Genome-wide scan for loci influencing quantitative immune response traits in the Belém family study: comparison of methods and summary of results.
Ann Hum Genet
; 70(Pt 1): 78-97, 2006 Jan.
Article
em En
| MEDLINE
| ID: mdl-16441259
ABSTRACT
Here we report the results from a genome-wide linkage scan to identify genes and chromosomal regions that influence quantitative immune response traits, using multi-case leprosy and tuberculosis families from north-eastern Brazil. Total plasma IgE, antigen-specific IgG to Mycobacterium leprae soluble antigen (MLSA), M. tuberculosis soluble antigen (MTSA) and M. tuberculosis purified protein derivative (PPD), and antigen-specific lymphocyte proliferation (stimulation index or SI) and interferon-gamma (IFN-gamma) release to MLSA and PPD, were measured in 16 tuberculosis (184 individuals) and 21 leprosy (177 individuals) families. The individuals were genotyped at 382 autosomal microsatellite markers across the genome. The adjusted immune-response phenotypes were analysed using a variety of variance components and regression-based methods. These analyses highlighted a number of practical issues and problems with regard to implementation of the methods and, interestingly, differences were observed between several standard statistical and genetic analysis packages used. From this we determined that, for this set of traits in these pedigrees, significant p values for linkage using variance components analysis, supported by significance using the Visscher-Hopper modification of the Haseman-Elston method, provided the most compelling evidence for linkage. Using these criteria, linkage (5.8 x 10(-5) < p < 0.008) was seen for total plasma IgE on chromosome 2; IgG to MLSA on chromosomes 8, 17 and 21; IgG to PPD on chromosome 12; SI to PPD on chromosome 1; IFN-gamma to MLSA on chromosomes 6, 7, 10, 12 and 14; and IFN-gamma to PPD on chromosomes 1, 16 and 19.
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Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Tuberculose
/
Genoma Humano
/
Locos de Características Quantitativas
/
Imunidade
/
Hanseníase
/
Ligação Genética
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
País/Região como assunto:
America do sul
/
Brasil
Idioma:
En
Revista:
Ann Hum Genet
Ano de publicação:
2006
Tipo de documento:
Article