DO: 9074;
Cytogenetic location: 4p16-p15.2 Genomic coordinates (GRCh38): 4:1-27,700,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 4p16-p15.2 | {Systemic lupus erythematosus, susceptibility to, 3} | 605480 | 2 |
For a phenotypic description and a discussion of genetic heterogeneity of systemic lupus erythematosus, see 152700.
Gray-McGuire et al. (2000) presented the result of a genome scan of 126 pedigrees with 2 or more cases of SLE, including 469 sib pairs (affected and unaffected) and 175 affected relative pairs. Using the revised multipoint Haseman-Elston regression technique for concordant and discordant sib pairs and a conditional logistic regression technique for affected relative pairs, they identified linkage to chromosome 4p16-p15.2 (p = 0.0003, lod = 3.84) and presented evidence of an epistatic interaction between 4p16-p15.2 and chromosome 5p15 in European American families. Using data from an independent pedigree collection, they confirmed the linkage to 4p16-p15.2 in European American families. The most significant linkage that they found in the African American subset was to the previously identified region on 1q (SLEB1; 601744).
Nath et al. (2002) found that lod scores were higher when linkage analysis was confined to families in which at least 1 SLE patient was diagnosed with the presence of neuropsychiatric manifestations such as seizures and psychosis. The authors stated that the segregation behavior of this linked locus suggested a dominant mode of inheritance with an almost 100% homogeneous genetic effect in these pedigrees.
Xing et al. (2007) reanalyzed the 77 European American families consisting of 301 full sib pairs previously studied by Gray-McGuire et al. (2000) and confirmed significant linkage at 4p (p = 0.000087). The linkage signal at 4p16 was replicated in another cohort of 76 European American families consisting of 221 full sib pairs (p = 0.0047). Two-point and multipoint model-based linkage analyses in all 153 families yielded maximum lod scores of 3.51 and 4.84 at D4S3007, respectively, under a recessive model with penetrance of 0.8. Haplotype analysis using densely spaced microsatellite markers in the linkage region localized the potential SLE susceptibility locus telomeric to D4S2928. A genomewide linkage scan revealed significant interaction between 4p16 and 2p11 (p = 0.003) and 19q13 (p = 0.0094), with marginal interaction at 12q24 (p = 0.066).
Gray-McGuire, C., Moser, K. L., Gaffney, P. M., Kelly, J., Yu, H., Olson, J. M., Jedrey, C. M., Jacobs, K. B., Kimberly, R. P., Neas, B. R., Rich, S. S., Behrens, T. W., Harley, J. B. Genome scan of human systemic lupus erythematosus by regression modeling: evidence of linkage and epistasis at 4p16-15.2. Am. J. Hum. Genet. 67: 1460-1469, 2000. [PubMed: 11078476] [Full Text: https://doi.org/10.1086/316891]
Nath, S. K., Kelly, J. A., Reid, J., Lam, T., Gray-McGuire, C., Namjou, B., Aston, C. E., Harley, J. B. SLEB3 in systemic lupus erythematosus (SLE) is strongly related to SLE families ascertained through neuropsychiatric manifestations. Hum. Genet. 111: 54-58, 2002. [PubMed: 12136236] [Full Text: https://doi.org/10.1007/s00439-002-0743-1]
Xing, C., Sestak, A. L., Kelly, J. A., Nguyen, K. L., Bruner, G. R., Harley, J. B., Gray-McGuire, C. Localization and replication of the systemic lupus erythematosus linkage signal at 4p16: interaction with 2p11, 12q24 and 19q13 in European Americans. Hum. Genet. 120: 623-631, 2007. [PubMed: 16983533] [Full Text: https://doi.org/10.1007/s00439-006-0248-4]