HIGH-RESOLUTION PHYSICAL MAP OF THE REGION SURROUNDING THE SPINAL MUSCULAR-ATROPHY GENE

被引:49
作者
THOMPSON, TG
MORRISON, KE
KLEYN, P
BENGTSSON, U
GILLIAM, TC
DAVIES, KE
WASMUTH, JJ
MCPHERSON, JD
机构
[1] UNIV CALIF IRVINE,COLL MED,DEPT BIOL CHEM,IRVINE,CA 92717
[2] JOHN RADCLIFFE HOSP,INST MOLEC MED,OXFORD OX3 9DU,ENGLAND
[3] DEPT PSYCHIAT,UNIT 23,NEW YORK,NY 10032
基金
英国医学研究理事会;
关键词
D O I
10.1093/hmg/2.8.1169
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Spinal muscular atrophy (SMA) is the second most common lethal, autosomal recessive disease in Caucasians, second only to cystic fibrosis. In an effort to identify the causative gene in SMA, we have used radiation hybrid (RH) mapping to prepare a high resolution physical map of the proximal region of chromosome 5 (5q11-13) which contains the SMA gene. The map of the SMA region, which spans approximately 4 Mb, contains 19 loci including 9 polymorphic DNA markers, 8 monomorphic sequence tagged sites (STS) and two genes. Based upon the RH map the two polymorphic loci which most closely flank the SMA locus were estimated to be separated by approximately 750 kb. Using two different directional cloning schemes, several new clones between the genetic markers which most closely flank SMA were isolated. These new clones within the SMA candidate region, together with cosmid clones prepared from one RH hybrid which retains an approximately 1 Mb segment spanning the SMA region as its only human DNA, will greatly facilitate efforts to identify the gene for SMA. In addition, analysis of cloned DNA segments from within the SMA candidate region has identified the presence of a novel, chromosome 5-specific, low copy repeated sequence which is distributed throughout the region containing the SMA gene as well as in at least four other regions of chromosome 5. Whether or not these novel repeated sequences throughout the SMA region are involved in the disease remains to be determined.
引用
收藏
页码:1169 / 1176
页数:8
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