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PMID: 15256512 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Segmental duplications flank the multiple sclerosis locus on chromosome 17q.

Genome research ·Vol. 14 ·No. 8 ·2004-08-00 ·Pages 1483-92

Chen DC, Saarela J, Clark RA, Miettinen T, Chi A, Eichler EE, Peltonen L, Palotie A

Abstract

Large chromosomal rearrangements, duplications, and inversions are relatively common in mammalian genomes. Here we report interesting features of DNA strands flanking a Multiple Sclerosis (MS) susceptibility locus on Chromosome 17q24. During the positional cloning process of this 3-Mb locus, several markers showed a radiation hybrid clone retention rate above the average (1.8-fold), suggestive for the existence of duplicated sequences in this region. FISH studies demonstrated multiple signals with three of the tested regional BACs, and 24 BACs out of 187 showed evidence for duplication in shotgun sequence comparisons of the 17q22-q24 region. Specifically, the MS haplotype region proved to be flanked by palindromic sequence stretches and by long segmental intrachromosomal duplications in which highly homologous DNA sequences (>96% identity) are present at both ends of the haplotype. Moreover, the 3-Mb DNA segment, flanked by the duplications, is inverted in the mouse genome when compared with the orientation in human and chimp. The segmental duplication architecture surrounding the MS locus raises the possibility that a nonallelic homologous recombination between duplications could affect the biological activity of the regional genes, perhaps even contributing to the genetic background of MS.

MeSH Terms
Animals Chromosomes, Human, Pair 11 Chromosomes, Human, Pair 17 Gene Duplication Genetic Markers Genome, Human Haplotypes Humans Mice Models, Molecular Multiple Sclerosis/genetics Polymorphism, Single Nucleotide Radiation Hybrid Mapping/methods Sequence Homology, Nucleic Acid
Chemicals
Genetic Markers
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Chen Daniel C
Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California 90095, USA.
Saarela Janna
Clark Royden A
Miettinen Timo
Chi Anthony
Eichler Evan E
Peltonen Leena
Palotie Aarno
References (39)
39 references, click to expand
  1. Regional and temporal variation in the incidence of multiple sclerosis in Finland 1979-1993.
    Neuroepidemiology. 2000 Mar-Apr;19(2):67-75 PMID: 10686531
  2. Mechanically stretched chromosomes as targets for high-resolution FISH mapping.
    Genome Res. 1995 Aug;5(1):13-20 PMID: 8717051
  3. Construction of a detailed physical and transcript map of the candidate region for Russell-Silver syndrome on chromosome 17q23-q24.
    Genomics. 2001 Jan 15;71(2):174-81 PMID: 11161811
  4. Use of population isolates for mapping complex traits.
    Nat Rev Genet. 2000 Dec;1(3):182-90 PMID: 11252747
  5. Olfactory receptor-gene clusters, genomic-inversion polymorphisms, and common chromosome rearrangements.
    Am J Hum Genet. 2001 Apr;68(4):874-83 PMID: 11231899
  6. Comprehensive copy number and gene expression profiling of the 17q23 amplicon in human breast cancer.
    Proc Natl Acad Sci U S A. 2001 May 8;98(10):5711-6 PMID: 11331760
  7. Segmental duplications: organization and impact within the current human genome project assembly.
    Genome Res. 2001 Jun;11(6):1005-17 PMID: 11381028
  8. Congenic mapping confirms a locus on rat chromosome 10 conferring strong protection against myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis.
    Immunogenetics. 2001 Jul;53(5):410-5 PMID: 11486278
  9. Genetic susceptibility to MS: a second stage analysis in Canadian MS families.
    Neurogenetics. 2001 Jul;3(3):145-51 PMID: 11523565
  10. The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men.
    Nat Genet. 2001 Nov;29(3):279-86 PMID: 11687796
  11. Implications of the human genome for understanding human biology and medicine.
    JAMA. 2001 Nov 14;286(18):2296-307 PMID: 11710896
  12. Human-specific duplication and mosaic transcripts: the recent paralogous structure of chromosome 22.
    Am J Hum Genet. 2002 Jan;70(1):83-100 PMID: 11731936
  13. Diversity in the mechanisms of gene regulation by estrogen receptors.
    Bioessays. 2002 Mar;24(3):244-54 PMID: 11891761
  14. Molecular-evolutionary mechanisms for genomic disorders.
    Curr Opin Genet Dev. 2002 Jun;12(3):312-9 PMID: 12076675
  15. Chromosomal regions containing high-density and ambiguously mapped putative single nucleotide polymorphisms (SNPs) correlate with segmental duplications in the human genome.
    Hum Mol Genet. 2002 Aug 15;11(17):1987-95 PMID: 12165560
  16. Recent segmental duplications in the human genome.
    Science. 2002 Aug 9;297(5583):1003-7 PMID: 12169732
  17. Genomewide scan of multiple sclerosis in Finnish multiplex families.
    Am J Hum Genet. 1997 Dec;61(6):1379-87 PMID: 9399895
  18. Consortium study on 1280 breast carcinomas: allelic loss on chromosome 17 targets subregions associated with family history and clinical parameters.
    Cancer Res. 1998 Mar 1;58(5):1004-12 PMID: 9500463
  19. Golli-MBP gene in multiple sclerosis susceptibility.
    J Neuroimmunol. 1998 Jan;81(1-2):158-67 PMID: 9521617
  20. Factors affecting inverted repeat stimulation of recombination and deletion in Saccharomyces cerevisiae.
    Genetics. 1998 Apr;148(4):1507-24 PMID: 9560370
  21. New genetic loci that control susceptibility and symptoms of experimental allergic encephalomyelitis in inbred mice.
    J Immunol. 1998 Aug 15;161(4):1860-7 PMID: 9712054
  22. Gene silencing: repeats that count.
    Cell. 1999 Apr 16;97(2):157-60 PMID: 10219236
  23. The role of Alu repeat clusters as mediators of recurrent chromosomal aberrations in tumors.
    Genes Chromosomes Cancer. 2002 Oct;35(2):97-112 PMID: 12203773
  24. Fine mapping of a multiple sclerosis locus to 2.5 Mb on chromosome 17q22-q24.
    Hum Mol Genet. 2002 Sep 15;11(19):2257-67 PMID: 12217954
  25. Initial sequencing and comparative analysis of the mouse genome.
    Nature. 2002 Dec 5;420(6915):520-62 PMID: 12466850
  26. Multiple sclerosis in Finland: incidence trends and differences in relapsing remitting and primary progressive disease courses.
    J Neurol Neurosurg Psychiatry. 2003 Jan;74(1):25-8 PMID: 12486261
  27. The constitutional t(17;22): another translocation mediated by palindromic AT-rich repeats.
    Am J Hum Genet. 2003 Mar;72(3):733-8 PMID: 12557125
  28. Genome-wide detection of segmental duplications and potential assembly errors in the human genome sequence.
    Genome Biol. 2003;4(4):R25 PMID: 12702206
  29. Structural dynamics of eukaryotic chromosome evolution.
    Science. 2003 Aug 8;301(5634):793-7 PMID: 12907789
  30. Refinement of a chimpanzee pericentric inversion breakpoint to a segmental duplication cluster.
    Genome Biol. 2003;4(8):R50 PMID: 12914658
  31. Enrichment of segmental duplications in regions of breaks of synteny between the human and mouse genomes suggest their involvement in evolutionary rearrangements.
    Hum Mol Genet. 2003 Sep 1;12(17):2201-8 PMID: 12915466
  32. Molecular and functional analysis of PRKAR1A and its locus (17q22-24) in sporadic adrenocortical tumors: 17q losses, somatic mutations, and protein kinase A expression and activity.
    Cancer Res. 2003 Sep 1;63(17):5308-19 PMID: 14500362
  33. Hotspots of mammalian chromosomal evolution.
    Genome Biol. 2004;5(4):R23 PMID: 15059256
  34. Genetic susceptibility to multiple sclerosis linked to myelin basic protein gene.
    Lancet. 1992 Oct 24;340(8826):987-91 PMID: 1383661
  35. Faster sequential genetic linkage computations.
    Am J Hum Genet. 1993 Jul;53(1):252-63 PMID: 8317490
  36. Long DNA palindromes, cruciform structures, genetic instability and secondary structure repair.
    Bioessays. 1994 Dec;16(12):893-900 PMID: 7840768
  37. A genome screen in multiple sclerosis reveals susceptibility loci on chromosome 6p21 and 17q22.
    Nat Genet. 1996 Aug;13(4):464-8 PMID: 8696343
  38. A full genome search in multiple sclerosis.
    Nat Genet. 1996 Aug;13(4):472-6 PMID: 8696345
  39. Fine-scale comparative mapping of the human 7q11.23 region and the orthologous region on mouse chromosome 5G: the low-copy repeats that flank the Williams-Beuren syndrome deletion arose at breakpoint sites of an evolutionary inversion(s).
    Genomics. 2000 Oct 1;69(1):1-13 PMID: 11013070
Article Info
Journal
Genome research
Abbr.
Genome Res
ISSN
1088-9051
DOI
10.1101/gr.2340804
Published
2004-08-00
Epub
2004-00-15
Pages
1483-92
Language
English
Region
United States
NLM ID
9518021
PMCID
PMC509257
Subset
IM
Grants
NINDS NIH HHS · R01 NS043559 · United States
NINDS NIH HHS · R01 NS 43559 · United States
External Links
PubMed source DOI: 10.1101/gr.2340804 PMC Full Text View journal details
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