The diastrophic dysplasia gene encodes a novel sulfate transporter: Positional cloning by fine-structure linkage disequilibrium mapping
Abstract
Diastrophic dysplasia (DTD) is a well-characterized autosomal recessive osteochondrodysplasia with clinical features including dwarfism, spinal deformation, and specific joint abnormalities. The disease occurs in most populations, but is particularly prevalent in Finland owing to an apparent founder effect. DTD maps to distal chromosome 5q and, based on linkage disequilibrium studies in the Finnish population, we had previously predicted that the DTD gene should lie about 64 kb away from the CSF1R locus. Here, we report the positional cloning of the DTD gene by fine-structure linkage disequilibrium mapping. The gene lies in the predicted location, approximately 70 kb proximal to CSF1R, and encodes a novel sulfate transporter. Impaired function of its product is likely to lead to undersulfation of proteoglycans in cartilage matrix and thereby to cause the clinical phenotype of the disease. These results demonstrate the power of linkage disequilibrium mapping in isolated populations for positional cloning.
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The DTD mutation was later found at a distance of 70 kb.
“It was later found at a distance of 70 kb129.”
From Linkage disequilibrium--understanding the evolutionary past and mapping the medical future. (2008) · cites this paper as [129]
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- Authors
- Hästbacka, J., de la Chapelle, A., Mahtani, M. M., Clines, G., Reeve-Daly, M. P., Daly, M., Hamilton, B. A., Kusumi, K., Trivedi, B., Weaver, A., Coloma, A., Lovett, M., Buckler, A., Kaitila, I., & Lander, E. S.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- The University of Texas Southwestern Medical Center (US)
- Massachusetts General Hospital (US)
- University of Helsinki (FI)
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1994-09
- Volume
- 78
- Issue
- 6
- Pages
- 1073-1087
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2153039235
- Cited by
- 744
- References
- 3
- Citations by year
- 2026: 7 · 2025: 2 · 2024: 6 · 2023: 7 · 2022: 8 · 2021: 15 · 2020: 11 · 2019: 8 · 2018: 8 · 2017: 11 · 2016: 19 · 2015: 12 · 2014: 14 · 2013: 13 · 2012: 11
- FWCI
- 28.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (9r01ar041970-04, 5r01hg000882-02)
- National Human Genome Research Institute (HG-00098, HG00882)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR41970)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Keywords
- diastrophic dysplasia, sulfate transporters, positional cloning, association mapping, skeletal dysplasia, cartilage matrix, CSF1R, chromosome 5q, founder effect, Finnish population, autosomal recessive inheritance
- MeSH terms
- Sulfate Transporters, Amino Acid Sequence, Base Sequence, Carrier Proteins, Chromosome Mapping, Chromosomes, Human, Pair 5, Cloning, Molecular, Female, Finland, Genes, Recessive, Genetic Markers, Humans, Male, Membrane Proteins, Molecular Sequence Data, Mutation, Osteochondrodysplasias, Pedigree, Proteins, Sialyltransferases, Sulfates, Genomic Library, Linkage Disequilibrium, Sequence Homology, Amino Acid, Sequence Analysis, DNA, Antiporters, Membrane Transport Proteins, Anion Transport Proteins, Chloride-Bicarbonate Antiporters
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