Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0312414 (Spotting)
 88 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The KIT proto-oncogene encodes a tyrosine kinase receptor which plays a critical role in haemopoiesis. We have screened genomic DNA from bone marrow mononuclear cells of 46 patients with myelodysplasia (MDS) for mutations/deletions of exons 6, 13, 17, and 21 of the KIT gene (stem cell factor receptor) using polymerase chain reaction (PCR), polyacrylamide gel electrophoresis, and autoradiography to detect single-stranded conformational polymorphisms (SSCP). These exons include positions analogous to those mutated in the FMS gene (colony-stimulating factor-1 receptor) in myelodysplastic syndrome (MDS) and mutated/deleted in the Dominant White Spotting mouse (W locus) which results in macrocytic anaemia. Two different gel running conditions were used for each exon. Polymorphisms were identified only at 4 degrees C in exon 17 (three out of 44 MDS samples and two of 21 DNA samples from normal subjects), and in the non-coding region of exon 21 (five out of 34 MDS samples and seven out of 19 normals). Direct sequencing identified a G to A base change at nucleotide 3169 within exon 21, and a C to T change at position 2415 in exon 17. No conformational changes suggestive of mutations or deletions have been found to date, although we cannot rule out low frequency clonal abnormalities undetectable by our method, which has a sensitivity in our hands of approximately 5%. Polymorphisms occur frequently in the KIT gene. Together with this study, a total of five have been described.
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PMID:Two new polymorphisms but no mutations of the KIT gene in patients with myelodysplasia at positions corresponding to human FMS and murine W locus mutational hot spots. 769 8

White spotting is the absence of melanocytes (pigment cells) from part or all of the locations in the body where they are normally found. At least in the case of the W (kit) locus, white spotting has been attributed to apoptosis. In addition to the death of melanoblasts, white spotting might result from their failure to migrate to their normal locations. These developmental failures are known to be melanocyte-specific in some instances and environment-specific in others. The environment is defined as the tissues surrounding the melanoblast. Patterns of white spotting were examined on mice mutant at the piebald (s), patch (Ph), dominant spotting (W(J2)) rumpwhite (Rw) or belted (bt) loci. The dominant spotting locus has been cloned and found to encode KIT; it has been suggested that Patch encodes the linked alpha-PDGF receptor. Piebald encodes the endothelin beta receptor. In each case, the phenotypes expressed when the allele was backcrossed onto one inbred strain C57BL/6 (B6), were compared with phenotypes expressed when the allele was backcrossed onto a different inbred strain, JU/CtLm (JU). The literature documents genetic loci that influence the extent of the white spotted area; we herein demonstrate that genetic loci also influence the location where the white spot (absence of melanocytes) will occur over the body of the mouse. Spotting occurs in a more anterior direction on JU mice that are piebald, patch or dominant-spotted compared with similar B6 mice. The relationship is reversed in rumpwhite mice, where white spotting is more anterior in the C57BL/6 mice than in the JU mice. The spotting pattern of belted mice was not modified by the background genome. Thus, the Mendelian observations indicate that several loci, which differ in JU compared with B6 mice, influence the size and the location of white spots on the mouse.
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PMID:Strain-specific white-spotting patterns in laboratory mice. 1061 78