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Genomic anatomy of the Tyrp1 (brown) deletion complex.


ABSTRACT: Chromosome deletions in the mouse have proven invaluable in the dissection of gene function. The brown deletion complex comprises >28 independent genome rearrangements, which have been used to identify several functional loci on chromosome 4 required for normal embryonic and postnatal development. We have constructed a 172-bacterial artificial chromosome contig that spans this 22-megabase (Mb) interval and have produced a contiguous, finished, and manually annotated sequence from these clones. The deletion complex is strikingly gene-poor, containing only 52 protein-coding genes (of which only 39 are supported by human homologues) and has several further notable genomic features, including several segments of >1 Mb, apparently devoid of a coding sequence. We have used sequence polymorphisms to finely map the deletion breakpoints and identify strong candidate genes for the known phenotypes that map to this region, including three lethal loci (l4Rn1, l4Rn2, and l4Rn3) and the fitness mutant brown-associated fitness (baf). We have also characterized misexpression of the basonuclin homologue, Bnc2, associated with the inversion-mediated coat color mutant white-based brown (B(w)). This study provides a molecular insight into the basis of several characterized mouse mutants, which will allow further dissection of this region by targeted or chemical mutagenesis.

SUBMITTER: Smyth IM 

PROVIDER: S-EPMC1450144 | biostudies-literature | 2006 Mar

REPOSITORIES: biostudies-literature

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Genomic anatomy of the Tyrp1 (brown) deletion complex.

Smyth Ian M IM   Wilming Laurens L   Lee Angela W AW   Taylor Martin S MS   Gautier Phillipe P   Barlow Karen K   Wallis Justine J   Martin Sancha S   Glithero Rebecca R   Phillimore Ben B   Pelan Sarah S   Andrew Rob R   Holt Karen K   Taylor Ruth R   McLaren Stuart S   Burton John J   Bailey Jonathon J   Sims Sarah S   Squares Jan J   Plumb Bob B   Joy Ann A   Gibson Richard R   Gilbert James J   Hart Elizabeth E   Laird Gavin G   Loveland Jane J   Mudge Jonathan J   Steward Charlie C   Swarbreck David D   Harrow Jennifer J   North Philip P   Leaves Nicholas N   Greystrong John J   Coppola Maria M   Manjunath Shilpa S   Campbell Mark M   Smith Mark M   Strachan Gregory G   Tofts Calli C   Boal Esther E   Cobley Victoria V   Hunter Giselle G   Kimberley Christopher C   Thomas Daniel D   Cave-Berry Lee L   Weston Paul P   Botcherby Marc R M MR   White Sharon S   Edgar Ruth R   Cross Sally H SH   Irvani Marjan M   Hummerich Holger H   Simpson Eleanor H EH   Johnson Dabney D   Hunsicker Patricia R PR   Little Peter F R PF   Hubbard Tim T   Campbell R Duncan RD   Rogers Jane J   Jackson Ian J IJ  

Proceedings of the National Academy of Sciences of the United States of America 20060227 10


Chromosome deletions in the mouse have proven invaluable in the dissection of gene function. The brown deletion complex comprises >28 independent genome rearrangements, which have been used to identify several functional loci on chromosome 4 required for normal embryonic and postnatal development. We have constructed a 172-bacterial artificial chromosome contig that spans this 22-megabase (Mb) interval and have produced a contiguous, finished, and manually annotated sequence from these clones. T  ...[more]

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