still be associated with breast cancer, as both genes are implicated with processes involved in the disease as well as their mutual partaking in the Wnt signaling pathway.

Cardiovascular diseases are the leading cause of death worldwide. Essential hypertension is a major risk factor for the development of other cardiovascular diseases and is caused by a combination of environmental and genetic factors, with up to 50% of blood pressure variance currently attributed to an individual's genetic makeup. By studying genes that cause monogenic forms of hypertension and pathways relevant to blood pressure control, a number of polymorphisms have been identified that increase an individual's risk of developing high blood pressure. We report on candidate gene association studies and genome-wide association studies that have been performed to date in the field of hypertension research. It is becoming clear that for the majority of people there is no single gene polymorphism that causes hypertension, but rather a number of common genetic variants, each having a small effect. Using pharmacogenomics to personalize the treatment of hypertension holds promise for achieving and sustaining normotensive pressures quickly, while minimizing the risk of adverse reactions and unwanted side-effects. This will decrease the risk of stroke and myocardial infarction in individuals and lead to a reduced burden of disease upon society as a whole.

Les études épidemiologiques ont mis en évidence une agrégation familiale de la schizophrénie et ont permis de préciser l’étendue du spectre (cf. Tableaux I et II).

Cependant, ces résultats n’impliquent pas automatiquement l’existence d’une composante génétique dans le déterminisme de la maladie. Pour établir la présence de cette composante, on utilise les analyses de ségrégation, de linkage et d’association. Les études de ségrégation, bien qu’elles souffrent de nombreuses limitations, sont plutôt en faveur d’une transmission polygénique avec effet de seuil. Les études de linkage utilisant la méthode des Lod Scores sont encore rares et, comme dans toutes les maladies oú le mode de transmission n’est pas connu, leur emploi pose des problémes méthodologiques complexes. Il semble toutefois que si la détermination de la distance entre le géne pathologique et le marqueur utilisé est sensible á des erreurs sur les paramétres caractérisant le locus de susceptibilité, on ne puisse conclure á un faux linkage á partir de données erronées. Pour effectuer un test de linkage, on peut également employer la méthode des germains malades (Affected Sib Pair), qui, bien que moins puissante, offre des avantages lorsque le mode de transmission de la maladie est mal connu. Enfin, l’interêt d’une étude d’association en utilisant des polymorphismes de restriction au voisinage de génes candidats est souligné. De toute évidence, ces différentes approches devront être combinées dans la recherche des facteurs génétiques prédisposant á la schizophrénie.