Genome screening in human systemic lupus erythematosus: results from a second Minnesota cohort and combined analyses of 187 sib-pair families.
Am J Hum Genet
; 66(2): 547-56, 2000 Feb.
Article
en En
| MEDLINE
| ID: mdl-10677315
ABSTRACT
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a loss of immunologic tolerance to a multitude of self-antigens. Epidemiological data suggest an important role for genes in the etiology of lupus, and previous genetic studies have implicated the HLA locus, complement genes, and low-affinity IgG (Fcgamma) receptors in SLE pathogenesis. In an effort to identify new susceptibility loci for SLE, we recently reported the results of a genomewide microsatellite marker screen in 105 SLE sib-pair families. By using nonparametric methods, evidence for linkage was found in four intervals 6p11-21 (near the HLA), 16q13, 14q21-23, and 20p12.3 (LOD scores >/=2.0), and weaker evidence in another nine regions. We now report the results of a second complete genome screen in a new cohort of 82 SLE sib-pair families. In the cohort 2 screen, the four best intervals were 7p22 (LOD score 2.87), 7q21 (LOD score 2.40), 10p13 (LOD score 2.24), and 7q36 (LOD score 2.15). Eight additional intervals were identified with LOD scores in the range 1.00-1.67. A combined analysis of MN cohorts 1 and 2 (187 sib-pair families) showed that markers in 6p11-p21 (D6S426, LOD score 4.19) and 16q13 (D16S415, LOD score 3.85) met the criteria for significant linkage. Three intervals (2p15, 7q36, and 1q42) had LOD scores in the range 1.92-2.06, and another 13 intervals had LOD scores in the range of 1.00-1.78 in the combined sample. These data, together with other available gene mapping results in SLE, are beginning to allow a prioritization of genomic intervals for gene discovery efforts in human SLE.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Genoma Humano
/
Pruebas Genéticas
/
Predisposición Genética a la Enfermedad
/
Escala de Lod
/
Lupus Eritematoso Sistémico
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Screening_studies
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
País/Región como asunto:
America do norte
Idioma:
En
Revista:
Am J Hum Genet
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos