Chromosomal regions containing high-density and ambiguously mapped putative single nucleotide polymorphisms (SNPs) correlate with segmental duplications in the human genome

Xavier P. Estivill, Joseph Cheung, Miguel Angel Pujana, Kazuhiko Nakabayashi, Stephen W. Scherer, Lap Chee Tsui

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

We have explored the National Center for Biotechnology Information (NCBI) single nucleotide polymorphisms (SNPs) database for a correlation between the density of putative SNPs, as well as SNPs that map to different chromosomal locations (ambiguously mapped SNPs), and segmental duplications of DNA in chromosome regions involved in genomic disorders. A high density of SNPs (14.4 and 12.4 SNPs per kb) was detected in the low copy repeats (LCRs) responsible for the chromosome 17p12 duplication and deletion that cause peripheral neuropathies. None of the SNPs at the PMP22 gene were ambiguously mapped, but 93% of the, SNPs at LCRs mapped on both LCR copies, indicating that they are in fact variants in paralogous sequences. Similarly, a high SNP density was found in the LCR regions flanking the neurofibromatosis type 1 (NF1) gene, with 80% of SNPs mapping on both LCR copies. A high density of SNPs was found within LCR sequences involved in the deletions that mediate contiguous gene syndromes on chromosomes 7q11, 15q11-q13 and 22q11. We have analyzed the whole sequence of chromosome 22, which contains 14% of ambiguously mapped SNPs, and have found a good correlation between these SNPs and segmental duplications detected by BLAST analysis. We have identified several segments of ambiguously mapped SNPs, four corresponding to LCRs involved in the chromosome 22q11 microdeletion syndromes. Our data indicate that most SNPs in LCR segments are in fact paralogous sequence variants (PSVs), and suggest that a significant proportion of the SNPs in the NCBI database correspond to PSVs within segmental duplications of the human genome sequence.

Original languageEnglish
Pages (from-to)1987-1995
Number of pages9
JournalHuman Molecular Genetics
Volume11
Issue number17
Publication statusPublished - 15 Aug 2002
Externally publishedYes

Fingerprint

Genomic Segmental Duplications
Human Genome
Single Nucleotide Polymorphism
Information Centers
Chromosomes
Biotechnology
Nucleotide Mapping
Neurofibromatosis 1 Genes
Chromosome Duplication
Databases
Chromosomes, Human, Pair 22
Chromosome Deletion
Neurofibromatosis 1

ASJC Scopus subject areas

  • Genetics

Cite this

Chromosomal regions containing high-density and ambiguously mapped putative single nucleotide polymorphisms (SNPs) correlate with segmental duplications in the human genome. / Estivill, Xavier P.; Cheung, Joseph; Pujana, Miguel Angel; Nakabayashi, Kazuhiko; Scherer, Stephen W.; Tsui, Lap Chee.

In: Human Molecular Genetics, Vol. 11, No. 17, 15.08.2002, p. 1987-1995.

Research output: Contribution to journalArticle

Estivill, Xavier P. ; Cheung, Joseph ; Pujana, Miguel Angel ; Nakabayashi, Kazuhiko ; Scherer, Stephen W. ; Tsui, Lap Chee. / Chromosomal regions containing high-density and ambiguously mapped putative single nucleotide polymorphisms (SNPs) correlate with segmental duplications in the human genome. In: Human Molecular Genetics. 2002 ; Vol. 11, No. 17. pp. 1987-1995.
@article{4abfd809f00b4e7390d92a072210cee7,
title = "Chromosomal regions containing high-density and ambiguously mapped putative single nucleotide polymorphisms (SNPs) correlate with segmental duplications in the human genome",
abstract = "We have explored the National Center for Biotechnology Information (NCBI) single nucleotide polymorphisms (SNPs) database for a correlation between the density of putative SNPs, as well as SNPs that map to different chromosomal locations (ambiguously mapped SNPs), and segmental duplications of DNA in chromosome regions involved in genomic disorders. A high density of SNPs (14.4 and 12.4 SNPs per kb) was detected in the low copy repeats (LCRs) responsible for the chromosome 17p12 duplication and deletion that cause peripheral neuropathies. None of the SNPs at the PMP22 gene were ambiguously mapped, but 93{\%} of the, SNPs at LCRs mapped on both LCR copies, indicating that they are in fact variants in paralogous sequences. Similarly, a high SNP density was found in the LCR regions flanking the neurofibromatosis type 1 (NF1) gene, with 80{\%} of SNPs mapping on both LCR copies. A high density of SNPs was found within LCR sequences involved in the deletions that mediate contiguous gene syndromes on chromosomes 7q11, 15q11-q13 and 22q11. We have analyzed the whole sequence of chromosome 22, which contains 14{\%} of ambiguously mapped SNPs, and have found a good correlation between these SNPs and segmental duplications detected by BLAST analysis. We have identified several segments of ambiguously mapped SNPs, four corresponding to LCRs involved in the chromosome 22q11 microdeletion syndromes. Our data indicate that most SNPs in LCR segments are in fact paralogous sequence variants (PSVs), and suggest that a significant proportion of the SNPs in the NCBI database correspond to PSVs within segmental duplications of the human genome sequence.",
author = "Estivill, {Xavier P.} and Joseph Cheung and Pujana, {Miguel Angel} and Kazuhiko Nakabayashi and Scherer, {Stephen W.} and Tsui, {Lap Chee}",
year = "2002",
month = "8",
day = "15",
language = "English",
volume = "11",
pages = "1987--1995",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "17",

}

TY - JOUR

T1 - Chromosomal regions containing high-density and ambiguously mapped putative single nucleotide polymorphisms (SNPs) correlate with segmental duplications in the human genome

AU - Estivill, Xavier P.

AU - Cheung, Joseph

AU - Pujana, Miguel Angel

AU - Nakabayashi, Kazuhiko

AU - Scherer, Stephen W.

AU - Tsui, Lap Chee

PY - 2002/8/15

Y1 - 2002/8/15

N2 - We have explored the National Center for Biotechnology Information (NCBI) single nucleotide polymorphisms (SNPs) database for a correlation between the density of putative SNPs, as well as SNPs that map to different chromosomal locations (ambiguously mapped SNPs), and segmental duplications of DNA in chromosome regions involved in genomic disorders. A high density of SNPs (14.4 and 12.4 SNPs per kb) was detected in the low copy repeats (LCRs) responsible for the chromosome 17p12 duplication and deletion that cause peripheral neuropathies. None of the SNPs at the PMP22 gene were ambiguously mapped, but 93% of the, SNPs at LCRs mapped on both LCR copies, indicating that they are in fact variants in paralogous sequences. Similarly, a high SNP density was found in the LCR regions flanking the neurofibromatosis type 1 (NF1) gene, with 80% of SNPs mapping on both LCR copies. A high density of SNPs was found within LCR sequences involved in the deletions that mediate contiguous gene syndromes on chromosomes 7q11, 15q11-q13 and 22q11. We have analyzed the whole sequence of chromosome 22, which contains 14% of ambiguously mapped SNPs, and have found a good correlation between these SNPs and segmental duplications detected by BLAST analysis. We have identified several segments of ambiguously mapped SNPs, four corresponding to LCRs involved in the chromosome 22q11 microdeletion syndromes. Our data indicate that most SNPs in LCR segments are in fact paralogous sequence variants (PSVs), and suggest that a significant proportion of the SNPs in the NCBI database correspond to PSVs within segmental duplications of the human genome sequence.

AB - We have explored the National Center for Biotechnology Information (NCBI) single nucleotide polymorphisms (SNPs) database for a correlation between the density of putative SNPs, as well as SNPs that map to different chromosomal locations (ambiguously mapped SNPs), and segmental duplications of DNA in chromosome regions involved in genomic disorders. A high density of SNPs (14.4 and 12.4 SNPs per kb) was detected in the low copy repeats (LCRs) responsible for the chromosome 17p12 duplication and deletion that cause peripheral neuropathies. None of the SNPs at the PMP22 gene were ambiguously mapped, but 93% of the, SNPs at LCRs mapped on both LCR copies, indicating that they are in fact variants in paralogous sequences. Similarly, a high SNP density was found in the LCR regions flanking the neurofibromatosis type 1 (NF1) gene, with 80% of SNPs mapping on both LCR copies. A high density of SNPs was found within LCR sequences involved in the deletions that mediate contiguous gene syndromes on chromosomes 7q11, 15q11-q13 and 22q11. We have analyzed the whole sequence of chromosome 22, which contains 14% of ambiguously mapped SNPs, and have found a good correlation between these SNPs and segmental duplications detected by BLAST analysis. We have identified several segments of ambiguously mapped SNPs, four corresponding to LCRs involved in the chromosome 22q11 microdeletion syndromes. Our data indicate that most SNPs in LCR segments are in fact paralogous sequence variants (PSVs), and suggest that a significant proportion of the SNPs in the NCBI database correspond to PSVs within segmental duplications of the human genome sequence.

UR - http://www.scopus.com/inward/record.url?scp=0037101840&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037101840&partnerID=8YFLogxK

M3 - Article

VL - 11

SP - 1987

EP - 1995

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 17

ER -