Chromosomal mapping of enzyme loci in the domestic cat: GSR to C2, ADA and ITPA to A3, and LDHA-ACP2 to D1

A panel of 42 rodent X cat somatic cell hybrids segregating individual cat chromosomes in different combinations was used to assign five isozyme structural loci to cat chromosomes. The feline homolog for glutathione reductase (GSR) was mapped to chromosome C2. Adenosine deaminase (ADA) and inosine triphosphatase (ITPA) were located on chromosome A3. Lactate dehydrogenase-A (LDHA) and acid phosphatase-2 (ACP2) were reassigned to chromosome D1. Localization of these genes increases the known feline genetic map and extends the known syntenic homologies between the cat and other mammalian species.     

Definition of mouse chromosome 1 and 3 gene linkage groups that are conserved on human chromosome 1: Evidence that a conserved linkage group spans the centromere of human chromosome 1

Comparative mapping between the human and the mouse genomes allows characterization of linkage groups that have been conserved over evolution. In this study, genes previously localized to adjacent regions of human chromosome 1 were mapped to discrete regions on distal mouse chromosomes 1 and 3 using an interspecific cross. Linkage analysis in mouse defined two groups in which the gene order appears to be the same as that in humans: 15 genes localized between human chromosome 1q21 and 1q32 were found to span 29.5 cM on distal mouse chromosome 1; 6 genes localized between human chromosome 1q21 and 1p22 spanned 15.6 cM on distal mouse chromosome 3. These data suggest that gene order within large chromosome segments may remain stable over long periods of evolution and that the position of the centromere may reflect a late event in the evolution of higher eukaryotic organisms. These studies provide a model for examination of specific evolutionary events.     

Regional assignment of the mouse alpha A2-crystallin gene (Crya-1) to chromosome 17A3----B by in situ hybridization

Previously, we assigned the alpha A2-crystallin (Crya-1) structural gene to mouse chromosome 17 via Southern blot hybridization analysis of mouse x Chinese hamster somatic cell hybrids. Using in situ hybridization, we have now localized this gene to 17A3----B, a subchromosomal region containing several genes whose linkage relationships have been shown to be conserved on human chromosome 6. In man, however, the homologous gene (CRYA1) is located on human chromosome 21, indicating that internal rearrangements can occur within highly conserved chromosomal regions during the divergence of man and mouse.     

Linkage of Agt and Actsk-1 to distal mouse Chromosome 8 loci: a new conserved linkage

Angiotensinogen is an ₂ involved in the maintenance of blood pressure and electrolyte balance. We have refined the position of the mouse angiotensinogen locus (Agt) on Chromosome (Chr) 8 and have also confirmed the assignment of the human angiotensinogen locus (AGT) to Chr 1. The segregation of several restriction fragment length variants (RFLVs) was followed in two interspecific backcross sets and in four recombinant inbred (RI) mouse sets. Analysis of the segregation patterns closely linked Agt to Aprt and Emv-2, which places the angiotensionogen locus on the distal end of mouse Chr 8. Additionally, a literature search has revealed that the strain distribution pattern (SDP) for the mouse skeletal -actin locus 1 (Actsk-1, previously Actal, Acta, or Acts) is nearly identical to the SDP for Agt in two RI sets. On the basis of this information we were able to reassign Actsk-1 to mouse Chr 8. By screening a panel of human-mouse somatic cell hybrids, we confirmed that the human angiotensioogen locus lies on Chr 1. This information describes a new region of conserved linkage homology between mouse Chr 8 and human Chr 1. It also defines the end of a large region of conserved linkage homology between mouse Chr 8 and human Chr 16.     

Localization of the mouse Mcf-2 (Dbl) protooncogene within a conserved linkage group on the mouse X chromosome

A mouse cDNA probe homologous to the human MCF2 transforming sequence has been identified and partially cloned, and is used here to localize the gene on the mouse X chromosome. The human gene has been physically mapped to within 60 kb of the gene for coagulation factor IX, within a large conserved linkage group between the mouse and human genomes which extends from HPRT to G6PD on the X chromosomes of both mammalian species. In situ hybridization of the mouse Mcf-2 probe onto mouse metaphase chromosomes indicates that this gene lies in the same region of the X chromosome as Cf-9, the mouse gene for coagulation factor IX. Moreover, segregation of species-specific genomic DNA polymorphisms for Mcf-2 and Cf-9 in a total of 203 individuals derived from two large interspecific mouse backcross populations (which are also segregating for 17 other X-linked molecular markers) demonstrates that the mouse genes are separated by only 0.5 +/- 0.5 cM. Despite this short distance we were able to order Mcf-2 and Cf-9 relative to one another and other genes in this region. The mouse gene order Hprt-Cf-9-Mcf-2-G6pd predicts a similar ordering of genes on the human X chromosome, a gene order which has only recently been demonstrated by physical mapping. Thus, the map location and linkage relationships of the Mcf-2 gene are similar in man and mouse, and this unique protooncogenic locus is part of a conserved linkage group on the mammalian X chromosome.     

A molecular genetic linkage map of mouse chromosome 2

Interspecific backcross mice were used to create a molecular genetic linkage map of chromosome 2. Genomic DNAs from N2 progeny were subjected to Southern blot analysis using molecular probes that identified the Abl, Acra, Ass, C5, Cas-1, Fshb, Gcg, Hox-5.1, Jgf-1, Kras-3, Ltk, Pax-1, Prn-p, and Spna-2 loci; these loci were added to the 11 loci previously mapped to the distal region of chromosome 2 in the same interspecific backcross to generate a composite multilocus linkage map. Several loci mapped near, and may be the same as, known mutations. Comparisons between the mouse and the human genomes indicate that mouse chromosome 2 contains regions homologous to at least six human chromosomes. Mouse models for human diseases are discussed.     

Possible linkage between uncoiler chromosome Un 1 and mylase polymorphism Amy 2 loci

Summary A family has been investigated in which 7 from 12 members bear the uncoiler chromosome number 1 pair. In all these members with uncoiler chromosome 1 heterozygous amylase polymorphism variant Amy 2^A2^B has been estimated (with exception of one 3-month-old boy in whom the phenotype of amylase variant is not yet fully developed). This pedigree represents a typical double back-cross family which enables to suppose very probably the close linkage between both gene loci Un 1 and Amy 2 and also to assign Amy 2 locus to chromosome 1.

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Zusammenfassung Wir berichten über eine Familie, in welcher 7 unter insgesamt 12 untersuchten Familienmitgliedern ein asymmetrisches Chromosom des ersten Chromosompaares mit den sehr verlängerten langen Armen (uncoiler chromosome) gefunden wurde. Bei allen diesen Familienmitgliedern mit, uncoiler chromosome 1 wurde auch gleichzeitig die heterozygote Variante des Amylase-Polymorphismus Amy 2^A2^B gefunden (mit Ausnahme eines 3 Monate alten Knaben, bei welchem das Phenotyp der Amylase-Variante noch nicht völlig entwickelt wurde). Dieser Stammbaum stellt eine typische double back-cross-Familie vor, aus welcher mit großer Wahrscheinlichkeit die linkage zwischen beiden Genorten Un 1 und Amy 2 und damit auch die Lokalisation des Genortes Amy 2 auf dem Chromosom 1 hervorgeht.

     

Efficient linkage of 10 loci in the proximal region of the mouse X chromosome

Interspecific Mus species crosses were used to construct a multilocus genetic map of the mouse X chromosome that extends for more than 50 cM. In these studies, we established the segregation of eight loci in more than 200 backcross progeny from crosses of M. musculus and M. spretus with a common inbred strain (C57BL/6JRos). Genetic divergence at the level of the nucleotide sequences makes these crosses a useful cumulative genetic resource for mapping additional genes defined by genomic or cDNA probes in a highly efficient manner. We have therefore devised a mapping strategy that uses a subset of these backcrosses that are recombinant between successive anchor loci to both localize and order an additional set of six genes without necessarily resorting to an analysis of the entire backcross series. Using this approach, we have defined the linkage of cytochrome b245 beta-chain (Cybb), synapsin (Syn-1), and two members of the X-linked lymphocyte-regulated gene family (Xlr-1, Xlr-2), as well as DXSmh141 and DXSmh172, two loci defined by random genomic probes. All six loci have been localized to the proximal portion of the mouse X chromosome and their order has been defined as Cybb, Otc, Syn-1/Timp, DXSmh141/Xlr-1, DXSmh172, Hprt, Xlr-2, Cf-9. Gene order was established by minimizing multiple recombination events across the region spanning an estimated 20 cM of the proximal X chromosome. The possible significance of the Xlr loci is discussed with respect to other X-chromosome loci that regulate the immune response.     

Mapping of PRM1 to human chromosome 16 and tight linkage of Prm-1 and Prm-2 on mouse chromosome 16

The protamines are small, arginine-rich nuclear proteins that replace histones and transition proteins late in the haploid phase of spermatogenesis in mammals. The two mouse genes encoding protamines--Prm-1 and Prm-2--have been molecularly cloned and mapped to mouse chromosome 16 (MMU 16). A cDNA clone of mouse Prm-1 that hybridized to the corresponding human gene was used to analyze a panel of somatic cell hybrids made between human lymphoblasts and the E36 hamster cell line. The human gene, which we have designated PRM 1, was syntenic with human chromosome 16 (HSA 16) and discordant with all other human chromosomes. Linkage analysis in the mouse was accomplished using the backcross (Czech II x BALB/c Pt) x Czech II to map Prm-1 and Prm-2 to a position near the 5' terminus of MMU 16. No recombination between Prm-1 and Prm-2 was observed among 89 progeny of the Czech II x BALB/c cross or among 94 progeny of the backcross (CBA/J x BALB/cJ) x BALB/cJ, demonstrating that the two loci are separated by less than 1.6 cM on MMU 16. This tight linkage may be of functional significance, as Prm-1 and Prm-2 are among a limited number of genes known to be expressed postmeiotically in male haploid germ cells.     

Probable assignment of the serum cholinesterase (E1) and transferrin (Tf) loci to chromosome 1 in man.

Suggestions of linkage in males between the E1 and Rh loci (Z = + 1.849; THETA = 0.20) and between the Tf and Rh loci (Z = + 0.595; THETA = 0.35) are presented. The assignment of the E1 and Tf loci to chromosome 1 and the order Tf:E1:PGD:Rh:PGM1 are cautiously proposed.     

A molecular genetic linkage map of mouse chromosome 13 anchored by the beige (bg) and satin (sa) loci

A molecular genetic linkage map of mouse chromosome 13 was constructed using cloned DNA markers and interspecific backcross mice from two independent crosses. The map locations of Ctla-3, Dhfr, Fim-1, 4/12, Hexb, Hilda, Inhba, Lamb-1.13, Ral, Rrm2-ps3, and Tcrg were determined with respect to the beige (bg) and satin (sa) loci. The map locations of these genes confirm and extend regions of homology between mouse chromosome 13 and human chromosomes 5 and 7, and identify a region of homology between mouse chromosome 13 and human chromosome 6. The molecular genetic linkage map of chromosome 13 provides a framework for establishing linkage relationships between cloned DNA markers and known mouse mutations and for identifying homologous genes in mice and humans that may be involved in disease processes.     

Mapping of Abll within a conserved linkage group on distal mouse chromosome 1 syntenic with human chromosome 1 using an interspecific cross

A human Abelson related gene (ABLL) cDNA clone was used to detect restriction fragment length polymorphisms (RFLPs) on mouse Southern blots. Abll was mapped to mouse chromosome 1 by analysis of segregation with other distal chromosome 1 genetic polymorphisms by using a panel of DNAs from [(C3H/HeJ-gld/gld x Mus spretus) F1 x C3H/HeJ-gld/gld] interspecific backcross mice. The data indicate the following gene order: (centromere)-CD45-6.5 cM-Lamb-2-1 cM-Abll-2 cM-At-3. The results extend the analysis of a large conserved linkage group spanning nearly 30 cM on distal mouse chromosome 1 syntenic with human chromosome 1q21-32. Within this linkage group similar relative positions have been characterized in both species for C4BP, REN, CD45, LAMB2, ABLL, AT3, APOA2, and SPTA.     

PKU locus: Genetic linkage with human amylase (Amy) loci and assignment to linkage group I

Summary The linked alpha-amylase loci Amy 1 and Amy 2 were evaluated for their linkage relationship to the PKU locus using data collected from two (one Czech and one Polish) groups of families. The five sibships informative for Amy 1: PKU give a score of 1.505 at =0.00 and the eight sibships informative for Amy 2: PKU give a score of 2.709 at =0.00. Due to the tandem position of Amy 1 and Amy 2 loci, these data could be combined, and linkage between Amy and PKU loci established with a score 4.214 at =0.00. The practical significance of the linkage, especially for identifying PKU allele carriers, is emphasized.     

Genetic effects of chromosomal rearrangements in Chinese hamster ovary cells: expression and chromosomal assignment of TK, GALK, ACP1, ADA, and ITPA loci.

Polyethylene glycol-mediated fusion of Chinese hamster ovary (CHO) cells with mouse Cl1D cells produced interspecific somatic cell hybrids which slowly segregated CHO chromosomes. Cytogenetic and isozyme analysis of HAT- and bromodeoxyuridine-selected hybrid subclones and of members of a hybrid clone panel retaining different combinations of CHO chromosomes enabled provisional assignments of the following enzyme loci to CHO chromosomes: TK, GALK, and ACP1 to chromosome 7; TK and GALK to chromosome Z13; ACP1, ADA, and ITPA to chromosome Z8; and ADA and ITPA to chromosome Z9. These genetic markers reflect the origin of each of these Z group chromosomes and indicate the functional activity of alleles located on rearranged chromosomes. Identification of diploid electrophoretic shift mutations for ADA and ITPA was consistent with those observations. Assignment of the functional TK locus in TK+/- CHO-AT3-2 cells indicated that gene deletion may be responsible for TK hemizygosity in this subline.     

Provisional assignment of the gene for uridine monophosphatase-2 (Umph-2) to mouse chromosome 11

The segregation of the mouse gene for uridine monophosphatase-2 (Umph-2) was examined in 14 independent mouse-Syrian hamster hybrids and 10 hybrid subclones. Umph-2 cosegregated with the mouse galactokinase (Glk) gene in 23 of the 24 hybrids and showed at least four discordances with all other mouse marker isozymes examined. The observed synteny of Umph-2 and Glk, which has also been observed in humans, indicates that the mouse Umph-2 gene is on chromosome 11.     

The alpha 2 chain of type 1 collagen does not map to mouse chromosome 16 but maps close to the Met proto-oncogene on mouse chromosome 6

The gene locus for the alpha 2 chain of type 1 collagen (Cola-2) was previously assigned to chromosome 16. Here we demonstrate, utilising both somatic cell hybrid analysis and genetic linkage analysis, in an interspecific Mus domesticus x Mus spretus cross that Cola-2 fails to cosegregate with mouse chromosome 16, but is linked to the Met proto-oncogene on chromosome 6.