Abstract
In an attempt to isolate candidate genes for autosomal dominant polycystic kidney disease, a number of CpG-rich islands have been identified from a region defined genetically as the site of disease mutations. Genomic fragments adjacent to one of these islands were used to isolate cDNAs from both HeLa cells and cultured cystic epithelium that encode a 155-amino acid peptide having four putative transmembrane domains. The corresponding transcript was found in all tissues tested but was most abundant in brain and kidney. Potential control response elements were identified in the genomic region 5′ to the initiation codon. The deduced amino acid sequence has 93% similarity to the 16-kDa proteolipid component that is believed to be part of the proton channel of the vacuolar H+-ATPase. Possible roles for a mutated proton channel in the pathogenesis of cystic disease were considered. However, sequencing of cDNAs corresponding to both alleles of an affected individual revealed no differences in the deduced amino acid sequence. Moreover, transcript size and abundance were not altered in cystic kidney.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4289-4293 |
| Number of pages | 5 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 88 |
| Issue number | 10 |
| State | Published - May 15 1991 |
| Externally published | Yes |
Fingerprint
Keywords
- cDNA
- DNA sequence homology
- Ion channel
- PKD1 locus
- Positional cloning
ASJC Scopus subject areas
- General
- Genetics
Cite this
CpG island in the region of an autosomal dominant polycystic kidney disease locus defines the 5′ end of a gene encoding a putative proton channel. / Gillespie, Gerald A J; Somlo, Stefan; Germino, Gregory G.; Weinstat-Saslow, Debra; Reeders, Stephen T.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 88, No. 10, 15.05.1991, p. 4289-4293.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CpG island in the region of an autosomal dominant polycystic kidney disease locus defines the 5′ end of a gene encoding a putative proton channel
AU - Gillespie, Gerald A J
AU - Somlo, Stefan
AU - Germino, Gregory G.
AU - Weinstat-Saslow, Debra
AU - Reeders, Stephen T.
PY - 1991/5/15
Y1 - 1991/5/15
N2 - In an attempt to isolate candidate genes for autosomal dominant polycystic kidney disease, a number of CpG-rich islands have been identified from a region defined genetically as the site of disease mutations. Genomic fragments adjacent to one of these islands were used to isolate cDNAs from both HeLa cells and cultured cystic epithelium that encode a 155-amino acid peptide having four putative transmembrane domains. The corresponding transcript was found in all tissues tested but was most abundant in brain and kidney. Potential control response elements were identified in the genomic region 5′ to the initiation codon. The deduced amino acid sequence has 93% similarity to the 16-kDa proteolipid component that is believed to be part of the proton channel of the vacuolar H+-ATPase. Possible roles for a mutated proton channel in the pathogenesis of cystic disease were considered. However, sequencing of cDNAs corresponding to both alleles of an affected individual revealed no differences in the deduced amino acid sequence. Moreover, transcript size and abundance were not altered in cystic kidney.
AB - In an attempt to isolate candidate genes for autosomal dominant polycystic kidney disease, a number of CpG-rich islands have been identified from a region defined genetically as the site of disease mutations. Genomic fragments adjacent to one of these islands were used to isolate cDNAs from both HeLa cells and cultured cystic epithelium that encode a 155-amino acid peptide having four putative transmembrane domains. The corresponding transcript was found in all tissues tested but was most abundant in brain and kidney. Potential control response elements were identified in the genomic region 5′ to the initiation codon. The deduced amino acid sequence has 93% similarity to the 16-kDa proteolipid component that is believed to be part of the proton channel of the vacuolar H+-ATPase. Possible roles for a mutated proton channel in the pathogenesis of cystic disease were considered. However, sequencing of cDNAs corresponding to both alleles of an affected individual revealed no differences in the deduced amino acid sequence. Moreover, transcript size and abundance were not altered in cystic kidney.
KW - cDNA
KW - DNA sequence homology
KW - Ion channel
KW - PKD1 locus
KW - Positional cloning
UR - http://www.scopus.com/inward/record.url?scp=0025759904&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025759904&partnerID=8YFLogxK
M3 - Article
C2 - 1709739
AN - SCOPUS:0025759904
VL - 88
SP - 4289
EP - 4293
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 10
ER -