• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of ajhgLink to Publisher's site
Am J Hum Genet. Feb 1992; 50(2): 422–426.
PMCID: PMC1682451

Molecular characterization of beta-thalassemia in the Sardinian population.


This study reports the molecular characterization of beta-thalassemia in the Sardinian population. Three thousand beta-thalassemia chromosomes from prospective parents presenting at the genetic service were initially analyzed by dot blot analysis with oligonucleotide probes complementary to the most common beta-thalassemia mutations in the Mediterranean at-risk populations. the mutations which remained uncharacterized by this approach were defined by denaturing gradient gel electrophoresis (DGGE) followed by direct sequence analysis on amplified DNA. We reconfirmed that the predominant mutation in the Sardinian population is the codon 39 nonsense mutation, which accounts for 95.7% of the beta-thalassemia chromosomes. The other two relatively common mutations are frameshifts at codon 6 (2.1%) and at codon 76 (0.7%), relatively uncommon in other Mediterranean-origin populations. In this study we have detected a novel beta-thalassemia mutation, i.e., a frameshift at codon 1, in three beta-thalassemia chromosomes. The DGGE procedure followed by direct sequencing on amplified DNA is a powerful approach for the characterization of unknown mutations in this genetic system. The results herein presented allowed an expansion of the applicability of prenatal diagnosis by DNA analysis, to all couples at risk for beta-thalassemia in our population.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (681K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Cai SP, Kan YW. Identification of the multiple beta-thalassemia mutations by denaturing gradient gel electrophoresis. J Clin Invest. 1990 Feb;85(2):550–553. [PMC free article] [PubMed]
  • Di Marzo R, Dowling CE, Wong C, Maggio A, Kazazian HH., Jr The spectrum of beta-thalassaemia mutations in Sicily. Br J Haematol. 1988 Jul;69(3):393–397. [PubMed]
  • Fischer SG, Lerman LS. DNA fragments differing by single base-pair substitutions are separated in denaturing gradient gels: correspondence with melting theory. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1579–1583. [PMC free article] [PubMed]
  • Gyllensten UB, Erlich HA. Generation of single-stranded DNA by the polymerase chain reaction and its application to direct sequencing of the HLA-DQA locus. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7652–7656. [PMC free article] [PubMed]
  • Losekoot M, Fodde R, Harteveld CL, van Heeren H, Giordano PC, Bernini LF. Denaturing gradient gel electrophoresis and direct sequencing of PCR amplified genomic DNA: a rapid and reliable diagnostic approach to beta thalassaemia. Br J Haematol. 1990 Oct;76(2):269–274. [PubMed]
  • Orkin SH, Kazazian HH, Jr, Antonarakis SE, Goff SC, Boehm CD, Sexton JP, Waber PG, Giardina PJ. Linkage of beta-thalassaemia mutations and beta-globin gene polymorphisms with DNA polymorphisms in human beta-globin gene cluster. Nature. 1982 Apr 15;296(5858):627–631. [PubMed]
  • Ristaldi MS, Pirastu M, Rosatelli C, Monni G, Erlich H, Saiki R, Cao A. Prenatal diagnosis of beta-thalassaemia in Mediterranean populations by dot blot analysis with DNA amplification and allele specific oligonucleotide probes. Prenat Diagn. 1989 Sep;9(9):629–638. [PubMed]
  • Rosatelli C, Leoni GB, Tuveri T, Scalas MT, Di Tucci A, Cao A. Beta thalassaemia mutations in Sardinians: implications for prenatal diagnosis. J Med Genet. 1987 Feb;24(2):97–100. [PMC free article] [PubMed]
  • Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Sheffield VC, Cox DR, Lerman LS, Myers RM. Attachment of a 40-base-pair G + C-rich sequence (GC-clamp) to genomic DNA fragments by the polymerase chain reaction results in improved detection of single-base changes. Proc Natl Acad Sci U S A. 1989 Jan;86(1):232–236. [PMC free article] [PubMed]
  • Trecartin RF, Liebhaber SA, Chang JC, Lee KY, Kan YW, Furbetta M, Angius A, Cao A. beta zero thalassemia in Sardinia is caused by a nonsense mutation. J Clin Invest. 1981 Oct;68(4):1012–1017. [PMC free article] [PubMed]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • OMIM
    OMIM record citing PubMed
  • PubMed
    PubMed citations for these articles
  • SNP
    PMC to SNP links
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...