DOI: 10.1101/gr.7.5.441. A 1.1-Mb Transcript Map of the Hereditary Hemochromatosis Locus

A 1.1-Mb Transcript Map of the Hereditary Hemochromatosis Locus

10.1101/gr.7.5.441

Crossref journal-article

Cold Spring Harbor Laboratory

Genome Research (246)

Abstract

In the process of positionally cloning a candidate gene responsible for hereditary hemochromatosis (HH), we constructed a 1.1-Mb transcript map of the region of human chromosome 6p that lies 4.5 Mb telomeric toHLA-A. A combination of three gene-finding techniques, direct cDNA selection, exon trapping, and sample sequencing, were used initially for a saturation screening of the 1.1-Mb region for expressed sequence fragments. As genetic analysis further narrowed the HH candidate locus, we sequenced completely 0.25 Mb of genomic DNA as a final measure to identify all genes. Besides the novel MHC class 1-like HH candidate geneHLA-H, we identified a family of five butyrophilin-related sequences, two genes with structural similarity to a type 1 sodium phosphate transporter, 12 novel histone genes, and a gene we namedRoRetbased on its strong similarity to the 52-kDRo/SSAlupus and Sjogren’s syndrome auto-antigen and theRETfinger protein. Several members of the butyrophilin family and theRoRetgene share an exon of common evolutionary origin called B30-2. The B30-2 exon was originally isolated from the HLA class 1 region, yet has apparently “shuffled” into several genes along the chromosome telomeric to the MHC. The conservation of the B30-2 exon in several novel genes and the previously described amino acid homology ofHLA-Hto MHC class 1 molecules provide further support that this gene-rich region of 6p21.3 is related to the MHC. Finally, we performed an analysis of the four approaches for gene finding and conclude that direct selection provides the most effective probes for cDNA screening, and that as much as 30% of ESTs in this 1.1-Mb region may be derived from noncoding genomic DNA.[The sequence data described in this paper have been submitted to GenBank under accession nos.U90543–U90548,U90550–U90552, andU91328.]

Bibliography

Ruddy, D. A., Kronmal, G. S., Lee, V. K., Mintier, G. A., Quintana, L., Domingo, R., Meyer, N. C., Irrinki, A., McClelland, E. E., Fullan, A., Mapa, F. A., Moore, T., Thomas, W., Loeb, D. B., Harmon, C., Tsuchihashi, Z., Wolff, R. K., Schatzman, R. C., & Feder, J. N. (1997). A 1.1-Mb Transcript Map of the Hereditary HemochromatosisâLocus. Genome Research, 7(5), 441â456.

Authors 19

David A. Ruddy (first)
Gregory S. Kronmal (additional)
Vincent K. Lee (additional)
Gabriel A. Mintier (additional)
Leah Quintana (additional)
Rodolfo Domingo (additional)
Nicole C. Meyer (additional)
Alivelu Irrinki (additional)
Erin E. McClelland (additional)
Amy Fullan (additional)
Felipa A. Mapa (additional)
Theodore Moore (additional)
Winston Thomas (additional)
Deborah B. Loeb (additional)
Cyrus Harmon (additional)
Zenta Tsuchihashi (additional)
Roger K. Wolff (additional)
Randall C. Schatzman (additional)
John N. Feder (additional)

References 31 Referenced 66

10.1101/gr.6.9.829
10.1006/jmbi.1990.9999
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Lauer, P., N.C. Meyer, C.E. Prass, S.M. Starnes, R.K. Wolff, and A. Gnirke. 1997. Clone-contig and STS maps of the hereditary hemochromatosis region on human chromosome 6p21.3-p22. Genome Res. (this issue).. (10.1101/gr.7.5.457)
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10.1126/science.272.5259.258

Dates

Type	When
Created	8 years, 3 months ago (May 2, 2017, 8:25 p.m.)
Deposited	2 years ago (Aug. 23, 2023, 7:22 a.m.)
Indexed	6 days, 12 hours ago (Aug. 23, 2025, 1:14 a.m.)
Issued	28 years, 3 months ago (May 1, 1997)
Published	28 years, 3 months ago (May 1, 1997)
Published Online	28 years, 3 months ago (May 1, 1997)
Published Print	28 years, 3 months ago (May 1, 1997)

Funders 0

None

BibTeX

@article{Ruddy_1997, title={A 1.1-Mb Transcript Map of the Hereditary Hemochromatosis Locus}, volume={7}, ISSN={1549-5469}, url={http://dx.doi.org/10.1101/gr.7.5.441}, DOI={10.1101/gr.7.5.441}, number={5}, journal={Genome Research}, publisher={Cold Spring Harbor Laboratory}, author={Ruddy, David A. and Kronmal, Gregory S. and Lee, Vincent K. and Mintier, Gabriel A. and Quintana, Leah and Domingo, Rodolfo and Meyer, Nicole C. and Irrinki, Alivelu and McClelland, Erin E. and Fullan, Amy and Mapa, Felipa A. and Moore, Theodore and Thomas, Winston and Loeb, Deborah B. and Harmon, Cyrus and Tsuchihashi, Zenta and Wolff, Roger K. and Schatzman, Randall C. and Feder, John N.}, year={1997}, month=may, pages={441–456} }

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