       Document 0970
 DOCN  M9460970
 TI    Mapping the chromosomal location of the genes for X-linked
       lymphoproliferative disease and Waardenburg syndrome.
 DT    9406
 AU    Wu B; Boston Univ.
 SO    Diss Abstr Int [B]; 54(2):658 1993. Unique Identifier : AIDSLINE
       ICDB/94696674
 AB    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)
 DE    Chromosome Banding  Chromosome Deletion  Chromosome Mapping  Human  In
       Situ Hybridization, Fluorescence  *Linkage (Genetics)
       Lymphoproliferative Disorders/*GENETICS  Male  Waardenburg's
       Syndrome/*GENETICS  *X Chromosome  THESIS

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

