Neurogenetics

, Volume 5, Issue 1, pp 35–40 | Cite as

Specific mutations in the HEXA gene among Iraqi Jewish Tay-Sachs disease carriers: dating of founder ancestor

  • Mazal Karpati
  • Ephraim Gazit
  • Boleslaw Goldman
  • Amos Frisch
  • Roberto Colombo
  • Leah Peleg
Original Article
First Online:
Received:
Accepted:

Abstract

The incidence of Tay-Sachs disease (TSD) carriers, as defined by enzyme assay, is 1:29 among Ashkenazi Jews and 1:110 among Moroccan Jews. An elevated carrier frequency of 1:140 was also observed in the Iraqi Jews (IJ), while in other Israeli populations the world’s pan-ethnic frequency of approximately 1:280 has been found. Recently a novel mutation, G749T, has been reported in 38.7% of the IJ carriers (24/62). Here we report a second novel HEXA mutation specific to the IJ TDS carriers: a substitution of cytosine 1351 by guanosine (C1351G), resulting in the change of leucine to valine in position 451. This mutation was found in 33.9% (21/62) of the carriers and in none of 100 non-carrier IJ. In addition to the two specific mutations, 14.5% (9/62) of the IJ carriers bear a known “Jewish” mutation (Ashkenazi or Moroccan) and 11.3% (7/62) carry a known “non-Jewish” mutation. In 1 DNA sample no mutation has yet been detected. To investigate the genetic history of the IJ-specific mutations (C1351G and G749T), the allelic distribution of four polymorphic markers (D15S131, D15S1025, D15S981, D15S1050) was analyzed in IJ heterozygotes and ethnically matched controls. Based on linkage disequilibrium, recombination factor (θ) between the markers and mutated loci, and the population growth correction, we deduced that G749T occurred in a founder ancestor 44.8±14.2 generations (g) ago [95% confidence interval (CI) 17.0–72.6 g] and C1351G arose 80.4±35.9 g ago (95% CI 44.5–116.3 g). Thus, the estimated dates for introduction of mutations are: 626±426 A.D. (200–1052 A.D.) for G749T and 442±1077 B.C. (1519 B.C. to 635 A.D.) for C1351G.

Keywords

HEXA gene Tay-Sachs disease Iraqi Jews Founder effect Linkage disequilibrium 
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Notes

Acknowledgements

We thank Dr. O. Zolotkovski, Mrs. L. Baram, and Mrs. Z. Rachmani for technical assistance and advice regarding historical sources. We declare that our experiments comply with the current laws of Israel. Electronic data, accession number, and URLs for data in this article are as follows: deCODE genetic map, deCODE Genetics, Reykjavic, http://www.decode.com (for genetic distance); Genome Database, The, http://www.gdb.org (for D15S981, accession number 607971, D15S131, accession number 188733, D15S1050, accession number 614673, and for allele sets; http://www.ncbi.nlm.nih.gov/entrez for D15S1025 gi:1235337; Human Reference Sequence, UCSC Genome Bioinformatics, The University of California, Santa Cruz, http://genome.ucsc.edu for physical distance (bp).

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Mazal Karpati
    • 1
    • 4
  • Ephraim Gazit
    • 2
    • 4
  • Boleslaw Goldman
    • 1
    • 4
  • Amos Frisch
    • 3
    • 4
  • Roberto Colombo
    • 5
  • Leah Peleg
    • 1
    • 4
  1. 1.Danek Gertner Institute of Human GeneticsSheba Medical CenterTel HashomerIsrael
  2. 2.Department of PediatricsSheba Medical CenterTel HashomerIsrael
  3. 3.Felsenstein Medical Research CenterRabin Medical CenterPetah-TikvaIsrael
  4. 4.Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  5. 5.Laboratory of Human Molecular Biology and Genetics, Faculty of PsychologyCatholic University of the Sacred HeartMilanItaly

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