Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
Mapping the chromosomal location of the genes for X-linked lymphoproliferative disease and Waardenburg syndrome.
Diss Abstr Int [B]; 54(2):658 1993. Unique Identifier : AIDSLINE ICDB/94696674 Wu B; Boston Univ.
Abstract:
X-linked lymphoproliferative disease (XLP) is initiated by Epstein-Barr virus infection and results in fatal infectious mononucleosis, severe immunodeficiency and malignant lymphoma. A physical map of the region containing the XLP locus on the X chromosome is necessary for positional cloning of the XLP gene. To confirm a correlation between the genetic linkage map and an XLP deletion, blot hybridization was used to find DNA sequences missing in the XLP male who lacked part of chromosomal band Xq25. Probes corresponding to the deleted sequences were used to identify two additional males with deletions resulting in XLP. The new deletions were also detectable using high resolution G-banding. All three deletions have an overlapping region containing DXS982, DXS739 and DXS75 loci. XLP is the only known consequence of these deletions. To map this XLP candidate gene region physically, fluorescence in situ hybridization (FISH) was employed for high resolution mapping of probes near the XLP locus. Metaphase FISH showed that DXS12 and DXS42 mapped to proximal Xq25, while DXS10 and DXS177 mapped to proximal Xq26.1. DXS6, DXS982, DXS739, DXS75 and DXS100 were in Xq25. The order of probes deduced from metaphase and interphase FISH was as follows: Xq24-(DXS12, DXS42)-DXS6-DXS982-DXS739-DXS75-DXS100-DXS10-DXS177-Xq26.2. This FISH map estimated that the entire region between DXS12 and DXS177 is about 5 megabases (Mb), and confines the XLP locus to a 1.5-Mb interval between DXS6 and DXS100. Field inversion gel electrophoresis (FIGE) was employed to deduce a long range restriction map containing the XLP locus. Sfi I, Sal I, Fsp I and Eag I maps were deduced based on partial and double digestion products. The localization of the 1.5-Mb interval was refined. The FISH and FIGE maps agree in the order and distance between the probes. To physically map the candidate gene region for Waardenburg syndrome type 1 (WS1), FISH was used to localize the PAX3, FN1, ALPI and ALPP genes. FISH and high resolution G-banding showed that two unrelated WS1 patients with interstitial deletion of 2q35-q36.1 and 2q35-q36.2 retained ALPP, ALPI and FN1 on the deleted chromosome 2. FISH also showed that the human PAX3 gene was only absent in the deleted chromosome 2 in both patients. The FISH results confirm the conclusion from linkage analysis and support the contention that mutation of the PAX3 gene causes Waardenburg syndrome. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD93-17458)
Keywords: Chromosome Banding Chromosome Deletion Chromosome Mapping Human In Situ Hybridization, Fluorescence *Linkage (Genetics) Lymphoproliferative Disorders/*GENETICS Male Waardenburg's Syndrome/*GENETICS *X Chromosome THESIS 940630
M9460926
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Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
