Strong selection signatures for Aleutian disease tolerance acting on novel candidate genes linked to immune and cellular responses in American mink (Neogale vison).

Aleutian disease (AD) is a multi-systemic infectious disease in American mink (Neogale vison) caused by Aleutian mink disease virus (AMDV). This study aimed to identify candidate regions and genes underlying selection for response against AMDV using whole-genome sequence (WGS) data. Three case-control selection signatures studies were conducted between animals (N = 85) producing high versus low antibody levels against AMDV, grouped by counter immunoelectrophoresis (CIEP) test and two enzyme-linked immunosorbent assays (ELISA). Within each study, selection signals were detected using fixation index (FST) and nucleotide diversity (θπ ratios), and validated by cross-population extended haplotype homozygosity (XP-EHH) test. Within- and between-studies overlapping results were then evaluated. Within-studies overlapping results indicated novel candidate genes related to immune and cellular responses (e.g., TAP2, RAB32), respiratory system function (e.g., SPEF2, R3HCC1L), and reproduction system function (e.g., HSF2, CFAP206) in other species. Between-studies overlapping results identified three large segments under strong selection pressure, including two on chromosome 1 (chr1:88,770-98,281 kb and chr1:114,133-120,473) and one on chromosome 6 (chr6:37,953-44,279 kb). Within regions with strong signals, we found novel candidate genes involved in immune and cellular responses (e.g., homologous MHC class II genes, ITPR3, VPS52) in other species. Our study brings new insights into candidate regions and genes controlling AD response.

Genetic and phenotypic correlations between Aleutian disease tests with body weight, growth, and feed efficiency traits in mink.

The ineffectiveness of vaccination, medicine, and culling strategy leads mink farmers to control Aleutian disease (AD) by selecting AD-resilient mink based on AD tests. However, the genetic background of AD tests and their correlations with economically important or AD-resilient traits are limited. This study estimated the genetic and phenotypic correlations between four AD tests and seven body weight (BW) traits, six growth parameters from the Richards growth model, and eight feed-related traits. Univariate models were used to test the significance (P < 0.05) of fixed effects (sex, color type, AD test year, birth year, and row-by-year), random effects (additive genetic, maternal genetic, and permanent environmental), and a covariate of age using ASReml 4.1. Likewise, pairwise bivariate analyses were conducted to estimate the phenotypic and genetic correlations among the studied traits. Both antigen- and virus capsid protein-based enzyme-linked immunosorbent assay tests (ELISA-G and ELISA-P) showed significant (P < 0.05) moderate positive genetic correlations (±SE) with maturation rate (from 0.36 ± 0.18 to 0.38 ± 0.19). ELISA-G showed a significant negative genetic correlation (±SE) with average daily gain (ADG, -0.37 ± 0.16). ELISA-P showed a significant positive moderate genetic correlation (±SE) with off-feed days (DOF, 0.42 ± 0.17). These findings indicated that selection for low ELISA scores would reduce the maturation rate, increase ADG (by ELISA-G), and minimize DOF (by ELISA-P). The iodine agglutination test (IAT) showed significant genetic correlations with DOF (0.73 ± 0.16), BW at 16 weeks of age (BW16, 0.45 ± 0.23), and BW at harvest (HW, -0.47 ± 0.20), indicating that selection for lower IAT scores would lead to lower DOF and BW16, and higher HW. These estimated genetic correlations suggested that the selection of AD tests would not cause adverse effects on the growth, feed efficiency, and feed intake of mink. The estimates from this study might strengthen the previous finding that ELISA-G could be applied as a reliable and practical indicator trait in the genetic selection of AD-resilient mink in AD-positive farms.

The selection of Aleutian disease-resistant individuals based on Aleutian disease (AD) tests is seen as a potential method to control AD effectively. However, the knowledge regarding the genetic background of AD tests is limited. This study estimated the genetic and phenotypic correlations between Aleutian disease tests and body weight, growth, and feed-related traits in mink. The estimates in this study indicated that the growth, feed efficiency, and feed intake of mink would not be adversely influenced by the selection of AD tests. In the meantime, the estimates further illustrate that the antigen-based enzyme-linked immunosorbent assay test could be applied as the most reliable and practical indicator trait to select AD-resilient mink in AD-positive farms.

Detection of selection signatures for response to Aleutian mink disease virus infection in American mink.

Aleutian disease (AD) is the most significant health issue for farmed American mink. The objective of this study was to identify the genomic regions subjected to selection for response to infection with Aleutian mink disease virus (AMDV) in American mink using genotyping by sequencing (GBS) data. A total of 225 black mink were inoculated with AMDV and genotyped using a GBS assay based on the sequencing of ApeKI-digested libraries. Five AD-characterized phenotypes were used to assign animals to pairwise groups. Signatures of selection were detected using integrated measurement of fixation index (FST) and nucleotide diversity (θπ), that were validated by haplotype-based (hap-FLK) test. The total of 99 putatively selected regions harbouring 63 genes were detected in different groups. The gene ontology revealed numerous genes related to immune response (e.g. TRAF3IP2, WDR7, SWAP70, CBFB, and GPR65), liver development (e.g. SULF2, SRSF5) and reproduction process (e.g. FBXO5, CatSperß, CATSPER4, and IGF2R). The hapFLK test supported two strongly selected regions that contained five candidate genes related to immune response, virus-host interaction, reproduction and liver regeneration. This study provided the first map of putative selection signals of response to AMDV infection in American mink, bringing new insights into genomic regions controlling the AD phenotypes.

Application of real-time PCR to detect Aleutian Mink Disease Virus on environmental farm sources.

The Aleutian Mink Virus (AMDV) causes the Aleutian Mink Disease (AMD) or Mink Plasmacytosis, a disease responsible of high economic losses for industry worldwide. Despite there is evidence of the environmental persistence of the virus, there is not literature on the detection of this virus in environmental samples in farms and this fact would have great importance in the control programs of the disease. In order to detect contamination caused by AMDV on farms, several environmental samples were taken and examined using qPCR. 93.9% of samples taken from farms confirmed to be infected tested positive. The virus was also detected on a farm which, despite having no previous positive results, was sharing personnel with an infected farm. All samples taken from AMD-free farms tested negative, including a farm where an eradication procedure by stamping out had been performed during the preceding months. Higher contamination levels were observed in samples from those surfaces in direct contact with animals. These results are the first demonstration of environmental contamination in farms, hitherto suggested by epidemiological evidences, caused by AMDV on surfaces, furniture and equipments inside mink farms. qPCR is an useful tool for evaluating the spread of AMDV into the environment, and it may have important applications within the disease control programs.

A frameshift mutation in the LYST gene is responsible for the Aleutian color and the associated Chédiak-Higashi syndrome in American mink.

One of the colors of mink is Aleutian (aa)-a specific gun-metal gray pigmentation of the fur-commonly used in combination with other color loci to generate popular colors such as Violet (aammpp) and Sapphire (aapp). The Aleutian color allele is a manifestation of mink Chédiak-Higashi syndrome (CHS), which has been described in humans and several other species. As with forms of CHS in other species, we report that the mink CHS is linked to the lysosomal trafficking regulator ( LYST ) gene. Furthermore, we have identified a base deletion (c.9468delC) in exon 40 of LYST, which causes a frameshift and virtually terminates the LYST product prematurely (p.Leu3156Phefs*37). We investigated the blood parameters of three wild-type mink and three CHS mink. No difference in the platelet number between the two groups was observed, but an accumulation of platelets between the groups appears different when collagen is used as a coagulant. Microscopic analysis of peripheral blood indicates giant inclusions in the neutrophils of the Aleutian mink types. Molecular findings at the LYST locus enable the development of genetic tests for analyzing the color selection in American mink.

Chediak-Higashi syndrome.

PURPOSE OF REVIEW: Chediak-Higashi syndrome, a rare autosomal recessive disorder, was described over 50 years ago. Patients show hypopigmentation, recurrent infections, mild coagulation defects and varying neurologic problems. Treatment is bone marrow transplant, which is effective in treating the hematologic and immune defects, however the neurologic problems persist. The CHS1/LYST gene was identified over 10 years ago and homologous CHS1/LYST genes are present in all eukaryotes. This review will discuss the advances made in understanding the clinical aspects of the syndrome and the function of CHS1/LYST/Beige. RECENT FINDINGS: Clinical reports of Chediak-Higashi syndrome have identified mutations throughout the CHS1/LYST gene. The nature of the mutation can be a predictor of the severity of the disease. Over the past decade the CHS1/LYST family of proteins has been analyzed using model organisms, two-hybrid analysis, overexpression phenotypes and dominant negatives. These studies suggest that the CHS1/LYST protein is involved in either vesicle fusion or fission. SUMMARY: Although CHS is a rare disease, the Chediak-like family of proteins is providing insight into the regulation of vesicle trafficking. Understanding the basic mechanisms that govern vesicle trafficking will provide essential information regarding how loss of CHS1/LYST affects hematologic, immunologic and neurologic processes.

The abundant R2 mRNA generated by aleutian mink disease parvovirus is tricistronic, encoding NS2, VP1, and VP2.

The abundant R2 mRNA encoded by the single left-end promoter of Aleutian mink disease parvovirus is tricistronic; it not only expresses the capsid proteins VP1 and VP2 but is also the major source for the nonstructural protein NS2. A cis-acting sequence within the NS2 gene was shown to be required for efficient capsid protein production, and its effect displayed a distinct location dependence. Ribosome transit through the upstream NS2 gene region was necessary for efficient VP1 and VP2 expression; however, neither ablation nor improvement of the NS2 initiating AUG had an effect on capsid protein production, suggesting that the translation of the NS2 protein per se had little influence on VP1 and VP2 expression. Thus, proper control of the alternative translation of the tricistronic R2 mRNA, a process critical for viral replication, is governed in a complex manner.

[Some molecular-biological and immunological aspects of Aleutian disease of mink]. / Nekotorye molekuliarno-biologicheskie i immunologichskie aspekty patogeneza Aleutskoi bolezni norok.

Information on the development of the infectious process in the Aleutian disease of minks (ADM) on the molecular level, are updated. In particular, the decisive role played by the ABM virus infection of the cells of the immune system (B lymphocytes, macrophages, follicular dendritic cells) and the possible involvement of the mechanism of the antibody-dependent aggravation of this infection are pointed out. In addition, the role of the weak ADM virus promoter p36, the immune status of minks and their age in the determination of the acute or "slow" character of the course of the disease are considered.

Nucleotide sequence and polymerase chain reaction/restriction fragment length polymorphism analyses of Aleutian disease virus in ferrets in Japan.

Two ferrets with spontaneous Aleutian disease (AD) were found in Japan. The diagnosis was verified by polymerase chain reaction (PCR) amplification of part of the capsid gene specific to AD virus (ADV). The nucleotide sequences (365 bp in length) of the amplified fragments from the 2 ferrets differed by a single nucleotide, producing an amino acid alteration. Compared with other types of ADV, these isolates had 96% sequence similarity to a published ferret ADV (FADV) in contrast to <91% homology to various types of mink ADV (MADV). The phylogenetic tree of ADVs indicates that these 2 isolates and the published FADV belong to the same genetic group and definitely are divergent from MADVs. The predicted amino acid sequence of the hypervariable segment in the capsid gene was conserved among the 3 types of FADV. These results indicated that the 2 isolates found in Japan were new DNA types of FADV and could have been derived from FADV(s). A restriction fragment length polymorphism (RFLP) method to distinguish the ferret types of ADV from the mink types of ADV was developed on the basis of differences in their nucleotide sequences. Digestion of the PCR products with Afal or ScaI provided different cleavage patterns for FADV and MADV. This PCR/RFLP analysis of the ADV capsid gene will be a valuable asset for diagnosis of this virus infection in ferrets.

Pathogenesis of Aleutian mink disease parvovirus infection: effects of suppression of antibody response on viral mRNA levels and on development of acute disease.

We suppressed the B-cell development and antibody response in mink by using treatment with polyclonal anti-immunoglobulin M (anti-IgM) to study the effects of antiviral antibodies on development of Aleutian mink disease parvovirus (ADV)-induced disease in more detail. Newborn mink kits were injected intraperitoneally with 1 mg of either anti-IgM or a control preparation three times a week for 30 to 34 days. At 21 days after birth, groups of mink kits were infected with the highly virulent United isolate of ADV. At selected time points, i.e., postinfection days 9, 13, 29, and 200, randomly chosen mink kits were sacrificed, and blood and tissues were collected for analyses. The efficacy of immunosuppressive treatment was monitored by electrophoretic techniques and flow cytometry. Effects of treatment on viral replication, on viral mRNA levels, and on development of acute or chronic disease were determined by histopathological, immunoelectrophoretic, and molecular hybridization techniques. Several interesting findings emerged from these studies. First, antiviral antibodies decreased ADV mRNA levels more than DNA replication. Second, suppression of B-cell development and antibody response in mink kits infected at 21 days of age resulted in production of viral inclusion bodies in alveolar type II cells. Some of these kits showed mild clinical signs of respiratory disease, and one kit died of respiratory distress; however, clinical signs were seen only after release of immunosuppression, suggesting that the production of antiviral antibodies, in combination with the massive amounts of free viral antigen present, somehow is involved in the induction of respiratory distress. It is suggested that the antiviral antibody response observed in mink older than approximately 14 days primarily, by a yet unknown mechanism, decreases ADV mRNA levels which, if severe enough, results in restricted levels of DNA replication and virion production. Furthermore, such a restricted ADV infection at low levels paves the way for a persistent infection leading to immunologically mediated disease. The potential mechanisms of antibody-mediated restriction of viral mRNA levels and mechanisms of disease induction are discussed.

Comparison of promoter activity in Aleutian mink disease parvovirus, minute virus of mice, and canine parvovirus: possible role of weak promoters in the pathogenesis of Aleutian mink disease parvovirus infection.

Aleutian mink disease parvovirus (ADV) infection causes both acute and chronic disease in mink, and we have previously shown that it is the level of viral gene expression that determines the disease pattern. To study the gene regulation of ADV, we have cloned the P3 ADV and P36 ADV promoters in front of a reporter gene, the chloramphenicol acetyltransferase (CAT) gene, and analyzed these constructs by transient transfection in a feline kidney cell line and mouse NIH 3T3 cells. The genes for ADV structural proteins (VP1 and VP2) and the nonstructural proteins (NS-1, NS-2, and NS-3) were cloned into a eukaryotic expression vector, and their functions in regulation of the P3 ADV and P36 ADV promoters were examined in cotransfection experiments. The ADV NS-1 protein was able to transactivate the P36 ADV promoter and, to a lesser degree, the P3 ADV promoter. Constitutive activities of the P3 ADV and P36 ADV promoters were weaker than those of the corresponding promoters from the prototypic parvovirus minute virus of mice (MVM) and canine parvovirus (CPV). Also, the level of transactivation of the P36 ADV promoter was much lower than those of the corresponding P38 MVM and P38 CPV promoters transactivated with MVM NS-1. Moreover, the ADV NS-1 gene product could transactivate the P38 MVM promoter to higher levels than it could transactivate the P36 ADV promoter, while the P36 ADV promoter could be transactivated by MVM NS-1 and ADV NS-1 to similar levels. Taken together, these data indicated that cis-acting sequences in the P36 ADV promoter play a major role in determining the low level of transactivation observed. The P3 ADV and P4 MVM promoters could be transactivated to some degree by their respective NS-1 gene products. However, in contrast to the situation for the late promoters, switching NS-1 proteins between the two viruses was not possible. This finding may indicate a different mechanism of transactivation of the early promoters (P3 ADV and P4 MVM) compared with the late (P36 ADV and P38 MVM) promoters. In summary, the constitutive levels of expression from the ADV promoters are weaker than the levels from the corresponding promoters of MVM and CPV. Moreover, the level of NS-1-mediated transactivation of the late ADV promoter is impaired compared with the level of transactivation of the late promoters of MVM and CPV.(ABSTRACT TRUNCATED AT 400 WORDS)

Expression of Aleutian mink disease parvovirus capsid proteins by a recombinant vaccinia virus: self-assembly of capsid proteins into particles.

A portion of a cDNA clone containing coding sequences for both structural proteins (VP1 and VP2) of Aleutian mink disease parvovirus (ADV) was inserted into recombinant vaccinia viruses, VV:ADSP. Immunohistochemical staining of VV:ADSP-infected cells revealed that the ADV antigen was readily detected and localized in the nuclei of infected cells. Analysis of VV:ADSP-infected cell lystates indicated that both VP1 and VP2 were produced and comigrated with authentic VP1 and VP2 from ADV-infected Crandell feline kidney cells. These results suggested, therefore, that both VP1 and VP2 were synthesized from a single cloned transcript. CsCl density gradient centrifugation of partially purified VV:ADSP-infected cell lysates indicated that the majority of the antigen was located in a fraction with a density near 1.33 g/ml, indicative of empty ADV particles. Subsequent electron microscopic examination revealed the presence of 27-nm icosahedral virion-like structures at the same density, suggesting that the proteins self-assembled into empty virions. Furthermore, sera from eight of eight mice inoculated with VV:ADSP contained ADV-specific antibodies and two of these eight serum samples had neutralizing activity, indicating that the particles produced in VV:ADSP-infected cells were immunogenic. Finally, when lysates from VV:ADSP-infected cells were compared with standard ADV antigens in counterimmunoelectrophoresis assays, a similar pattern of specific reactivity was observed for sera from normal and infected mink.

[Activation of expression of two immunoglobulin SN-genes in the American mink with Aleutian disease]. / Aktivatsiia ékspressii dvukh SN-genov immunoglobulinov amerikanskoi norki pri aleutskoi bolezni.

110 ranch-raised minks were injected with the Aleutian disease virus. Allotypes of constant regions of gamma-heavy chains of the mink immunoglobulins secreted have been analysed during 3 months. Activation of the expression of two markers (H3 and/or H4) up to minor or to nominal level (above 200 micrograms/ml) was observed. No such enhancement of expression of two other allotypes (H6 and H8) was found. The results suggest that the expression of two mink immunoglobulin CH genes induced by viral infection has allotype-specific regulation.

Genetic polymorphism of IgG in the mink. 7. Expression of the C gamma-allotypes in domestic mink infected with the Aleutian disease virus.

The Aleutian disease (AD), i.e., viral plasmocytosis in mink can be used as a model of the natural development of immune complex pathology in man. The immunogenetic aspect of AD was studied with the help of genetic markers of the constant region of the mink immunoglobulin gamma-heavy chain (the C gamma allotypes H2, H3, H4, H6, H7 and H8). The frequencies of 2 of the 6 allotypes, H3 and H4, were significantly higher in the AD-infected than in normal minks from the same population. This supports and extends the data in the literature indicating that the frequencies of certain human Gm allotypes are significantly higher among patients with multiple sclerosis, some oncological and other diseases compared with normal humans. Individual testing of 110 adult Standard minks before and after artificial inoculation with the AD virus demonstrated that change in allotype frequencies results from the activation of the expression of H3 and/or H4 in many individuals. The obtained results make it possible to consider the regulation of the expression of the two CH genes of immunoglobulins as allotype-specific.

[Mink IgG-allotypes and Aleutian disease]. / IgG-allotipy norok i aleutskaia bolezn'.

IgG polymorphism (allotypes H3, H4, H6 and H8 of constant region of the gamma-chain) was investigated in healthy and affected with Aleutian disease (AD) minks from two Siberian and one Danish populations. In all three populations, the expression of H3 and H4 allotypes was strongly associated with AD. Among the AD minks the frequency of H6, H8 phenotype was found to be decreased, whereas the frequency of H3, H4, H6, H8 phenotype was significantly increased. At the same time, the populational distribution of the rest phenotypes was similar among healthy and AD minks. The H3, H4, H6, H8 minks showed the highest pathomorphological characteristics of AD. Based on the data concerning mink H3 and H4, and human Gm allotypes, their role as possible genetic markers for hereditary susceptibility to distinct disease is discussed.

Analysis of parvovirus infections using strand-specific hybridization probes.

The autonomous parvoviruses cause a broad spectrum of acute and chronic infections of animals and man. The discrimination of sites of viral replication from sites of viral sequestration is an important goal in elucidating the pathogenesis of these diseases. It is possible to employ strand-specific RNA hybridization probes in such analyses because a 'plus' sense probe will react with single stranded virion DNA and duplex replicative form DNA, but a 'minus' sense probe will react preferentially with obligate replicative intermediates (duplex replicative form DNA and mRNA). Strand-specific RNA hybridization probes were developed for the Aleutian mink disease parvovirus (ADV) and were used to study acute and chronic infections of mink. Such probes were capable of differentiating replicative intermediates (duplex replicative form DNA and mRNA) from single-stranded virion DNA in Southern blot analysis and in strand-specific in situ hybridization. ADV infection of seronegative newborn mink kits causes an acute, cytopathic infection of type II alveolar cells. Replication in these cells is highly permissive and is characterized by high levels of replicative intermediates and virion DNA. A fatal respiratory distress syndrome and hyaline membrane formation result from impaired surfactant production by the infected type II cells. On the other hand, ADV infection of adult mink is associated with a persistent infection and a disorder of the immune regulation. The target cells for viral replication in adult mink are confined to the lymphoid system and the bone marrow. Replication in these cells, which are probably lymphocytes, is restricted, and characterized by greatly reduced levels of replicative intermediates and virion DNA. It, therefore, seems that disease in the infected adult mink results from a restricted infection by ADV. Large amounts of virion DNA can also be demonstrated in locations where replication cannot be detected and apparently represents sequestration of virion particles by elements of the reticuloendothelial system. Thus, replication and sequestration can, in fact, be distinguished by the strand-specific in situ hybridization. These studies indicate that strand-specific in situ hybridization is a potentially valuable method for studying the pathogenesis of parvovirus infections.

[Study of the Lpm-system of mink allotypes in relation to Aleutian mink disease]. / Issledovanie Lpm-sistemy allotipov norki v sviazi s aleutskoi bolezn'iu.

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.

Analysis of Aleutian disease virus infection in vitro and in vivo: demonstration of Aleutian disease virus DNA in tissues of infected mink.

Aleutian disease virus (ADV) infection was analyzed in vivo and in vitro to compare virus replication in cell culture and in mink. Initial experiments compared cultures of Crandell feline kidney (CRFK) cells infected with the avirulent ADV-G strain or the highly virulent Utah I ADV. The number of ADV-infected cells was estimated by calculating the percentage of cells displaying ADV antigen by immunofluorescence (IFA), and several parameters of infection were determined. Infected cells contained large quantities of viral DNA (more than 10(5) genomes per infected cell) as estimated by dot-blot DNA-DNA hybridization, and much of the viral DNA, when analyzed by Southern blot hybridization, was found to be of a 4.8-kilobase-pair duplex monomeric replicative form (DM DNA). Furthermore, the cultures contained 7 to 67 fluorescence-forming units (FFU) per infected cell, and the ADV genome per FFU ratio ranged between 2 X 10(3) and 164 X 10(3). Finally, the pattern of viral antigen detected by IFA was characteristically nuclear, although cytoplasmic fluorescence was often found in the same cells. Because no difference was noted between the two virus strains when cultures containing similar numbers of infected cells were compared, it seemed that both viruses behaved similarly in infected cell culture. These data were used as a basis for the analysis of infection of mink by virulent Utah I ADV. Ten days after infection, the highest levels of viral DNA were detected in spleen (373 genomes per cell), mesenteric lymph node (MLN; 750 genomes per cell), and liver (373 genomes per cell). In marked contrast to infected CRFK cells, the predominant species of ADV DNA in all tissues was single-stranded virion DNA; however, 4.8-kilobase-pair DM DNA was found in MLN and spleen. This observation suggested that MLN and spleen were sites of virus replication, but that the DNA found in liver reflected sequestration of virus produced elsewhere. A final set of experiments examined MLN taken from nine mink 10 days after Utah I ADV infection. All of the nodes contained ADV DNA (46 to 750 genomes per cell), and although single-stranded virion DNA was always the most abundant species, DM DNA was observed. All of the lymph nodes contained virus infectious for CRFK cells, but when the genome per FFU ratio was calculated, virus from the lymph nodes required almost 1,000 times more genomes to produce an FFU than did virus prepared from infected cell cultures.(ABSTRACT TRUNCATED AT 400 WORDS)

[Shift in the allele frequencies of the Ld locus in mink stock infected with Aleutian disease]. / Sdvig chastot allelei Ld-lokusa v stadakh norok, porazhennykh aleutskoi bolezn'iu.

An idea on organization of the Ld-system of low density lipoprotein in the domestic mink as on a "closed" immunogenetic system with two codominant alleles Ld1 and Ld2 was confirmed. Significant differences in frequencies of genes and genotypes of the Ld-system between state farm "populations" unaffected with Aleutian disease and those which were centres of this epizootic were established. The results obtained confirm the assumption made earlier on subvitality of the Ld2 gene.