title: 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.
authors.affiliation: Medical Research Council Human Genetics Unit, Edinburgh EH4 2XU, United Kingdom.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Smyth
authors.forename: Laurens
authors.initials: L
authors.lastname: Wilming
authors.forename: Angela W
authors.initials: AW
authors.lastname: Lee
authors.forename: Martin S
authors.initials: MS
authors.lastname: Taylor
authors.forename: Phillipe
authors.initials: P
authors.lastname: Gautier
authors.forename: Karen
authors.initials: K
authors.lastname: Barlow
authors.forename: Justine
authors.initials: J
authors.lastname: Wallis
authors.forename: Sancha
authors.initials: S
authors.lastname: Martin
authors.forename: Rebecca
authors.initials: R
authors.lastname: Glithero
authors.forename: Ben
authors.initials: B
authors.lastname: Phillimore
authors.forename: Sarah
authors.initials: S
authors.lastname: Pelan
authors.forename: Rob
authors.initials: R
authors.lastname: Andrew
authors.forename: Karen
authors.initials: K
authors.lastname: Holt
authors.forename: Ruth
authors.initials: R
authors.lastname: Taylor
authors.forename: Stuart
authors.initials: S
authors.lastname: McLaren
authors.forename: John
authors.initials: J
authors.lastname: Burton
authors.forename: Jonathon
authors.initials: J
authors.lastname: Bailey
authors.forename: Sarah
authors.initials: S
authors.lastname: Sims
authors.forename: Jan
authors.initials: J
authors.lastname: Squares
authors.forename: Bob
authors.initials: B
authors.lastname: Plumb
authors.forename: Ann
authors.initials: A
authors.lastname: Joy
authors.forename: Richard
authors.initials: R
authors.lastname: Gibson
authors.forename: James
authors.initials: J
authors.lastname: Gilbert
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hart
authors.forename: Gavin
authors.initials: G
authors.lastname: Laird
authors.forename: Jane
authors.initials: J
authors.lastname: Loveland
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mudge
authors.forename: Charlie
authors.initials: C
authors.lastname: Steward
authors.forename: David
authors.initials: D
authors.lastname: Swarbreck
authors.forename: Jennifer
authors.initials: J
authors.lastname: Harrow
authors.forename: Philip
authors.initials: P
authors.lastname: North
authors.forename: Nicholas
authors.initials: N
authors.lastname: Leaves
authors.forename: John
authors.initials: J
authors.lastname: Greystrong
authors.forename: Maria
authors.initials: M
authors.lastname: Coppola
authors.forename: Shilpa
authors.initials: S
authors.lastname: Manjunath
authors.forename: Mark
authors.initials: M
authors.lastname: Campbell
authors.forename: Mark
authors.initials: M
authors.lastname: Smith
authors.forename: Gregory
authors.initials: G
authors.lastname: Strachan
authors.forename: Calli
authors.initials: C
authors.lastname: Tofts
authors.forename: Esther
authors.initials: E
authors.lastname: Boal
authors.forename: Victoria
authors.initials: V
authors.lastname: Cobley
authors.forename: Giselle
authors.initials: G
authors.lastname: Hunter
authors.forename: Christopher
authors.initials: C
authors.lastname: Kimberley
authors.forename: Daniel
authors.initials: D
authors.lastname: Thomas
authors.forename: Lee
authors.initials: L
authors.lastname: Cave-Berry
authors.forename: Paul
authors.initials: P
authors.lastname: Weston
authors.forename: Marc R M
authors.initials: MR
authors.lastname: Botcherby
authors.forename: Sharon
authors.initials: S
authors.lastname: White
authors.forename: Ruth
authors.initials: R
authors.lastname: Edgar
authors.forename: Sally H
authors.initials: SH
authors.lastname: Cross
authors.forename: Marjan
authors.initials: M
authors.lastname: Irvani
authors.forename: Holger
authors.initials: H
authors.lastname: Hummerich
authors.forename: Eleanor H
authors.initials: EH
authors.lastname: Simpson
authors.forename: Dabney
authors.initials: D
authors.lastname: Johnson
authors.forename: Patricia R
authors.initials: PR
authors.lastname: Hunsicker
authors.forename: Peter F R
authors.initials: PF
authors.lastname: Little
authors.forename: Tim
authors.initials: T
authors.lastname: Hubbard
authors.forename: R Duncan
authors.initials: RD
authors.lastname: Campbell
authors.forename: Jane
authors.initials: J
authors.lastname: Rogers
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Jackson
mesh_terms: D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D005260:Female; D005313:Fetal Death / Q000235:genetics; D005804:Genes, Lethal; D006200:Hair Color / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010088:Oxidoreductases / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy
chemical_list: D008562:Membrane Glycoproteins; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse