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A statistical model for dissecting genomic imprinting through genetic mapping.

As a result of nonequivalent genetic contribution of maternal and paternal genomes to offsprings, genomic imprinting or called parent-of-origin effect, has been broadly identified in plants, animals and humans. Its role in shaping organism's development has been unanimously recognized. However, statistical methods for identifying imprinted quantitative trait loci (iQTL) and estimating the imprinted effect have not been well developed. In this article, we propose an efficient statistical procedure for genomewide estimating and testing the effects of significant iQTL underlying the quantitative variation of interested traits. The developed model can be applied to two different genetic cross designs, backcross and F(2) families derived from inbred lines. The proposed procedure is built within the maximum likelihood framework and implemented with the EM algorithm. Extensive simulation studies show that the proposed model is well performed in a variety of situations. To demonstrate the usefulness of the proposed approach, we apply the model to a published data in an F(2) family derived from LG/S and SM/S mouse stains. Two partially maternal imprinting iQTL are identified which regulate the growth of body weight. Our approach provides a testable framework for identifying and estimating iQTL involved in the genetic control of complex traits.

Algorithms↗

Genetic map of bacteriophage T3.

About 200 amber mutants of phage T3 were found to lie in 14 different genes. These genes are homologous to known T7 genes. The genetic map of T3 is very similar to that of T7.

Coliphages↗

[Genetic mapping of unstable chloramphenicol resistance determinant in Streptomyces coelicolor A3(2)].

The results indicative of chromosomal localization of the unstable chloramphenicol resistance determinant in Streptomyces coelicolor A3(2) have been obtained. Independent mutations specifying chloramphenicol sensitivity in different strains of S. coelicolor A3(2), S18 and A617M are localized in the same region flanked by markers argA1 and cysD18 on the genetic map. Mutations restoring chloramphenicol resistance are also localized in this region. Different locations of the genetically unstable determinant of chloramphenicol resistance detected in various laboratories are discussed, in relation to the results showing that transfer to chloramphenicol sensitivity is due to a set of various rearrangements (deletions, amplifications, deamplifications, etc.), differing in separate variants.

Chloramphenicol Resistance↗

Mapping genetic systems by the supratype method.

Kinship mapping and population supratypes provide information on order and relative genetic position of loci within a system too small to map by recombination. These methods are compared for the RH, beta-globin, HLA, and GM systems, where recombination between loci is estimated as 0.0002-0.0069. Supratype analysis does not appreciably improve kinship mapping. Mean recombination within systems appears to be 10(-4) morgans/kb, an order of magnitude greater than the average for the whole genome. Possible implications of this discrepancy are discussed.

Chromosome Mapping↗

Genome-wide characterization of Tetrahymena thermophila chromosome breakage sites. II. Physical and genetic mapping.

The chromosomes of the macronuclear (expressed) genome of Tetrahymena thermophila are generated by developmental fragmentation of the five micronuclear (germline) chromosomes. This fragmentation is site specific, directed by a conserved chromosome breakage sequence (Cbs element). An accompanying article in this issue reports the development of a successful scheme for the genome-wide cloning and identification of functional chromosome breakage sites. This article reports the physical and genetic characterization of 30 functional chromosome breakage junctions. Unique sequence tags and physical sizes were obtained for the pair of macronuclear chromosomes generated by fragmentation at each Cbs. Cbs-associated polymorphisms were used to genetically map 11 junctions to micronuclear linkage groups and macronuclear coassortment groups. Two pairs of junctions showed statistically significant similarity of the sequences flanking the Cbs, suggestive of relatively recent duplications of entire Cbs junctions during Tetrahymena genome evolution. Two macronuclear chromosomes that lose at least one end in an age-related manner were also identified. The whole-genome shotgun sequencing of the Tetrahymena macronucleus has recently been completed at The Institute for Genome Research (TIGR). By providing unique sequence from natural ends of macronuclear chromosomes, Cbs junctions will provide useful sequence tags for relating macro- and micronuclear genetic, physical, and whole-genome sequence maps.

Animals↗

The C system of cattle blood groups. 2. Partial genetic map of the system.

20 cases of irregular inheritance of phenogroups in the C system of cattle blood groups were used to deduce a partial genetic map of this system, taking into consideration the 11 internationally recognized antigenic factors and the 4 additional factors recently described by Grosclaude et al. (1980). This partial map bears resemblance to that established by Bouw et al. (1974) in Dutch cattle. The operational length of the DNA sequence coding for the C system was estimated to be 0.3 centimorgan, a value which is approximately half of that obtained for the B system by Grosclaude et al. (1979). It is concluded that the phenogroups of the C system. like those of the B system, are controlled by a cluster of loci.

Animals↗

Physical and genetic map of the organomercury resistance (Omr) and inorganic mercury resistance (Hgr) loci of the IncM plasmid R831b.

Tn7 insertion mutagenesis has been used to facilitate the generation of a physical (restriction endonuclease) and genetic map of the IncM plasmid, R831b. The only selectable phenotypes carried by this 90-kb conjugative plasmid are resistances to inorganic mercury [Hg(II)] and to organomercury compounds. Mutants in the Hgr locus of R831b complemented previously described mutants in the mer operon of the IncFII plasmid R100, indicating functional homology of the locus in each of these different plasmids. However, the R831b Hgr locus is not notably similar in restriction site pattern to either the mer operon of R100 or the mercury resistance transposon, Tn501. Although the enzymes they encode are co-ordinately regulated, the Omr locus of R831b maps approx. 13.5 kb away from the Hgr locus. Three insertions which affect neither phenotype lie between the Hgr and Omr loci; thus, the loci are separated both physically and genetically. One mutant was obtained which tentatively identifies the position of the Tra locus of R831b as adjacent to the Hgr locus.

Chromosome Mapping↗

An integrated physical and genetic map spanning chromosome band 10q24.

Chromosome band 10q24 is rich in genes involved in development, tumorigenesis, neurological disorders, hormone metabolism, and environmentally induced disease susceptibility. We have constructed an STS-based integrated physical and genetic map of 10q24 derived from the CEPH-Généthon mega-YAC contig data for this region. This map consists of 42 fluorescence in situ hybridization-mapped overlapping CEPH mega-YACs spanning approximately 15 Mb to which 49 STS markers have been assigned, including 24 Généthon CA repeat genetic markers, 10 known gene loci from the 10q24 region (IFI56, IDE, PDE6C, RBP4, CYP2C, CD39, DNTT, GOT1, WNT8B, and PAX2) and 11 additional expressed sequences of unknown function.

Chromosome Banding↗

Issues concerning ethical conduct and genetic mapping raised at Montreal meeting.

Ethical concerns about the Human Genome Diversity Project were discussed in Montreal last year during the 1st International Conference on DNA Sampling and Banking. This article, the second in a 2-part series, looks at the potential for misuse and commercialization of DNA samples and discusses some of the ethical concerns surrounding genetic mapping.

Canada↗

Genetic map of 16 polymorphic markers forming three linkage groups assigned to rat chromosome 4.

Sixteen polymorphic markers, including markers for eight new loci, forming three linkage groups, were assigned to rat Chromosome (Chr) 4 by linkage analysis of the progeny of an F2 intercross of Fischer (F344/N) and Lewis (LEW/N) inbred rats. One gene, Igk, was mapped by restriction fragment length polymorphism (RFLP) analysis. One marker for Tcrb was identified by the polymorphic insertion of a repetitive LINE element. The remaining 14 markers contained polymorphic simple sequence repeats (SSRs). Ten were identified in genes (Tgfa, Npy, Prss1, Prss2, Aldr1, Iapp, Prp, Eno2, Cacnl1a1, and Il6), one was identified in a sequence related to a gene (Egr4l1), and three were identified in anonymous DNA segments. The SSR markers were highly polymorphic in 16 inbred rat strains. These markers expand the genetic map of the rat and should be useful in future genetic studies of inbred rats.

Animals↗

The genetic map of the B system of cattle blood groups as observed in French breeds.

40 cases of irregular inheritance of phenogroups in the B system of cattle blood groups, that were presumed to have arisen from single crossing-over, have been used to establish a partial genetic map of this system. In addition, the relative positions in the map of several antigenic factors were inferred from relationships observed between particular phenogroups occurring in French breeds. The tentative map thus obtained shows an overall similarity to that established by Ruiterkamp et al. (1977) in Dutch Friesian cattle. This result, in addition to other arguments, supports the hypothesis that the genetic structure of the B system of cattle blood groups is basically the same in all taurine breeds. Evidence is given, for the first time, for the occurrence in the B system of genetic events other than single crossing-over (double crossing-over or gene conversion, and possibly deletion). The rate of recombination between the genetic determinants of the terminal factors of the system, Q and I', was calculated in the progeny of some Normande bulls heterozygous for these two determinants (447 gametes); a value of 1.34 centimorgan was obtained. However complementary data indicate that 0.7 centimorgan would be a better estimate.

Animals↗

High-density genetic map of the BRCA1 region of chromosome 17q12-q21.

To facilitate the positional cloning of the breast-ovarian cancer gene BRCA1, we constructed a high-density genetic map of the 8.3-cM interval between D17S250 and GIP on chromosome 17q12-q21. Markers were mapped by linkage in the CEPH and in extended kindreds in our breast cancer series. The map comprises 33 ordered polymorphisms, including 12 genes and 21 anonymous markers, yielding an average of one polymorphism every 250 kb. Twenty-five of the markers are PCR-based systems. The order of polymorphic genes and markers is cen-D17S250-D17S518-HER2-THRA1-RARA-D17S80 -KRT10-[D17S800-D17S857]-GAS- D17S856-EDH17B-D17S855-D17S859-D17S858-[++ +PPY-D17S78]-D17S183-EPB3-D17S579- D17S509-[D17S508-D17S190 = D17S810]-D17S791-[D17S181 = D17S806]-D17S797- HOX2B-GP3A-[D17S507 = GIP]-qter. BRCA1 lies in the middle of the interval, between THRA1 and D17S183. Markers from this map can be used to determine whether cancer is linked to BRCA1 in families, to evaluate whether tumors have lost heterozygosity at loci in the region, and to identify probes for characterizing chromosomal rearrangements from patients and from tumors.

Alleles↗

[Localization of the gene coding for adenine phosphoribosyltransferase on the genetic map of chromosome 8 in the mouse].

Polymorphism of electrophoretic mobility of adenine phosphoribosyltransferase (APRT) was found in a population of domestic mice, Mus musculus bactrianus. The Aprt gene was mapped using two markers: plasma esterase 1 coded by the gene Es-1 situated at the distance of 26 morgans from the centromere, and a Robertsonian translocation Rb (8.17) 1 Iem which marks the centromere. The results of linkage analysis permitted to localize the gene Aprt at 51 morgans from the centromere, and 25 morgans distal from the gene Es-1 on the genetic map of chromosome 8. It is found that emotional stress does not alter the recombination rate at chromosome 8, when spermatocytes are at the pachytene stage.

Adenine Phosphoribosyltransferase↗

High-resolution genetic mapping at the Bph15 locus for brown planthopper resistance in rice (Oryza sativa L.).

Resistance to the brown planthopper (BPH), Nilaparvata lugens Stal, a devastating sucking insect pest of rice, is an important breeding objective in rice improvement programs. Bph15, one of the 17 major BPH resistance genes so far identified in both cultivated and wild rice, has been identified in an introgression line, B5, and mapped on chromosome 4 flanked by restriction fragment length polymorphism markers C820 and S11182. In order to pave the way for positional cloning of this gene, we have developed a high-resolution genetic map of Bph15 by positioning 21 DNA markers in the target chromosomal region. Mapping was based on a PCR-based screening of 9,472 F(2) individuals derived from a cross between RI93, a selected recombinant inbred line of B5 bearing the resistance gene Bph15, and a susceptible variety, Taichung Native 1, in order to identify recombinant plants within the Bph15 region. Recombinant F(2) individuals with the Bph15 genotype were determined by phenotype evaluation. Analysis of recombination events in the Bph15 region delimited the gene locus to an interval between markers RG1 and RG2 that co-segregated with the M1 marker. A genomic library of B5 was screened using these markers, and bacterial artificial chromosome clones spanning the Bph15 chromosome region were obtained. An assay of the recombinants using the sub-clones of these clones in combination with sequence analysis delimited the Bph15 gene to a genomic segment of approximately 47 kb. This result should serve as the basis for eventual isolation of the Bph15 resistance gene.

Animals↗

The physical and genetic map surrounding the Lyst gene on mouse chromosome 13.

During the recent cloning of the mouse Lyst gene we developed both a high-resolution genetic map and a complete YAC and BAC contig of the Lyst critical region on mouse Chromosome 13. We also report the mapping of the human homologue of the mouse Lyst gene (LYST) to 1q43. These data are consistent with LYST being the gene for the human Chediak-Higashi Syndrome and strengthen the synteny relationship between MMU13 and human 1q43.

Animals↗

Refining the genetic map for the region flanking the X-linked hypophosphataemic rickets locus (Xp22.1-22.2).

We have screened fourteen kindreds with X-linked hypophosphataemic rickets with four microsatellite markers, viz AFM163yh2, DXS999 (AFM234yf12), DXS443 and DXS365, in order to refine the genetic map flanking the gene, and to define a close flanking interval for the construction of a yeast artificial chromosome (YAC) and cosmid contig. The genetic data were enhanced after the isolation of a large 1.2-megabase YAC derived from AFM163yh2, in which marker DXS274 was present but not DXS365 or DXS443. Against HYP, DXS365, AFM163yh2 and DXS443 showed no recombinants (Zmax = 18.1, Zmax = 9.9, and Zmax = 16.0 respectively). DXS999 gave Zmax = 9.6 at 4% recombination and lies distal to HYP but proximal to DXS197 and DXS43. The disease gene and markers AFM163yh2 and DXS365 are flanked by DXS443 and DXS274. Combining the genetic and physical data, we are able to propose the following gene marker order: Xptel-DXS43-DXS197-DXS999-DXS443-[(DXS3 65-AFM163yh2), HYP]-DXS274-DXS41-Xcen.

Base Sequence↗

A genetic map of bovine chromosome 7 with an interspecific hybrid backcross panel.

A genetic linkage map of bovine Chromosome (Chr) 7 was generated with a Bos taurus x Bos gaurus interspecific hybrid backcross panel. This study included six previously mapped microsatellites and five unmapped expressed genes that were identified by PCR-based restriction fragment length variants (RFLVs). The gene order (from centromere to telomere) and the map distances (in centimorgans) are as follows: cen-BM2607-11.2-LDLR-3.6-AMH,CSF2-11. 2-BP41-19-BM6117-19-SPARC-14.4-FGFA-15.5-BM18 53-11.2-RASA-18. 8-ILSTS006. Previous comparative synteny mapping demonstrated that bovine Chr 7 shares homologous regions with both HSA5q and HSA19p. A break or fusion between AMH and CSF2 in an ancestral chromosome is suggested to account for the current arrangement of these homologous segments in the human and bovine genomes. In this study, we demonstrate that a short proximal portion of BTA7 is homologous with HSA19p, while a larger distal portion of BTA7 is homologous with human Chr 5q. The orientation of these conserved human segments on BTA7 is also demonstrated. Our data show that the linear order of genes has not been conserved within the homologous region of HSA5 and BTA7, and one chromosomal translocation or inversion is proposed to account for this difference.

Animals↗