Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Progress in complete genomic sequencing of human chromosome 21 relies on the construction of high-quality bacterial clone maps spanning large chromosomal regions. To achieve this goal, we have applied a strategy based on nonradioactive hybridizations to contig building. A contiguous sequence-ready map was constructed in the Down syndrome congenital heart disease (DS-CHD) region in 21q22.2, as a framework for large-scale genomic sequencing and positional candidate gene approach. Contig assembly was performed essentially by high throughput nonisotopic screenings of genomic libraries, prior to clone validation by (1) restriction digest fingerprinting, (2) STS analysis, (3) Southern hybridizations, and (4) FISH analysis. The contig contains a total of 50 STSs, of which 13 were newly isolated. A minimum tiling path (MTP) was subsequently defined that consists of 20 PACs, 2 BACs, and 5 cosmids covering 3 Mb between D21S3 and MX1. Gene distribution in the region includes 9 known genes (c21-LRP, WRB, SH3BGR, HMG14, PCP4, DSCAM, MX2, MX1, and TMPRSS2) and 14 new additional gene signatures consisting of cDNA selection products and ESTs. Forthcoming genomic sequence information will unravel the structural organization of potential candidate genes involved in specific features of Down syndrome pathogenesis.
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PMID:A contiguous 3-Mb sequence-ready map in the S3-MX region on 21q22.2 based on high- throughput nonisotopic library screenings. 1020 58

Spf1p is a P-type ATPase that is mainly localized to the endoplasmic reticulum (ER) in Saccharomyces cerevisiae. The protein is involved in the maintenance of ion homeostasis in the ER. To investigate the intracellular role of Spf1p in more detail, we performed a genetic screen for mutations that lead to synthetic lethality in combination with a disruption of SPF1; the mutations identified have been termed lws (for lethal with spf1) mutations. Mutant alleles of five LWS genes (MDM39, RIC1, LAS21, TUP1 and BTS1) were recovered. The identification of these genes provides clues to the physiological relationships between Spf1p function and the secretory pathway. Among the five genes identified, MDM39 encodes a membrane protein that is similar to the protein CHD5/WRB, which is involved in the pathogenesis of Down syndrome-associated congenital heart disease in humans. We localized Mdm39p to the ER. The Deltamdm39 mutant exhibited defects in glycosylation, cell wall organization and the unfolded protein response. It also showed calcium-related phenotypes and synthetic lethal interactions with deletion mutations in other LWS genes. Our findings imply a homeostatic role for Mdm39p, which may be related to the regulation of calcium ion fluxes in the ER, and is indispensable for mutants that lack Spf1p.
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PMID:Cooperative function of the CHD5-like protein Mdm39p with a P-type ATPase Spf1p in the maintenance of ER homeostasis in Saccharomyces cerevisiae. 1590 63

The congenital heart disease 5 (CHD5)/tryptophan rich basic protein (WRB) is a protein containing a tryptophan-rich carboxy-terminal region, which was discovered in the human fetal heart. In humans, this CHD5/WRB is located between the markers ACTL5-D21S268 within the Down syndrome (DS) Region-2 at chromosome 21. Congenital heart disease is commonly linked to DS patients. The functions of this gene product are unknown. To identify the functions of CHD5/WRB in heart formation during embryogenesis, the medaka CHD5 cDNA (mCHD5) was isolated and its gene expression pattern and the localization of its gene product were investigated. The obtained mCHD5 belongs to the CHD5 superfamily, whose members include coiled-coil proteins. The mCHD5 gene was found to be expressed in the developing heart after stage 28 at which the chamber (ventricle and atrium) differentiation in the heart tube is initiated in the embryo. Its gene product was also detected in the developing heart at embryonic stage 28 and 35. Knocking-down of mCHD5 function caused severe cardiac disorder, including abnormal chamber differentiation, abnormal looping and ocular abnormality such as Cyclops. Our results provide the mCHD5 gene expression pattern as well as its physiological role during heart formation in a vertebrate model system.
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PMID:Expression of the congenital heart disease 5/tryptophan rich basic protein homologue gene during heart development in medaka fish, Oryzias latipes. 1920 81

The identification and characterization of the cellular and molecular pathways involved in the differentiation and morphogenesis of specific cell types of the developing heart are crucial to understanding the process of cardiac development and the pathology associated with human congenital heart disease. Here, we show that the cardiac transcription factor CASTOR (CASZ1) directly interacts with congenital heart disease 5 protein (CHD5), which is also known as tryptophan-rich basic protein (WRB), a gene located on chromosome 21 in the proposed region responsible for congenital heart disease in individuals with Down's syndrome. We demonstrate that loss of CHD5 in Xenopus leads to compromised myocardial integrity, improper deposition of basement membrane, and a resultant failure of hearts to undergo cell movements associated with cardiac formation. We further report that CHD5 is essential for CASZ1 function and that the CHD5-CASZ1 interaction is necessary for cardiac morphogenesis. Collectively, these results establish a role for CHD5 and CASZ1 in the early stages of vertebrate cardiac development.
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PMID:Congenital heart disease protein 5 associates with CASZ1 to maintain myocardial tissue integrity. 2499 40