Mammalian Genome

Juriloff, D. M.; Harris, M. J.; Mah, D. G.; Benson, A.

doi: 10.1007/s003359900121pmid: 8662232

Complex nonadditive interactions between specific alleles at multiple loci may underlie many so-called multifactorial threshold birth defects. The open-eyelids-at-birth defect in mice is a good model for these defects, and an understanding of its genetic complexity begins with mapping the participating loci. The open-eyelids defect can be part of a syndrome or can occur with no other obvious phenotypic effects. Of the latter nonsyndromic forms, the lidgap series includes four extant mutations that are considered to be alleles based on complementation tests. All show genetic complexity in segregation ratios. None has been mapped previously. On the basis of a strategy of mapping the mutation with the simplest inheritance pattern first, we generated an extensive exclusion map for lidgap-Gates, lgGa, using morphological and protein polymorphisms. We then screened the non-excluded regions in a congenic strain, AEJ.LGG—lgGa, for SSLP markers and located the differential chromosome segment containing the lgGa locus in a region near the distal end of mouse Chromosome (Chr) 13. This linkage was confirmed and refined by typing SSLPs in 64 F2 and 74 BC1 progeny of a cross of LGG/Bc (lgGa/lgGa) to SWV/Bc. The lgGa mutation maps to a 1- to 2-cM region between D13Mit76 and D13Mit53. Integrin alpha 1 and integrin alpha 2, which map to the same general region, are possible candidate loci, based on their embryonic expression and cellular function. Evidence is also presented for a common unlinked recessive suppressor of the open eyelids trait caused by lgGa.

Markel, P. D.; Bennett, B.; Beeson, M. A.; Gordon, L.; Simpson, V. J.; Johnson, T. E.

doi: 10.1007/s003359900122pmid: 8662220

We present the strain distribution patterns (SDPs) of 118 SSLP markers and three pigmentation genes that have been characterized in 27 strains from the LSXSS RI series. This coarse map provides a resource for linkage studies of phenotypes that are heritable in the LSXSS RI series. The LSXSS recombinant inbred (RI) strains were derived from the Long-Sleep (LS) and Short-Sleep (SS) selected lines of mice that were selected for differential sensitivity to ethanol but are also differentially sensitive to a variety of other alcohols, barbiturates, sedative hypnotics, and general anesthetics. Since the parents were not inbred, two atypical factors are present in these SDPs. First, more than two alleles are frequently found in these RIs, and second, some alleles can be uniquely associated with one or the other parent while other alleles may be found in both parental lines. To validate the markers found in the parental line, we genotyped all parental mice from one generation of both the LS and SS lines, thus leading to a set of marker SDPs that are useful for further phenotypic association and identification of provisional QTLs.

Marine, J. -C.; Gilbert, D. J.; Bellefroid, E. J.; Martial, J. A.; Ihle, J. N.; Copeland, N. G.; Jenkins, N. A.

doi: 10.1007/s003359900123pmid: 8662221

The mammalian genome contains hundreds if not thousands of zinc finger protein (Zfp) genes. While the function of most of these genes remains to be determined, it is clear that a few of them play important roles in gene regulation and development. In studies described here, we have used an interspecific mouse back-cross mapping panel to determine the chromosomal location of 15 KRAB-containing zinc finger loci. These loci map to nine different mouse autosomes and the X Chromosome (Chr). Two Chrs, 7 and 9, contain cosegregating pairs of KRAB-containing Zfp genes, indicating that the KRAB-containing Zfp genes have evolved through processes involving regional as well as genome-wide duplication events.

Griffith, A. J.; Radice, G. L.; Burgess, D. L.; Kohrman, D. C.; Hansen, G. M.; Justice, M. J.; Johnson, K. R.; Davisson, M. T.; Meisler, M. H.

doi: 10.1007/s003359900124pmid: 8662222

The location of three mutations on proximal Chromosome (Chr) 18 was determined by analysis of the offspring of several backcrosses. The results demonstrate that ataxia and the insertional mutation TgN9257Mm are separated by less than 1 cM and are located approximately 3 cM from the centromere, while the balding locus is 7 cM more distal. Previous data demonstrated that the twirler locus also maps within 1 cM of ataxia. The corrected locations will contribute to identification of appropriate candidate genes for these mutations. Two polymorphic microsatellite markers for proximal Chr 18 are described, D18Umil and D18Umi2. The Lama3 locus encoding the α3 subunit of nicein was mapped distal to ataxia and did not recombine with Tg9257.

Li, X. M.; Salido, E. C.; Gong, Y.; Kitada, K.; Serikawa, T.; Yen, P. H.; Shapiro, L. J.

doi: 10.1007/s003359900125pmid: 8662223

Although the human steroid sulfatase (STS) gene has been cloned and characterized in detail, several attempts to clone its mouse homologue, with either anti-human STS antibodies or human STS cDNA probes, have failed, suggesting a substantial divergence between these genes. However, partial amino-terminal sequence from purified rat liver STS is very similar to its human counterpart, and sequence comparisons have revealed several domains that are conserved among all the sulfatases characterized to date. Thus, we used a degenerate-primer RT-PCR approach to amplify a 321-bp fragment from rat liver cDNA, which was used as a probe to clone and characterize the complete cDNA. Comparison of the protein coding region between the rat and human genes showed 66% homology both at the DNA and the protein levels. STS activity was conferred to STS(-) A9 cells upon transfection with a rat Sts expression construct, indicating the authenticity of the cloned cDNA. While Sts has been shown to be located in the mouse pseudoautosomal region, both physical and genetic mapping demonstrate that Sts is not pseudoautosomal in the rat. The overall genomic organization of rat Sts and human STS is very similar, except that the insertion site for intron 1 in the rat is 26 bp upstream from that in the human. Rat Sts is only 8.2 kb long, while the human STS spans over 146 kb.

Yeung, R. S.; Buetow, K. H.; Scherpbier-Heddema, T.; Bell, D. W.; Testa, J. R.

doi: 10.1007/s003359900126pmid: 8662224

A map of rat Chromosome (Chr) 10 was generated from 21 markers, mostly of conserved structural genes, by linkage analysis and fluorescence in situ hybridization. The study emphasizes the proximal third of the chromosome which, until now, has been relatively devoid of markers. Based on comparative analysis, our data suggest that genes on rat Chr 10 are conserved on mouse Chr 11, 16, 17 and human Chr 16, 5, and 17.

Baron, B.; Fernandez, M. A.; Carignon, S.; Toledo, F.; Buttin, G.; Debatisse, M.

doi: 10.1007/s003359900127pmid: 8662225

We studied a polygenic region located on Chromosome (Chr) lq in Chinese hamster cells that is coamplified along with the AMPD2 gene. Previous sequence analysis identified both members of the GSTM family and the GNAI3 gene within a cloned 120-kb region surrounding the AMPD2 locus. We show here that the GNAT2 gene, which is inactive in the fibroblastic cells, lies within the 20 kb separating the transcriptionally active GNAI3 and AMPD2 genes. We map most gene ends by sequence comparison with human homologs; one is inferred from the presence of an unmethylated CpG island. This Chinese hamster locus corresponds to a region of conserved linkage between human Chr 1 (locus lp 13) and mouse Chr 3 (position 52.5 cM), where Gnai-3 and Gnat-2 have been mapped. The AMPD2 gene is presently unlocalized in human genome; its proposed position on mouse Chr 3 is at 53.4 cM. Our results, obtained by physical mapping, strongly suggest that the order and possibly the tight linkage of these genes are conserved on all three genomes.

Signer, E. N.; Gu, F.; Jeffreys, A. J.

doi: 10.1007/s003359900128pmid: 8662226

By cloning tandemly repeated sequences from the pig genome by use of non-porcine minisatellite probes for library screening, five novel polymorphic VNTR loci were isolated: three minisatellites and two satellite-like loci. Four of them could be mapped onto chromosomes by linkage analysis and/or in situ hybridization. They were assigned to Chromosomes (Chrs) 5, 6, 14, and 16. Physical mapping on both presumed satellites and on one of the minisatellites revealed that the former resided near or at the centromere and the latter towards the chromosome ends. The location of the minisatellite is of particular interest since, together with data on three other minisatellites previously isolated, it supports the idea that, as in humans, minisatellites may preferentially be subtelomeric also in pigs.

Robic, A.; Riquet, J.; Yerle, M.; Milan, D.; Lahbib-Mansais, Y.; Dubut-Fontana, C.; Gellin, J.

doi: 10.1007/s003359900129pmid: 8662227

Recently two main genetic maps [Rohrer et al. Genetics 136, 231 (1994); Archibald et al. Mamm. Genome 6, 157 (1995)] and a cytogenetic map [Yerle et al. Mamm. Genome 6,175 (1995)] for the porcine genome were reported. As only a very few microsatellites are located on the cytogenetic map, it appears to be important to increase the relationships between the genetic and cytogenetic maps. This document describes the regional mapping of 100 genetic markers with a somatic cell hybrid panel. Among the markers, 91 correspond to new localizations. Our study enabled the localization of 14 new markers found on both maps, of 54 found on the USDA map, and of 23 found on the PiGMaP map. Now 21% and 43% of the markers on the USDA and PiGMaP linkage maps respectively are physically mapped. This new cytogenetic information was then integrated within the framework of each genetic map. The cytogenetic orientation of the USDA linkage maps for Chromosomes (Chrs) 3, 8, 9, and 16 and of PiGMaP for Chr 8 was determined. USDA and PiGMaP linkage maps are now oriented for all chromosomes, except for Chrs 17 and 18. Moreover, the linkage group “R” from the USDA linkage map was assigned to Chr 6.

Hayes, P. D.; Schmitt, K.; Jones, H. B.; Gyapay, G.; Weissenbach, J.; Goodfellow, P. N.

doi: 10.1007/s003359900130pmid: 8662228

The UK HGMP Resource Centre’s collection of human partial cDNA sequences (ESTs) have been examined for suitability for mapping by PCR on a panel of somatic cell hybrids. The chromosomal assignments of 92 ESTs were determined with a monochromosomal hybrid panel, and a subset of 45 were linked to genetic markers with a panel of whole-genome radiation hybrids (WG-RHs). These results demonstrate the potential of WG-RHs to construct a transcript map of the human genome.