Localization of the properdin factor complement locus Pfc to band A3 on the mouse X chromosome

The locus for properdin (properdin factor complement, Pfc), a plasma glycoprotein, has been mapped to band A3 of the mouse X chromosome by in situ hybridization to metaphase spreads containing an X;2 Robertsonian translocation. The X-linkage of the locus has also been confirmed by analysis of Mus musculus x Mus spretus interspecific crosses. The XA3 localization for Pfc places it in the chromosomal segment conserved between man and mouse which is known to contain at least six other homologous loci (Cybb, Otc, Syn-1 Maoa, Araf, Timp).     

The locus for apolipoprotein E (apoE) is close to the Lutheran (Lu) blood group locus on chromosome 19

Summary Linkage has been described between the loci for apolipoprotein E (apoE) and the complement C3 (C3) on chromosome 19. C3 is known to belong to a linkage group with gene order C3-Se-Lu. The present study revealed linkage between Se and apoE with peak lod score +3.3 at recombination fraction 0.08 in males and +1.36 at 0.22 in females, and linkage between apoE and Lu with lod score +4.52 at zero recombination in sexes combined. The C3-apoE linkage gives lod score +4.00 at = 0.18 in males, but +0.04 at =0.45 in females. Triple heterozygote families confirm that apoE is on the Se side and on the Lu side of C3. Allelic association between apoE and Lu has not been ruled out. Combining our data with published data on C3-Se and Se-Lu, this segment of chromosome 19 has an average sex ratio of female/male recombination of 2.3.     

The Kell blood group locus is close to the cystic fibrosis locus on chromosome 7

Summary Linkage analysis confirmed the assignment of the Kell blood group locus to chromosome 7.     

Localization of the properdin structural locus to Xp11.23-Xp21.1

Properdin is a serum protein belonging to the alternative pathway of complement activation whose absence is often associated with fatal bacterial infections. Properdin deficiency segregates with an X-linked recessive pattern and its position has been recently refined by genetic linkage analysis to the proximal part of the X-chromosome short arm near the OTC and DXS7 loci. We have hybridized an 0.8-kb genomic clone encoding part of the human properdin gene to a panel of somatic cell hybrids retaining different portions of the human X chromosome and thereby localized the probe to Xcen-Xp21.1. Furthermore, in situ hybridization of the same probe to replication banded metaphase chromosomes refined this localization to the region Xp11.23-Xp21.1 (with a peak grain distribution in the region equivalent to Xp11.4). As OTC and DXS7 map to Xp21.1 and Xp11.3, respectively, the data presented here strongly suggest that the X-linked deficiency syndrome is due to a defect in the locus encoding the structural properdin gene or in a physically close regulatory locus.     

Chromosome polymorphisms close to the cm-ADE1 locus of Candida maltosa

The imperfect yeast Candida maltosa has an ill-defined genetic constitution; it is nominally diploid, but probably highly aneuploid, in nature. We report on polymorphisms specifically affecting those chromosomes which bear the cm-ADE1 gene. This gene encodes phosphoribosylaminoimidazole-succinocarboxamide synthetase, an enzyme in the adenine biosynthetic pathway. By electrophoretic karyotype analysis, three differently sized chromosomes were demonstrated to carry cm-ADE; the size (but not the number) of these chromosomes was also found to vary, both between strains and during the mitotic growth of a single strain. Four different alleles of cm-ADE1 have been cloned and sequenced from one prototrophic strain. DNA sequence divergence between these different alleles is as high as 8%, with the greatest divergence being found in the upstream region. Mitotic recombination events that led to changes in the karyotype were followed by using cm-ADE1 DNA as an hybridization probe. A recombination hot-spot in the neighbourhood of the gene appears to be responsible for the instability of the chromosomes on which it resides.     

The Kidd (JK) blood group locus assigned to chromosome 18 by close linkage to a DNA-RFLP

Summary The close linkage between the PstI-restriction fragment length polymorphism (RFLP) disclosed by the L2.7 genomic DNA probe and the Kidd blood group locus is described. The maximum lod score is+8.53 at recombination fraction . The upper probability limit of the recombination fraction is θ =₁ 0.11. The L2.7 probe, previously assigned provisionally to chromosome 17, is by the present study assigned to chromosome 18. This also assigns the Kidd blood group locus (JK) to chromosome 18. Accepting previous deletion mapping, the shortest regions of overlap (SRO) for JK is 18q11-12, whereas one of our hybrids assigns L2.7 to 18q11-pter, suggesting centromeric localisation of the linkage group. JK has been assigned previously to chromosome 2 because of its provisional linkage to IGK which in turn has been mapped to 2p12. Our own JK-IGK linkage data do in fact support the previous positive lod scores at high recombination fractions (total lods+4.12 at θ₁ = 0.30). No obvious explanation for the conflicting gene mapping data is found.     

The structural gene for F liver protein (Flp) maps to chromosome 5 of the mouse

The BXD and AKXL panels of recombinant inbred mouse strains have been typed for the F liver protein alloantigen. The structural gene for F liver protein gene (Flp) is placed on the distal part of chromosome 5, between the known markers Bcd-1 and Gus-s. This excludes the possibility that F liver protein is a major histocompatibility complex molecule, and in turn raises a question about the uniqueness of F and certain other proteins as purgers of self-reactivity among T but not B cells. The typed RI strains have then been used for the immunogenetic studies presented in the succeeding article.     

Localization of the inosine triphosphatase locus (Itp) on chromosome 2 of the mouse

An electrophoretic variant of the enzyme inosine triphosphatase was found by screening inbred strains of mice. Strains with the slower-migrating variant include BALB/cJ, DBA/1J, and PL/J. The Itp locus was mapped between the -2-microglobulin (B2m) and the agouti (a) loci on chromosome 2. The mapping of Itp on chromosome 2 identifies a chromosomal segment that has been conserved since the divergence of lineages leading to mouse and man.This work was supported by Grants GM18684 and CA33093 from the National Institutes of Health. The Jackson Laboratory is fully accredited by the American Association for Accreditation of Laboratory Animal Care.     

Location of phosphorylase kinase (Phk) in the mouse X chromosome

The phosphorylase kinase deficiency (Phk) locus has been located in the mouse X chromosome, the order of genes being centromere-Bn-Phk-Ta-jp. Since the Phk locus of the mouse may be identical to the locus responsible for the X-linked phosphorylase kinase deficiency trait of man, and there may be a high degree of gene-order homology in the X chromosome of all mammals, the location of Phk in the mouse reported here may aid in locating the phosphorylase kinase gene on the X chromosome of man.This research was supported by grants AM 13359 (to F.H.) and AM 14461 (to D.L.C.) from the National Institute of Arthritis and Metabolic Diseases, and by an allocation (to E.M.E.) from NIH General Research Support Grant RR-05545 from the Division of Research Resources to The Jackson Laboratory. F.H. is a recipient of a Research Career Development Award (AM 46 421) of the National Institute of Arthritis and Metabolic Diseases.     

The mouse polycystic kidney disease mutation (cpk) is located on proximal chromosome 12

The mouse congenital polycystic kidney (cpk) mutation produces a condition that resembles human autosomal recessive polycystic kidney disease (ARPKD) in its pattern of inheritance, clinical progression, and histopathology. Inheritance of this mouse mutation in crosses segregating the Rb(12.14)8Rma translocation chromosome and various DNA markers of Chromosome 12 have localized cpk to a site near D12Nyu2, approximately 7 cM from the centromere of Chromosome 12. This result suggests that the homologous PKD2 gene should be localized to either human chromosome 2p23-p25 or chromosome 7q22-q31.     

The chronic proliferative dermatitis mouse mutation (cpdm): mapping of the mutant gene locus

The chronic proliferative dermatitis (cpdm) mouse mutation was mapped to mouse Chromosome 15 using an intraspecific cross between C57BL/KaLawRij cpdm/cpdm and BALB/cJ mice. A second autosomal recessive mutation that resulted in a phenotype similar to that of cpdm arose spontaneously in a colony of OcB-3/Dem recombinant congenic mice. This new mutation was found to be allelic with cpdm. Therefore, the gene symbol for the allelic mutation is cpdm^Dem. The phenotype of these mutant mice consists of eosinophil-driven severe and progressive inflammatory changes in multiple organs including the skin and lungs.