Genetic, physical, and comparative map of the subtelomeric region of mouse Chromosome 4

Abstract

The subtelomeric region of mouse chromosome (Chr) 4 harbors loci with effects on behavior, development, and disease susceptibility. Regions near the telomeres are more difficult to map and characterize than other areas because of the unique features of subtelomeric DNA. As a result of these problems, the available mapping information for this part of mouse Chr 4 was insufficient to pursue candidate gene evaluation. Therefore, we sought to characterize the area in greater detail by creating a comprehensive genetic, physical, and comparative map. We constructed a genetic map that contained 30 markers and covered 13.3 cM; then we created a 1.2-Mb sequence-ready BAC contig, representing a 5.1-cM area, and sequenced a 246-kb mouse BAC from this contig. The resulting sequence, as well as approximately 40 kb of previously deposited genomic sequence, yielded a total of 284 kb of sequence, which contained over 20 putative genes. These putative genes were confirmed by matching ESTs or cDNA in the public databases to the genomic sequence and/or by direct sequencing of cDNA. Comparative genome sequence analysis demonstrated conserved synteny between the mouse and the human genomes (1p36.3). DNA from two strains of mice (C57BL/6ByJ and 129P3/J) was sequenced to detect single nucleotide polymorphisms (SNPs). The frequency of SNPs in this region was more than threefold higher than the genome-wide average for comparable mouse strains (129/Sv and C57BL/6J). The resulting SNP map, in conjunction with the sequence annotation and with physical and genetic maps, provides a detailed description of this gene-rich region. These data will facilitate genetic and comparative mapping studies and identification of a large number of novel candidate genes for the trait loci mapped to this region.

Pseudogenization of a Sweet-Receptor Gene Accounts for Cats' Indifference toward Sugar

“…Further, in Drosophila, the behavioral and electrophysiological responses to trehalose are diminished in two mutants that carry deletions in the trehalose recognition gene, Gr5a [27]. In the mouse, variation in preference for sweet-tasting stimuli maps to the gene for T1R3, located within the Sac locus [28,29]. This gene is allelic in mice, and several reports identify a missense mutation (I60T) as being the most likely mutation accounting for the phenotypic differences [13,14,16,30–33].…”

“…Tas1r2 and Tas1r3 overgo probes were radioactively labeled by the random hexa-nucleotide method, and hybridization and washing of membranes were as described [29]. We identified 47 positive BAC clones for cat Tas1r2 and cat Tas1r3, and sequenced all of the positive BAC ends.…”

Genetics of sweet taste preferences

“…Studies using crosses between different inbred mouse strains have mapped the Sac locus to the subtelomeric region of mouse chromosome 4 and have shown that it affects sweetener preferences and the afferent responses of gustatory nerves to sweeteners . Our positional cloning study has shown that the Sac locus corresponds to the Tas1r3 gene and that Tas1r3 sequence variants are associated with sweetener preference phenotypes in genealogically diverse mouse strains . Additional evidence for identity of Sac and Tas1r3 was obtained in studies using congenic, transgenic and knockout mice .…”

Receptor, signal transduction and evolution of sweet, umami and bitter taste

“…The discovery and identification of T1R as the receptors of sweet or umami stimuli were reviewed by Bachmanov and Beauchamp (2007) and Montmayeur and Matsunami (2002). Briefly, the mouse sac gene was found to encode a sweet taste receptor T1R3 (Bachmanov et al 1997(Bachmanov et al , 2001Li et al 2001Li et al , 2002a. Studies of functional expression in heterogeneous cells further showed that T1R3 combined with T1R2 can recognize all kinds of sweet substances including natural sugars, artificial sweeteners and d-amino acids (Li et al 2002a, b;Nelson et al 2001).…”