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K P Clancy

Publications and source records attributed to K P Clancy.

8 recordsLinked to original sources
PubMed2000

A new locus for autosomal dominant cataract on chromosome 12q13.

PURPOSE: To map the gene for autosomal dominant cataracts (ADC) in an American white family of European descent. METHODS: Ophthalmic examinations and linkage analyses using a variety of polymorphisms were performed; two-point lod scores calculated. RESULTS: Affected individuals (14 studied) exhibited variable expressivity of embryonal nuclear opacities based on morphology, location within the lens, and density. This ADC locus to 12q13 was mapped on the basis of statistically significantly positive lod scores and no recombinations (theta(m) = theta(f) = 0) with markers D12S368, D12S270, D12S96, D12S359, D12S1586, D12S312, D12S1632, D12S90, and D12S83; assuming full penetrance, a maximum lod score of 4.73 was calculated between the disease locus and D12S90. CONCLUSIONS: The disease in this family represents the first ADC locus on chromosome 12; major intrinsic protein of lens fiber (MIP) is a candidate gene.

Cataract↗
PubMed1998

An expression map from human chromosome 14q24.3.

We have constructed an expression map of chromosome 14q24.3 between markers D14S42 and D14S63. cDNA selection with YACs from 14q24.3 was used to generate expressed sequence tags (ESTs). The localization of ESTs was confirmed on a YAC contig. PCR products of ESTs were used as probes to screen cDNA libraries leading to the isolation of transcripts for known and unknown genes. In total, the expression map contains 7 known genes previously mapped to 14q24.3, 6 cDNA transcripts, and 15 anonymous ESTs. The addition of 21 unique transcribed loci from an approximately 5- to 7-Mb region of chromosome 14q24.3 will facilitate future efforts to identify human disease genes from this region.

Chromosome Mapping↗
PubMed1996

Localization of the L-glutamine synthetase gene to chromosome 1q23.

Glutamine synthetase (E.C. 6.3.1.2) is expressed throughout the body and plays an important role in controlling body pH and in removing ammonia from the circulation. The enzyme clears L-glutamate, the major neurotransmitter in the central nervous system, from neuronal synapses. The enzyme is a very sensitive marker of many disease and aging processes, especially those involving reactive oxygen species. This report describes the localization of the enzyme to chromosome 1 by PCR analysis of a human/rodent somatic cell hybrid panel. We also describe the localization of a recently described pseudogene to chromosome 9. Further localization of the glutamine synthetase gene locus to 1q23 was accomplished by fluorescence in situ hybridization. The glutamine synthetase gene was mapped to five CEPH megaYACs between the polymorphic PCR markers D1S117 and D1S466 by analysis of the Whitehead Institute's recently described chromosome 1 contig map.

Animals↗
PubMed1995

Human steroidogenic acute regulatory protein: functional activity in COS-1 cells, tissue-specific expression, and mapping of the structural gene to 8p11.2 and a pseudogene to chromosome 13.

Steroidogenic acute regulatory protein (StAR) appears to mediate the rapid increase in pregnenolone synthesis stimulated by tropic hormones. cDNAs encoding StAR were isolated from a human adrenal cortex library. Human StAR, coexpressed in COS-1 cells with cytochrome P450scc and adrenodoxin, increased pregnenolone synthesis > 4-fold. A major StAR transcript of 1.6 kb and less abundant transcripts of 4.4 and 7.5 kb were detected in ovary and testis. Kidney had a lower amount of the 1.6-kb message. StAR mRNA was not detected in other tissues including placenta. Treatment of granulosa cells with 8-bromo-adenosine 3',5'-cyclic monophosphate for 24 hr increased StAR mRNA 3-fold or more. The structural gene encoding StAR was mapped using somatic cell hybrid mapping panels to chromosome 8p. Fluorescence in situ hybridization placed the StAR locus in the region 8p11.2. A StAR pseudogene was mapped to chromosome 13. We conclude that StAR expression is restricted to tissues that carry out mitochondrial sterol oxidations subject to acute regulation by cAMP and that StAR mRNA levels are regulated by cAMP.

Animals↗
PubMed1995

Analysis of aldehyde oxidase and xanthine dehydrogenase/oxidase as possible candidate genes for autosomal recessive familial amyotrophic lateral sclerosis.

Recently, point mutations in superoxide dismutase 1 (SOD1) have been shown to lead to a subset of autosomal dominantly inherited familial amyotrophic lateral sclerosis (ALS). These findings have led to the hypothesis that defects in oxygen radical metabolism may be involved in the pathogenesis of ALS. Therefore, we decided to analyze other enzymes involved in oxygen radical metabolism for possible involvement in other forms of ALS. We report here analysis of two genes encoding the molybdenum hydroxylases aldehyde oxidase (AO) and xanthine dehydrogenase/oxidase (XDH) for involvement in ALS. Of particular interest, one gene identified as encoding aldehyde oxidase is shown to map to 2q33, a region recently shown to contain a gene responsible for a familial form of ALS with autosomal recessive inheritance (FALS-AR). The AO gene appears to be located within 280,000 bp of simple sequence repeat marker D2S116, which shows no recombination with the FALS-AR locus. The AO gene is highly expressed in glial cells of human spinal cord. In addition, we mapped a gene for XDH to 2p22, a region previously shown to contain a highly homologous but different form of XDH. Neither of these XDH genes appears to be highly expressed in human spinal cord. This evidence suggests that AO may be a candidate gene for FALS-AR.

Aldehyde Oxidase↗
PubMed1994

Cloning, sequencing, and mapping of the human chromosome 14 heat shock protein gene (HSPA2).

A genomic clone for the human heat shock protein (HSP) 70 gene located on chromosome 14 was isolated and sequenced. The gene, designated HSPA2, has a single open reading frame of 1917 bp that encodes a 639-amino acid protein with a predicted molecular weight of 70,030 Da. Analysis of the sequence indicates that HSPA2 is the human homologue of the murine Hsp70-2 gene with 91.7% identity in the nucleotide coding sequence and 98.2% in the corresponding amino acid sequence. HSPA2 has less amino acid homology to other members of the human HSP70 gene family, 83.3% to the heat-inducible HSP70-1 gene and 86.1% with the human heat shock cognate gene HSC70. HSPA2 is constitutively expressed in most tissues, with very high levels in testis and skeletal muscle. Significant but lower levels are also expressed in ovary, small intestine, colon, brain, placenta, and kidney. A yeast artificial chromosome (YAC) clone containing HSPA2 (YAC741H4) that also contained the polymorphic marker D14S63 was identified. This 670-kb YAC was mapped to 14q24.1 by fluorescence in situ hybridization (FISH). Subsequent two-color FISH and genetic mapping placed HSPA2/D14S63 proximal to the markers D14S57 and D14S77.

Amino Acid Sequence↗
PubMed1993

The c-fos gene and early-onset familial Alzheimer's disease.

A gene for early-onset familial Alzheimer's disease (FAD) is located on chromosome 14q24.3. The c-fos gene (FOS) is also located in the same band of this chromosome and is thus a candidate for the FAD locus. A yeast artificial chromosome (YAC) clone was identified which contains FOS. This YAC also contains the short-tandem repeat polymorphic (STRP) locus D14S76, placing FOS in the FAD region between D14S53 and D14S43. No recombinants were observed between D14S76 and FAD, and a maximum positive LOD score of 7.20 at a recombination fraction of 0.001 was observed for linkage of this marker to FAD. DNA sequence analysis was used to examine FOS in two affected subjects from an FAD family in which the chromosome 14 FAD locus is clearly responsible for the disease. The coding regions and parts of the 5' and 3' untranslated sequences of FOS were sequenced; no FAD-related mutations were observed. This work suggests that the FOS gene is not the chromosome 14 FAD locus although we cannot exclude the possibility that a mutation in an as yet unknown regulatory region is responsible for the disease. A new polymorphism was detected in the third intron of the gene.

Alleles↗