skip to main content
Tipo de recurso Mostra resultados com: Mostra resultados com: Índice

Discordant Haplotype Sequencing Identifies Functional Variants at the 2q33 Breast Cancer Risk Locus

Camp, Nicola J ; Lin, Wei-Yu ; Bigelow, Alex ; Burghel, George J ; Mosbruger, Timothy L ; Parry, Marina A ; Waller, Rosalie G ; Rigas, Sushilaben H ; Tai, Pei-Yi ; Berrett, Kristofer ; Rajamanickam, Venkatesh ; Cosby, Rachel ; Brock, Ian W ; Jones, Brandt ; Connley, Dan ; Sargent, Robert ; Wang, Guoying ; Factor, Rachel E ; Bernard, Philip S ; Cannon-Albright, Lisa ; Knight, Stacey ; Abo, Ryan ; Werner, Theresa L ; Reed, Malcolm W R ; Gertz, Jason ; Cox, Angela

Cancer research (Chicago, Ill.), 2016-04, Vol.76 (7), p.1916-1925 [Periódico revisado por pares]

United States

Texto completo disponível

Citações Citado por
  • Título:
    Discordant Haplotype Sequencing Identifies Functional Variants at the 2q33 Breast Cancer Risk Locus
  • Autor: Camp, Nicola J ; Lin, Wei-Yu ; Bigelow, Alex ; Burghel, George J ; Mosbruger, Timothy L ; Parry, Marina A ; Waller, Rosalie G ; Rigas, Sushilaben H ; Tai, Pei-Yi ; Berrett, Kristofer ; Rajamanickam, Venkatesh ; Cosby, Rachel ; Brock, Ian W ; Jones, Brandt ; Connley, Dan ; Sargent, Robert ; Wang, Guoying ; Factor, Rachel E ; Bernard, Philip S ; Cannon-Albright, Lisa ; Knight, Stacey ; Abo, Ryan ; Werner, Theresa L ; Reed, Malcolm W R ; Gertz, Jason ; Cox, Angela
  • Assuntos: Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; Female ; Genetic Predisposition to Disease ; Genetic Variation - genetics ; Haplotypes ; Humans ; Polymorphism, Single Nucleotide ; Risk
  • É parte de: Cancer research (Chicago, Ill.), 2016-04, Vol.76 (7), p.1916-1925
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    current address: Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK
    current address: School of Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford, BD7 1DP, UK
    current address: Brighton and Sussex Medical School, University of Sussex, Brighton, BN1 9RH, UK.
    current address: Intermountain Heart Institute, Intermountain Medical Center, Salt Lake City, UT 84107, USA
    current address: Cancer Research UK Manchester Institute, University of Manchester, Manchester, M20 4BX, UK
    current address: Dana-Farber Cancer Institute, Boston, MA 02215, USA
    current address: Manchester Centre for Genomic Medicine, Manchester, M13 9WL, UK
  • Descrição: The findings from genome-wide association studies hold enormous potential for novel insight into disease mechanisms. A major challenge in the field is to map these low-risk association signals to their underlying functional sequence variants (FSV). Simple sequence study designs are insufficient, as the vast numbers of statistically comparable variants and a limited knowledge of noncoding regulatory elements complicate prioritization. Furthermore, large sample sizes are typically required for adequate power to identify the initial association signals. One important question is whether similar sample sizes need to be sequenced to identify the FSVs. Here, we present a proof-of-principle example of an extreme discordant design to map FSVs within the 2q33 low-risk breast cancer locus. Our approach employed DNA sequencing of a small number of discordant haplotypes to efficiently identify candidate FSVs. Our results were consistent with those from a 2,000-fold larger, traditional imputation-based fine-mapping study. To prioritize further, we used expression-quantitative trait locus analysis of RNA sequencing from breast tissues, gene regulation annotations from the ENCODE consortium, and functional assays for differential enhancer activities. Notably, we implicate three regulatory variants at 2q33 that target CASP8 (rs3769823, rs3769821 in CASP8, and rs10197246 in ALS2CR12) as functionally relevant. We conclude that nested discordant haplotype sequencing is a promising approach to aid mapping of low-risk association loci. The ability to include more efficient sequencing designs into mapping efforts presents an opportunity for the field to capitalize on the potential of association loci and accelerate translation of association signals to their underlying FSVs. Cancer Res; 76(7); 1916-25. ©2016 AACR.
  • Editor: United States
  • Idioma: Inglês

Buscando em bases de dados remotas. Favor aguardar.