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Vol. 9, Issue 1, 53-61, January 1999

LETTER
Comparative Sequence of Human and Mouse BAC Clones from the mnd2 Region of Chromosome 2p13

Wonhee Jang,1 Axin Hua,2 Sandra V. Spilson,1 Webb Miller,3 Bruce A. Roe,2 and Miriam H. Meisler1,4

1 Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109-0618 USA; 2 Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019 USA; 3 Department of Computer Science and Engineering, Pennsylvania State University, University Park, Pennsylvania 16802 USA

The mnd2 mutation on mouse chromosome 6 produces a progressive neuromuscular disorder. To determine the gene content of the 400-kb mnd2 nonrecombinant region, we sequenced 108 kb of mouse genomic DNA and 92 kb of human genomic sequence from the corresponding region of chromosome 2p13.3. Three genes with the indicated sizes and intergenic distances were identified: D6Mm5e (>= 81 kb)-787 bp-DOK (2 kb)-845 bp-LOR2 (>= 6 kb). D6Mm5e is expressed in many tissues at very low abundance and the predicted 526-residue protein contains no known functional domains. DOK encodes the p62dok rasGAP binding protein involved in signal transduction. LOR2 encodes a novel lysyl oxidase-related protein of 757 amino acid residues. We describe a simple search protocol for identification of conserved internal exons in genomic sequence. Evolutionary conservation proved to be a useful criterion for distinguishing between authentic exons and artifactual products obtained by exon amplification, RT-PCR, and 5' RACE. Conserved noncoding sequence elements longer than 80 bp with >= 75% nucleotide sequence identity comprise ~1% of the genomic sequence in this region. Comparative analysis of this human and mouse genomic DNA sequence was an efficient method for gene identification and is independent of developmental stage or quantitative level of gene expression.

[The sequence data described in this paper have been submitted to the GenBank data library under the following accession numbers: AC003061, mouse BAC clone 245c12; AC003065, human BAC clone h173(E10); AF053368, mouse Lor2 cDNA; AF084363, 108-kb contig from mouse BAC 245c12; AF084364, mouse D6Mm5e cDNA.]

4   Corresponding author.

9:53-61 ©1999 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/99 $5.00
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