Genome Research International Con Genetics

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nickerson, D. A.
Right arrow Articles by Sing, C. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nickerson, D. A.
Right arrow Articles by Sing, C. F.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Vol. 10, Issue 10, 1532-1545, October 2000

LETTER
Sequence Diversity and Large-Scale Typing of SNPs in the Human Apolipoprotein E Gene

Deborah A. Nickerson,1,7 Scott L. Taylor,1 Stephanie M. Fullerton,2,3 Kenneth M. Weiss,2 Andrew G. Clark,3 Jari H. Stengård,4 Veikko Salomaa,4 Eric Boerwinkle,5 and Charles F. Sing6

1 Department of Molecular Biotechnology, University of Washington, Seattle, Washington 98195, USA; 2 Department of Anthropology, 3 Institute of Molecular Evolutionary Genetics, Department of Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA; 4 National Public Health Institute, Department of Epidemiology and Health Promotion, Helsinki, Finland; 5 Human Genetics Center, University of Texas Health Science Center, Houston, Texas 77225, USA; 6 Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA

A common strategy for genotyping large samples begins with the characterization of human single nucleotide polymorphisms (SNPs) by sequencing candidate regions in a small sample for SNP discovery. This is usually followed by typing in a large sample those sites observed to vary in a smaller sample. We present results from a systematic investigation of variation at the human apolipoprotein E locus (APOE), as well as the evaluation of the two-tiered sampling strategy based on these data. We sequenced 5.5 kb spanning the entire APOE genomic region in a core sample of 72 individuals, including 24 each of African-Americans from Jackson, Mississippi; European-Americans from Rochester, Minnesota; and Europeans from North Karelia, Finland. This sequence survey detected 21 SNPs and 1 multiallelic indel, 14 of which had not been previously reported. Alleles varied in relative frequency among the populations, and 10 sites were polymorphic in only a single population sample. Oligonucleotide ligation assays (OLA) were developed for 20 of these sites (omitting the indel and a closely-linked SNP). These were then scored in 2179 individuals sampled from the same three populations (n = 843, 884, and 452, respectively). Relative allele frequencies were generally consistent with estimates from the core sample, although variation was found in some populations in the larger sample at SNPs that were monomorphic in the corresponding smaller core sample. Site variation in the larger samples showed no systematic deviation from Hardy-Weinberg expectation. The large OLA sample clearly showed that variation in many, but not all, of OLA-typed SNPs is significantly correlated with the classical protein-coding variants, implying that there may be important substructure within the classical varepsilon 2, varepsilon 3, and varepsilon 4 alleles. Comparison of the levels and patterns of polymorphism in the core samples with those estimated for the OLA-typed samples shows how nucleotide diversity is underestimated when only a subset of sites are typed and underscores the importance of adequate population sampling at the polymorphism discovery stage.

[The sequence data described in this paper have been submitted to the GenBank data library under accession no. AF261279.]

7 Corresponding author.

10:1532-1545 ©2000 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/00 $5.00
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Gerontol. A Biol. Sci. Med. Sci.Home page
D. C. Ewbank
Differences in the Association Between Apolipoprotein E Genotype and Mortality Across Populations
J. Gerontol. A Biol. Sci. Med. Sci., August 1, 2007; 62(8): 899 - 907.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
J. H. Stengard, S. L. R. Kardia, S. C. Hamon, R. Frikke-Schmidt, A. Tybjaerg-Hansen, V. Salomaa, E. Boerwinkle, and C. F. Sing
Contribution of regulatory and structural variations in APOE to predicting dyslipidemia
J. Lipid Res., February 1, 2006; 47(2): 318 - 328.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. Seitz, D. Gourevitch, X.-M. Zhang, L. Clark, P. Chen, M. Kragol, N. Levenkova, J. Rux, S. Samulewicz, and E. Heber-Katz
Sense and antisense transcripts of the apolipoprotein E gene in normal and ApoE knockout mice, their expression after spinal cord injury and corresponding human transcripts
Hum. Mol. Genet., September 15, 2005; 14(18): 2661 - 2670.
[Abstract] [Full Text] [PDF]

Home page
 BioinformaticsHome page
A. S. Rodin and E. Boerwinkle
Mining genetic epidemiology data with Bayesian networks I: Bayesian networks and example application (plasma apoE levels)
Bioinformatics, August 1, 2005; 21(15): 3273 - 3278.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
G. Kimmel and R. Shamir
GERBIL: Genotype resolution and block identification using likelihood
PNAS, January 4, 2005; 102(1): 158 - 162.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
K. Ding, K. Zhou, J. Zhang, J. Knight, X. Zhang, and Y. Shen
The Effect of Haplotype-Block Definitions on Inference of Haplotype-Block Structure and htSNPs Selection
Mol. Biol. Evol., January 1, 2005; 22(1): 148 - 159.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
X. Ke, C. Durrant, A. P. Morris, S. Hunt, D. R. Bentley, P. Deloukas, and L. R. Cardon
Efficiency and consistency of haplotype tagging of dense SNP maps in multiple samples
Hum. Mol. Genet., November 1, 2004; 13(21): 2557 - 2565.
[Abstract] [Full Text] [PDF]

Home page
 Genome Res.Home page
B. V. Halldorsson, V. Bafna, R. Lippert, R. Schwartz, F. M. De La Vega, A. G. Clark, and S. Istrail
Optimal Haplotype Block-Free Selection of Tagging SNPs for Genome-Wide Association Studies
Genome Res., August 1, 2004; 14(8): 1633 - 1640.
[Abstract] [Full Text] [PDF]

Home page
 J. Gerontol. A Biol. Sci. Med. Sci.Home page
D. C. Ewbank
The APOE Gene and Differences in Life Expectancy in Europe
J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2004; 59(1): B16 - 20.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
J. W. Gaynor, M. Gerdes, E. H. Zackai, J. Bernbaum, G. Wernovsky, R. R. Clancy, M. F. Newman, A. M. Saunders, P. J. Heagerty, J. A. D'Agostino, et al.
Apolipoprotein E genotype and neurodevelopmental sequelae of infant cardiac surgery
J. Thorac. Cardiovasc. Surg., December 1, 2003; 126(6): 1736 - 1745.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
S. H. Orzack, D. Gusfield, J. Olson, S. Nesbitt, L. Subrahmanyan, and V. P. Stanton Jr.
Analysis and Exploration of the Use of Rule-Based Algorithms and Consensus Methods for the Inferral of Haplotypes
Genetics, October 1, 2003; 165(2): 915 - 928.
[Abstract] [Full Text] [PDF]

Home page
 Genome Res.Home page
W. S. Watkins, A. R. Rogers, C. T. Ostler, S. Wooding, M. J. Bamshad, A.-M. E. Brassington, M. L. Carroll, S. V. Nguyen, J. A. Walker, B.V. R. Prasad, et al.
Genetic Variation Among World Populations: Inferences From 100 Alu Insertion Polymorphisms
Genome Res., July 1, 2003; 13(7): 1607 - 1618.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
K. V. N. Rao, P. W. Stevens, J. G. Hall, V. Lyamichev, B. P. Neri, and D. M. Kelso
Genotyping single nucleotide polymorphisms directly from genomic DNA by invasive cleavage reaction on microspheres
Nucleic Acids Res., June 1, 2003; 31(11): e66 - e66.
[Abstract] [Full Text] [PDF]

Home page
 Genome Res.Home page
R. C.J. Twells, C. A. Mein, M. S. Phillips, J. F. Hess, R. Veijola, M. Gilbey, M. Bright, M. Metzker, B. A. Lie, A. Kingsnorth, et al.
Haplotype Structure, LD Blocks, and Uneven Recombination Within the LRP5 Gene
Genome Res., May 1, 2003; 13(5): 845 - 855.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
K. D. Makova, M. Ramsay, T. Jenkins, and W.-H. Li
Human DNA Sequence Variation in a 6.6-kb Region Containing the Melanocortin 1 Receptor Promoter
Genetics, July 1, 2001; 158(3): 1253 - 1268.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
J. C. Venter, M. D. Adams, E. W. Myers, P. W. Li, R. J. Mural, G. G. Sutton, H. O. Smith, M. Yandell, C. A. Evans, R. A. Holt, et al.
The Sequence of the Human Genome
Science, February 16, 2001; 291(5507): 1304 - 1351.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Genes Dev. Learn. Mem.
Protein Science RNA Genome Res.