Home LiteratureArticle Details
PMID: 3006023 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Genetic analysis of the fragile-X mental retardation syndrome with two flanking polymorphic DNA markers.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 83 ·No. 4 ·1986-02-00 ·Pages 1016-20

Oberlé I, Heilig R, Moisan JP, Kloepfer C, Mattéi GM, Mattéi JF, Boué J, Froster-Iskenius U, Jacobs PA, Lathrop GM

Abstract

The fragile-X mental retardation syndrome, one of the most prevalent chromosome X-linked diseases (approximately equal to 1 of 2000 newborn males), is characterized by the presence in affected males and in a portion of carrier females of a fragile site at chromosomes band Xq27. We have performed a linkage analysis in 16 families between the locus for the fragile-X syndrome, FRAXQ27, and two polymorphic DNA markers that correspond to the anonymous probe St14 and to the coagulation factor IX gene F9. Our results indicate that the order of loci is centromere-F9-FRAXQ27-St14-Xqter. The estimate of the recombination fraction for the linkage F9-FRAXQ27 is 0.12 (90% confidence limits: 0.044-0.225) and 0.10 for FRAXQ27-St14 (90% confidence limits: 0.040-0.185). Recombination between St14 and F9 does not appear to be significantly different in normal and fragile-X families. The two flanking probes were used for diagnosis of the carrier state and for detection of transmission of the disease through phenotypically normal males. They should also allow first-trimester diagnosis with a reliability of about 98% in 40% of the families. Used in conjunction with the cytogenetic analysis, the segregation studies with both probes should improve the genetic counseling for the fragile-X syndrome and should be useful for the formal genetic analysis of this unique disease.

MeSH Terms
DNA/analysis DNA Restriction Enzymes Factor IX/genetics Female Fragile X Syndrome/genetics Genes Genetic Carrier Screening Genetic Linkage Genetic Markers Humans Intellectual Disability/genetics Male Pedigree Polymorphism, Genetic Sex Chromosome Aberrations/genetics
Chemicals
Genetic Markers Factor IX DNA DNA Restriction Enzymes
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Oberlé I
Heilig R
Moisan J P
Kloepfer C
Mattéi G M
Mattéi J F
Boué J
Froster-Iskenius U
Jacobs P A
Lathrop G M
References (28)
28 references, click to expand
  1. Analysis of crossingover in man.
    Cytogenet Cell Genet. 1978;22(1-6):15-36 PMID: 752468
  2. Genetic linkage heterogeneity in the fragile X syndrome.
    Hum Genet. 1985;71(1):11-8 PMID: 2993154
  3. X-linked mental retardation: a study of 7 families.
    Am J Med Genet. 1980;7(4):471-89 PMID: 7211957
  4. Feasibility of fragile X chromosome prenatal diagnosis demonstrated.
    Lancet. 1981 Dec 5;2(8258):1292 PMID: 6118704
  5. Expression in lymphocyte and fibroblast culture of the fragile X chromosome: a new technical approach.
    Hum Genet. 1981;59(2):166-9 PMID: 7327576
  6. Marker X syndrome in an oriental family with probable transmission by a normal male.
    Am J Med Genet. 1982 Jun;12(2):205-17 PMID: 7102725
  7. The diagnosis and frequency of X-linked conditions in a cohort of moderately retarded males with affected brothers.
    Am J Med Genet. 1983 Apr;14(4):713-24 PMID: 6682625
  8. A polymorphic DNA marker genetically linked to Huntington's disease.
    Nature. 1983 Nov 17-23;306(5940):234-8 PMID: 6316146
  9. Close linkage of fragile X-mental retardation syndrome to haemophilia B and transmission through a normal male.
    Nature. 1983 Dec 15-21;306(5944):701-4 PMID: 6689201
  10. Marker (X)-linked mental retardation.
    Adv Hum Genet. 1983;13:83-112 PMID: 6362362
  11. Regional localization on the human X chromosome and polymorphism of the coagulation factor IX gene (hemophilia B locus).
    Proc Natl Acad Sci U S A. 1984 Jan;81(2):498-502 PMID: 6320191
  12. Easy calculations of lod scores and genetic risks on small computers.
    Am J Hum Genet. 1984 Mar;36(2):460-5 PMID: 6585139
  13. The marker (X) syndrome: a cytogenetic and genetic analysis.
    Ann Hum Genet. 1984 Jan;48(Pt 1):21-37 PMID: 6712153
  14. Carrier detection of Hemophilia B by using a restriction site polymorphism associated with the coagulation Factor IX gene.
    J Clin Invest. 1984 May;73(5):1491-5 PMID: 6325506
  15. Genetic mapping of the human X chromosome by using restriction fragment length polymorphisms.
    Proc Natl Acad Sci U S A. 1984 May;81(9):2836-9 PMID: 6326147
  16. Strategies for multilocus linkage analysis in humans.
    Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443-6 PMID: 6587361
  17. Linkage analysis of X-linked mental retardation with and without fragile-X using factor IX gene probe.
    Lancet. 1984 Aug 11;2(8398):349 PMID: 6146889
  18. [Mental retardation linked to fragility of chromosome X: current knowledge].
    J Genet Hum. 1984 Jul;32(3):167-92 PMID: 6237176
  19. Exclusion of haemophilia B in male fetus by chorionic villus biopsy.
    Lancet. 1984 Oct 20;2(8408):932 PMID: 6148652
  20. Transmission of the marker X syndrome trait by unaffected males: conclusions from studies of large families.
    Hum Genet. 1984;67(4):419-27 PMID: 6593289
  21. The fragile X syndrome. A study of 83 families.
    Clin Genet. 1984 Dec;26(6):497-528 PMID: 6499265
  22. Carrier detection in haemophilia B using two further intragenic restriction fragment length polymorphisms.
    Nucleic Acids Res. 1984 Dec 11;12(23):8861-72 PMID: 6096810
  23. Cytological mapping of the human glucose-6-phosphate dehydrogenase gene distal to the fragile-X site suggests a high rate of meiotic recombination across this site.
    Proc Natl Acad Sci U S A. 1984 Dec;81(24):7855-9 PMID: 6595664
  24. First trimester prenatal diagnosis of a male fetus with fragile X.
    Lancet. 1985 Apr 13;1(8433):870 PMID: 2858725
  25. Further segregation analysis of the fragile X syndrome with special reference to transmitting males.
    Hum Genet. 1985;69(4):289-99 PMID: 3838733
  26. Localization by in situ hybridization of the coagulation factor IX gene and of two polymorphic DNA probes with respect to the fragile X site.
    Hum Genet. 1985;69(4):327-31 PMID: 2985491
  27. The telomeric region of the human X chromosome long arm: presence of a highly polymorphic DNA marker and analysis of recombination frequency.
    Proc Natl Acad Sci U S A. 1985 May;82(9):2824-8 PMID: 2986139
  28. Detection of specific RNAs or specific fragments of DNA by fractionation in gels and transfer to diazobenzyloxymethyl paper.
    Methods Enzymol. 1979;68:220-42 PMID: 94421
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.83.4.1016
Published
1986-02-00
Pages
1016-20
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC323001
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.83.4.1016 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2