@article {309736,
	title = {Spread of an inactive form of caspase-12 in humans is due to recent positive selection.},
	journal = {Am J Hum Genet},
	volume = {78},
	year = {2006},
	month = {2006 Apr},
	pages = {659-70},
	abstract = {<p>The human caspase-12 gene is polymorphic for the presence or absence of a stop codon, which results in the occurrence of both active (ancestral) and inactive (derived) forms of the gene in the population. It has been shown elsewhere that carriers of the inactive gene are more resistant to severe sepsis. We have now investigated whether the inactive form has spread because of neutral drift or positive selection. We determined its distribution in a worldwide sample of 52 populations and resequenced the gene in 77 individuals from the HapMap Yoruba, Han Chinese, and European populations. There is strong evidence of positive selection from low diversity, skewed allele-frequency spectra, and the predominance of a single haplotype. We suggest that the inactive form of the gene arose in Africa approximately 100-500 thousand years ago (KYA) and was initially neutral or almost neutral but that positive selection beginning approximately 60-100 KYA drove it to near fixation. We further propose that its selective advantage was sepsis resistance in populations that experienced more infectious diseases as population sizes and densities increased.</p>
},
	keywords = {Base Sequence, Caspase 12, Caspases, Codon, Terminator, DNA Primers, Haplotypes, Humans, Molecular Sequence Data, Mutation, Phylogeny, Polymorphism, Genetic, Selection, Genetic},
	issn = {0002-9297},
	doi = {10.1086/503116},
	author = {Xue, Yali and Daly, Allan and Yngvadottir, Bryndis and Liu, Mengning and Coop, Graham and Kim, Yuseob and Sabeti, Pardis and Chen, Yuan and Stalker, Jim and Huckle, Elizabeth and Burton, John and Leonard, Steven and Rogers, Jane and Tyler-Smith, Chris}
}
