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Haplotypes within genes of beta-chemokines in 17q11 are associated with multiple sclerosis: a second phase study.
Hum Genet 2005; 118(1):67-75HG

Abstract

We previously defined haplotypes of single nucleotide polymorphisms (SNP) with possible relevance to multiple sclerosis (MS) in 2 CC chemokine ligand (CCL) clusters in chromosome 17q11. The 17q11 region was also identified as a susceptibility locus by a meta-analysis of linkage studies. To confirm and refine the previous finding in a second, high resolution SNP scan in a new set of families. We genotyped 232 SNPs in 1369 individuals in 361 MS families. Transmission of marker alleles and haplotypes from unaffected parents to affected offspring was tested by using the pedigree disequilibrium test, the TRANSMIT 2.5 program, and the family and haplotype based association tests. Distribution of linkage disequilibrium (LD) was assessed by ldmax. In consensus with observations in the first scan, the present study identified haplotypes within CCL3 and CCL15 in the telomeric CCL cluster. There was also an overlap in the findings in the centromeric CCL cluster. Strong and extensive LD was detected both within the centromeric and telomeric CCL gene clusters. The present study replicates our previous findings and further suggests the existence of MS associated haplotypes within genes of CCL3 and CCL15. Haplotypes of interest are also present within the centromeric gene cluster (including CCL2, CCL7, CCL11, CCL8, and CCL13), but extensive LD prevents further refinement of these haplotypes by using the methods applied. Sequencing of the identified chromosomal segments and their flanking regions will be necessary to define specific variants with direct relevance to MS pathogenesis.

Authors+Show Affiliations

Department of Neurology, Saint Luke's Roosevelt Hospital Center, Columbia University, 432 West 58th Street, Room 226, New York, NY, 10019, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16078049

Citation

Vyshkina, Tamara, and Bernadette Kalman. "Haplotypes Within Genes of Beta-chemokines in 17q11 Are Associated With Multiple Sclerosis: a Second Phase Study." Human Genetics, vol. 118, no. 1, 2005, pp. 67-75.
Vyshkina T, Kalman B. Haplotypes within genes of beta-chemokines in 17q11 are associated with multiple sclerosis: a second phase study. Hum Genet. 2005;118(1):67-75.
Vyshkina, T., & Kalman, B. (2005). Haplotypes within genes of beta-chemokines in 17q11 are associated with multiple sclerosis: a second phase study. Human Genetics, 118(1), pp. 67-75.
Vyshkina T, Kalman B. Haplotypes Within Genes of Beta-chemokines in 17q11 Are Associated With Multiple Sclerosis: a Second Phase Study. Hum Genet. 2005;118(1):67-75. PubMed PMID: 16078049.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Haplotypes within genes of beta-chemokines in 17q11 are associated with multiple sclerosis: a second phase study. AU - Vyshkina,Tamara, AU - Kalman,Bernadette, Y1 - 2005/08/03/ PY - 2005/03/21/received PY - 2005/05/08/accepted PY - 2005/8/4/pubmed PY - 2006/6/7/medline PY - 2005/8/4/entrez SP - 67 EP - 75 JF - Human genetics JO - Hum. Genet. VL - 118 IS - 1 N2 - We previously defined haplotypes of single nucleotide polymorphisms (SNP) with possible relevance to multiple sclerosis (MS) in 2 CC chemokine ligand (CCL) clusters in chromosome 17q11. The 17q11 region was also identified as a susceptibility locus by a meta-analysis of linkage studies. To confirm and refine the previous finding in a second, high resolution SNP scan in a new set of families. We genotyped 232 SNPs in 1369 individuals in 361 MS families. Transmission of marker alleles and haplotypes from unaffected parents to affected offspring was tested by using the pedigree disequilibrium test, the TRANSMIT 2.5 program, and the family and haplotype based association tests. Distribution of linkage disequilibrium (LD) was assessed by ldmax. In consensus with observations in the first scan, the present study identified haplotypes within CCL3 and CCL15 in the telomeric CCL cluster. There was also an overlap in the findings in the centromeric CCL cluster. Strong and extensive LD was detected both within the centromeric and telomeric CCL gene clusters. The present study replicates our previous findings and further suggests the existence of MS associated haplotypes within genes of CCL3 and CCL15. Haplotypes of interest are also present within the centromeric gene cluster (including CCL2, CCL7, CCL11, CCL8, and CCL13), but extensive LD prevents further refinement of these haplotypes by using the methods applied. Sequencing of the identified chromosomal segments and their flanking regions will be necessary to define specific variants with direct relevance to MS pathogenesis. SN - 0340-6717 UR - https://www.unboundmedicine.com/medline/citation/16078049/Haplotypes_within_genes_of_beta_chemokines_in_17q11_are_associated_with_multiple_sclerosis:_a_second_phase_study_ L2 - https://dx.doi.org/10.1007/s00439-005-0003-2 DB - PRIME DP - Unbound Medicine ER -