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Indonesian native chickens are considered an important genetic resource, particularly with respect to their excellent traits for meat and egg production. However, few molecular genetic studies of these native chickens have been conducted. We analyzed the genetic diversity and differentiation of 4 populations of Indonesian native chickens: Black Kedu (BK), Kedu (KD), Kampung (LOC), and Arab (AR). Blood samples from 188 individuals were collected in central and western Java. Genomic DNA was genotyped using 98 autosomal SNP markers, of which 87 were found to be polymorphic. The proportion of polymorphic loci and the average heterozygosity of each population were in the range of 0.765 to 0.878 and 0.224 to 0.263, respectively. The 4 populations of Indonesian chickens appeared to be derived from 3 genetic populations (K = 3): maximum likelihood clustering showed that the BK variety and AR breed were each assigned to a distinct cluster, whereas the LOC ecotype and KD variety were admixed populations with similar proportions of membership. Principal components analysis revealed that eigenvector 1 separated BK and AR from the other 2 populations. Neighbor-joining trees constructed from pairwise distance matrix (F(ST)) estimates, for individuals and between populations, corroborated that the LOC ecotype and KD variety were related closely, whereas the BK variety and AR breed diverged at greater distances. These results also confirmed the usefulness of SNP markers for the study of genetic diversity.

Approximately 20-25% of all schizophrenic patients are resistant to, or are intolerant of, repeated attempts at treatment with a number of antipsychotic agents from different chemical classes. This form of the disease is generally known as 'treatment-resistant schizophrenia (TRS)' (Cohen and Buchanan, 1997). The observation that a broad range of antipsychotics is ineffective against TRS raises the possibility that a common pharmacokinetic process, such as absorption or distribution, is involved. Consequently, the focus of the study was P-glycoprotein (PGP), a membrane protein that functions as a multi-drug efflux pump. We therefore hypothesized that the ATP-binding cassette subfamily B member 1 (ABCB1) gene, which encodes PGP, is associated with the poor drug response in TRS patients or the occurrence of side effects of antipsychotics.To validate this hypothesis, a statistical analysis of the frequency of the G2677A/T and C3435T single nucleotide polymorphisms (SNPs) in ABCB1 was conducted between 16 TRS patients and 84 non-TRS patients, who were divided using the criteria established by Kane et al. (1988). In addition, the occurrence of major side effects of antipsychotics, including extrapyramidal symptoms, postural hypotension, dysuria, and constipation, were also assessed by clinical charts. The assessments were performed by two trained psychiatrists who were blind to all genotypic data. The genotype of each individual at the ABCB1 locus was determined by polymerase chain reaction restriction fragment-length polymorphism assays as described previously (Cascorbi et al., 2001). Differences in allele frequency were compared between populations with use of the Fisher's exact test. A P value of less than 0.05 was considered to indicate statistical significance. No significant differences in characteristics, including age, sex or subtype distributions, were observed between TRS and non-TRS individuals. The allelic frequencies of G2677A/T were 0.47 for the wild type versus 0.17/0.36 for the variants. Likewise, the frequencies for C3435T were 0.57 versus 0.43. These frequencies are similar to those from previous reports on Japanese individuals (Sakaeda et al., 2002). The allelic frequencies of G2677A/T and C3435T did not differ significantly between TRS and non-TRS individuals (P = 0.44, odds ratio = 0.73, 95% confidence interval 0.34-1.56; P = 0.56, odds ratio = 0.76, 95% confidence interval 0.35-1.67, respectively). Furthermore, there were no significant differences in allele frequencies that could be ascribed to the occurrences of side effects.To our knowledge, this report is the first study that demonstrates the impact of ABCB1 SNPs on the clinical antipsychotic response for schizophrenia. Recent in-vitro reports demonstrated that most antipsychotics show varying degrees of affinity for PGP, and that the penetration of atypical antipsychotics into the brain is also influenced by PGP activity, denoting the significance of PGP function or expression for the effectiveness of neurotropics. In particular, PGP at the b...

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