JCI - Discovery of common human genetic variants of GTP cyclohydrolase 1 (GCH1) governing nitric oxide, autonomic activity, and cardiovascular risk

Discovery of common human genetic variants of GTP cyclohydrolase 1 (GCH1) governing nitric oxide, autonomic activity, and cardiovascular risk

Lian Zhang, Fangwen Rao, Kuixing Zhang, Srikrishna Khandrika, Madhusudan Das, Sucheta M. Vaingankar, Xuping Bao, Brinda K. Rana, Douglas W. Smith, Jennifer Wessel, Rany M. Salem, Juan L. Rodriguez-Flores, Sushil K. Mahata, Nicholas J. Schork, Michael G. Ziegler, Daniel T. O’Connor

Published in Volume 117, Issue 9

J Clin Invest. 2007; 117(9):2658–2671 doi:10.1172/JCI31093

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Figure 1

Polymorphism at GCH1: distribution across the gene.

(A) Local genomic region. GCH1 resequencing strategy and identified variants. Sequences conserved between mouse and human GCH1 were visualized with VISTA (http://genome.lbl.gov/vista/index.shtml). Location of common (upper) and rare (lower) SNPs relative to exons and conserved noncoding sequences is indicated by position. Red lines represent nonsynonymous SNPs, while black rods represent synonymous SNPs. Nucleotides in red in the chimpanzee haplotype indicate the minor allele in the human sequence. Computationally reconstructed haplotypes are indicated, along with their relative frequencies in ethnogeographic groups within our sample population. Nucleotide deletions in haplotype sequences are indicated by an asterisk. n = 42 variants were discovered; n = 13 were common (≥5%), while n = 29 were rare (<5%). (B) Functional domains and coding region SNPs. The distribution of variants across GCH1 exons and functional protein domains is illustrated. ATG, translational start codon; Cap, transcriptional initiation site; ORF, open reading frame.