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A genetic map of microsatellite markers on rat chromosome 7.

Nine microsatellite loci were mapped to rat Chromosome (Chr) 7 by genetic linkage and somatic cell hybrid analysis. These loci include the gene encoding a member of the IID sub-family of cytochrome P450 (Cyp2d), a gene with repetitive sequences expressed during myotube formation (D7Arb1e), four anonymous loci, D7Arb81, D7Arb208, D7Arb569, D7Arb609a, and three DNA loci defined by MapPair markers R245, R513, and R1071. The nine loci were all identified by PCR-based microsatellite polymorphism analysis and were characterized in 40 F2 intercross progeny of Fischer (F344/N) and Lewis (LEW/N) rats for segregation analysis. These markers formed a single linkage group spanning 76.8 cM with the following order and distances: D7Arb569-11.4 cM-D7Arb81-9.7 cM-R513-2.6 cM-Cyp2d-0.0 cM-R245-1.3 cM-D7Arb1e-10.4 cM-R1071-15.9 cM-D7Arb609a-15.4 cM-D7Arb208. Physical mapping of Cyp2d by somatic cell hybrid analysis allowed us to assign this linkage group to rat Chr 7. For each marker, two to six alleles were detected in a panel of 16 inbred rat strains (ACI/N, BN/SsN, BUF/N, DA/Bkl, F344/N, LER/N, LEW/N, LOU/MN, MNR/N, MR/N, SHR/N, SR/Jr, SS/Jr, WBB1/N, WBB2/N, WKY/N).

Alleles↗

Mouse scrapie responsive gene 1 (Scrg1): genomic organization, physical linkage to sap30, genetic mapping on chromosome 8, and expression in neuronal primary cell cultures.

We have previously reported a transcript of a novel mouse gene (Scrg1) with increased expression in transmissible spongiform encephalopathies and the cloning of the human mRNA analogue. In this paper, we present the genomic organization of the mouse and human SCRG1 loci, which exhibit a high degree of conservation. The genes are composed of three exons; the two downstream exons contain the protein coding region. The mouse gene is expressed in brain tissue essentially as a 0.7-kb message but also as a minor 2.6-kb mRNA. We have sequenced 20 kb of DNA at the mouse Scrg1 locus and found that the longer transcript is the prolongation of the 0.7-kb mRNA to a polyadenylation site located about 2 kb further downstream. Sequencing revealed that the mouse Scrg1 gene is physically linked to Sap30, a gene that encodes a protein of the histone deacetylase complex, and genetic linkage mapping assigned the localization of Scrg1 to chromosome 8 between Ant1 and Hmg2. Northern blot analysis showed that Scrg1 is under strict developmental control in mouse embryo and is expressed by cells of neuronal origin in vitro. Comparison of the rat, mouse, and human SCRG1 proteins identified a box of 35 identical contiguous amino acids and a characteristic cysteine distribution pattern defining a new protein signature.

Amino Acid Sequence↗

Genetic mapping of xenotropic leukemia virus-inducing loci in two mouse strains.

In genetic studies of C57BL/10 and BALB/c mice, inducibility of xenotropic murine leukemia virus from tissue cultures by treatment with 5-iododeoxyuridine shows single gene segregation ratios. In both strains, the virus-inducing loci are on chromosome 1, linked to the Dip-1/isozyme locus, but the two may not be at allelic sites.

Animals↗

Genetic mapping of X-linked ocular albinism: linkage analysis in a large Newfoundland kindred.

Genetic linkage studies in a large Newfoundland family affected by X-linked ocular albinism (OA1) showed linkage to markers from Xp22.3. One recombinant mapped the disease proximal to DXS143 (dic56) and two recombinants mapped the disease distal to DXS85 (782). Combining the data with that from 16 British families previously published confirmed close linkage between OA1 and DXS143 (dic56; Zmax = 21.96 at theta = 0.01, confidence interval (CI) 0.0005-0.05) and linkage to DXS85 (782; Zmax = 17.60 at theta = 0.07, CI = 0.03-0.13) and DXS237 (GMGX9; Zmax = 15.20 at theta = 0.08, CI = 0.03-0.15). Multipoint analysis (LINKMAP) gave the most likely order as Xpter-XG-DXS237-DXS 143-OA1-DXS85, with odds of 48:1 over the order Xpter-XG-DXS237-OA1-DXS143-DXS85, and odds exceeding 10(10):1 over other locations for the disease locus.

Albinism, Ocular↗

An integrated physical and genetic map of a 35 Mb region on chromosome Xp22.3-Xp21.3.

We have constructed a detailed physical map of the 35 Mb region spanning human chromosome Xp22.3-Xp21.3. The backbone of the map is represented by a single oriented contiguous stretch of 585 overlapping yeast artificial chromosome (YAC) clones covering the entire region. The map is formatted with 615 map objects that include 324 YACs, 185 sequence tagged sites, 28 genes, 85 chromosomal breakpoints and 37 highly polymorphic markers. Physical mapping was both guided and confirmed using 183 bins defined by chromosomal breakpoints and by overlapping regions of YAC clones. The localization of polymorphic markers in the physical map permits the integration of physical and genetic data across the region. These data establish chromosome Xp22.3-Xp21.3 as one of the best characterized large regions in the human genome. The map should greatly facilitate finer scale mapping and sequencing as well as the identification of disease genes from this portion of the human genome.

Base Sequence↗

Physical and genetic mapping at the ATA/ATC locus on chromosome 11q22-23.

Genetic heterogeneity in ataxia-telangiectasia (A-T) points to four different genes responsible for this disease. The two major A-T genes, ATA and ATC, were localized by genetic analysis close to each other on chromosome 11q22-23, prompting efforts of positional cloning. Essential steps in positional cloning are long-range cloning of the genomic region of interest, and derivation of highly polymorphic markers that would allow further reduction of the interval carrying the A-T gene. We constructed genomic contigs across the D11S611-D1S424 region harbouring the ATA and ATC genes in yeast artificial chromosome (YAC) vectors. These contigs were used as a fine mapping tool and enabled us to localize along the A-T region, eight microsatellite markers generated randomly by genome mapping centres. In addition, we used specific YAC clones to generate five new microsatellite markers based on polymorphic CA repeats. Recombination mapping based on Israeli A-T families indicates that the ATC gene is distal to the locus D11S1817. Further linkage analysis using these markers is expected to reduce the major A-T locus considerably to a size appropriate for cosmid cloning and identification of transcribed sequences.

Ataxia Telangiectasia↗

Physical and genetic mapping of amplified fragment length polymorphisms and the leaf rust resistance Lr3 gene on chromosome 6BL of wheat.

The Argentinian wheat cultivar Sinvalocho MA carries the Lr3 gene for leaf rust resistance on distal chromosome 6BL. In this cultivar, 33 spontaneous susceptible lines were isolated and cytogenetically characterized by C-banding. The analysis revealed deletions on chromosome 6BL in most lines. One line was nulli-6B, two lines were ditelo 6BS, two, three, and ten lines had long terminal deletions of 40, 30, and 20%, respectively, three lines showed very small terminal deletions, and one line had an intercalary deletion of 11%. Physical mapping of 55 amplified fragment length polymorphism (AFLP) markers detected differences between deletions and led to the division of 6BL into seven bins delimited by deletion breakpoints. The most distal bin, with a length smaller than 5% of 6BL, contained 22 AFLP markers and the Lr3 gene. Polymorphism for nine AFLPs between Sinvalocho MA and the rust leaf susceptible cultivar Gamma 6 was used to construct a linkage map of Lr3. This gene is at a genetic distance of 0.9 cM from a group of seven closely linked AFLPs. The location of the gene in a high recombinogenic region indicated a physical distance of approximately 1 Mb to the markers.

Chromosome Banding↗

Genetic mapping of a locus predisposing to human colorectal cancer.

Genetic linkage analysis was used to determine whether a specific chromosomal locus could be implicated in families with a history of early onset cancer but with no other unique features. Close linkage of disease to anonymous microsatellite markers on chromosome 2 was demonstrated in two large kindreds. The pairwise lod scores for linkage to marker D2S123 in these kindreds were 6.39 and 1.45 at zero recombination, and multipoint linkage with flanking markers resulted in lod scores of 6.47 and 6.01. These results prove the existence of a genetically determined predisposition to colorectal cancer that has important ramifications for understanding and preventing this disease.

Chromosome Mapping↗

Physical and genetic mapping of human chromosome 3 loci containing microsatellite repeats.

One hundred and six microsatellite repeat-containing loci, including 59 CA-containing repeats from the CEPH/Genethon collection, were regionally assigned on human chromosome 3 using a somatic cell hybrid mapping panel, diving the chromosome into 14 intervals. The others were dinucleotide and tetranucleotide repeat-containing loci newly developed for human chromosome 3, of which 26 were also localized by means of genetic linkage analysis against selected CEPH microsatellites. The regional assignment of these two marker sets in a common mapping panel facilitates their integration. Incorporation of these highly polymorphic loci into the developing physical and genetic maps should provide useful information for studies of various diseases involving chromosome 3.

Base Sequence↗

Cloning and genetic mapping of zebrafish BMP-2.

The BMP family of polypeptide growth factors has been shown to play diverse roles in establishing embryonic patterning and tissue fates. We report the cloning of the zebrafish homologue of BMP-2, examine its expression during embryogenesis, and find that it is localized to the distal end of the long arm of zebrafish chromosome 20. A missense mutation of the bmp2 gene has recently been shown to be responsible for the early dorsalized phenotype of the zebrafish swirl mutant [Kishimoto et al., 1997]. Given the dynamic expression of bmp2 in the developing embryo and the complex interactions of BMP signaling response in vertebrates, it is possible that other mutant phenotypes, due to altered bmp2 gene expression, will eventually map to or interact with this genetic locus.

Amino Acid Sequence↗

Genetic mapping of chronic childhood-onset spinal muscular atrophy to chromosome 5q11.2-13.3.

SPINAL muscular atrophy (SMA) describes a group of heritable degenerative diseases that selectively affect the alpha-motor neuron. Childhood-onset SMAs rank second in frequency to cystic fibrosis among autosomal recessive disorders, and are the leading cause of heritable infant mortality. Predictions that genetic heterogeneity underlies the differences between types of SMA, together with the aggressive nature of the most-severe infantile form, make linkage analysis of SMA potentially complex. We have now analysed 13 clinically heterogeneous SMA families. We find that 'chronic' childhood-onset SMA (including intermediate SMA or SMA type II, and Kugelberg-Welander or SMA type III) is genetically homogeneous, mapping to chromosomal region 5q11.2-13.3.

Adolescent↗

Genetic mapping and assignment of a long-range repeat cluster to band D of chromosome 1 in Mus musculus and M. spretus.

A cluster (D1Lub1) of a long-range repeat family was mapped to the proximal part of the Giemsa-negative band D in Chromosome 1 of Mus musculus and M. spretus by in situ hybridization with cloned probes of the long-range repeat family. By making use of restriction fragment length polymorphisms in DNAs from interspecific backcross mice, the cluster could be mapped to a position 5.3 +/- 2.1 cM distal to the Inha locus and the same distance proximal to the Bcl-2 locus. D1Lub1 was inseparable in 114 meiotic events from Acrg, Sag, and Akp-3. Taken together, the data may serve as a reference for coordinating the genetic and cytogenetic maps of Mus Chromosome 1. High-copy-number variants of the cluster, which appear cytogenetically as homogeneously staining regions at the same chromosome location, presumably arose by amplification of the long-range repeat family in situ.

Animals↗

Optimal allele-sharing statistics for genetic mapping using affected relatives.

The choice of allele-sharing statistics can have a great impact on the power of robust affected relative methods. Similarly, when allele-sharing statistics from several pedigrees are combined, the weight applied to each pedigree's statistic can affect power. Here we describe the direct connection between the affected relative methods and traditional parametric linkage analysis, and we use this connection to give explicit formulae for the optimal sharing statistics and weights, applicable to all pedigree types. One surprising consequence is that under any single gene model, the value of the optimal allele-sharing statistic does not depend on whether observed sharing is between more closely or more distantly related affected relatives. This result also holds for any multigene model with loci unlinked, additivity between loci, and all loci having small effect. For specific classes of two-allele models, we give the most powerful statistics and optimal weights for arbitrary pedigrees. When the effect size is small, these also extend to multigene models with additivity between loci. We propose a useful new statistic, S(rob dom), which performs well for dominant and additive models with varying phenocopy rates and varying predisposing allele frequency. We find that the statistic S(_#alleles), performs well for recessive models with varying phenocopy rates and varying redisposing allele frequency. We also find that for models with large deviation from null sharing, the correspondence between allele-sharing statistics and the models for which they are optimal may also depend on which method is used to test for linkage.

Alleles↗

Genetic map of the beginning of the rIIB cistron of bacteriophage T4.

In this report the herefore uncharacterized mutants at the beginning of the rIIB cistron of bacteriophage T4 have been connected to the main part of the map and have been shown not to be in any way unusual. The temperature sensitive mutant HD263 appears to be the earliest mutant in the cistron.

2-Aminopurine↗