SEQUENCE VARIATIONS IN THE 1ST EXON OF ALPHA-GALACTOSIDASE-A

被引:37
作者
DAVIES, JP
WINCHESTER, BG
MALCOLM, S
机构
[1] INST CHILD HLTH,DIV BIOCHEM & GENET,MOLEC GENET UNIT,30 GUILFORD ST,LONDON WC1N 1EH,ENGLAND
[2] INST CHILD HLTH,DIV BIOCHEM & GENET,ENZYMOL UNIT,LONDON WC1N 1EH,ENGLAND
关键词
D O I
10.1136/jmg.30.8.658
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The alpha-galactosidase A gene (GALA), which is deficient in males with Anderson-Fabry disease, is shown to be remarkably polymorphic in the 5' untranslated region. GALA contains seven exons. The first exon contains 60 bp of 5' untranslated sequence before the methionine initiation codon. Single strand conformation polymorphism (SSCP) screening has shown three polymorphic variants from the published sequence within the 60 base pairs. The sequence changes involved are C to T at - 10, G to A at - 12 (which removes an MspI site), and G to A at - 30 (which removes a SacII site). The combined frequency of these is 10%. A further insertion-deletion polymorphism is detected by SSCP of a 400 bp fragment including exon 3. Both polymorphisms can be easily detected using small polyacrylamide gels and ethidium bromide staining. Nine of 20 women were informative for one of these polymorphisms and this simple SSCP analysis should be of great assistance in family studies of Anderson-Fabry disease. Such a high level of polymorphism has not been previously reported in the 5' untranslated region of a human gene and is unusual in any such short stretch of DNA.
引用
收藏
页码:658 / 663
页数:6
相关论文
共 29 条
  • [1] FABRY DISEASE - 6 GENE REARRANGEMENTS AND AN EXONIC POINT MUTATION IN THE ALPHA-GALACTOSIDASE GENE
    BERNSTEIN, HS
    BISHOP, DF
    ASTRIN, KH
    KORNREICH, R
    ENG, CM
    SAKURABA, H
    DESNICK, RJ
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (04) : 1390 - 1399
  • [2] STRUCTURAL ORGANIZATION OF THE HUMAN ALPHA-GALACTOSIDASE A-GENE - FURTHER EVIDENCE FOR THE ABSENCE OF A 3' UNTRANSLATED REGION
    BISHOP, DF
    KORNREICH, R
    DESNICK, RJ
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (11) : 3903 - 3907
  • [3] HUMAN ALPHA-GALACTOSIDASE-A - NUCLEOTIDE-SEQUENCE OF A CDNA CLONE ENCODING THE MATURE ENZYME
    BISHOP, DF
    CALHOUN, DH
    BERNSTEIN, HS
    HANTZOPOULOS, P
    QUINN, M
    DESNICK, RJ
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (13) : 4859 - 4863
  • [4] FABRY DISEASE - ISOLATION OF A CDNA CLONE ENCODING HUMAN ALPHA-GALACTOSIDASE A
    CALHOUN, DH
    BISHOP, DF
    BERNSTEIN, HS
    QUINN, M
    HANTZOPOULOS, P
    DESNICK, RJ
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (21) : 7364 - 7368
  • [5] DEAN KJ, 1979, J BIOL CHEM, V262, P2062
  • [6] FABRY DISEASE - MOLECULAR DIAGNOSIS OF HEMIZYGOTES AND HETEROZYGOTES
    DESNICK, RJ
    BERNSTEIN, HS
    ASTRIN, KH
    BISHOP, DF
    [J]. ENZYME, 1987, 38 (1-4) : 54 - 64
  • [7] DESNICK RJ, 1973, J LAB CLIN MED, V81, P157
  • [8] DESNICK RJ, 1989, METABOLIC BASIS INHE, P1751
  • [9] Ejiofor A, 1978, J Inherit Metab Dis, V1, P71, DOI 10.1007/BF01801848
  • [10] VARIATION OF THE CGG REPEAT AT THE FRAGILE-X SITE RESULTS IN GENETIC INSTABILITY - RESOLUTION OF THE SHERMAN PARADOX
    FU, YH
    KUHL, DPA
    PIZZUTI, A
    PIERETTI, M
    SUTCLIFFE, JS
    RICHARDS, S
    VERKERK, AJMH
    HOLDEN, JJA
    FENWICK, RG
    WARREN, ST
    OOSTRA, BA
    NELSON, DL
    CASKEY, CT
    [J]. CELL, 1991, 67 (06) : 1047 - 1058