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Strong conservation of the human NF2 locus based on sequence comparison in five species

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Abstract

We analyzed 137 kb covering human neurofibromatosis 2 (NF2) tumor suppressor locus and orthologous loci from baboon, mouse, rat, and pufferfish Takifugu rubripes. A predominant feature of human-rodent conservation is a very similar distribution of conserved islands, regarding length, position, and degree of identity. By use of a threshold of 75% identity over ≥100 bp of gap-free alignment, comparisons of human-mouse sequences resulted in 3.58% for extra-exonic conservation, which can be compared to 4.5% of exonic sequence content within the human locus. We identified a duplication of neurofibromin 2 in pufferfish, which resulted in two putative proteins with 74% and 76% identity to the human protein. One distinct island (called inter 1), conserved between all analyzed species, was located between promoters of the NIPSNAP1 and NF2 genes. Inter 1 might represent a novel regulatory element, important for the function of this locus. The high level of intronic conservation in the NF2 locus suggests that a number of unknown regulatory elements might exist within this gene. These elements could be affected by disease-causing mutations in NF2 patients and NF2-associated tumors. Alternatively, this conservation might be explained by presence of not yet characterized transcriptional unit(s) within this locus.

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Acknowledgements

The authors thank Dr. Wyeth Wasserman for critical review of the manuscript. This work was supported by grants from the U.S. Army Medical Research and Material Command, award no. DAMD17-00-1-0536, the Swedish Cancer Foundation, the Swedish Research Council, Uppsala University to J.P. Dumanski, and NIH grant HG02153 to B.A. Roe.

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Authors and Affiliations

  1. Department of Genetics and Pathology, Rudbeck Laboratory, 3rd floor, Dag Hammarskjöds väg 20, Uppsala University, 751 85 Uppsala, Sweden

    Caisa M. Hansson, Haider Ali, Carl E. G. Bruder, Sindy Kluge, Uwe Menzel & Jan P. Dumanski

  2. Department of Molecular Medicine, CMM Building L8:00, Karolinska Hospital, 171 76 Stockholm, Sweden

    Ingegerd Fransson

  3. Center for Genomics and Bioinformatics, Karolinska Institutet, Berzelius väg 35, S-171 77 Stockholm, Sweden

    Björn Andersson

  4. Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, USA

    Bruce A. Roe

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  1. Caisa M. Hansson
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Correspondence to Jan P. Dumanski.

Additional information

Sequence data from this article have been deposited with the EMBL/GenBank/DDBJ data library under accession numbers: Mouse: AC007550; Baboon: AY123427, AY123428, AY123429, AY123430, AY123431, AY123432, AY123433, AY123434, AY123435, AY123436, AY123437, AY123438, AY123439; Rat: AC127480. Present address (Carl E.G. Bruder): AstraZenenca R&D, Transgenics and Comparative Genomics, 43183 Mölndal, Sweden.

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Hansson, C.M., Ali, H., Bruder, C.E. et al. Strong conservation of the human NF2 locus based on sequence comparison in five species . Mamm Genome 14, 526–536 (2003). https://doi.org/10.1007/s00335-003-3011-3

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