ILAR Journal Online, Volume 39(2/3) 1998: Comparative Gene Mapping

Online Issues

<< All Back-issues

<< This Issue's Table of Contents

ILAR Journal V39(2/3) 1998
Comparative Gene Mapping

The American Mink Gene Map
O. L. Serov

O. L. Serov, Ph.D., is Head of the Laboratory of Developmental Genetics at the Institute of Cytology and Genetics, Academy of Sciences of Russia, Siberian Department, Novosibirsk, Russia.

INTRODUCTION

The American mink (Mustela vison) represents the large family Mustelidae. The family belongs to the order of Carnivora and includes many dozens of species living in a broad range of biotopes, from the Arctic to tropical zones.

Carnivores are of great interest in comparative gene mapping in mammals. Giemsa banding with trypsin analysis has shown that chromosome divergence in Mustelidae, despite the considerable variation in number and morphology of chromosomes, mainly resulted from rearrangements of virtually constant elements, probably representing the remains of an ancestral karyotype (Graphodatsky and others 1989; Wuster-Hill and Centerwall 1982). A similar situation was reported in the families Canidae and Ursidae (Graphodatsky and others 1995; Nash and O'Brien 1987; Wurster-Hill and Centerwall 1982). Moreover, the comparison of the Giemsa-banding chromosomes of Carnivora and species belonging to other orders--primates, rodents, or ungulates--demonstrated that in some cases there is a similarity in the Giemsa-banding patterns for large chromosome regions of the distantly related species (Graphodatsky 1989; Nash and O'Brien 1982). However, supplementary data on gene mapping are needed to decide whether this similarity reflects true homology and to reach reliable conclusions about the chromosome evolution of mammals (O'Brien and others 1993; Wakefield and Graves 1996).

For a long time, the efforts of mink breeders were focused on the identification of mutations affecting coat color genes. At the time of this writing, approximately 30 coat color mutations have been identified in mink. Most of them (at least 20) are controlled by independent autosomal loci (Nes and others 1988; Robinson 1975; Shackelford 1948). it is reasonable to expect that some of them are linked because a haploid set of mink chromosomes contains 14 autosomes plus the X or Y sex chromosome (Christensen and others 1996; Mandahl and Fredga 1975). However, there has been only I description of linkage of 2 coat color mutations, Ebony (Eb) and royal pastel (b) (Shackelford 1949). in this paper, I present the current state of gene mapping of mink, based on data obtained from traditional breeding, somatic cell hybridization, chromosome-mediated or interphase nuclei-mediated gene transfer procedures, and in situ hybridization.

CHROMOSOMAL LOCALIZATION OF MINK GENES USING SOMATIC CELL HYBRIDS

Chromosomal localization of mink genes was based mainly on the use of 2 panels of clones: mink-Chinese hamster hybrid cells (Rubtsov and others 1981) and mink-mouse hybrid cells (Pack and others 1992). Segregation analysis of mink chromosomes and markers in the hybrid cells made it possible to assign the mink genes to particular chromosomes. Assignment of a gene to a chromosome requires both a high level of concordant segregation of the gene and the chromosome and a sufficiently high level of discordant segregation of the gene and all other chromosomes (Cowmeadow and Ruddle 1978; Rubtsov and others 1981; Wijnen and others 1977). Segregation analysis of mink chromosomes in the panels of mink-rodent hybrids showed that the percentage of discordant clones for any chromosome pair was more than 20% (no fewer than 5 among 23 or 25 hybrid clones) (Pack and others 1992; Rubtsov and others 1981; Serov and others 1987). This degree of discordance rendered the panels reliably stable for gene mapping.

As seen in Figure 1, the mink gene map includes 77 genes, which mark all mink chromosomes except the Y. More than 30 gene assignments made with the panel of mink-Chinese hamster cell hybrids were also supported by results from another panel of mink-mouse hybrids. Only 2 previous chromosomal localizations, those of NP and PKM2, have been revised by these data (Pack and others 1992; Serov and Pack 1993).

REGIONAL ASSIGNMENTS OF MINK GENES

In mink, 21 genes have been regionally mapped on chromosomes 1, 2, 8, and X (Figure 1). These data were obtained from a variety of studies using different approaches.

Regional assignments of genes ME1, HK1, PP, GOT1, ADK, PGM1, PGD, ENO1, and G6PD were based on the use of the well-identified rearrangements of mink chromosomes 1, 2, and X (Pack and others 1992; Serov and others 1987; Zhdanova and others 1985, 1988). Two translocations involving mink chromosomes I and 8 were revealed in 2 mink-mouse hybrid clones of independent origin: t(1;8) (1qter-1 cen::8cen-8pter), containing the entire long arm of mink chromosome 1; and t(1;8) (1qter-1q21::8q24-p26), containing the distal part of the long arm of mink chromosome 1 (Pack and others 1992). No mink ME1 activity was detectable in the 2 clones, suggesting the assignment of the ME1 gene to the short arm of mink chromosome 1 (Pack and others 1992; Figure 1).

The different rearrangements of mink chromosome 2 have been identified by cytogenetic analysis of 2 mink cell lines (MV and MVTK cells) and a mink-Chinese hamster hybrid clone, CO113 (Rubtsov and others 1981; Serov and others 1987; Zhdanova and others 1985). Clone CO113 contained a large deletion that involved the 2p11-pter region of the short arm. In the clone, mink HKI, PP, GOT1, and ADK activities were not detected. These results made it possible to assign the genes HK1, PP, GOT1, and ADK to the short arm of chromosome 2 and the remaining genes (PGM1, ENO1, and PGD) to its long arm. A total of 105 subclones were derived from CO113 (Zhdanova and others 1985). Of these, mink PGD activity was present in 103; mink PGD, PGM1, and ENO1 were absent in 1 derivative; and in another derivative, mink PGM1 (but not PGD and ENO1) activity was detected. Cytogenetic analysis revealed a deletion 2q24.4-qter in the latter derivative, which allowed us to provisionally assign PGD and ENO1 to that region (Zhdanova and others 1985; Figure 1) and PGM1 to p11.1-q24.4 of mink chromosome 2 (Serov and others 1987). Subchromosomal localization of PP, GOT1, HK, and ADK was determined by a set of mink-mouse hepatoma clones (Serov and others 1987). The MVTK- cells (mink cells deficient in thymidine kinase) were fused with mouse hepatoma cells, BWTG, and 19 primary hybrid clones were isolated (Zhdanova and others 1985). MVTK- cells contained an intact chromosome 2 and a chromosome 2 containing a small deletion in the region 2p22-pter (Rubtsov and others 1981; Serov and others 1987; Zhdanova and others 1985). Among mink-mouse hepatoma hybrid clones, 13MV1 was found to contain an intact and a deleted mink chromosome 2. Fifteen secondary clones were derived from the clone 13MV1 (Zhdanova and others 1985). Because the segregation of mink PP, GOT1, and HK1 was concordant with the terminal region of the short arm, those 3 genes were provisionally assigned to 2pter-p22, whereas ADK was assigned to pter-p11.1 (Serov and others 1987; Zhdanova and others 1985; Figure 1).

The order of 4 X-linked genes in mink was established using the method developed by Goss and Harris (1977). Segregation of the mink markers (GALA, PGK1, HPRT, and G6PD) was analyzed in more than 180 independent hybrid clones obtained by fusion between gamma-irradiated mink fibroblasts with Chinese hamster cells as well as in 31 mink-mouse hepatoma hybrid clones. Statistical analysis of the segregation patterns revealed the following order of the 4 genes on the mink X chromosome: GALA-PGK1-HPRT-G6PD (Zhdanova and others 1988; Figure 1). Moreover, cytogenetic analysis of 5 mink-Chinese hybrid clones expressing mink GALA, PGK1, and HPRT, but lacking G6PD, allowed identification of small deletions involving the terminal part of the X-chromosome and the tentative assignment of G6PD to Xq15.22-qter (Zhdanova and others 1988).

For subchromosomal localization of ESD, TK1, GALK, ALDC, UMPH2, and ADH2 (presumed aldehyde dehydrogenase-3, ALDH3) on mink chromosome 8, the method of chromosome-mediated gene transfer was used (Gradov and others 1985; Pack and others 1989, 1992). Mink genes were transferred into mutant mouse cells (LMTK cells deficient in thymidine kinase activity) by a chromosome-mediated transfer technique using isolated metaphase chromosomes of mink (Sukoyan and others 1984). As a result, 16 independent transformants were isolated. Cytogenetic analysis demonstrated that 8 of them contained fragments of different sizes from mink chromosome 8. Analysis of ESD, TK1, GALK, ALDC, UMPH2, and ADH2 in the transformants made it possible to establish regional localization for these genes on chromosome 8 (Figure 1). The close linkage of mink TK1 and GALK genes was also supported by another gene transfer experiment. Isolated nuclei from mink fibroblasts were encapsulated in artificial lipid membranes (liposomes). After treatment of murine mutant (LMTK-) cells, a set of clones carrying the selective marker gene of mink origin was isolated (Sukoyan and others 1985). Five of the 14 transformants expressed mink TK1 together with GALK, but not ALDC or ESD. It is notable that gene transfer technology made it possible to establish gene order as qter-(HOXB, UMPH2)-ALDC-GALK-TK1-ADH2 on the long arm of the chromosome 8 (the former nomenclature) (Pack and others 1989; Figure 1).

The development of the in situ hybridization technique offered an efficient technology for regional gene assignment. Since 1996, more than 50 single copy sequences (at least 1 for each mink chromosome) have been localized (Christensen and others 1996). In 1998, Christensen and others (1998), using in situ hybridization, demonstrated that the genes for 5S ribosomal RNA (5SrRNA) are located in 3 sites on the long arm of mink chromosome 2. Two are at the proximal and the distal edges of the largest G-band, and the third site maps close the centromere. Although the use of heterologous DNA probes seldom leads to a good result, the genes for ESD and WARS were assigned to mink 8q22-25 and 2p21-24, respectively (a nomenclature of Mandahl and Fredga 1975), using human probes (Graphodatsky and others 1991). It is important to note that the assignment of the ESD gene in the region was supported by chromosome-mediated gene transfer (see above; Gradov and others 1985).

The isolation of DNA fragments homologous to human or mouse genes from mink DNA libraries can provide probes for gene assignment by in situ hybridization. This strategy has already been used to assign the mink GH gene to mink 8p25-23 (Malchenko and others 1994).

GENE MAPPING BY COMBINING SOMATIC CELL HYBRIDIZATION AND BREEDING TESTS IN MINK

In a special population study of more than 40 biochemical markers of the American mink, polymorphisms have been found for the following genes: ES1, ES2, ES3, ESR, PEPB, PEPD, PI (alpha-protease inhibitor), GC (group-specific component), and LPM (high density lipoprotein) (Borodin and others 1995; Mullakandov and others 1986; Serov and others 1987). Breeding tests have demonstrated that ES1, ES2, ES3, ESR, and PEPD belong to 1 linkage group with distances of 14 cM between ES1 and ES3, 10 cM between ES1 and PEPD, and 24 cM between ES3 and PEPD. No recombinants between the loci for ES1, ES2, and ESR were found. I suggest the following putative order for these loci: ES3--ES1,ES2,ESR--PEPD. The chromosomal localization for ES3 and PEPD on chromosome 7 was established using mink-rodent hybrid clones (Pack and others 1989; Serov and others 1987); hence, the linkage group ES3-ES1,ES2,ESR--PEPD is located on the same chromosome (Figure 1).

Breeding tests have demonstrated that PEPB and LPM are linked (11 cM apart) (Yermolaev and others 1989). Because PEPB has already been localized on chromosome 12 (Mullakandov and others 1986), we may infer that LPM is located on the same chromosome (Figure 1). Since 1995, the results of studies using breeding tests have ruled out the possibility of linkage of ESI, PEPD, and PEPB with coat color mutations S (black-cross), p (silver-blue), a (Aleutian), and h (white-hedlund) (unpublished data), as well as between the PI, GC, and coat color gene Cr (Crystal) (Borodin and others 1995; Trapezov 1997).

COMPARATIVE GENE MAPPING: MINK AND OTHER MAMMALS

At the time of this writing, the 77 genes that comprise the genetic map of the American mink mark all chromosomes except the Y (Figure 1), making it possible to compare the mink map with the genetic maps of other mammals. The comparison shows that there are more than 10 large associations of syntenic genes common to mink, human, mouse, and other mammalian species. Some syntenic groups of mink genes are characteristic of 3 or more orders of mammals. For instance, TK1, GALK, ALDC, UMPH2, GH, HOXB, and NF1 mark a large conserved region in mink covering approximately 30 cM in the mouse gene map (World Wide Web site http://www.informatics.jax.org). This region is common to primates, carnivores, ungulates, rodents (Wakefield and Graves 1996), and insectivores (Matyakhina and others 1997; Serov and others 1998). The presence of this large conserved group of syntenic genes in different mammalian species reflects its evolutionary conservation and probably represents the remains of ancestral genome.

Another large conserved region common to carnivores, primates, rodents, ungulates and even fishes (Wakefield and Graves 1996) is marked by ITPA, ADA, and PRNP. This region covers 18 cM of the mouse gene map. Ten other conserved regions are located on mink chromosomes 1 (on both arms), 2 (on the short and the long arms), 6, 7, and 8 (on the short and the long arms), and 12 and 13 (see Wakefield and Graves 1996).

New data on the comparison of mink and human chromosomes using the zoological fluorescence in situ hybridization (ZOO-FISH) technique have appeared in the late 1990s. Hameister and others (1997) demonstrated that specific DNA probes for 22 human autosomes cross-hybridized with 32 large regions of mink chromosomes. In some cases, chromosomal DNA probes showed positive staining on only I mink chromosome region. For example, the human chromosome 9 probe hybridized only to the entire mink chromosome 9, the probe for the human chromosome 10 stained only the long arm of mink chromosome 2, and the probe for the long arm of human chromosome 17 hybridized only to the short arm of mink chromosome 5. In other cases, mink chromosomes were painted by probes derived from 2 or 3 different human chromosomes. For instance, the short arm of mink chromosome 8 was painted by a DNA probe specific to human chromosome 20, and the long arm of the same chromosome, by a DNA probe specific to human chromosome 2.

Results obtained with the zoological fluorescence in situ hybridization technique are in remarkable agreement with the gene mapping data in mink described above (Hameister and others 1997). Thus, there is significant evidence in support of a previous conclusion (Serov and others 1987, 1991) concerning the existence of large conserved regions in mink common to human and mouse as well as other mammalian species. The nature of the conservation of large syntenic gene associations during evolution of mammals is unknown. However, the existence of conserved regions common to many vertebrates may be interpreted as a result of natural selection.

According to the estimates of Ehrlich and others (1997), rates of syntenic disruption during evolution differ significantly among mammalian lineages, from 0.05 (cat and Chinese hamster) to 0.90 (human, mouse, and rat) syntenic disruptions per million years. The rate of syntenic disruption in the mink lineage is moderate (0.30) and similar to that in baboons, chimpanzees, and cattle (Ehrlich and others 1997). Early cytogenetic data showing substantial variability in chromosome rearrangements among mammalian lineages support these estimates (Busch and others 1977; Graphodatsky 1989; Wilson and others 1974). However, it is unclear whether the rate of syntenic disruptions is constant in the lineage or, as suggested by Graphodatsky (1989), is possibly higher during the origin of higher taxonomic categories (family, order) than in late speciation within taxa. In any case, the nature of substantial variation in rates of syntenic disruptions is no less mysterious than those of the origin of the large conserved regions in mammalian genome.

Nevertheless, a syntenic group specific to mink has been found (Khlebodarova and others 1995). This group includes genes GPT, PGP, and PSP located on mink chromosome 14 (Figure 1 ), which is the smallest in the mink karyotype. The homologous human genes are all located on distinct chromosomes: 8 (GPT), 16 (PGP), and 7 (PSP) (O'Brien 1993). The GPT and PSP genes are located on mouse chromosomes 15 and 5, respectively (O'Brien 1993). Probably, the GPT, PGP, and PSP syntenic group has arisen de novo in the Mustelidae. A comparative analysis of the Geimsa banding with trypsin patterns of the chromosomes of more than 20 species representing 6 genera of the Mustelidae family revealed that all of them possess a chromosome similar to mink chromosome 14 (Graphodatsky and others 1989). According to data of Hameister and others (1997), human DNA probes derived from chromosome 7 and 16, but not from chromosome 8, cross-hybridized with mink chromosome 14. These human probes painted 2 distinct chromosomes (B4pter-p and E3) in cat, suggesting that this syntenic group is probably unique for the Mustelidae but not the Felidae family.

Based on the existence of conserved regions of syntenic genes in phylogenetically distant mammalian species, comparative mapping data may be used to search for important genes in fur bearing animals. It is possible to use the gene maps as Mendeleev's periodical system. In searching for the location ora gene in mink, one should first determine whether this particular gene belongs to a syntenic group in other species. If so, it is reasonable to use the other member(s) of this syntenic group for which the location is known in mink as a candidate marker for the linkage experiment. This rationale can be applied to search for the location of the color genes.

REFERENCES

Bindixen C, Sunjevaric I, Batschwitz R, Rothstein R. 1994. Identification of a mouse homologue of Saccharomyces cerevisiae recombination and repair gene, RAD52. Genomics 23:300-303.

Borodin GP, Perelygin AV, Axenovich TI, Trapezov OV, Serov OL. 1995. Genetic control of PI and GC variants in the American mink. Anim Genet 26:435-437.

Busch GL, Case SM, Wilson AC, Patton JL. 1977. Rapid speciation and chromosomal evolution in mammals. Proc Natl Acad Sci U S A 74:3942-3946.

Christensen K, Brusgaard K, Malchenko S, Lohi O, Serov O. 1996. Standardization of the American mink (Mustela vison) karyotype and some cosmid in situ hybridization results. Arch Zootec 45:259-265.

Christensen K, Lomholt B, Nielsen KV, Hallenberg C. 1998. Mink 5SrRNA genes map to 2q in three loci suggesting a syntenic relation to human 1q. Hereditas (Forthcoming).

Cowmeadow MP, Ruddle FH. 1978. Computer-assisted statistical procedures for somatic gene assignment. Cytogenet Cell Genet 22:694 697.

Ehrlich J, Sankoff D, Nadeau JH. 1997. Synteny conservation and chromosome rearrangements during mammalian evolution. Genetics 147:289-296.

Goss S J, Harris H. 1977. Gene transfer by means of cell fusion. I. Statistical mapping of the human X chromosome by analysis of radiation gene segregation. J Cell Sci 25:17-38.

Gradov AA, Pack SD, Sukoyan MA, Rubtsov NB, Bochkarev MN, Serov OL. 1985. Regional assignment of the genes for TK1, GALK, ALDC, and ESD on chromosome 8 in the American mink by chromosome-mediated gene transfer. Mol Gen Genet 200:433-438.

Graphodatsky AS. 1989. Conserved and variable elements of mammalian chromosomes. In: Halnan CRE, editor. Cytogenetics of Animals. Oxon: CAB International. p 95-123.

Graphodatsky AS, Beklemisheva VR, Dolf G. 1995. High-resolution GTG-banding patterns of dog and silver fox chromosomes: Description and comparative analysis. Cytogenet Cell Genet 69:226-231.

Graphodatsky AS, Lushnikova TP, Biltueva LS, Eremina VR, Rubtsov NB, Filippov V, Shumny T, Ermolaev V, Ruvinsky A. 1991. Localization of some human genes to mammalian chromosomes by in situ hybridization. Cytogenet Cell Genet 58:198-203.

Graphodatsky AS, Sharshov AA, Ternovsky DV, Ternovskaya YG. 1989. Comparative cytogenetics of Mustelidae (Carnivorae). Zool J 68:96-106 (In Russian).

Hameister H, Klett C, Bruch J, Dixkens C, Vogel W, Christensen K. 1997. ZOO-FISH analysis: The American mink (Mustela vison) resembles the cat caryotype. Chromosome Res 5:5-11.

Khlebodarova TM, Malchenko SN, Matveeva NM, Pack SD, Sokolova OV, Alabiev BY, Belousov ES, Peremislov VV, Nayakshin AM, Brusgaard K, Serov OL. 1995. Chromosomal and regional localization of the loci for IGKC, IGGC, ALDB, HOXB, GPT, and PRNP in the American mink (Mustela vison): Comparisons with human and mouse. Mamm Genome 6:705-709.

Malchenko NS, Golovin SY, Matveeva NM, Beklemisheva VR, Graphodatsky AS, Brusgaard K, Christensen K, Serov OL. 1994. The mink growth hormone gene: Characterization of cDNA and subchromosomal localization. Proceedings of the 11th European Colloquium on Cytogenetics of Domestic Animals. p 140-144.

Mandahl N, Fredga K. 1975. Q, G and C-band patterns of the mink chromosomes. Hereditas 81:211-220.

Matyakhina LD, Koroleva IV, Malchenko SN, Bendixen C, Cheryaukene OV, Pack SD, Searle JB, Borodin PM, Serov OL. 1997. Chromosome location of sixteen genes in the common shrew, Sorex araneus L. (Mammalia, Insectivora). Cytogenet Cell Genet 77:201-204.

Mullakandov MR, Gradov AA, Zakijan SM, Rubtsov NB, Serov OL. 1986. Peptidases A, B, C, D and S in the American mink: Polymorphism and chromosome localization. Theor Appl Genet 73:272-277.

Nash WG, O'Brien SJ. 1982. Conserved regions of homologous G-banded chromosomes between orders in mammalian evolution: Carnivores and primates. Proc Natl Acad Sci U S A 79:6631-6635.

Nash WG, O'Brien SJ. 1987. A comparative chromosome banding analysis of the Ursidae and their relationship to other carnivores. Cytogenet Cell Genet 45:206-212.

Nes NN, Einarson EJ, Lohi O, Jorgensen G. 1988. Beautiful Fur Animals and Their Color Genetics. Glostrup Denmark: Scientifur.

O'Brien S J, editor. 1993. Genetic Maps. Locus Maps of Complex Genomes. 6th ed. Cold Spring Harbor NY: Cold Spring Harbor Laboratory Press.

O'Brien S J, Peters J, Searle A, Womack J, Graves JM. 1993. Report of the committee on comparative gene mapping. Genome Priority Rep 1:758-809.

Pack SD, Bedanov VM, Sokolova OV, Zhdanova NS, Matveeva NM, Serov OL. 1992. Characterization of a new hybrid mink-mouse clone panel: Chromosomal and regional assignments of the GLO, ACE NP, CKBB, ADH2, and MEI loci in mink (Mustela vison). Mamm Genome 3:112-118.

Pack SD, Zhdanova NS, Sukoyan MA, Serov OL. 1989. Chromosomal and regional localization of the genes for UMPH2, APRT, PEPD, PEPS, PSP. and PGP in mink: Comparison with man and mouse. Cytogenet Cell Genet 50:127 13 I.

Robinson R. 1975. The American mink (Mustela vison Schreber). In: Robinson R, editor. Handbook of Genetics. Vol 4. New York: Plenum. p 367-398.

Rubtsov NB, Radjabli SI, Gradov AA, Serov OL. 1981. Chinese hamster × American mink somatic cell hybrids: Characterization of a clone panel and assignment of the mink genes for malate dehydrogenase, NADP-1 and malate dehydrogenase, NAD-1. Theor Appl Genet 60:99-106.

Serov OL, Gradov AA, Rubtsov NB, Zhdanova NS, Pack SD, Sukoyan MA, Mullakandov MR, Zakijan SM. 1987. Genetic map of the American mink: Gene conservation and organization of chromosomes, In: Martkert CL, Scandalios JG, editors, lsozymes: Current Topics in Biological and Medical Research: Genetics, Development, and Evolution. Vol 15. New York: Alan R. Liss. p 179-215.

Serov OL, Matyakhina LD, Borodin PM, Searle JB. 1998. The common shrew gene map. ILAR J 39:195-202.

Serov OL, Pack SD. 1993. American mink (Mustela vison). In: O'Brien S J, editor. Genetic Maps. Locus Maps of Complex Genomes. Book 4, Nonhuman Vertebrates, 6th ed. Cold Spring Harbor NY: Cold Spring Harbor Laboratory Press. p 4.126-4.128.

Serov OL, Pack SD, Sokolova O. 1991. Conserved regions of syntenic genes and G-banding homologies in man, mouse and mink. International Workshop on Human Gene Mapping 11. August 18-23, 1991. London. Cytogenet Cell Genet 58:1917.

Shackelford RM. 1948. The nature of coat color differences in mink and foxes. Genetics 33:311-336.

Shackelford RM. 1949. Six mutations affecting coat color in ranchbred mink. Am Naturalist 83:49-86.

Sukoyan MA, Belyaev ND, Budker VG, Gradov AA., Pack SD, Serov OL. 1985. Transfer of mink genes into mouse cells by means of isolated lipid-encapsulated nuclei. Mol Gen Genet 201:487-491.

Sukoyan MA, Matveeva NM, Belyaev ND, Pack SD, Gradov AA, Shilov AG, Zhdanova NS, Serov OL. 1984. Cotransfer and phenotypic stabilization of syntenic and asyntenic mink genes into mouse cells by chromosome-mediated gene transfer. Mol Gen Genet 196:97-1(14.

Trapezov OV. 1997. Black crystal: A novel color mutant in the American mink (Mustela vison Schreber). J Hered 88:164-166.

Wakefield MJ, Graves JAM. 1996. Comparative maps of vertebrates. Mamm Genome 7:715-716.

Wijnen LMM, Grzeschik KH, Pearson PL, Meera Khan P. 1977. The human PGM-2 and its chromosome localization in man-mouse hybrids. Hum Genet 37:271-278.

Wilson AC, Sarich VM, Maxson LR. 1974. The importance of gene rearrangement in evolution: Evidence from studies on rates of chromosomal, protein and anatomical evolution. Proc Natl Acad Sci U S A 71:3028-3030.

Wurster-Hill DH, Centerwall WR. 1982. The relationships of chromosome banding patterns in canids, mustelids, hyena, and felids. Cytogenet Cell Genet 34:178-192.

Yermolaev VI, Karasik Gl, Khlebodarova TM, Matveeva NM, Mullakandov MR, Nayakshin AM, Shumny TV, Rubtsov NB, Serov OL. 1989. Localization of the alpha-macroglobulin gene and Lpm gene family on mink chromosome 9. Theor Appl Genet 78:93-96.

Zhdanova NS, Gradov AA, Rubtsov NB, Pack SD, Serov OL. 1985. Regional assignments of eight genes on chromosome 2 in the American mink. Cytogenet Cell Genet 39:296-298.

Zhdanova NS, Pack SD, Mazurok NA, Nesterova TB, Gradov AA, Serov OL. 1988. Subchromosomal localization and order of GALA, PGK1 HPRT, and G6PD loci on the X chromosome of the American mink (Mustela vison). Cytogenet Cell Genet 48:2-5.

FIGURE 1 Gene map of the American mink (Mustela vison) containing 77 biochemical loci marking all mink chromosomes, except the Y. The nomenclature of mink chromosomes is according to Christensen and others (1996), and former numbers of mink chromosomes (Mandahl and Fredga 1975) appear in parentheses. AATP, ATP-ase, alpha-subunit; ACON1, aconitase-1; ACP1, acid phosphatase-1 ACP2, acid phosphatase-2; ACY, aminoacylase; ADA, adenosine deaminase; ADH2,* alcohol dehydrogenase, subunit B; ADK, adenosine kinase; AK3, adenylate kinase-3; ALDB, aldolase B; ALDC, aldolase C; A2M, alpha-2-macroglobulin; APRT, adenine phosphoribosyl-transferase; BATP, ATP-ase, beta subunit; BLVR, biliverdin reductase; CKBB, creatine phosphokinase, brain type; ENO1, enoIase-1; ES1, esterase-1; ES2, esterase-2 (presumed); ES3, esterase-3; ESD, esterase D; ESR, esterase regulator; FNP1, fibronectin pseudogene-1 (presumed); GALK, galactokinase; GAPD, glyceraldehyde-3-phosphate-dehydrogenase; GH, growth hormone; GALA, alpha-galactosidase; GLO1, glyoxalase- 1; GOT1, glutamate-oxaloacetate transaminase-l; GPI, glucosephosphate isomerase; G6PD, glucose-6-phosphate dehydrogenase; GPT, glutamate-pyruvate transaminase; GSR, glutathione reductase; HK1, hexokinase-1; HOXB, homeo box B; HPRT, hypoxanthine phosphoribosyl transferase; IDH1, isocitrate dehydrogenase-1; IDH2, isocitrate dehydrogenase-2; IGGC, immunoglobulin gamma polypeptide, constant region; IGKC, immunoglobulin kappa polypeptide, constant region; IGLC, immunoglobulin lambda polypeptide, constant region; ITPA, inosine triphosphatase; LDHA, lactate dehydrogenase A; LDHB, lactate dehydrogenase B; LPM, lipoprotein of mink; ME1, malic enzyme-1; MDH1, malate dehydrogenase-1 (NAD dependent); MPI, mannose phosphate isomerase; NF1, neurofibromatose-1; NP, purine nucleoside phosphorylase; OTC, ornithine carbamoyltransferase; PEPA, peptidase A; PEPB, peptidase B; PEPC, peptidase C; PEPD, peptidase D; PEPS, peptidase S; PGD-6, phosphogluconate dehydrogenase; PGM 1, phosphoglucomutase- 1; PGK1, phosphoglycerate kinase-1; PGP, phosphoglycolate phosphatase; PKM2, pyruvate kinase, muscle type; PRL, prolactin; PRNP, prion protein; PSP, phosphoserin phosphatase; POMC, proopimelanocortin; PP, inorganic pyrophosphatase; QDPR, quinoid dihydropterine reductase; RAD52, RAD52 protein is a homologue of Saccharomyces cerevisiae recombination and repair protein (Bindixen and others 1994); 5SrRNA, 1 cluster of the genes for 5S ribosomal RNA; 5SrRNA,** another cluster of the genes for 5S ribosomal RNA; SOD1, superoxide dismutase-1; SOD2, superoxide dismutase-2; TK1, thymidine kinase-1; TPI, triosephosphate isomerase; UMPH2, uridine 5'-monophosphate phosphohydrolase-2; WARS, tryptophanyl-tRNA synthetase. *This enzyme is, in fact, aldehyde dehydrogenase-3 (ALDH3). Both ADH2 and ALDH3 have overlapping substrate specificity; hence, further study is necessary to accurately discriminate between them. **Two clusters of the 5S ribosomal RNA.