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Susceptibility to diabetes or the inherent potential to develop diabetes is controlled by genes, the hereditary elements of the cell. The identification of specific genes, which is called mapping, depends on several factors. The existence of a single major gene, genetic homogeneity (uniformity), and the availability of appropriate clinical material influence mapping the genes that determine susceptibility to diabetes. The ability to detect susceptibility genes depends on diabetic risk carried by relatives and on the location of the susceptibility genes in relation to genetic markers (which are elements that identify certain chromosomes, the threadlike structures in the cell nucleus that carry the genes). Insulin-dependent diabetes mellitus (IDDM) appears to be controlled by a single major locus, or gene site, and remaining polygenic factors, or elements with multiple gene components. The single major locus appears to consist of genes from the histocompatibility (HLA) complex, because the risk of developing IDDM seems to be controlled by specific genotypes or gene profiles. Mapping the residual polygenic factors will be a long and difficult task. The risk of developing non-insulin-dependent diabetes mellitus (NIDDM) appears to be controlled by few genes with a moderate effect and, to a greater extent, by residual polygenic factors, environmental effects, and genetic heterogeneity (variation). (Consumer Summary produced by Reliance Medical Information, Inc.)

The reconstruction of all of Ciona savignyi chromosomes via the development of a comprehensive genetic map, without using a physical map intermediate, s presented. The chromosomal reconstruction allowed to study the evolution of genome structure in highly polymorphic species by comparing the genome of C. savignyi to its divergent sister species, Ciona intestinalis.

A Markov chain Monte Carlo (MCMC) algorithm, HASH (haplotype assembly for single human) to assemble haplotypes from sequenced DNA fragments that were mapped to a reference genome assembly is presented. The MCMC algorithm provides a general framework for haplotype assembly that could be applied to sequence data generated by other sequencing technologies.

A detailed comparative characterization was performed to identify a large imprinted domain mapping to chromosome 7q21 in humans and proximal chromosome 6 in mice. Results revealed a novel placenta-specific transcript, TFP12, which is expressed from the maternal allele in both humans and mice.

Several genome-wide analyses and mapping techniques are employed to study and characterize the active promoters in mouse embryonic cells and adult organs including heart, kidney and liver. The promoters with CpG islands are found to be highly non-tissue specific and generally associated with the RNA polymerase II.

The cline analysis is employed to study the various genome-wide patterns of gene flow across a hybrid zone that is related closely to a house mouse. The various biological processes associated with such clines are found to highly affect their survival and reproduction.

The specific 64-to-20 mapping found in the genetic code may be optimized to carry other information such as signals for splicing, folding, localization and regulation, besides carrying a protein sequence. This property of the DNA code could have evolved to reduce damaging effects of frameshift errors.

A novel analytical approach, in combination with the allelic transcript ratio mapping is employed to accurately define the genomic location of cis-acting regulatory elements. The method provides a tactable approach for dissecting the complexities of gene regulation, as it is completely unaffected by other environmental and trans-acting genetic factors and sources of variation.

The microarray analysis of RNA from different wild species and subspecies of the house mouse is done to show that the regulatory changes in genes involved in reproduction are the main targets for divergence during the process of speciation. The results of the analysis show that all the comparisons between subspecies yield a very small number of genes with extremely different expression levels in the testis.

A comprehensive analysis using conventional and molecular cytogenetic mapping of common fragile sites (CFSs) and their expression frequencies in two mouse strains, BALB/c and C57BL/6, and in human probands is presented. It is demonstrated that induced mouse CFSs relate to sites of spontaneous gaps and breaks and CFS expression levels in chromosome bands are conserved between the two mouse strains and between syntenic mouse and human DNA segments.

An estimated ten regions located on seven different chromosomes show a significantly higher than average regional proportion of single nucleotide polymorphisms (SNPs) with alleles alternatively fixed in the two subspecies. The findings verified by sequencing fragment from regions detected as high and low differentiation in wild-derived domesticus and masculus mice, revealed a significantly higher differentiation in the former category than in the latter, in apparent agreement with the SNP analyses.

A study used the juxtacentromeric region of human chromosome 21 as a model system to map for the first time at less than or equal to 100-kb resolution a transition from constitutive heterochromatin to euchromatin. Results revealed that the juxtacentromeric region of the long arm of chromosome 21 is composed of a proximal compartment that is separated from the euchromatic compartment of the chromosome arm by a cluster of histone isoforms H3K9Me3 and H3K27Me 715-822 kb from the centromeric [alpha]-satellite block.

New resources for genomic studies in the rat were created. They are three physical maps- first comprising of fingerprinted bacterial artificial chromosome(BAC), second yeast artificial chromosome(YAC) and third an integration of both maps.

The draft genomic sequence of the rat provides essential information for annotating rat quantitative trait locus(QTL) maps. Successful computational alignments of 6108 mapped rat ESTs in the mouse genome helped in construction of comparative genome maps between rat and mouse.

A large genomic toolset culminating in the release of the rat draft genome sequence is developed. The rat draft sequence used data from the Radiation Hybrid(RH) map of the rat along with a variety of assembly package as part of their validation.

A computational method for identifying regulatory regions within three-way DNA alignments of human, mouse, and rat is developed. The resulting Regulatory Potential(RP) score is generalized.