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Genetic mapping based on radiation hybrid data.

Radiation hybrid mapping is a recently developed technique for constructing high-resolution maps of mammalian chromosomes. The chromosome of interest is exposed to X rays, which cause it to break into numerous fragments. The fragments are randomly recovered into hamster cells. The resulting hybrids are then analyzed for the presence or absence of DNA markers of interest. A simple method for using this information to order the markers on the chromosome is developed here. For any particular ordering of the loci, the least number of breaks consistent with the data can be determined. The best order is taken to be that which minimizes this number of obligatory breaks. Some statistical properties of the method are examined, both theoretically and by use of a simulation study. Except for some extreme cases, the method gives good results, which compare well with results obtained by a full maximum likelihood analysis. The method is used to order a set of 14 loci on chromosome 21 with encouraging results.

Animals↗

A rehabilitation of the genetic map of the 84B-D region in Drosophila melanogaster.

A reanalysis of the 84B3 to 84D3,5 region of the polytene chromosomes of Drosophila melanogaster has led to the identification and localization of 16 genes. These genes include 11 vital loci, four genes exhibiting nonlethal visible mutant phenotypes and one gene encoding a nonessential enzyme. The identity of the gene products of two of the vital genes has been determined to be alpha-tubulin and glucose dehydrogenase (Gld). Three newly identified genes, sticking (stk), half out (hat) and trapped (ted), as well as Gld are required for eclosion. Among the nonessential genes are roughened eye (roe) and ruffed eye (rue), which affect eye texture. The roe phenotype is greatly enhanced by deletions that simultaneously remove roe and an unidentified locus in 84E. Mutations in another nonessential gene, rotund (rn), are characterized by pattern deletions of most adult appendages.

Animals↗

Inheritance and genetic mapping of the Campus syndrome (CPS): a high-frequency tremor disease in pigs.

A new progressive tremor disorder called Campus syndrome (CPS) was observed among the progeny of a normal boar of the Pietrain breed in Germany. Extensive backcross experiments indicate that CPS is inherited as an autosomal dominant trait, and the founder boar, Campus, is believed to be a gonadal mosaic. A linkage analysis of 57 animals mapped the CPS gene to a region on porcine chromosome 7 flanked by the markers SW1418 and SW352, which is homologous to a part of human chromosome (HSA) 14. Human dominant distal myopathy type 1 (MPD1) has been mapped to the homologous region of HSA14. As the myopathological findings in MDP1 show striking similarities to CPS, this porcine disorder may serve as an animal model for MPD1.

Animals↗

Regional localization of polymorphic markers on chromosome 10 by physical and genetic mapping.

The human vimentin gene and a random DNA segment (D10S39) were mapped to the short arm of human chromosome 10 by linkage analysis. A panel of somatic cell hybrids and monosomy cell-lines, which divide chromosome 10 into seven regions, was used to localize 10 polymorphic markers on this chromosome. The physical map locations obtained correlate well with linkage maps of chromosome 10. Two markers which have been shown to be closely linked to the gene for multiple endocrine neoplasia type 2A map distal to a translocation breakpoint in band 10q11.2.

Animals↗

Fine genetic mapping of diffuse non-epidermolytic palmoplantar keratoderma to chromosome 12q11-q13: exclusion of the mapped type II keratins.

Diffuse non-epidermolytic palmoplantar keratoderma (NEPPK) belongs to the heterogeneous group of skin diseases characterized by thickening of the stratum corneum of the palms and soles (1). This autosomal dominant PPK is characterized by a diffuse pattern of palmar and plantar hyperkeratosis giving the affected areas a thickened yellowish appearance with a marked erythematous edge. Linkage of diffuse NEPPK to chromosome 12q11-q13 has been demonstrated in two independent reports (2, 3). In this study, we describe detailed haplotyping with microsatellite markers mapping to this chromosomal region in three diffuse NEPPK pedigrees from the south of England. Fine mapping of a previously identified recombination event and the identification of a common disease haplotype segregating in the three pedigrees places the diffuse NEPPK locus proximal to the type II keratin gene cluster.

Chromosome Mapping↗

Genetic mapping of endogenous mouse mammary tumor viruses: locus characterization, segregation, and chromosomal distribution.

The restriction endonuclease EcoRI has been used to study the inheritance of strain difference in endogenous mouse mammary tumor virus DNA sequences. This enzyme, which cleaves at only one site within the nondefective viral genome, generates DNA fragments containing mouse mammary tumor virus sequences which vary in size according to the locations of EcoRI restriction sites in the flanking mouse sequences, thereby defining unique integration sites of the viral genome. Recombinant inbred strains of mice have been used to study the inheritance of these DNA fragments which hybridize to mouse mammary tumor virus cDNA sequences. The results define 11 segregating units consisting of 1 or 2 fragments. These units were shown to segregate among the recombinant inbred strains, and in some instances linkage was established. Two units were shown to be linked on chromosome 1. Another unit was mapped to chromosome 7, which is presumably identical to the previously defined genetic locus Mtv- 1. One other mouse mammary tumor virus locus was tentatively assigned to chromosome 6. The results are consistent with the view that integration of mouse mammary tumor virus can take place at numerous sites within the genome, and once inserted, these proviruses appear to be relatively stable genetic entities.

Animals↗

Genetic mapping of the Mx influenza virus resistance gene within the region of mouse chromosome 16 that is homologous to human chromosome 21.

A total of 318 progeny from four backcrosses involving different laboratory strains and subspecies of Mus musculus were analyzed to map the Mx gene to the region of mouse chromosome 16 (MMU 16) which is homologous to human chromosome 21 (HSA 21). This result suggests that Mx will be found in the region of HSA 21 which has been implicated in Down syndrome when inherited in three copies.

Animals↗

Genetic mapping of a cone and rod dysfunction (Aland Island eye disease) to the proximal short arm of the human X chromosome.

A five generation family with an X linked ocular disorder has been investigated. The major clinical features were reduced visual acuity, nystagmus, and myopia. Although impaired night vision was not a symptom, using psychophysical and electrophysiological testing both rod and cone function were found to be abnormal in all affected males. No abnormality was detected in carrier females. Gene location studies showed X linked transmission of a gene that maps to proximal Xp11. The findings observed in this cohort are similar to those previously reported in both congenital stationary night blindness type 2 (CSNB2) and Aland Island eye disease (AIED). This study addresses whether CSNB2 and AIED are a single entity or whether the latter is a subset of the former.

Adult↗

A refined genetic map of the region of chromosome 17 surrounding the von Recklinghausen neurofibromatosis (NF1) gene.

The von Recklinghausen neurofibromatosis (NF1) gene has been mapped to the pericentromeric region of chromosome 17. We conducted linkage analyses of NF1 by using 10 polymorphic DNA markers from this chromosomal region. We ascertained 20 American Caucasian NF1 families (163 individuals, 98 NF1 affected) in Michigan and Ohio and also studied a large family ascertained primarily in North Carolina. The following markers were used in this study: HHH202, TH17.19, D17Z1, ERBA1, EW203, EW206, EW207, EW301, CRI-L581, and CRI-L946. NF1 did not recombine with either TH17.19 or HHH202 in any of the informative meioses surveyed (maximum lod scores of 17.04 and 7.21, respectively, at a recombination fraction of .00), indicating that these markers map very close to the NF1 gene. We also report evidence of three instances of recombination between NF1 and the centromeric marker D17Z1 (maximum lod score of 13.43 at a recombination fraction of .04), as well as two crossovers between pairs of marker loci. We find no evidence of locus heterogeneity, and our results support the localization of the NF1 gene to proximal chromosome 17q.

Chromosome Mapping↗

[Genetic mapping of chromosome X: known localizations].

To be a linkage between the clinician and the molecular biologist is the aim of this paper. All the known genes on the X chromosome are usually reported in most of the human gene mapping catalogs. Here, X-linked diseases precisely mapped on the X chromosome are classified by systems. Gene mapping of the phenotypes is given for each system.

Bone Diseases↗

Genetic mapping of the chromosome of the cyanobacterium, Anabaena variabilis. Proximity of the structural genes for nitrogenase and ribulose-bisphosphate carboxylase.

A cosmid library of DNA from the chromosome of the nitrogen-fixing cyanobacterium, Anabaena variabilis, has been organized into about 40 linkage groups on the basis of cosmid-cosmid hybridization. Nitrogenase and ribulose-bisphosphate carboxylase are protein complexes that are, respectively, active in heterocysts and absent from vegetative cells, and active in vegetative cells and absent from heterocysts. The structural genes for the proteins of these two complexes are found to be in close proximity within one of the linkage groups. Other genes have also been tentatively localized on the basis of heterologous hybridization. Possible methods for linking the defined linkage groups are discussed.

Chromosome Mapping↗