Abstract:
:A genomic region on distal mouse chromosome 1 and its syntenic human counterpart 1q23-42 show strong evidence of harboring lupus susceptibility genes. We found evidence of linkage at 1q32.2 in a targeted genome scan of 1q21-43 in 126 lupus multiplex families containing 151 affected sibpairs (nonparametric linkage score 2.52, P = 0.006). A positional candidate gene at 1q32.2, complement receptor 2 (CR2), is also a candidate in the murine Sle1c lupus susceptibility locus. To explore its role in human disease, we analyzed 1,416 individuals from 258 Caucasian and 142 Chinese lupus simplex families and demonstrated that a common three-single-nucleotide polymorphism CR2 haplotype (rs3813946, rs1048971, rs17615) was associated with lupus susceptibility (P = 0.00001) with a 1.54-fold increased risk for the development of disease. Single-nucleotide polymorphism 1 (rs3813946), located in the 5' untranslated region of the CR2 gene, altered transcriptional activity, suggesting a potential mechanism by which CR2 could contribute to the development of lupus. Our findings reveal that CR2 is a likely susceptibility gene for human lupus at 1q32.2, extending previous studies suggesting that CR2 participates in the pathogenesis of systemic lupus erythematosus.
journal_name
Proc Natl Acad Sci U S Aauthors
Wu H,Boackle SA,Hanvivadhanakul P,Ulgiati D,Grossman JM,Lee Y,Shen N,Abraham LJ,Mercer TR,Park E,Hebert LA,Rovin BH,Birmingham DJ,Chang DM,Chen CJ,McCurdy D,Badsha HM,Thong BY,Chng HH,Arnett FC,Wallace DJ,Yu CYdoi
10.1073/pnas.0609101104subject
Has Abstractpub_date
2007-03-06 00:00:00pages
3961-6issue
10eissn
0027-8424issn
1091-6490pii
0609101104journal_volume
104pub_type
杂志文章abstract::Tikal has long been viewed as one of the leading polities of the ancient Maya realm, yet how the city was able to maintain its substantial population in the midst of a tropical forest environment has been a topic of unresolved debate among researchers for decades. We present ecological, paleoethnobotanical, hydraulic,...
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