مورد إلكتروني
Molecular mechanism for duplication 17p11.2- the homologous recombination reciprocal of the Smith-Magenis microdeletion.
| العنوان: | Molecular mechanism for duplication 17p11.2- the homologous recombination reciprocal of the Smith-Magenis microdeletion. |
|---|---|
| المؤلفون: | Potocki, L, Potocki, L, Chen, KS, Park, SS, Osterholm, DE, Withers, MA, Kimonis, V, Summers, AM, Meschino, WS, Anyane-Yeboa, K, Kashork, CD, Shaffer, LG, Lupski, JR |
| المصدر: | Nature genetics; vol 24, iss 1, 84-87; 1061-4036 |
| بيانات النشر: | eScholarship, University of California 2000-01-01 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Recombination between repeated sequences at various loci of the human genome are known to give rise to DNA rearrangements associated with many genetic disorders. Perhaps the most extensively characterized genomic region prone to rearrangement is 17p12, which is associated with the peripheral neuropathies, hereditary neuropathy with liability to pressure palsies (HNPP) and Charcot-Marie-Tooth disease type 1A (CMT1A;ref. 2). Homologous recombination between 24-kb flanking repeats, termed CMT1A-REPs, results in a 1.5-Mb deletion that is associated with HNPP, and the reciprocal duplication product is associated with CMT1A (ref. 2). Smith-Magenis syndrome (SMS) is a multiple congenital anomalies, mental retardation syndrome associated with a chromosome 17 microdeletion, del(17)(p11.2p11.2) (ref. 3,4). Most patients (>90%) carry deletions of the same genetic markers and define a common deletion. We report seven unrelated patients with de novo duplications of the same region deleted in SMS. A unique junction fragment, of the same apparent size, was identified in each patient by pulsed field gel electrophoresis (PFGE). Further molecular analyses suggest that the de novo17p11.2 duplication is preferentially paternal in origin, arises from unequal crossing over due to homologous recombination between flanking repeat gene clusters and probably represents the reciprocal recombination product of the SMS deletion. The clinical phenotype resulting from duplication [dup(17)(p11.2p11.2)] is milder than that associated with deficiency of this genomic region. This mechanism of reciprocal deletion and duplication via homologous recombination may not only pertain to the 17p11.2 region, but may also be common to other regions of the genome where interstitial microdeletion syndromes have been defined. |
| مصطلحات الفهرس: | Chromosomes, Human, Pair 17, Humans, Abnormalities, Multiple, Chromosome Aberrations, Syndrome, In Situ Hybridization, Fluorescence, Pedigree, Recombination, Genetic, Genotype, Female, Male, Intellectual Disability, Human Genome, Genetics, Peripheral Neuropathy, Neurodegenerative, Rare Diseases, Neurosciences, Developmental Biology, Biological Sciences, Medical and Health Sciences, article |
| URL: | |
| الإتاحة: | Open access content. Open access content CC-BY |
| ملاحظة: | application/pdf Nature genetics vol 24, iss 1, 84-87 1061-4036 |
| أرقام أخرى: | CDLER oai:escholarship.org:ark:/13030/qt3qt4j3cb qt3qt4j3cb https://escholarship.org/uc/item/3qt4j3cb https://escholarship.org/ 1325586228 |
| المصدر المساهم: | UC MASS DIGITIZATION From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1325586228 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |