Some genetic disorders of vestibular apparatus in animal models are considered in this review. These disorders mainly affect the formation or the entire vestibu I ar system, or the semicircul ar chanals, as well as spheri cal sac, el l iptical sac or endolymphatic sac. Disorders may also involve neural or sensory components of the vestibular apparatus. Disorders of formation and functioning of otoconia and vestibu I ar endolymph are also considered. Some vestibul ar disorders in humans are discussed.

The review discusses role of human genetic factors in efficiency and complications of highly active antiretrovirus therapy (HAART). Genetic polymorphism of cytochrom P450 and multidrug resistance systems (specifically, CYP2B6 and MDR1/MRP1/P-gp, respectively) affects intracellular concentration of numerous antiretroviral drugs (AD) that may explain differences in clin i cal efficacy of HAART. Genetic background might also impact in rate of miscellaneous complications in patients receiving HAART. Thus hypersensitivity to reverse transcriptase inhibitors has been shown to be dependent on the presence of TNF alpha cytokine gene variant 308A or some alleles of HLA class I (HLA-B*5701,HLA-B*3505, HLA-B*14, HLA-Cw*4, HLA-Cw*8) or class II (HLA-DRB1*0101) loci. Protection from lipodistrophia that represents serious complication of HAART depends on presence of parficu i ar ali eles of polymorphic cytokine genes IL-1, IL-18 and TNF beta. Vice versa, susceptibility to enhanced trigleciride level foli owi ng HAART is associated with polymorphic alleles of APOC3, ARb2, ARb3, HFE, LPIN1 and POLG loci whereas increased risk of neuropathy is associated with genetic variants G516T and C983T of CYP2B6 gene. Various complications like hyperbilirubinemia,neutropenia and astma were found to be associated with UGT1A1*28 that controls small lipophilic molecules, A1203A (rs11568695) of MRP4and HLA-A*68, respectively. Data clearly demonstrates the need in personali zation through genetic profili ng in HAART to increase its efficiency and decrease the rate of complications.

FISH-analysis of sperm aneuploidy for chromosomes 13, 18, 21, X and Y was carried out for men with asthenoteratozoospermia and for men with vari ous severity of oligoasthenoteratozoospermia. Among the maj ority of exam i ned men and their wives infertil ity or habitual noncarrying of pregnancy were directional diagnoses. It was shown that high frequency of meiotic non-disjunction of chromosomes is attended to mild and moderate oligoasthenoteratozoospermia among men with infertil ity. The mean frequencies of spermatozoa with disomy for chromosomes 13, 18, 21, and XX, XY, YY disomy among patients with OAT I-III were 0,28%, 0,13%, 0,59%, 0,1%, 0,64% and 0,16%, respectively.

Currently, there are conflicting data regarding the role of methylenetetrahydrofolate reductase polymorphism (MTHFR) in the formation of the risk of havi ng children with cleft lip and/or palate (Cl/P). The paper presents the analysis of the gene MTHFR C677T polymorphism in 102 children with nonsyndromic Cl/p.

An association of polymorphic markers Arg72Pro of TP53 gene and T309G of MDM2 gene with risk of breast cancer in females of Moscow region has been studied. We found an association of Pro/Pro genotype of polymorphic marker Arg72Pro with breast cancer development (OR=1.41, p=1x10~⁵) and with ductal and lobular breast cancer development(OR=1.33, p=0.0001, OR=1.68, p=0.006, respectively). In case of combined susceptible genotype Pro/Pro + TGof TP53 and MDM2 genes we have found highly reliable association with breast cancer and its most frequent subtype — ductal breast carcinoma (p=0.05; p=0.05, respectively).

Numerous studies indicate an extremely high rate of loss of heterozygosity on the short arm of chromosome 19, in the chromosomal segment 19p13.3, for different types of neoplasia: coion, cervical, breast cancers, myeloid leukemia. High rates of 19p13.3 loss of heterozygosity suggest that it contains one or more tumor suppressor genes. Our study of molecular pathology of the SEMA6B gene located in a critical area in breast cancer samples reveals features characteristic of the tumor suppressor gene. The frequency of abnormal methylation of the 5' region of the gene and the rate of loss of heterozygosity in breast cancer samples equal correspondingly 38% and 50%. A germinal mutation in an evolutionarily conserved region of the SEMA6B gene was detected in one of the breast cancer patients.

Werner mesomelic syndrome is an autosomal domi nant disorder characterized by hypo- or aplasia of the tibiae in addition to the preaxial polydactyly (PPD) and/or triphalangeal thumb. To date molecular-genetic cause of disease is mutations at position 404 of the zone of polarizing activity regulatory sequence (ZRS), a long-range limb-specific enhancer of the sonic hedgehog (SHH) gene, which situated in LMBR1 gene. This article reports about first family with Werner mesomelic syndrome with moiecuiar confirmation in Russia. New mutation in patient at position 403 within the ZRS region was detected. These data suggest that transitions not only at position 404 within the ZRS region lead to a more severe clini cal phenotype with the affection of tib i al development.