[Clinical polymorphism of autoimmune polyglandular syndrome of type 1. Role of molecular genetic diagnosis].

Autoimmune polyglandular syndrome type 1 (APS-1) is a rare monogenous disease with autosomal-recessive inheritance. The gene responsible for the development of this disease is designated as the gene AIRE and encodes for the protein autoimmune regulator whose function is unknown. The disease more frequently manifests itself in childhood. Its typical manifestations are chronic cutaneous and mucous candidiasis, hypoparathyroidism, and chronic adrenal insufficiency. The presence of 2 of these signs gives ground to establish its clinical diagnosis. However, the clinical manifestations of this disease are highly polymorphic. Thirty-nine patients with the established diagnosis of APS-1 were followed up. There was a high frequency of R2S7X mutation in the gene AIRE. Its clinical picture is untypical in 26% of cases despite the presence of the identical R257X mutation. The molecular genetic diagnosis permits diagnosis of untypical cases of APS-1.

[Tripeptidyl peptidase 1 deficiency in neuronal ceroid lipofuscinosis. A novel mutation]. / Nedostatochnost' tripeptidil peptidazy 1 pri neironal'nom tseroidnom lipofuktsinoze. Novaia mutatsiia.

The data on biochemical and molecular-genetic diagnostics of a hereditary lisosomal storage disease, late infantile neuronal ceroid lipofuscinosis (CLN2) are presented. The disease is associated with a hereditary deficiency of pepstatin-unsensitive peptidase--tripeptidylpeptidase 1 (TPP1)--caused by mutations in the TPP1-coding gene CLN2. Among the 30 patients with clinical manifestations of CLN, six patients with a pronounced decrease in TPP1 activity were revealed; these data were interpreted as indicating the presence of CLN2 in these patients. The analysis of the isolated DNA indicated the availability of the most widespread mutation g3670 C > T(R208X) leading to the untimely termination of TPP1 synthesis. It was shown that in 5 patients this mutation is present in homozygous state and in one patient, in the heterozygous state. In this patient a hitherto unknown mutation, g3665G > A (R206H), was revealed. The pathogenetic significance of this mutation and the importance of molecular-genetic diagnosis of CLN are discussed with regard to medico-genetic consulting and prenatal diagnosis of this disease.

[Genetico-demographic characteristics of the population from three districts of the Bryansk region]. / Genetiko-demograficheskie osobennosti naseleniia trekh raionov Brianskoi oblasti.

Results of genetic demographic investigation of three nations located in west Bryanskaya oblast (Klintsovskii, Klimovskii, and Starodubskii nations) are presented. A comparison is made with respect to a number of demographic parameters of "southern" (Krasnodar) and "northern" (Kirov) Russian populations. A low level of the Crow index, which is associated with a differential mortality rate, Im = 0.07, was established in the population studied. This fact significantly distinguishes the population of Bryanskaya oblast from other studied Russian populations. With respect to sex and age structure and the Crow index, the Bryansk population is comparable to the southern Krasnodar population, while in terms of level of isolation and inbreeding, the Bryansk population is similar to the northern Kirov population. Moreover, it was found that the Chernobyl meltdown in 1986 did not lead to any change in the genetic demographic situation in the three studied nations.

[Population sturcture of the Gorno-Mariiskii region of the Marii El Republic]. / Populiatsionnaia struktura Gorno-Mariiskogo raiona Respubliki Marii El.

The genetic structure of the population of the Gorno-Mariiskii raion, Marii El Republic, was studied. The population consists of two major groups, highland Mari and Russians. The former constitute the majority of the rural population, and the latter, the majority of the urban one. A marked ethnicity-related marriage assortation was found. The value of random inbreeding was estimated using frequencies of surnames. It varied from 0.00015 to 0.00069 (the weighted average was 0.00026). The local inbreeding (a) for Gorno-Mariiskii raion estimated according to Malecot was 0.00029. The local inbreeding for marriages between Mari (0.0022) was five times higher than for marriages between Russians. The indices of endogamy were 0.84 in the rural population and 0.14 in the urban population. The matrix of genetic distances and its image in the form of genetic landscape suggest a regularly distorted isolation by distance and realized panmixia.

[Family analysis of human "fingerprints" obtained using a phage M13 DNA probe]. / Semeinyi analiz "fingerprintov" cheloveka, poluchennykh s pomoshch'iu zonda DNK faga M13.

The human "fingerprints" detected by the phage M13 DNA probe from 40 simple families with some presumably genetic malformations were observed. When only one parent had a specific band, the mean segregation frequency of all the electrophoretic bands detected was equal to 0.485, which confirmed the hypothesis about the Mendelian inheritance and high level of heterozygosity of hypervariable loci. The mean new measure of similarity between the parents calculated by Li C.C. was 0.54 (this measure within only fathers and only mothers was equal to the mean population level of similarity 0.41).

[Genetic distances between various ethnic populations calculated on the basis of polymorphism of DNA detected by the hypervariable phage M13 DNA probe]. / Geneticheskie rasstoianiia mezhdu populiatsiiami razlichnoi étnicheskoi prinadlezhnosti, rasschitannye na osnove polimorfizma DNK, vyiavliaemogo gipervariabel'noi proboi DNK faga M13.

The frequencies of different electrophoretic bands in DNA "fingerprint" detected by the phage M13 DNA probe in six Russian populations from the Kirov district and Krasnodar, one from Chuvashia and one from Tuva were compared with each other and pseudo-genetic distances by Nei were calculated. The results corresponded well with a presumable extent of similarity between the populations observed.

[Load of autosomal recessive diseases in populations of Kirov Province and its relationship to consanguinity]. / Otiagoshchennost' autosomno-retsessivnoi patologiei populiatsii Kirovskoi oblasti i ee sviaz' inbridingom.

The dependence of the load of autosomal recessive disorders on a variation of random inbreeding in the populations of the 9th Districts of the Kirov Province was investigated. The values of the Fst varied between different districts from 0.00021 to 0.0011 and the values of load of AR--from 0.73 to 2.01 affected per 1000. There is a close significant correlation (r = 0.90) between the parameters in the population studied which increased under analysis of the population considering the coefficients of random inbreeding.

[Analysis of genetic distances between populations using human DNA "fingerprints" detected by a phage M13 DNA probe]. / Analiz geneticheskikh rasstoianii mezhdu populiatsiiami s pomoshch'iu "fingerprintov" DNK cheloveka, vyiavliaemykh zondom DNK faga M13.

The frequencies of different electrophoretic bands in DNA fingerprints detected by phage M13 DNA probe in two populations of the Kirov district were determined. The DNA polymorphisms observed in these two populations were compared with each other and with those of the Krasnodar populations, and pseudogenetic distances were calculated. The mean genetic distance between two Kirov populations was 0.072, this between every Kirov and Krasnodar population being 0.21 and 0.22.

[Use of DNA polymorphism detected by M13 phage DNA in population studies]. / Ispol'zovanie polimorfizma DNK, vyiavliaemogo s pomoshch'iu DNK faga M13 v populiatsionnykh issledovaniiakh.

Hypervariable "minisatellite" regions detected in human genome by wild-type phage M13 DNA were found to have high polymorphism and somatic stability. Analysis of individual specific patterns of hybridization of 44 human DNAs from the Kirov province is presented. Molecular weight of fragments varied from 2 to 6 kb. Mean frequency of a fragment in the population under study is p = 0.294 +/- 0.158. The mean number of fragments per individual is 11.6 +/- 1.8. Comparison between the Kirov population and that of Krasnodar studied earlier was carried out. The mean genetic distance between Kirov and Krasnodar populations calculated according to Nei is 0.2082. The possibility of using in population-genetic studies of hypervariable DNA markers having fingerprint type of hybridization is discussed.