[Biochip for determination of genetic markers of sporadic Alzheimer's disease in the Russian Slavic population].

A biological microchip (biochip) for the genetic predis- position to sporadic form of Alzheimer's disease studying has been developed. The biochip allows determina- tion of ten genetic polymorphisms within APOE, TOMM40, APOJ, EXOC3L2, GAB2, A2M, CR1, BIN1 and PICALM genes. The genotyping assay includes the amplification of loci of interest and further allele-specific hybridization of the fluorescent labeled amplicons with oligonucleotides immobilized on a biochip. Based on the results of genotyping of 166 patients and 128 controls APOE epsilon4 allele was found to be significantly associated with Alzheimer's disease susceptibility (OR = 2.275, 95% CI = 1.045-4.954,p = 0.034). Additionally, protective effects for the APOE epsilon2 allele and CLUT-allele (rs11136000) were observed (OR = 0.215, 95% CI = 0.090-0.516, p = 0.001 and OR = 0.679, 95% CI = 0.47-0.99, p = 0.042, respectively). Gene-gene interaction revealed two genotype combinations associated with Alzheimer's disease: APOE E3/E4 GAB2 G/G (OR = 2.49; CI = 1.43-4.32, p = 0.001) and APOE epsilon4 GAB2 G/G (OR = 3.55, CI = 1.23-10.24,p = 0.015). Based on the results of the combined multivariate analysis the algorithm for identifying of individuals at increased risk of Alzheimer's disease was developed.

[Interaction of mutant genes Fgf5(go-Y), we, and wal changes the duration of hair growth cycles in mice].

Mutant gene wallhaarig (wa) was acting as a modifier of the mutant gene waved alopecia (wal), substantially increasing hair loss rate in mice, as was previously shown in our laboratory. The current paper is devoted to a study of mutant gene angora- Y(Fgf5(go-Y)), which had extended anagen stage of the first and second generations hair growth cycles in triple heterozygotes (Fgf5(go-Y)/Fgf5(go-Y) we/we wal/wal). First generation guard hair in triple homozygotes had their anagen stage 4 days longer than the same stage in double homozygotes (+/+ we/we wal/wal). Hair loss started at a catagen stage in double homozygotes, while it started in triple homozygotes at the end of the same stage or even in a telogen. Such mutant gene interaction in hair follicle morphogenesis led to a partial recovery of a body hair coat in triple homozygotes.

[An association study of polymorphisms in HTR2A, BDNF and SLC6A4 genes with paranoid schizophrenia and suicidal behavior].

We have developed a biochip for the analysis of candidate genes for schizophrenia. Using this biochip, allele and genotype frequencies for the polymorphisms of HTR2A, BDNF and SLC6A4 genes in 198 patients with schizophrenia and 192 healthy individuals have been obtained. The allele T of the HTR2A polymorphism rs6314 was identified as protective against the development of paranoid schizophrenia (p=0,014). An analysis of gene-gene interactions using the Multifactor-Dimensionality Reduction (MDR) algorithm has shown a statistically significant association of combined genotypes rs6311 G/-, rs6313 C/-, rs6314 C/C, rs7997012 G/- with the disease (p=0.019). Also it has been shown that the G/G genotype of the polymorphism rs6311 (p=0.013) and the C/C genotype of the polymorphism rs6313 (p=0.008) in the HTR2A gene are associated with the suicide attempt in schizophrenic patients. Correspondingly, an A allele, А/- genotypes of the polymorphism rs6311 G>A and a T allele, T/- genotypes of the polymorphism rs6313 C>T were found to be less frequent in schizophrenic patients with a history of suicide attempt than in schizophrenic patients without a history of suicide attempt, thus suggesting their protective role in the development of suicidal behavior. The results confirm the hypothesis that the HTR2A plays an important role in the etiology of schizophrenia and suicidal behavior.