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At least 163 records · Page 9Linked to original sources
PubMed2006

Genome-wide scan for type 1 diabetic nephropathy in the Finnish population reveals suggestive linkage to a single locus on chromosome 3q.

Diabetic nephropathy (DN) is the primary cause of morbidity and mortality in patients with type 1 as well as type 2 diabetes, and accounts for 40% of end-stage renal disease in the Western world. Familial clustering of DN suggests importance of genetic factors in the development of the disease. In the present study, we performed a two-stage genome-wide scan to search for chromosomal loci containing susceptibility genes for nephropathy in patients with type 1 diabetes. In total, 83 discordant sib pairs (DSPs), sibs concordant for type 1 diabetes but discordant for nephropathy, were collected from Finland, a homogeneous population with one of the highest incidences of type 1 diabetes. To map loci for DN, we applied DSP analysis to detect linkage. In the initial scan, 73 DSPs were typed using 900 markers with an average intermarker distance of approximately 4 cM. Multipoint DSP analysis identified five chromosome regions (3q, 4p, 9q, 16q, and 22p) with maximum logarithm of odds (LOD) score (MLS) >or=1.0 (corresponding to a nominal P-value <or=0.015). In the second stage, additional 43 markers flanking these five loci were genotyped in all 83 DSPs. Using simulations, we determined the empirical threshold with LOD score of 1.76 and 3.12 for suggestive and significant linkage, respectively. No locus reached the genome-wide significance of 5%. However, one locus on 3q reached suggestive linkage with MLS of 2.67 (P=4.4 x 10(-4)). These results, together with data from others, suggest that the locus on 3q most likely has a susceptibility gene for DN.

Adolescent↗
PubMed1980

Genes for three Drosophila heat-shock-induced proteins at a single locus.

Two plasmids containing cDNA inserts complementary to the messenger RNAs for the 26,000 and 23,000 molecular weight heat-shock-induced proteins from Drosophila melanogaster were identified. Both of these probes hybridized to a site of a major heat-shock-induced puff, 67B. Hybridization by the gel transfer technique with genome DNA that had been cleaved by a restriction endonuclease indicated that the two genes are closely linked. This expectation was validated through isolation of a DNA fragment generated by BamHI endonuclease containing genes for the 26,000 and 23,000 molecular weight heat-shock-induced proteins and also a gene encoding the 27,000 molecular weight heat-shock-induced protein.

Animals↗
PubMed1998

Multiple forms of arginase are differentially expressed from a single locus in Neurospora crassa.

The Neurospora crassa catabolic enzyme, arginase (L-arginine amidinohydrolase, EC 3.5.3.1), exists in multiple forms. Multiple forms of arginase are found in many vertebrates, but this is the only reported example in a microbial organism. The two major forms are structurally similar with subunit sizes of 36 and 41 kDa, respectively. The larger form is produced by mycelia growing in arginine-supplemented medium. Both forms are localized in the cytosol. The structural gene for arginase, aga, has been cloned and sequenced; it contains a 358-codon open reading frame with three in-frame ATGs at the amino terminus. Mutagenesis of these ATGs revealed that the first ATG initiates the 41-kDa protein and the third ATG initiates the 36-kDa protein. Mutation of the second ATG has no effect on translation. Northern analysis demonstrated that a 1.4-kilobase (kb) transcript is synthesized in minimal medium and both a 1.4- and 1.7-kb transcript are produced in arginine-supplemented medium. Primer extension identified the 5' ends of each transcript and demonstrated that the first and third ATG of the open reading frame are the initial AUGs of the 1.7- and 1. 4-kb mRNA, respectively. The results suggest that a basal promoter produces the 1.4-kb transcript and an arginine "activated" promoter is responsible for the 1.7-kb transcript. Tandem promoters are rare in eukaryotic organisms, and they often regulate developmental or tissue-specific gene expression. The possibility that arginase has a role in differentiation in N. crassa is being investigated.

Amino Acid Sequence↗
PubMed2001

Hereditary vascular retinopathy, cerebroretinal vasculopathy, and hereditary endotheliopathy with retinopathy, nephropathy, and stroke map to a single locus on chromosome 3p21.1-p21.3.

We performed a genomewide search for linkage in an extended Dutch family with hereditary vascular retinopathy associated with migraine and Raynaud phenomenon. Patients with vascular retinopathy are characterized by microangiopathy of the retina, accompanied by microaneurysms and telangiectatic capillaries. The genome search, using a high throughput capillary sequencer, revealed significant evidence of linkage to chromosome 3p21.1-p21.3 (maximum pairwise LOD score 5.25, with D3S1578). Testing of two additional families that had a similar phenotype, cerebroretinal vasculopathy, and hereditary endotheliopathy with retinopathy, nephropathy, and stroke, revealed linkage to the same chromosomal region (combined maximum LOD score 6.30, with D3S1588). Haplotype analysis of all three families defined a 3-cM candidate region between D3S1578 and D3S3564. Our study shows that three autosomal dominant vasculopathy syndromes with prominent cerebroretinal manifestations map to the same 3-cM interval on 3p21, suggesting a common locus.

Chromosome Mapping↗
PubMed1992

The maintenance of single-locus polymorphism. IV. Models with mutation from existing alleles.

The ability of viability selection to maintain allelic polymorphism is investigated using a constructionist approach. In extensions to the models we have previously proposed, a population is bombarded with a series of mutations whose fitnesses in conjunction with other alleles are functions of the corresponding fitnesses with a particular allele, the parent allele, already in the population. Allele frequencies are iterated simultaneously, thus allowing alleles to be driven to extinction by selection. Such models allow very high levels of polymorphism to evolve: up to 38 alleles in one case. Alleles that are lethal as homozygotes can evolve to surprisingly high frequencies. The joint evolution of allele frequencies and viabilities highlights the necessity to consider more than the current morphology of a population. Comparisons are made with the neutral theory of evolution and it is suggested that failure to reject neutrality using the Ewens-Watterson test cannot be regarded as evidence for the neutral theory.

Mathematics↗
PubMed1998

Genetic diversity at a single locus under viability selection and facultative apomixis: equilibrium structure and deviations from Hardy-Weinberg frequencies.

We extensively analyze the maintenance of genetic variation and deviations from Hardy-Weinberg frequencies at a diallelic locus under mixed mating with apomixis and constant viability selection. Analytical proofs show that: (1) at most one polymorphic equilibrium exists, (2) polymorphism requires overdominant or underdominant selection, and (3) a simple, modified overdominance condition is sufficient to maintain genetic variation. In numerical analyses, only overdominant polymorphic equilibria are stable, and these are stable whenever they exist, which happens for approximately 78% of random fitness and mating parameters. The potential for maintaining both alleles increases with increasing apomixis or outcrossing and decreasing selfing. Simulations also indicate that equilibrium levels of heterozygosity will often be statistically indistinguishable from Hardy-Weinberg frequencies and that adults, not seeds, should usually be censused to maximize detecting deviations. Furthermore, although both censuses more often have an excess rather than a deficit of heterozygotes, analytical sign analyses of the fixation indices prove that, overall, adults are more likely to have an excess and seeds a deficit at equilibrium.

Adult↗
PubMed1995

Microsatellite instability at a single locus (D11S988) on chromosome 11p15.5 as a late event in mammary tumorigenesis.

Replication errors at microsatellite repeats are markers for genomic instability in hereditary nonpolyposis colon carcinoma and in some sporadic cancers. Microsatellite sequences may show alterations in one or both alleles in some tumors, suggesting an error in the DNA replication of dinucleotide repeats. We have investigated microsatellite instability (MSI) in sporadic breast tumors at several loci on the short arm of chromosome 11. Among microsatellites studied we found a high frequency of MSI at one specific locus, D11S988 on chromosome 11p15.5. Most colorectal tumors that exhibit MSI display abnormalities of at least one other locus and usually more. By contrast we have detected only one abnormal microsatellite in all the tumors examined. This marker lies between the TH and HBB genes, a subregion previously suggested to harbor a putative tumor suppressor gene for breast cancer. Loss of heterozygosity for chromosome markers at 11p15 has earlier been correlated with poor prognosis. In an unselected panel of primary breast tumors, we observed that 20 of 69 showed mobility shifts of D11S988 in tumor compared with corresponding normal DNA samples. Tumors with instability at D11S988 were rapidly proliferating compared with tumors without MSI. DNA aneuploidy, estrogen receptor positivity and moderate to poorly differentiated tumor phenotype were also characteristics of tumors with MSI at this locus and the majority also exhibited loss of heterozygosity at one or more of the six 11p loci analyzed. Taken together these data suggest that MSI at the D11S988 locus is a late event in mammary tumorigenesis and may be associated with progression of breast carcinomas.

Alleles↗
PubMedDate not supplied

Single-locus inheritance in the allotetraploid Coffea arabica L. and interspecific hybrid C. arabica x C. canephora.

Molecular cytogenetic analysis has indicated that Coffea arabica is an amphidiploid formed from the hybridization between two closely related diploid progenitor species, C. canephora and C. eugenioides. Our aim was to determine the mode of inheritance in C. arabica and in a tetraploid interspecific hybrid (called arabusta) between C. arabica and C. canephora as revealed by segregation analyses of restriction fragment length polymorphism (RFLP) loci markers. The observed RFLP allele segregations in an F(2) progeny of C. arabica conform to disomic inheritance as expected, with regular bivalent pairing of homologous chromosomes in the F1 hybrid. In contrast, RFLP loci followed tetrasomic inheritance in the arabusta interspecific hybrid, although bivalents have been reported to predominate greatly at meiosis in its hybrid. These results suggest that homologous chromosomes do not pair in C. arabica, not as a consequence of structural differentiation, but because of the functioning of pairing regulating factors. Moreover, the arabusta hybrid seems to offer the possibility of gene exchange between the homologous genomes.

Alleles↗
PubMed1996

Single locus microsatellites isolated using 5' anchored PCR.

Microsatellites are widely used as genetic markers because they are co-dominant, multiallelic, easily scored and highly polymorphic. A major drawback of microsatellite markers is the time and cost required to characterise them. We have developed a novel technique to reduce this cost by producing a microsatellite-rich PCR profile from genomic DNA which was cloned to yield a genomic library enriched for microsatellites. Sequence data and subsequent allele scoring within pedigrees revealed that these microsatellites retained their original repeat length and segregated normally. This technique permits genomic amplification with only one specific primer. Together with enrichment, the savings in primer costs reduces the cost of microsatellite characterisation considerably.

DNA Primers↗
PubMedDate not supplied

On the displacement of single-locus polymorphisms.

And where, along the evolutionary track, some mutant gene did arise which was advantageous in its heterozygous degree of expression but deleterious homozygously, that gene, though temporarily multiplied as a make-shift arrangement, would usually have become replaced, after a while, by mutant genes of less deviant expression, occupying the same or other loci, which gave an equivalent advantage when they were present homozygously. For such genes would make possible a more uniform, and therefore (when all individuals were averaged) a closer approach to the adaptational optimum.

Alleles↗
PubMed2001

Chromosome-specific single-locus FISH probes allow anchorage of an 1800-marker integrated radiation-hybrid/linkage map of the domestic dog genome to all chromosomes.

We present here the first fully integrated, comprehensive map of the canine genome, incorporating detailed cytogenetic, radiation hybrid (RH), and meiotic information. We have mapped a collection of 266 chromosome-specific cosmid clones, each containing a microsatellite marker, to all 38 canine autosomes by fluorescence in situ hybridization (FISH). A 1500-marker RH map, comprising 1078 microsatellites, 320 dog gene markers, and 102 chromosome-specific markers, has been constructed using the RHDF5000-2 whole-genome radiation hybrid panel. Meiotic linkage analysis was performed, with at least one microsatellite marker from each dog autosome on a panel of reference families, allowing one meiotic linkage group to be anchored to all 38 dog autosomes. We present a karyotype in which each chromosome is identified by one meiotic linkage group and one or more RH groups. This updated integrated map, containing a total of 1800 markers, covers >90% of the dog genome. Positional selection of anchor clones enabled us, for the first time, to orientate nearly all of the integrated groups on each chromosome and to evaluate the extent of individual chromosome coverage in the integrated genome map. Finally, the inclusion of 320 dog genes into this integrated map enhances existing comparative mapping data between human and dog, and the 1000 mapped microsatellite markers constitute an invaluable tool with which to perform genome scanning studies on pedigrees of interest.

Animals↗