Complex high-resolution linkage disequilibrium and haplotype patterns of single-nucleotide polymorphisms in 2.5 Mb of sequence on human chromosome 21

Michael Olivier, Valerie I. Bustos, Michelle R. Levy, Geoff A. Smick, Ismael P Moreno, Jannette M. Bushard, Annalisa A. Almendras, Kelly Sheppard, Deborah L. Zierten, Amita Aggarwal, Chris S. Carlson, Brian D. Foster, Nu Vo, Libusha Kelly, Xia Liu, David R. Cox

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

One approach to identify potentially important segments of the human genome is to search for DNA regions with nonrandom patterns of human sequence variation. Previous studies have investigated these patterns primarily in and around candidate gene regions. Here, we determined patterns of DNA sequence variation in 2.5 Mb of finished sequence from five regions on human chromosome 21. By sequencing 13 individual chromosomes, we identified 1460 single-nucleotide polymorphisms (SNPs) and obtained unambiguous haplotypes for all chromosomes. For all five chromosomal regions, we observed segments with high linkage disequilibrium (LD), extending from 1.7 to > 81 kb (average 21.7 kb), disrupted by segments of similar or larger size with no significant LD between SNPs. At least 25% of the contig sequences consisted of segments with high LD between SNPs. Each of these segments was characterized by a restricted number of observed haplotypes, with the major haplotype found in over 60% of all chromosomes. In contrast, the interspersed segments with low LD showed significantly more haplotype patterns. The position and extent of the segments of high LD with restricted haplotype variability did not coincide with the location of coding sequences. Our results indicate that LD and haplotype patterns need to be investigated with closely spaced SNPs throughout the human genome, independent of the location of coding sequences, to reliably identify regions with significant LD useful for disease association studies.

Original languageEnglish (US)
Pages (from-to)64-72
Number of pages9
JournalGenomics
Volume78
Issue number1-2
DOIs
StatePublished - Sep 1 2001
Externally publishedYes

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Chromosomes, Human, Pair 21
Linkage Disequilibrium
Human Chromosomes
Haplotypes
Single Nucleotide Polymorphism
Human Genome
Chromosomes
Chromosomes, Human, Pair 13
DNA
Genes

Keywords

  • Chromosome 21
  • Haplotype
  • Linkage disequilibrium
  • Single-nucleotide polymorphism

ASJC Scopus subject areas

  • Genetics

Cite this

Complex high-resolution linkage disequilibrium and haplotype patterns of single-nucleotide polymorphisms in 2.5 Mb of sequence on human chromosome 21. / Olivier, Michael; Bustos, Valerie I.; Levy, Michelle R.; Smick, Geoff A.; Moreno, Ismael P; Bushard, Jannette M.; Almendras, Annalisa A.; Sheppard, Kelly; Zierten, Deborah L.; Aggarwal, Amita; Carlson, Chris S.; Foster, Brian D.; Vo, Nu; Kelly, Libusha; Liu, Xia; Cox, David R.

In: Genomics, Vol. 78, No. 1-2, 01.09.2001, p. 64-72.

Research output: Contribution to journalArticle

Olivier, M, Bustos, VI, Levy, MR, Smick, GA, Moreno, IP, Bushard, JM, Almendras, AA, Sheppard, K, Zierten, DL, Aggarwal, A, Carlson, CS, Foster, BD, Vo, N, Kelly, L, Liu, X & Cox, DR 2001, 'Complex high-resolution linkage disequilibrium and haplotype patterns of single-nucleotide polymorphisms in 2.5 Mb of sequence on human chromosome 21', Genomics, vol. 78, no. 1-2, pp. 64-72. https://doi.org/10.1006/geno.2001.6646
Olivier, Michael ; Bustos, Valerie I. ; Levy, Michelle R. ; Smick, Geoff A. ; Moreno, Ismael P ; Bushard, Jannette M. ; Almendras, Annalisa A. ; Sheppard, Kelly ; Zierten, Deborah L. ; Aggarwal, Amita ; Carlson, Chris S. ; Foster, Brian D. ; Vo, Nu ; Kelly, Libusha ; Liu, Xia ; Cox, David R. / Complex high-resolution linkage disequilibrium and haplotype patterns of single-nucleotide polymorphisms in 2.5 Mb of sequence on human chromosome 21. In: Genomics. 2001 ; Vol. 78, No. 1-2. pp. 64-72.
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AU - Moreno, Ismael P

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AU - Carlson, Chris S.

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