Homology between the Lpm system of allotypes in the American mink and the Gp system of allotypes in the domestic pig]

The 5 alpha-macroglobulin allotypes alpha M1, alpha M2, alpha M3, alpha M4 and alpha M5 were identified in pig. The alpha M1 allotype was reported as a marker of pig alpha-macroglobulin, the latter being homologous to alpha 2-macroglobulins in human and in mink. The allotypes alpha M2-alpha M5 were specified as markers of the second isotypical variant of pig alpha-macroglobulins, which was homologous to mink Lpm macroglobulin (alpha 1M). As seen from data obtained by International Comparative Test ISABR 87-88, alpha M1 is a new allotype, while allotypes alpha M2--alpha M5 correspond to four allotypes in the Gp system (Janik et al.). Based on these data, a conclusion was made on the homology between the Lpm system in american mink and the Gp system in pig. Since the allotypes studied are the part of alpha-macroglobulins, a locus controlling them was designated the AM locus. We also find it more advantageous to apply the same name to the homologous locus in mink, instead of the Lpm used earlier. Genetic control of 5 allotypes was studied and the structure of the AM locus in pig analysed in detail. Comparative study of organization of the above locus and the homologous locus in mink was carried out.     

Localization of the multigene Lpm locus in chromosome 9 of the American mink

The results of genetic study on linkage of Lpm locus with peptidase B gene are presented. Investigation of 111 offspring back-crosses shows that Lpm allotypes and allelic variants of peptidase B are inherited in concert. The frequency of recombination between the Lpm locus and peptidase B gene is 11 +/- 3% in male. Since it was earlier established that peptidase B gene is a marker of chromosome 9, our data indicate that the Lpm loci family is situated in the chromosome 9 of domestic mink.     

Immunogenetics of immunoglobulins of the American mink. VI. Deviation from Mendelian segregation for Cgamma-allotypes H2, H3 and H4

The non-expression of parental allotype among mink F1 offsprings of monohybrid analyzing crosses was established for C gamma-allotypes. A phenotype ratio 0:1, instead of the expected Mendelian 1:1, was observed in some families. The non-expression of allotype may occur in the progeny of mink with normal allotypic specificity. Deviations of allotypic expression had both qualitative and quantitative nature and did not depend on the direction of crossings. Sometimes, the appearance of allotype in a mink could not be expected on the basis of its pedigree. Instability of expression and inheritance of H2, H3 and H4 in many families may have masked the allelic or linkage relationships of these genetic markers.     

Genetic control over 7 Lpm-system allotypes of very high-density serum alpha2-lipoprotein the mink]

Population and hybridological analyses have demonstrated that the alloantigenic markers of very high density alpha2-lipoprotein of mink serum, Lpm7 and Lpm8, along with Lpm1, Lpm2, Lpm3, Lpm4, Lpm5, belong to a common immunogenetic system. 21 Lpm-phenotypes are determined at least by 36 genotypes; each of the 11 phenotypes is conditioned by a single genotype, each of the remaining 10 are conditioned by 2, 3 or 4 genotypes. The Lpm allotypes and allogroups are coded by the genetic units Lpm8, Lpm4, Lpm4,8, Lpm4,7, Lpm3,4,8, Lpm1,8, Lpm1,2,7, Lpm2,4,5,7, which behave as alleles. The last, six seem to be haploid sets of closely linked genes.     

Genetic variability of antigenic structure of the Lpm-protein and alpha2-macroglobulin among non-mustelid mammals

The data on interspecific distribution and antigenic variability of homologues of mink Lpm-protein (Lpm) and alpha 2M-globulin (alpha 2M) among 43 species of 6 orders of mammals are presented. Strong variability of antigenic structure of Lpm and alpha 2M of Rodentia and Artiodactyla orders was established. This fact allows to classify the macroglobulins studied as belonging to the group of evolutionary high-speed plasma globulins. In the plasma of human and green marmoset (Cercopithecus aephiops) the only homologue of alpha 2M was found. The lack of reaction to Lpm in above-mentioned species allows to postulate significant differences between Carnivora and Primates in the organization of this gene cluster. Unique features of antigenic variability of Lpm and alpha 2M were also fixed among other systematical groups tested. Taken together, the data obtained stimulate scientific interest to the study of molecular organization of the Lpm and alpha 2M gene families.     

Identification of the mink alpha2-lipoprotein Lpm-allotypes by the method of preparatory ultracentrifugation]

The density class accessory of 8 mink alpha2-lipoprotein allotypes are determined by means of preparative ultracentrifugation. It is found that Lpm1, Lpm2, Lpm2, Lpm3, Lpm4, Lpm5, Lpm7 and Lpm8 are determinants of lipoproteins with density exceeding 1.210, i.e. they are VHDL. The allotypic marker 6, which has been earlier assigned by other criteria to Lpm group, belongs to mink lipoprotein, which distributes during ultracentrifugation at the region of low and, partially, high density.     

3 new allotypes of mink blood serum alpha2-lipoproteins--Lpm 6, Lpm 7, Lpm 8]

Three new allotypes were discovered in mink sera by means of isoimmunization. Based on the results of identifications, they were referred to the Lpm system of serum alpha2-lipoprotein. They were designated as Lpm 6, Lpm 7 and Lpm 8. The allotyping of serum samples from 342 minks made possible to establish a relation between Lpm 7 and Lpm 8 using the chi2 method; it was also found that these two allotypes related to each of the first five Lpm as well as to their phenotypes, which was described earlier. There was a significant dependence of the expression of Lpm 6 on Lpm 5 indicating a genetic relation between Lpm 6 and other allotypes. The detection of Lpm 6, 7 and 8, which are the most likely under the control of the same gene (or a sustem of genes) as Lpm 1, 2, 3 and 5, is an evidence for the complex structure of the Lpm locus.     

Immunogenetic study on the polymorphism of serum α2-lipoprotein in mink. III. Ld1 allotype of low-density lipoprotein

Mink Ld1 antigen of serum low-density lipoprotein was demonstrated by alloantibodies. No genetic relation was found between Ld1 and the Lpm system of very-high-density lipoprotein. The existence of an autosomal dominant gene, coding for the new alloantigenic marker, is postulated on the basis of mink breeding data.     

Distribution of alpha 2M-globulin and Lpm-protein in the organs and tissues of the American mink

Distribution in the organs and tissues of two proteins of alpha-macroglobulin fraction, that differ in their antigenic structures, has been studied in the American mink. The both proteins (alpha 2M and Lpm) are present in hepatocytes, in cells of the follicular epithelium of the ovary, in the thymic bodies, in the alveolar macrophages of the lungs and in the splenic lymphoid nodes. Joint localization of alpha 2M and Lpm is revealed in the connective tissue of all the organs examined. The exception make the stomach and the uterine, where alpha 2M is revealed but not Lpm. The results obtained demonstrate a similar distribution of the two alpha-macroglobulins in the mink organism. They correspond to the literature data on morphofunctional topography of alpha 2M in the man. Certain individual differences in alpha 2M and Lpm localization can reflect peculiarities inherent in each of these alpha-macroglobulins of the American mink.     

Immunogenetic polymorphism of lipoproteins in swine

Five new antigenic markers (allotypes) of swine serum lipoproteins are described. Specific antiallotype reagents were obtained from alloimmune precipitating sera. Identification studies and genetic analysis indicate that the five serum alloantigens—designated Lpp6, Lpp11, Lpp12, Lpp13, and Lpp14—are markers of low-density lipoproteins (LDL),d 1.002–1.075 g/ml, and are members of a previously described Lpp system. The Lpp6 allotype belongs to the group of individual markers and is determined by a new codominant allelic gene,Lpp ⁶, whereas the remaining four antigens—Lpp11, Lpp12, Lpp13, and Lpp 14—named common specificities, behave as alternative variants to Lpp1, Lpp2, Lpp3, and Lpp4, respectively, forming pairs of mutually exclusive alloantigens. Each Lpp gene in a heterozygous animal expresses itself independently on separate molecules and each haplotype carries one individual and at least four common specificities. The relationship between common and individual specificities, together with their number in the complex haplotypes, seems to shed some light on evolution of Lpp genes. It is proposed in this concept that the original gene for low-density lipoproteins in swine, and also in rhesus monkeys and the human, consisted of genetic information for common specificities only, the individual specificities evolving later as a result of point mutations.     

Immunogenetics of immunoglobulins in domestic mink. VII. Features of phenotypic expression of gamma-heavy chain constant region allotypes mask linkage of IgCH genes]

Reduced expressivity and penetrance of allotypes H2-H4 and the regulation of allotype H6 expression by regulatory gene concealed the linkage of mink C genes in statistical analyses. Their linkage was demonstrated by di- and polyhybrid test crosses with 3, 4 and more generations.     

Genetic structure of Eurasian and North American mallard ducks based on mtDNA data

To elucidate the origin and genetic structure of the domesticated duck in Eurasia and North America, we sequenced 114 duck D-loop sequences and retrieved 489 D-loop sequences from GenBank. In total, 603 ducks including 50 duck breeds/populations from eight countries (China, France, Russia, India, Kazakhstan, Mongolia, Thailand and USA) were used in this study. One hundred and thirty-four haplotypes and 81 variable sites were detected. H49 was the predominant haplotype, which was considered to be the same dominant haplotype found in the previous studies, and was found in 309 birds. The smallest values for both genetic differentiation index (F(ST), 0.04156) and the number of the net nucleotide substitutions between two populations (D(A), 0.00018) were observed between Eurasian domestic ducks and Eurasian mallards. No geography, breed or population clusters were observed in the Eurasian domestic ducks and mallards. Five haplotypes were shared by USA mallards and Eurasian domestic duck/Eurasian mallards. Only one haplotype (H49) was shared by Eurasian domestic ducks and China spot-billed ducks. By combining phylogenetic analyses, haplotype network profile, genetic distances and shared haplotypes, we can draw two major conclusions: (i) Eurasian and North American mallards show a clear geographic distribution pattern; (ii) Eurasian domestic ducks are derived from the Eurasian mallards, not from the spot-billed ducks.     

Study of the Lpm-system of mink allotypes in relation to Aleutian mink disease

Data on comparative study of the Lpm system of allotypes in minks of sovkhoz populations affected and nonaffected by Aleutian disease are presented. Significant interpopulational differences for frequencies of several Lpm genes of the second category (of corresponding haplo-, allo- and phenotypes) are revealed. This category includes genes species-specific for Mustela vison which make the main contribution to Lpm polymorphism. Seven minks with Lpm 3, 4, 6, 9, 10, 11 and Lpm 3, 4, 6, 7, 9, 10, 11 phenotypes, unknown earlier, have been found in the stationary hotbeds of Aleutian disease. They are most probably caused by the appearance and spreading of the recombinant haplotype Lpm in these populations. The data obtained are discussed from the point of view of their possible connection with epizootic of Aleutian disease.     

Polymorphisms of mitochondrial ATPase 8/6 genes and association with milk production traits in holstein cows

The maternal effect has been widely proposed to affect the production traits in domestic animals. However, the sequence polymorphisms of mitochondrial DNA (mtDNA) and association with milk production traits in Holstein cows have remained unclear. In this study, we investigated the single nucleotide polymorphisms (SNPs) of mtDNA ATPase 8/6 genes and association with four milk production traits of interest in 303 Holstein cows. A total of 18 SNPs were detected among the 842?bp fragment of ATPase 8/6 genes, which determined six haplotypes of B. taurus (H1-H4) and B. indicus (H5-H6). The mixed model analysis revealed that there was significant association between haplotype and 305-day milk yield (MY). The highest MY was observed in haplotype H4. However, we did not detect statistically significant differences among haplotypes for the traits of milk fat (MF), milk protein (MP), and somatic cell count (SC). The overall haplotype diversity and nucleotide diversity of ATPase 8/6 genes were 0.563?±?0.030 and 0.00609?±?0.00043, respectively. The results suggested that mitochondrial ATPase 8/6 genes could be potentially used as molecular marker to genetically improve milk production in Holstein cows.     

Identification and genetic control of the Ld1-allotype of mink low-density serum lipoprotein]

Ld1, an antigen of serum low density lipoprotein, was identified by means of mink alloimmunization. No genetic relation was established between Ld1 and the Ipm-system of very high density lipoprotein. Based on the analysis of breeding data, the existence of an autosomal dominant gene, Ld1+, is postulated. This gene codes for the new alloantigenic marker. The existence of at least one other allotype of the Ld-system is suggested.     

The Igh-V locus of MRL mice: restriction fragment length polymorphism in eleven strains of mice as determined with VH and D gene probes

The MRL strain of mice is a model system that closely parallels the human autoimmune disease systemic lupus erythematosus. Our analysis of the variable region genes of MRL mice showed that the MRL/lpr D genes were similar to those of the C3H mouse (Igh-C allotype j). This result was unexpected, because previous studies of the MRL/lpr and MRL/+ substrains suggested that they are allotype a at the Igh-1 (gamma 2a) locus of the constant region. The Igh-V (heavy chain variable region) locus of the MRL/lpr and MRL/+ strains of mice and their parents were therefore examined by restriction fragment length polymorphism with probes for the DSP2 and DFL16 gene families and with two cloned VH probes. Five other strains of mice were also included because the heavy chain locus of the LG mouse, which is the major progenitor of the MRL strains, has not been studied. The MRL substrains and the LG and C3H parents were indistinguishable at all the Igh-V loci studied. These results suggest that the MRL substrains and their LG parent are haplotype j at the Igh-V locus. The results obtained with D gene probes show that the DSP2 gene family is more polymorphic than the DFL16 gene family, which is relatively conserved. We have assigned Igh-V haplotypes for the four VH loci to the 11 strains of mice studied.     

Genetics and evolution of the mink Lpm-system. VIII. Characteristic changes in the antigenic structure of Lpm-protein and alpha2- macroglobulin in Mustelidae family

Interspecific variability of the isotypic structure of two macroglobulins (Lpm and alpha 2M) in Mustelidae family was investigated using monospecific rabbit antisera against Lpm and alpha 2M Mustela vison. It was established that all the species studied may be divided into four groups, according to the degree of their homology with Lpm: 1) M. vison; 2) M. altaica, M. erminea, Kolonocus sibirica, Putorius eversmany, P. putorius, Luteola lutreola; 3) Vormela peregusna; 4) Martes martes, M. foina, M. zibellina. The greatest divergence of Martes gene species from M. vison and other species studied is determined by two different immunogenetic approaches, the first based on the whole isotype of Lpm and the other using allotypic markers of individual Lpm genes. The variability of the isotypic structure of alpha 2M was lower than that revealed in Lpm. V. peregusna is the only species which significantly differs from all above-mentioned species, including M. vison. The differences established for degree of variability between Lpm and alpha 2M in Mustelidae family may be connected with the evolutionary peculiarities of these two genetic system of serum alpha-macroglobulins, which being phylogenetically related, are still structurally divergent.     

Origin and domestication history of Peking ducks deltermined through microsatellite and mitochondrial marker analysis

In order to elucidate the domestication history of Peking ducks, 190 blood samples from six Chinese indigenous duck breeds were collected with186 individualsgenotyped by 15 microsatellite markers. Both the F_ST and Nei’s standard genetic distances (D_s) from the microsatellite data indicated high genetic differentiation between Peking duck and other Chinese indigenous breeds. The haplotype network with mtDNA data showed that most of the Peking duck haplotypes were distinctly different from those of other domestic breeds. Although the H01 haplotype was shared by all domesticated duck breeds, Peking ducks displayed 12 specific domestic duck haplotypes, including four similar haplotypes H02, H04, H08 and H22, that formed a single haplogroup (A). Both H02 and H22 haplotypes were also shared by mallard and Peking ducks, indicating that Peking ducks originated from wild mallard ducks.     

Genetic sophistication of human complement components C4A and C4B and RP-C4-CYP21-TNX (RCCX) modules in the major histocompatibility complex

Human populations are endowed with a sophisticated genetic diversity of complement C4 and its flanking genes RP, CYP21, and TNX in the RCCX modules of the major histocompatibility complex class III region. We applied definitive techniques to elucidate (a) the complement C4 polymorphisms in gene sizes, gene numbers, and protein isotypes and (b) their gene orders. Several intriguing features are unraveled, including (1) a trimodular RCCX haplotype with three long C4 genes expressing C4A protein only, (2) two trimodular haplotypes with two long (L) and one short (S) C4 genes organized in LSL configurations, (3) a quadrimodular haplotype with four C4 genes organized in a SLSL configuration, and (4) another quadrimodular structure, with four long C4 genes (LLLL), that has the human leukocyte antigen haplotype that is identical to ancestral haplotype 7.2 in the Japanese population. Long-range PCR and PshAI-RFLP analyses conclusively revealed that the short genes from the LSL and SLSL haplotypes are C4A. In four informative families, an astonishingly complex pattern of genetic diversity for RCCX haplotypes with one, two, three and four C4 genes is demonstrated; each C4 gene may be long or short, encoding a C4A or C4B protein. Such diversity may be related to different intrinsic strengths among humans to defend against infections and susceptibilities to autoimmune diseases.     

Isolation and purification of Lpm and alpha-2 M macroglobulins from mink serum]

A procedure for large-scale separation and purification of two mink serum macroglobulins, Lpm and alpha 2M, is described. Individual preparations of each of these macroglobulins were obtained in an immunologically pure state. After precipitation from the serum at 6.5-13% PEG 6000, Lpm and alpha 2M were separated by a pH stepwise gradient elution metal chelate affinity chromatography and purified by chromatographies on Biogel A 1.5 m and DEAE-Trisacryl M. Each of these macroglobulins was tested by counter-immunoelectrophoresis with the corresponding monospecific antiserum. The yields per 100 ml of the source serum were 23-44 mg of Lpm and 7-30 mg of alpha 2M which corresponded to 10-20% of their serum contents. Some of general biochemical properties of mink Lpm and alpha 2M and of all mammalian alpha-macroglobulins are discussed.