Skip Navigation


Human Molecular Genetics Advance Access originally published online on July 1, 2003
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
12/16/1973    most recent
ddg208v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (16)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Raby, B. A.
Right arrow Articles by Weiss, S. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Raby, B. A.
Right arrow Articles by Weiss, S. T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2003, Vol. 12, No. 16 1973-1979
DOI: 10.1093/hmg/ddg208
© 2003 Oxford University Press

Chromosome 12q harbors multiple genetic loci related to asthma and asthma-related phenotypes

Benjamin A. Raby1,*, Edwin K. Silverman1, Ross Lazarus1,2, Christoph Lange3, David J. Kwiatkowski4 and Scott T. Weiss1,5

1Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA, 2School of Public Health, University of Sydney, Australia, 3Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA, 4Hematology Division, Brigham and Women's Hospital, Boston, MA, USA and 5Harvard Partners Center for Genetics and Genomics, Boston, MA, USA

Received April 1, 2003; Revised June 2, 2003; Accepted June 16, 2003

Chromosome 12q13–24 is among the regions most frequently identified in genome-wide surveys for asthma susceptibility loci, with reports of two distinct clusters of positive linkage signals: one near the interferon gamma locus, the other near the nitric oxide synthase 1 locus. These results suggest that 12q harbors several asthma susceptibility loci. We evaluated this possibility in a subset of families ascertained through the Childhood Asthma Management Program (CAMP) Genetics Ancillary Study. Fifty-five nuclear families with at least two asthmatic siblings (212 individuals) were genotyped using 32 microsatellite markers. Non-parametric linkage analysis was performed for the asthma phenotype (qualitative). Multipoint variance component-based linkage analysis was performed for five quantitative asthma-related traits: (i) percent predicted forced expiratory volume in one second (FEV1); (ii) dose of methacholine resulting in 20% fall in FEV1 from baseline (PC20); (iii) post-bronchodilator percent change in FEV1 (BDPR); (iv) serum eosinophil levels (EOS); and (v) total serum IgE levels (IgE). Three separate and distinct loci demonstrated evidence suggestive of linkage: asthma at 68 cM (exact P-value=0.05), airways responsiveness (PC20) at 147 cM (P=0.01), and indices of pulmonary function (FEV1, BDPR) at 134 cM (P=0.05 and P<0.01, respectively). No linkage was observed for the atopy-related phenotypes. We provide further evidence supporting the presence of an asthma susceptibility locus at the proximal end of chromosome 12q, as well as new evidence for additional loci more distally that account for unique features of the asthma phenotype. Fine mapping efforts for these loci are warranted.

* To whom correspondence should be addressed at: Channing Laboratory, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA. Email: benjamin.raby{at}channing.harvard.edu


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 ChestHome page
C. Park, C. Stafford, and W. Lockette
Exercise-Induced Asthma May Be Associated With Diminished Sweat Secretion Rates in Humans
Chest, September 1, 2008; 134(3): 552 - 558.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
H. Sandig, J. McDonald, J. Gilmour, M. Arno, T. H. Lee, and D. J. Cousins
Human Th2 cells selectively express the orexigenic peptide, pro-melanin-concentrating hormone
PNAS, July 24, 2007; 104(30): 12440 - 12444.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
C. P Hersh, M. E Soto-Quiros, L. Avila, S. L Lake, C. Liang, E. Fournier, M. Spesny, J. S Sylvia, R. Lazarus, T. Hudson, et al.
Genome-wide linkage analysis of pulmonary function in families of children with asthma in Costa Rica
Thorax, March 1, 2007; 62(3): 224 - 230.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
C Brasch-Andersen, Q Tan, A D Borglum, A Haagerup, T R Larsen, J Vestbo, and T A Kruse
Significant linkage to chromosome 12q24.32-q24.33 and identification of SFRS8 as a possible asthma susceptibility gene
Thorax, October 1, 2006; 61(10): 874 - 879.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
B. A. Raby, K. Van Steen, J. C. Celedon, A. A. Litonjua, C. Lange, S. T. Weiss, and for the CAMP Research Group
Paternal History of Asthma and Airway Responsiveness in Children with Asthma
Am. J. Respir. Crit. Care Med., September 1, 2005; 172(5): 552 - 558.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
B. A. Raby, R. Lazarus, E. K. Silverman, S. Lake, C. Lange, M. Wjst, and S. T. Weiss
Association of Vitamin D Receptor Gene Polymorphisms with Childhood and Adult Asthma
Am. J. Respir. Crit. Care Med., November 15, 2004; 170(10): 1057 - 1065.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.