Alison Pilz

Report and abstracts of the Second International Workshop on Human Chromosome 9 Mapping 1993.

The Second International Workshop on Human Chromosome 9 was held in Chatham, Massachusetts on April 18--20, 1993. Fifty-three abstracts were received and the data presented on posters. The purpose of the meeting was to bring together all interested investigators working on the map of chromosome 9, many of whom had disease-specific interests. After a brief presentation of interests and highlighted results, the meeting broke up into the following subgroups for production of consensus maps: 9p; 9cen-q32; 9q32 ter. A global mapping group also met. Reports of each of these working groups is presented in the summary.

Comparative mapping of 50 human chromosome 9 loci in the laboratory mouse

We have set out to produce a comprehensive comparative map between human chromosome 9 (HSA9) and the laboratory mouse. The mouse homologues of 50 loci that were known to map to HSA9 were mapped by interspecific backcross linkage analysis. Ten loci from the short arm of HSA9 were mapped, and 40 from HSA9q, with 24 markers coming from the HSA9q33-q34 region--a part of the chromosome known to be very gene rich. Fifteen new assignments have been made--Ak3, Ctsl, Cntfr, C8g, D2H9S46E, Eng, Gcnt1, Irebp, Pappa, Ptgds, Snf212, Tal2, Tmod, Vav2, and Vldlr, the human homologues of which all map to HSA9. In addition, the assignment of Snf212 and Vldlr to MMU19 has defined a new region of synteny between the proximal portion of the short arm of HSA9 and the mouse.

Mapping of the human homologs of the murine paired-box-containing genes

Mutations in paired-box-containing (Pax) genes have recently been found to be the primary lesions underlying human genetic disorders such as Waardenburgs Syndrome type 1 and mouse developmental mutants such as undulated (un), splotch (Sp), and small eye (Sey). In addition, PAX-6 is a strong candidate gene for aniridia in man. Eight independent Pax genes have been isolated in the mouse. All eight map to distinct regions of the mouse genome; they do not appear to be clustered in the same way as some groups of homeobox-containing genes. We have now mapped the human homologs of all eight of these genes; PAX genes are found on human Chromosomes (Chr) 1, 2, 7, 9, 10, 11, and 20.

Comparative mapping of mouse chromosome 2 and human chromosome 9q: The genes for gelsolin and dopamine β-hydroxylase map to mouse chromosome 2

The mapping of human chromosome 9 (HSA9) and mouse chromosome 2 (MMU2) has revealed a conserved syntenic region between the distal end of the long arm of chromosome 9 and proximal mouse chromosome 2. Two genes that map to human chromosome 9q34, gelsolin (GSN) and dopamine beta-hydroxylase (DBH), have not previously been located in the mouse. We have used an interspecific backcross to map each of these genes, by Southern blot analysis, to mouse chromosome 2. Gelsolin (Gsn) is tightly linked to the gene for complement component C5 (Hc), and dopamine beta-hydroxylase (Dbh) is just proximal to the Abelson leukemia virus oncogene (Abl) and alpha-spectrin 2 (Spna-2). The loci for gelsolin and dopamine beta-hydroxylase therefore form part of the conserved synteny between HSA9q and MMU2.

REPORT on the Fourth International Workshop on Chromosome 9: held at Williamsburg, Virginia, USA, April 23–25, 1995

The Fourth International Workshop on Chromosome 9 was a highly successful endeavor in terms of the growth of the map, both genetic and physical, the amount of data entered into GDB, and the continued comradeship in the sharing of data and resources that was exemplified. SIGMA remained a stable and valuable part of the chromosome 9 mapping effort. A new subsection outlining the morbid anatomy of chromosome 9 was included. Finally, specific goals were set for the community to aim for over the upcoming months. These included extending the information about the ease of use of genetic markers, and coordinating across numerous groups the meiotic breakpoint mapping of many microsatellite markers. Workshop files are available by anonymous ftp from ftp.gene.ucl.ac.uk (128.40.82.1) in the subdirectory /pub/c9workshop/1995, or by using a World Wide Web browser (such as Mosaic or Netscape) via the Chromosome 9 Home Page (at the URL http:www.gene.ucl.ac.ukchr9home.html).

Transposition, amplification, and divergence in the origin of the DNF15 loci, a polymorphic repetitive sequence family on chromosomes 1 and 3

The loci DNF15S1 and DNF15S2 are members of a small repetitive sequence family at discrete chromosomal locations, namely, 1p36 and 3p21, respectively. Studies of the structure, arrangement, and interrelations of the family suggest that the single copy on chromosome 3 is the original member and that this gave rise to the several members on chromosome 1 by transposition, partial duplication, and amplification. Several restriction fragment length polymorphisms have been discovered at the DNF15S1 locus and these have been assigned to the different subfamilies of the repeat at this locus. The existence of these RFLPs, and the nonallelic restriction site variation also found in this sequence family, suggests that transposition and amplification occurred as discrete events. We sequenced across the ancient junction between chromosomes 1 and 3 and noted features which might explain the mechanics of the transposition and amplification events.

Chromosomal localisation of genes coding for human and mouse liver cytosolic cysteine dioxygenase

A panel of 22 hybrids was tested for the presence of the gene coding for human cysteine dioxygenase (CDO) by using human specific oligonucleotide primers in the polymerase chain reaction. Detection of human CDO completely correlated with the presence of human chromosome 5. A human total genome cosmid library was screened with a PCR product from the coding region of human CDO cDNA and the two positive clones identified were used in fluorescent in situ hybridisation (FISH) analysis on metaphase chromosome spreads. Fluorescent signals were seen on chromosome 5q22–23. Interspecific backcross mapping in the mouse indicated that Cdo, the mouse homologue of CDO, is situated in the central region of mouse chromosome 18 which shares a region of homology with human chromosome 5.

Chromosomal localization of three mouse diacylglycerol kinase (DAGK) genes: genes sharing sequence homology to the Drosophila retinal degeneration A (rdgA) gene ☆

There is growing evidence to support some form of light-activated phosphoinositide signal transduction pathway in the mammalian retina. Although this pathway plays no obvious role in mammalian phototransduction, mutations in this pathway cause retinal degenerations in Drosophila. These include the retinal degeneration A mutant, which is caused by an alteration in an eye-specific diacylglycerol kinase (DAGK) gene. In our efforts to consider genes mutated in Drosophila as candidates for mammalian eye disease, we have initially determined the map position of three DAGK genes in the mouse.

Comparative mapping of mouse chromosome 4 and human chromosome 9: Lv, Orm, and Hxb are closely linked on mouse chromosome 4

The genes for orosomucoid (ORM-1 and ORM-2), delta-aminolevulinate dehydratase (ALAD), and hexabrachion or tenascin (HXB) all map to the q31-qter region of human Chromosome (Chr) 9. The mouse homolog of each of these genes has been mapped to Chr 4, but hexabrachion has not previously been mapped by linkage analysis. We have now ordered Orm-1, Lv (the mouse homolog of ALAD), and Hxb in an interspecific backcross panel, by use of tyrosinase related protein-1, Tyrp-1, whose human homolog maps to 9p13-pter (Abbott et al., Genomics 1991) as a reference locus. No recombinants were identified in 124 animals between Lv and Orm-1. Hxb was found to be 1.6 cM distal to Lv and Orm-1, and 4.8 cM proximal to Tyrp-1, or b. These data therefore contribute to our knowledge of the conserved synteny between HSA 9q and MMU 4.

Linkage mapping of the Aldo-2, Pax-5, Ambp, and D4h9S3E loci on mouse chromosome 4 in the region of homology with human chromosome 9

The genes for aldolase-B (ALDOB), the alpha 1-microglobulin/bikunin precursor (AMBP), the paired box gene PAX5, and the anonymous DNA marker D9S3 map to human chromosome 9 (HSA9). We have set out to map the mouse homologues of each of these genes. The mouse genes for Pax-5 and Ambp previously have been shown to map to MMU4. We have used an interspecific backcross to confirm these localizations and to map the mouse homologues of ALDOB (Aldo-2) and D9S3 (D4H9S3E) to the same chromosome. These genes were mapped with respect to the four anchor loci for MMU4. In addition, the panel of backcross DNAs had previously been typed for delta-amino levulinate dehydratase (Lv), orosomucoid-1 (Orm-1), and hexabrachion (Hxb), the human homologues of which map to HSA9q. The recombination distances +/- the standard error between each pair of loci are D4Nds4-1.6 +/- 1.1-D4H9S3E-4.0 +/- 1.7-Galt-0.8 +/- 0.8-Pax-5-4.8 +/- 1.9-Aldo-2-6.3 +/- 2.2-(Lv, Orm-1, Ambp)-1.6 +/- 1.1-Hxb-4.0 +/- 1.7-Tyrp-1-4.8 +/- 1.9-Ifa. The data from this study have extended the known region of conserved synteny between human chromosome 9 and mouse chromosome 4.