Characterization of single-nucleotide polymorphisms in coding regions of human genes.

Article Details


Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES

Characterization of single-nucleotide polymorphisms in coding regions of human genes.

Nat Genet. 1999 Jul;22(3):231-8.

PubMed ID
10391209 [ View in PubMed

A major goal in human genetics is to understand the role of common genetic variants in susceptibility to common diseases. This will require characterizing the nature of gene variation in human populations, assembling an extensive catalogue of single-nucleotide polymorphisms (SNPs) in candidate genes and performing association studies for particular diseases. At present, our knowledge of human gene variation remains rudimentary. Here we describe a systematic survey of SNPs in the coding regions of human genes. We identified SNPs in 106 genes relevant to cardiovascular disease, endocrinology and neuropsychiatry by screening an average of 114 independent alleles using 2 independent screening methods. To ensure high accuracy, all reported SNPs were confirmed by DNA sequencing. We identified 560 SNPs, including 392 coding-region SNPs (cSNPs) divided roughly equally between those causing synonymous and non-synonymous changes. We observed different rates of polymorphism among classes of sites within genes (non-coding, degenerate and non-degenerate) as well as between genes. The cSNPs most likely to influence disease, those that alter the amino acid sequence of the encoded protein, are found at a lower rate and with lower allele frequencies than silent substitutions. This likely reflects selection acting against deleterious alleles during human evolution. The lower allele frequency of missense cSNPs has implications for the compilation of a comprehensive catalogue, as well as for the subsequent application to disease association.

DrugBank Data that Cites this Article

NameUniProt ID
Coagulation factor XIII A chainP00488Details
Coagulation factor VP12259Details
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1P14060Details
Growth hormone receptorP10912Details
Dopamine beta-hydroxylaseP09172Details
D(1B) dopamine receptorP21918Details
Coagulation factor XP00742Details
Lipoprotein lipaseP06858Details
Plasminogen activator inhibitor 1P05121Details
Coagulation factor VIIP08709Details
Coagulation factor IXP00740Details
Follicle-stimulating hormone receptorP23945Details
Integrin alpha-IIbP08514Details
5-hydroxytryptamine receptor 2AP28223Details
5-hydroxytryptamine receptor 1EP28566Details
Low-density lipoprotein receptorP01130Details
5-hydroxytryptamine receptor 2CP28335Details
Fibrinogen alpha chainP02671Details
3-hydroxy-3-methylglutaryl-coenzyme A reductaseP04035Details
D(3) dopamine receptorP35462Details
Tyrosine 3-monooxygenaseP07101Details
Sodium-dependent dopamine transporterQ01959Details
5-hydroxytryptamine receptor 1DP28221Details
Sex hormone-binding globulinP04278Details
Cytochrome P450 11B1, mitochondrialP15538Details
Sodium-dependent serotonin transporterP31645Details
Heparin cofactor 2P05546Details
Glucocorticoid receptorP04150Details
Adenosine receptor A2aP29274Details
Proteinase-activated receptor 1P25116Details
Tissue factor pathway inhibitorP10646Details
Plasminogen activator inhibitor 2P05120Details
Coagulation factor XIP03951Details
Platelet glycoprotein Ib alpha chainP07359Details
High affinity nerve growth factor receptorP04629Details
Beta-nerve growth factorP01138Details
Integrin beta-3P05106Details
Thromboxane-A synthaseP24557Details
Catechol O-methyltransferaseP21964Details
Fibrinogen beta chainP02675Details
Fibrinogen gamma chainP02679Details
Plasma serine protease inhibitorP05154Details
Neuroendocrine convertase 1P29120Details
Aromatic-L-amino-acid decarboxylaseP20711Details
Annexin A3P12429Details
Brain-derived neurotrophic factorP23560Details
Insulin-like growth factor IP05019Details
Thrombopoietin receptorP40238Details
Cholesteryl ester transfer proteinP11597Details
Cholesterol side-chain cleavage enzyme, mitochondrialP05108Details
Cytochrome P450 11B2, mitochondrialP19099Details
Very low-density lipoprotein receptorP98155Details
Steroid 21-hydroxylaseP08686Details
Apolipoprotein DP05090Details
Platelet-activating factor receptorP25105Details
Coagulation factor XIII B chainP05160Details