Promoter Sequence, Expression, and Fine Chromosomal Mapping of the Human Gene (MLP) Encoding the MARCKS-like Protein: Identification of Neighboring and Linked Polymorphic Loci forMLPandMACSand Use in the Evaluation of Human Neural Tube Defects
| Autor: | L.L. Haley, Anindya Dehejia, W. S. Young, Perry J. Blackshear, W. S. Lai, Roger L. Eddy, Sheila N.J. Sait, Deborah J. Stumpo, Marcy C. Speer, Thomas B. Shows, Mihael H. Polymeropoulos |
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| Rok vydání: | 1998 |
| Předmět: |
Genetic Markers
Meningomyelocele Genotype Genetic Linkage Sequence analysis Recombinant Fusion Proteins TATA box Molecular Sequence Data Gene Expression Mice Transgenic Biology Mice Gene mapping Genetic linkage Genetics Animals Humans Radiation hybrid mapping Neural Tube Defects RNA Messenger Cloning Molecular MARCKS Myristoylated Alanine-Rich C Kinase Substrate Promoter Regions Genetic Gene Protein Kinase C Brain Chemistry Base Sequence Microfilament Proteins Intracellular Signaling Peptides and Proteins Lumbosacral Region Chromosome Mapping Membrane Proteins Proteins DNA Sequence Analysis DNA beta-Galactosidase Molecular biology Chromosomes Human Pair 1 Genetic marker Protein Biosynthesis Calmodulin-Binding Proteins Polymorphism Restriction Fragment Length |
| Zdroj: | Genomics. 49:253-264 |
| ISSN: | 0888-7543 |
| Popis: | The MARCKS-like protein (MLP), also known as F52, MacMARCKS, or MARCKS-related protein, is a widely distributed substrate for protein kinase C (PKC). Recent studies using gene disruption in vivo have demonstrated the importance of both MARCKS and MLP to the development of the central nervous system; specifically, mice lacking either protein exhibit a high frequency of neural tube defects. We isolated a genomic clone for human MLP and discovered a directly linked polymorphism (MLP1) useful for genetic linkage analysis. The MLP promoter was 71% identical over 433 bp to that of the corresponding mouse gene, Mlp, with conservation of many putative transcription factor-binding sites; it was only 36% identical over 433 bp to the promoter of the human gene, MACS, which encodes the MLP homologue MARCKS. This 433-bp fragment drove expression of an MLP-beta-galactosidase transgene in a tissue-specific and developmental expression pattern that was similar to that observed for the endogenous gene, as shown by in situ hybridization histochemistry. In contrast to MACS, the MLP and Mlp promoters contain a TATA box approximately 40 bp 5' of the presumed transcription initiation site. MLP was localized to chromosome 1p34--1pter by analysis of human-mouse somatic cell hybrid DNA and to 1p34 by fluorescence in situ hybridization. Radiation hybrid mapping of MLP placed it between genetic markers D1S511 (LOD3.0) and WI9232. MACS was localized to 6q21 between D6S266 (LOD3.0) and AFM268uh5 by the same technique. We tested the novel MLP1 polymorphism and the MACS flanking markers in a series of 43 Caucasian simplex families in which the affected child had a lumbosacral myelomeningocele. We found no evidence of linkage disequilibrium, suggesting that these loci were not major genes for spina bifida in these families. Nonetheless, the identification of linked and neighboring polymorphisms for MACS and MLP should permit similar genetic studies in other groups of patients with neural tube defects and other neurodevelopmental abnormalities. |
| Databáze: | OpenAIRE |
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