[Breeding of the Russian sable: Stages of industrial domestication and genetic variability].

Creating farms for sable breeding was associated with the commercial destruction of natural populations and, consequently, the overall decline in the species number. The gene pool of the first farm-bred sable population in Russia, established in the vicinity of Moscow ("Pushkinskiy" fur farm), was formed by crossing of animals removed from nine natural populations. In the first eight years of farm operation, approximately one thousand animals were used for sable breeding; some of these animals were able to adapt to the farm management and, subsequently, to the selection for a number of quantitative traits in the period of industrial domestication. It took about ten years for breeders to work out the breeding and selection technologies, which became successfully employed in the established affiliated sable breeding farms. The main achievement in sable breeding over the 85-year historical period of breeding in Russia is the creation of two unique breeds, black sable (1969) and Saltykovskaya 1 (2007). In general, industrial domestication in fur farming and the subsequent breeding works made the fur of many species (mink, fox, Arctic fox) obtained from natural populations uncompetitive, which undoubtedly reduced the hunting interest in the animals living in the wild. Consequently, hunting for fur-bearing animals of most species decreased and has only local importance. Owing to the specific features of sable biology, the fur of farm-bred animals cannot yet completely replace the furs obtained by hunting; however, the farm-bred sable population is constantly growing. This review presents the results of the analysis of the level of genetic variability in natural and farm populations at nuclear and mitochondrial loci. The comparative analysis makes it possible to estimate the loss of genetic diversity upon the species adaptation to the new conditions of existence.

[Characterization of the Russian beef cattle breed gene pools using inter simple sequence repeat DNA analysis (ISSR analysis)].

The gene pools of beef cattle breeds bred in Russia were characterized on the basis of inter simple sequence repeat DNA analysis (ISSR analysis). Samples of Aberdeen Angus, Kalmyk, and Kazakh Whitehead breeds from Russia, as well as of Hereford breed, hybrids of Kazakh Whitehead and Hereford breeds, and Kazakh Whitehead breed from the Republic of Kazakhstan, were examined. In the examined breeds, 27 AG-ISSR fragments were identified, 25 of which were polymorphic. The examined breeds were different both in the fragment profiles (the presence/absence of individual ISSR fragments) and in their frequencies. It was demonstrated that the hybrid animals lacked some ISSR fragments that were present with high frequencies in parental forms, suggesting considerable genome rearrangement in the hybrid animals (at the regions of microsatellite localization) in crossings of the individuals from different breeds. The level of genetic diversity in Russian beef breeds was consistent with the values typical of farmed populations (breeds). The genetic diversity parameters assessed by applying Nei's gene diversity index and the Shannon index varied from 0.0218 to 0.0605 and from 0.0225 to 0.0819, respectively. The highest Shannon index value was detected in the Kalmyk breed (0.0837) and Kazakh Whitehead breed from Russia (0.0819), and the highest level of Nei's gene diversity index was found in the Kalmyk breed (0.0562) and in both populations of the Kazakh Whitehead breed (0.0509 and 0.0605). The high level of genetic similarity (according to Nei) was revealed between Russian beef cattle breeds and Hereford cattle: 0.839 (for the Kazakh Whitehead breed from Russia) and 0.769 (for the Kalmyk breed).

[Mitochondrial DNA Polymorphism in Different Populations of Spangled Orloff Chickens].

For the first time, the genetic diversity of the Spangled Orloff chickens was studied by analyzing the polymorphism of the hypervariable region in the D-loop of mitochondrial DNA (mtDNA). Samples for the analysis were collected at the farms ofthe All-Russia Poultry Research and Technological Institute (VNITIP), the All-Russia Institute of Farm Animal Genetics and Breeding (VNIIGRZh), and the Moscow Zoo. The D-loop partial sequences (between nucleotide positions 57 and 523) were determined according to the reference sequence of Gallus gallus spadiceus mtDNA, NC_007235 in 39 individuals obtained from these populations (GenBank Accession Nos. KM391754-KM391792). In the analyzed mtDNA fragment, a total of 20 polymorphic sites localized between positions 167 and 368, as well as at position 446, were described in Spangled Orloff chickens. One polymorphic site at position 221 (haplogroup E, haplotype ORL-2) was unique. All of the identified nucleotide changes were transition-type substitutions. Overall, based on the analysis of poly- morphic sites in the hypervariable fragment of the D-loop of Spangled Orloff chicken mtDNA, we found seven haplotypes belonging to four haplogroups (A, B, C, and E). Haplogroup E (haplotypes ORL-1, ORL-2, and ORL-3) was present in the majority of the studied individual, with the frequencies of 0.77 in the total sample and 0.47 in the VNIIGRZh farm population. Haplogroups A (haplotypes ORL-4 and ORL-7), B (ORL-6), and C (ORL-5) were found only in samples from the VNIIGRZh farm. The studied mtDNA region revealed a lower level of polymorphism in the VNITIP and Moscow Zoo populations, which only had the ORL-1 and ORL-3 haplotypes belonging to Haplogroup E, respectively. Our data suggested that the studied Spangled Orloff chicken populations differed in the composition and frequencies of mtDNA haplogroups and haplotypes.

[Polymorphisms of bGH, RORC, and DGAT1 genes in Russian beef cattle breeds].

We examined the allelic and genotypic polymorphisms of genes of the retinoic acid receptor-related orphan receptor C (RORC), diacylglycerol acyltransferase-1 (DGAT1), and growth hormone (bGH) in Russian beef cattle breeds in two populations of Kazakh white-headed cattle (of Kazakh and Russian selection) and in the Kalmyk cattle breed and Mongolian hogorogo breed, which is related to Kalmyk breed. The studied genes are associated with parameters of meat quality: marbleness (bGH and RORC) and tenderness (DGAT1). They are also associated with an increase in carcass weight (bGH). We found that Russian and Kazakh populations of the Kazakh white-headed.breed were characterized by a high content of the AA genotype of RORC (0.713 and 0.608, respectively) and of the AA genotype of DGAT1 (0.913 and 0.975), both of which are preferable for meat quality. The total frequencies for the combined genotypes for the bGH and RORC genes, which provide for superior meat quality and carcass weight, in the populations of Kazakh white-headed cattle (GG/AA and GC/AA-68.8% and 57% in the Russian and Kazakh populations, respectively) exceeded the frequencies in the two other studied breeds by two times. Overall, the obtained results point to the high genetic potential of both populations of Kazakh white-headed cattle breeds in beef production. Results of this study can be used to improve the selection of meat traits in industrial livestock.

[Comparative analysis of ISSR markers polymorphism in populations of yak (Bos mutus) and in F1 hybrids between yak and cattle in the Sayan-Altai region].

The genetic variability in seven yak populations from the Sayan-Altai region and in F1 hybrids between yak and cattle (khainags) was investigated with the help of a technique that involves the use of inter simple sequence repeat (ISSR) markers generated with PCR primers (AG)9C and (GA)9C. Samples for the analysis were collected in Mongolia, Tuva, and Altai from 2008 through 2012. The examined yak populations differed in in the presence/absence of ISSR fragments, as well as in their frequency. In total, 46 ISSR fragments were identified using two marker systems; the proportion of polymorphic loci constituted 76% and 90% for the AG-ISSR and GA-ISSR markers, respectively. For the total sample of yaks, total genetic diversity (Ht), within-population diversity (Hs), and interpopulation diversity (Gst) constituted 0.081, 0.044, and 0.459 for the AG-ISSR and 0.137, 0.057, and 0.582 for the GA-ISSR markers, respectively. Based on ISSR finger printing, species- and breed-specific DNA patterns were described for the three groups of animals (yaks, cattle, khainags). For the domestic yak, the species-specific profile was represented by eight ISSR fragments. Genetic relationships between the yak populations, cattle breeds, and khainags were examined with the help of four different approaches used in the analysis of population structure: estimation of phylogenetic similarity, multidimensional scaling, principal component analysis, and cluster analysis. Clear evidence on the differentiation of the populations examined at the interspecific, as well as at intraspecific, level were obtained. Similar (relative); as well as remote (isolated), yak populations were identified. Khainags occupy an intermediate position between yak and cattle. However, the data on the ISSR-PCR marker polymorphism (genome polymorphism, population structure).indicate that part of the analyzed khainag genome was more similar to the yak genome than to the cattle genome.

[Genomic diversity in cattle breeds assessed using polymorphism of intermicrosatellite markers].

Using (AG)9C and (GA)9C primers and analysis of multilocus profile of intermicrosatellite polymorphism (ISSR-PCR), in 19 cattle breeds, a total of 66 PCR products were revealed. The statistical processing of the data obtained using standard software programs enabled the identification of the ISSR markers, the polymorphism of which made the greatest contribution to the total genomic diversity of both individual breeds and the species Bos taurus in general. These DNA fragments deserve special interest for the further analysis of their localization and functions.

[Specific genetic features of the Russian forms of bovine leukemia virus].

Genetic peculiarities of bovine leukemia virus isolates (BLV) spread throughout Russia and Ukraine (BLV-1, BLV-2, and BLV-4) have been characterized based on pol gene polymorphism. Seven viral forms have been detected. The variability of BLV isolates did not exceed 1% within one form. Despite the recent inhabitation of BLV in Russia in the middle of 20th century, Russian BLV variants are characterized by several specific nucleotide substitutions. Point mutations that result in the changes in the aminoacid sequence of reverse transcriptase of BLV specific to distinct viral forms were observed. C --> G transition at the 2752 position (relatively to the reference genome AF033818), which results in the substitution of glutamic to asparaginic acid (GAG --> GAC), is specific to form BLV-2. This mutation was demonstrated in BLV isolates from Ukraine. The T --> G substitution at the 2758 position, which results in the substitution of isoleucine for methionine (ATT --> ATG), is specific to BLV-4 and BLV-7 forms. The BLV-4 form was only detected in Russia and Ukraine. The present study also includes a review of the published data concerning BLV variability. The existing classifications of BLV forms have been critically conceived and the new optimal classification of BLV forms with the maximal resolution has been suggested.

[Identification and classification of bovine leukemia virus isolates in Russia and Ukraine based on the pol viral gene polymorphism].

Bovine leukemia virus (BLV) is a widespread specific pathogen of cattle. Analysis of the pol viral gene polymorphism has been used to characterize the polymorphism of BLV isolates at stock-breeding farms in Russia and Ukraine. The fragments of the pol gene corresponding to the reverse transcriptase and integrase 494 and 233 bp in size, respectively, have been used for analysis. Phylogenetic analysis has revealed several variants of BLV clustered with a high bootstrap support in Russia and Ukraine. A new classification of BLV variants is suggested. Comparison of phylograms based on the polymorphism of the nucleotide sequences of the integrase and reverse transcriptase domains did not show topological conflicts. Therefore, recombination between BLV variants has not been found.

Distribution of BoLA-DRB3 allelic frequencies and identification of two new alleles in Iranian buffalo breed.

The role of the major histocompatibility complex (MHC) in the immune response makes it an attractive candidate gene for associations with disease resistance and susceptibility. This study describes genetic variability in the BoLA-DRB3 in Iranian buffaloes. Heminested PCR-RFLP method was used to identify the frequency of BoLA-DRB3 alleles. The BoLA-DRB3 locus is highly polymorphic in the study herd (12 alleles). Almost 63.50% of the alleles were accounted for by four alleles (BoLA-DRB3.2 ∗48, ∗20, ∗21, and obe) in Iranian buffalo. The DRB3.2 ∗48 allele frequency (24.20%) was higher than the others. The frequencies of the DRB3.2 ∗20 and DRB3.2 ∗21 are 14.52 and 14.00, respectively, and obe and gbb have a new pattern. Significant distinctions have been found between Iranian buffalo and other cattle breed studied. In the Iranian buffaloes studied alleles associated with resistance to various diseases are found.

[Comparison of ISSR polymorphism among cattle breeds].

Polymorphism analysis of DNA fragments flanked by (TC)9G and (CT)9G inverted dinucleotide microsatellite repeats in 766 animals of 19 cattle breeds and one breeding type revealed 66 fragments, of which 64 were polymorphic. The breeds proved to differ in the frequency and presence or absence of amplified DNA fragments at the genomic level, indicating that ISSR fingerprinting is informative for differentiating the PCR product spectra and cattle breeds. Multilocus ISSR polymorphism analysis identified the group of fragments that can be used as Bos taurus and B. indicus species markers to describe the standards of breeds, their genetic profiles, and breed-specific patterns. Based on ISSR polymorphism, a prototypal gene pool of cattle was constructed and the breeds closest to it were identified. Genetic diversity analysis made it possible to assume that an optimal mean heterozygosity is characteristic of cattle breeds and that deviations from this optimum are indicative of various processes occurring in the population (breed).

[The use of the ISSR-PCR method for identifying domesticated animal breeds and species, inferring their population structures, and assessing gene pool similarity].

The use of multilocus intermicrosatellite assay (ISSR-PCR) in combination with the method of k-clustering of population structures (Structure v2.2. program) has become a basis for a battery of tests of molecular genetic examination and for studying the gene pool of domesticated animal species. Possibilities are reviewed for analysis of the population structures of domesticated species at different levels (interspecific, interbreed, and intrabreed levels), for assessment of similarity of gene pools of breeds (intrabreed groups), as well as for identification of breeds and estimation of their consolidation, purity, and genealogical relationships.

[Polymorphism of the BoLA-DRB3 gene in the Mongolian, Kalmyk, and Yakut cattle breeds].

Polymorphism of the BoLA-DRB3 gene was studied with the use of the PCR-RFLP technique in three cattle breeds (Mongolian, Kalmyk, and Yakut) representing the Bos taurus turano-mongolicus group. 35 BoLA-DRB3.2 alleles were detected in the Mongolian breed and 34 alleles in the Kalmyk breed. The frequencies of alleles in both populations are distributed rather evenly: the frequencies of the most widely represented alleles (*18, *20, and *28) in the Mongolian cattle varied from 7.75 to 8.45%. The most frequent alleles in the Kalmyk cattle were *28(14.52%), *24(7.26%), and *12(6.45%). Only five alleles were identified in the Yakut cattle breed. The prevailing allele was *29 (77.3%); a relatively frequent allele was *1(13.1%), and the remaining three alleles constituted only 9.6%. Such a low level of diversity of BoLA-DRB3 gene alleles was not observed earlier in any other cattle breed. The Mongolian and Kalmyk breeds showed a wide diversity of BoLA-DRB3 genotypes (56 and 51 genotypes, respectively) and a high level of expected heterozygosity (He = 0.953 and 0.946, respectively). Both breeds had a deficiency of heterozygotes (Mongolian cattle: Ho = 0.775, D = -0.187; Kalmyk cattle: Ho = 0.708, D= -0.252). A low level ofgenotypic diversity for the BoLA-DRB3 locus (only seven genotypes; the frequency for the genotype *29/*29 is 71.4%) and a very low level of observed heterozygosity (Ho = 0.12) were revealed in the Yakut breed. BoLA-DRB3.2 alleles associated with resistance to persistent lymphocytosis caused by the bovine leukemia virus (total frequencies 15.49 and 24.19%) and to various forms of mastitis (total frequencies 12.68 and 20.96%, respectively) were identified in the Mongolian and Kalmyk animals. In the Yakut breed, alleles associated with resistance to diseases are represented only by the BoLA-DRB3.2 allele *7 (1.2%). Thus, the Mongolian and Kalmyk cattle breeds are characterized by a wide diversity of alleles and genotypes for the BoLA-DRB3 gene. In contrast, the population of Yakut cattle from the Verkhoyanskii raion of the Republic of Sakha has a poor diversity of alleles and genotypes for the BoLA-DRB3 gene and a very low level of heterozygosity, suggesting an unfavorable state of the population that is probably caused by inbreeding depression due to a long-term isolation and a small number of animals.

[Study of genetic variation in Yakutian cattle (Bos taurus L.) using the prolactin bPRL, growth hormone bGH, and transcription factor bPit-1 genes].

The genetic structure of the Yakutian cattle breed was studied using the following genes: bPRL (RsaI site in exon 3), bGH (AluI site in exon 5), and bPit-1 (HinfI site in exon 6). The values of observed heterozygosity were 0.36 for bPRL, 0.29 for bGH, and 0.16 for bPit-1. These values are within the range of values for this parameter established for a number of Bos taurus breeds. The results obtained show that genetic variation is preserved in this aboriginal Russian breed, despite a catastrophic reduction of the number of animals.

[Analysis of the genetic structure of Tuvinian short-fat-tailed sheep populations with the use of the ISSR-PCR method].

The genetic structure of populations of the Tuvinian short-fat-tailed sheep was studied with the use of the ISSR-PCR (Inter Simple Sequence Repeats) method in 18 farms of Tyva. Data on the spectrum of ISSR fragments of DNA were obtained using the (AG)9C primer. Analysis of intermicrosatellite polymorphism permitted us to determine genomic characteristics of the populations, their genealogical relations, and the parameters of genetic diversity within the populations and the breed as a whole. Three genetic notions were considered on the basis of the results of this analysis: gene pool profile, gene pool standard, and breed-specific pattern. The data obtained can be used to carry out population genetic monitoring, to develop a breeding strategy, and to conserve in situ the Tuvinian sheep breed and breeds of other domesticated species.

[Alteration of SEMA3B gene expression levels in epithelial tumors].

Gene expression decreasing in tumors permits to suggest tumor-suppressor activities for these genes. Thus, mRNA quantity decrease was found for SEMA3B gene in many cell lines of small cell (SCLC) and non-small cell lung carcinoma (NSCLC) and it is well-known that SEMA3B suppresses growth of the NCI-H1299 non-small cell lung carcinoma (NSCLC) cell line and tumor formation in nude mice. The aim of this work was to study spectrum of SEMA3B expression level in epithelial tumors of various locations. Using semi-quantitative RT-PCR it was shown for the first time decrease of SEMA3B mRNA quantity (10-250 times as much) in cell lines of renal, breast and ovarian tumors (4/11, 36%). SEMA3B expression profiles in primary tumors of five locations (kidney, lung, breast, ovary and colon) were studied for the first time. This analysis revealed decrease of mRNA quantity (5-1000 times as much) in clear cell renal cell carcinomas with significant high frequency: 25/51, 49% (cases with decrease of mRNA quantity) and 5/51, 10% (cases with increase), P < 0.0001 by Fisher exact test. In addition, the first data about comparatively frequent decrease of mRNA quantity in ovarian (5/16, 31% vs. 2/16, 12%) and colorectal carcinomas (6/11, 54% vs. 2/11,18%) were shown. These results permitted to suggest a possible role of SEMA3B in inhibiting of growth of renal, ovarian and colorectal cancer cells.

Distribution of BoLA-DRB3 allelic frequencies and identification of a new allele in the iranian cattle breed sistani (Bos indicus).

The distribution of the frequencies of BoLA-DRB3 gene alleles in the Iranian cattle breed Sistani was studied by the PCR-RFLP ("hemi-nested") assay using restriction endonucleases RsaI, HaeIII and BstYI. In the examined cattle breed (65 animals) 32 alleles have been identified one of which being described for the first time (6.15% frequency). The nucleotide sequence of the polymorphic region of exon 2 of this allele has been determined and submitted in the GeneBank database under accession number DQ486519. The submitted sequence has maximum homology (92%) with the previously described sequence DRB3-mRNA from Bos indicus (AccN X79346) and differs from it by 24 nucleotide substitutions which result in 16 amino acid substitutions. The peptide (on the basis of the reconstructed amino acid sequence) has 89% identity to the sequence encoded by the BIDRBF 188 locus (Bos indicus). The results obtained permit the sequence described by us to be considered as a new allele of the BoLA-DRB3 gene (DRB3.2**X). The total frequency of the main six alleles (DRB3.2*X, *10, *11, *20, *34 and *X) occurring with a frequency of over 5% is about 60% in Iranian Sistani cattle. Fifteen alleles have <1% frequency. The highest frequency was observed for DRB3.2*8 allele (21.54%) like in other previously described breeds of Bos indicus (up to 23.07%). The Iranian breed Sistani has a high level of similarity by the spectrum of BoLA-DRB3 alleles and their frequencies to other Bos indicus breeds and significantly differs by these criteria from the Bos taurus breeds. The Iranian Sistani herd under study includes alleles associated with to resistance to leukemia (DRB3.2*ll and *23) and to different forms of mastitis (DRB3.2*2, *7, *11, *23 and *24) although their frequencies are low (from 0.77 to 5.37%). On the whole, a high level of diversity of BoLA-DRB3 gene alleles and the availability of alleles associated with resistance to different diseases makes this breed of interest for breeding practice.

[A new member of the WAS genes family (WASF4)].

The exon-intron structure of the human WASF4 gene has been determined. The in silico analysis of the gene promoter region was performed and the presence of transcription factor binding sites was shown. The highest similarity between the WASF4 protein and the human WASF2 protein was revealed. The WASF4 gene homolog was found in chimpanzee and macaque genomes; WASF4 like nucleotide sequences were not found in other vertebrate genomes. The WASF4 gene expression in human tissues was not detected.

[Allelic polymorphism of kappa-casein gene (CSN3) in Russian cattle breeds and its informative value as a genetic marker].

The frequencies of the kappa-casein gene (CSN3) alleles and genotypes have been determined in five Russian cattle breeds (Bestuzhev, Kalmyk, Russian Black Pied, Yaroslavl, and Yakut breeds) by means of PCR-RFLP analysis using two independent restriction nucleases (HinfI and TaqI) and by allele-specific PCR. Typing alleles A and B of CSN3 is of practical importance, because allele B is correlated with commercially valuable parameters of milk productivity (protein content and milk yield) and improves the cheese yielding capacity. The frequencies of the B allele of CSN3 in the breeds studied vary from 0.16 to 0.50; and those of the AB and BB genotypes, from 0.27 to 0.60 and from 0.02 to 0.23, respectively. The Yaroslavl breed had the highest frequencies of CSN3 allele B and genotype BB (0.50 and 0.23, respectively). The frequencies of the B allele and BB genotype in other breeds studied varied from 0.25 to 0.32 and from 0.03 to 0.09, respectively. In none of the breeds studied have the observed and expected heterozygosities been found to differ from each other significantly. However, the observed genotype distributions significantly differ from the expected one in some herds (in most such cases, an excess of heterozygotes is observed). Two herds of the Yaroslavl breed dramatically differ from each other in the heterozygosity level: a deficit (D = -0.14) and an excess (D = 0.20) of heterozygotes have been observed at the Mikhailovskoe and Gorshikha farms, respectively. In general, however, the heterozygosity of the Yaroslavl breed corresponds to the expected level (D = 0.04). Analysis of breeds for homogeneity with the use of Kulback's test has shown that all cattle breeds studied are heterogeneous, the CSN3 diversity within breeds being higher than that among different breeds, which is confirmed by low Fst values (0.0025-0.0431). Thus, a DNA marker based on CSN3 gene polymorphism is extremely important for breeding practice as a marker of milk quality; however, it is inapplicable to marking differences between breeds or phylogenetic relationships between cattle breeds because of the high diversity with respect to this locus within breeds.

[Activation of RHOA gene transcription in epithelial tumors may be caused by gene amplification and/or demethylation of its promotor region].

RHOA protein, a member of small GTPases family, is implicated in cell morphogenesis, adhesion, and in cell cycle regulation. RHOA gene (3p21.31) exhibits cell transformation activity, and therefore gene is considered as a potential oncogene. The aim of this study was to investigate RHOA transcription and copy number changes in three epithelial tumors (breast, renal cell and epithelial ovarian carcinomas, 45 tumor/normal pairs altogether). EII, HhaI, AciI n Bsh1236I). Hypomethylation of the RHOA promoter region in tumor DNA was observed two times more frequently than increased methylation. Moreover, all (15) cancer cases with hypomethylation of the RHOA gene showed a 2-10 fold increased expression of RHOA. It was concluded that gene copy multiplication and demethylation of the RHOA promoter region can contribute to transcription activation of this gene in epithelial tumors.

TGFalpha reactivates imprinted Igf2 in the parthenogenetic mice embryos and placenta.

Imprinted genes play important roles in the mammalian development. In the parthenogenetic embryos (PE) there is only expression of maternally expressed genes. Therefore, PEs are appropriate experimental models to study genomic imprinting controlling mechanisms. The maternally expressed H19 and paternally expressed Igf2 are reciprocally imprinted genes in normal embryos. Here we studied effect of transforming growth factor alpha (TGFalpha) treatment in vitro (10 ng/ml at the morula stage) on the expression of Igf2/H19 locus in mice PE (9.5-days of gestation, 25 somites) and their placentas (PP). Using RT-PCR we showed that TGFalpha reactivated maternally imprinted Igf2 gene in parthenogenetic embryos and placentas. In spite of similar Tgfalpha expression in the pre-implantation stages, its expression in the 9.5-day parthenogenetic embryos is significantly less than in normal embryos (NE). In our experiments it was shown that reactivation of Igf2 gene occurred independently of H19 gene. In vitro TGFalpha treatment of mouse PE reactivated paternally expressed Igf2 gene in the PE and PP. In the PE and PP both Igf2 and H19 were expressed. It seems that TGFalpha can play an important role as modulator of the Igf2/H19 locus.