[Analysis of the DRD4 gene polymorphism in populations of Russia and neighboring countries]. / Issledovanie polimorfizma gena DRD4 v populiatsiiakh Rossia i sopredel'nykh stran.

Allele and genotype frequencies of the VNTR polymorphism in the third exon of human DRD4 gene were determined in 544 individuals living in Russia (Russians, Bashkirs, Tatars, and Mordovians) and in the neighboring countries (Kazakhs and Ukrainians). The data obtained were compared with the allele frequency distribution patterns reported for the populations of Eurasia. Similarly to other Eurasian populations, in our population samples R4 allele was prevalent (64 to 87%). The frequency of this allele in the populations of Western Europe constitute 61 to 71%, while in the populations of Asia it varies from 74 to 96%. In this respect, the populations studied occupied the intermediate position. In the samples examined the R7 allele frequency decreased from 7% in Ukrainians to 1% in Bashkirs, while in Kazakhs and Mordovians the allele was absent. This finding was consistent with the R7 allele distribution pattern in the populations of Eurasia, characterized by higher frequency in the West and lower frequency or absence of the allele in the East. In the group of 22 Eurasian populations, the R7 allele frequency negatively correlated with the frequency of the R4 allele (r = -0.86 at P < 0.001). Unlike the R4 and R7 alleles, the frequency of which changed in the eastward direction, the R2 allele frequency distribution displayed slightly expressed latitudinal increase southwards. The DRD4 genotype distribution deviated from the equilibrium in most of the samples examined. In some samples, statistically significant increase of the R2/R2 homozygotes frequency was demonstrated. One of the possible explanations of this phenomenon is assortative mating with respect to phenotypic (behavioral) allele manifestation. The data obtained can serve as the basis for the investigation of the possible role of the DRD4 alleles as the risk factors for the development of alcoholism and other types of addictions.

[Structural-functional characteristics of the 13q14 region of the human genome in the search for potential tumor suppressor genes]. / Strukturno-funktsional'naia kharakteristika oblastik 13q14 genoma cheloveka i poisk v nei potentsial'nykh genov-supressorov opukholevogo rosta.

Works on chromosome 13 mapping supported by the Russian program Human Genome are reviewed. Emphasis is placed on studies of region 13q14.3, which is often lost in some human tumors and potentially contains tumor suppressor genes (TSG). A strategy of TSG search is described. As the resolution of genome analysis improved, a minimal overlap of genetic loss in B-cell chronic lymphocytic leukemia (B-CLL) was established for chromosome 13. A map of expressed sequences was constructed for the region containing the overlap, and candidate TSG of chromosome 13q14 were identified. The candidate genes were analyzed both structurally and functionally, and their possible role in tumorigenesis was considered. Assuming haploinsufficiency as a genetic mechanism controlling B-CLL, a new strategy was proposed for mutation screening aimed at identifying potential TSG of region 13q14.

[Search for transcribed segments in the region of q14.3 of human chromosome 13 in silico]. / Poisk transkribiruemykh uchastkov v oblasati q14.3 khromosomy 13 cheloveka in silico.

Using computer-aided genomic methods, a complete map of the expressed sequence tags (EST) located in the human genome region 13q14.3 between the STS markers, D13S810 and D13S1469, was constructed. A total of 62 EST clusters were formed, of which 12 clusters corresponded to the already known human genes, 4 clusters represented pseudogenes, and 10 clusters were new human genes. The use of the method of reverse transcription in combination with polymerase chain reaction (RT-PCR) provided experimental confirmation of the existence of mRNA transcripts for the novel human genes revealed in silico.

[Transcription map of the 13q14 region, frequently deleted in B-cell chronic lymphocytic leukemia patients]. / Transkriptsionnaia karta raiona 13q14, chasto utrachivaemogo u bol'nykh B-kletochnym khronicheskim limfoleikozom.

Deletions in the region located between the STS markers D13S1168 and D13S25 on chromosome 13 are the most frequent genomic changes in patients with B-cell chronic lymphocytic leukemia (B-CLL). After sequencing of this region, two novel candidate genes were identified: C13orf1 (chromosome 13 open reading frame 1) and PLCC (putative large CLL candidate). Analysis of the repeat distribution revealed two subregions differing in composition of repetitious DNA and gene organization. The interval D13S1168-D13S319 contains 131 Alu repeats accounting for 24.8% of its length, whereas the interval GCT16C05-D13S25, which is no more than 180 kb away from the former one is extremely poor in Alu repeats (4.1% of the total length). Both intervals contain almost the same amount of the LINE-type repeats L1 and L2 (20.3 and 21.24%, respectively). In the chromosomal region studied, 29 Alu repeats were found to belong to the evolutionary young subfamily Y, which is still capable of amplifying. A considerable proportion of repeats of this type with similar nucleotide sequences may contribute to the recombinational activity of the chromosomal region 13q14.3, which is responsible for its rearrangements in some tumors in humans.