International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


ORAL PRESENTATION

TUESDAY OCTOBER 19

5.00pm – 5.15pm

SEQUENCE AND PHENOTYPE ANNOTATION OF THE TYRP1 DELETION COMPLEX ON CHROMOSOME 4

Smyth IM1, Taylor M1, Wilming L2, Du X3, Gautier P1, Edgar R1, White S1, Cross SH1, Botcherby M4, Rogers J2, Campbell RD4, Brown SDM5, Beutler B3, Justice MJ6, Jackson IJ1

1 MRC Human Genetics Unit, Edinburgh, United Kingdom, 2 Wellcome Trust Sanger Institute, Hinxton, United Kingdom, 3 Scripps Research Institute, La Jolla, United States, 4 MRC Rosalind Franklin Centre for Genomics Research, Hinxton, United Kingdom, 5 MRC Mouse Genome Centre, Harwell, United Kingdom, 6 Baylor College of Medicine, Houston, United States

The region of chromosome 4 around the Tyrp1 locus has been studied for many years, initially as a target for radiation mutagenesis in the specific locus test, which generated numerous deletions and other rearrangements. Historically these deletions served to define essential genes mapping in the region by examination of the phenotypes of homozygous and compound heterozygous deletion carriers. Subsequently the deletions have allowed screening for chemically induced mutations. Over 25 recessive ENU mutations have been isolated that map to this chromosomal interval.

We produced high quality, finished and annotated sequence of a 173 BAC contig across this 22 Mb region, and have anchored the sequence to the deletion map. The whole region is relatively gene poor, and includes a ~5Mb region that is devoid of coding sequence, but which is nevertheless conserved in other vertebrate genomes.

We have identified candidate genes for the deletion defined phenotypes l(4)1Rn, l(4)2Rn, l(4)3Rn and baf.  We have also identified a novel basonuclein homologue that is misexpressed through a chromosomal inversion in the radiation-induced white based brown mutation. We have characterised a candidate for the classical hair loss mutation, depilated.

We have identified two new ENU alleles of the blebbing mutation heb, and have shown that the gene underlying the phenotype is a novel gene Frem1. The classic heb mutation contains a LINE insertion, an ENU induced allele, bat, has a splice defect. We are using a systematic exon resequencing strategy to identify the base lesions in the other ENU mutations in the region.

[an error occurred while processing this directive]