Genomic anatomy of the Tyrp1 (brown) deletion complex.
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.
Smyth
Ian M
IM
Medical Research Council Human Genetics Unit, Edinburgh EH4 2XU, United Kingdom.
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
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
D008562:Membrane Glycoproteins; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse