@article {530836,
	title = {Health and population effects of rare gene knockouts in adult humans with related parents},
	journal = {Science},
	volume = {352},
	number = {6284},
	year = {2016},
	month = {2016 Apr 22},
	pages = {474-7},
	abstract = {Examining complete gene knockouts within a viable organism can inform on gene function. We sequenced the exomes of 3222 British adults of Pakistani heritage with high parental relatedness, discovering 1111 rare-variant homozygous genotypes with predicted loss of function (knockouts) in 781 genes. We observed 13.7\% fewer homozygous knockout genotypes than we expected, implying an average load of 1.6 recessive-lethal-equivalent loss-of-function (LOF) variants per adult. When genetic data were linked to the individuals{\textquoteright} lifelong health records, we observed no significant relationship between gene knockouts and clinical consultation or prescription rate. In this data set, we identified a healthy PRDM9-knockout mother and performed phased genome sequencing on her, her child, and control individuals. Our results show that meiotic recombination sites are localized away from PRDM9-dependent hotspots. Thus, natural LOF variants inform on essential genetic loci and demonstrate PRDM9 redundancy in humans.},
	keywords = {Adult, Consanguinity, DNA Mutational Analysis, Drug Prescriptions, Exome, Female, Fertility, Gene Knockout Techniques, Genes, Lethal, Genetic Loci, Genome, Human, Health, Histone-Lysine N-Methyltransferase, Homologous Recombination, Homozygote, Humans, Male, Mothers, Pakistan, Phenotype, United Kingdom},
	issn = {1095-9203},
	doi = {10.1126/science.aac8624},
	author = {Narasimhan, Vagheesh M and Hunt, Karen A and Mason, Dan and Baker, Christopher L and Karczewski, Konrad J and Barnes, Michael R and Barnett, Anthony H and Bates, Chris and Bellary, Srikanth and Bockett, Nicholas A and Giorda, Kristina and Griffiths, Christopher J and Hemingway, Harry and Jia, Zhilong and Kelly, M Ann and Khawaja, Hajrah A and Lek, Monkol and McCarthy, Shane and McEachan, Rosie and O{\textquoteright}Donnell-Luria, Anne and Paigen, Kenneth and Parisinos, Constantinos A and Sheridan, Eamonn and Southgate, Laura and Tee, Louise and Thomas, Mark and Xue, Yali and Schnall-Levin, Michael and Petkov, Petko M and Tyler-Smith, Chris and Maher, Eamonn R and Trembath, Richard C and Macarthur, Daniel G and Wright, John and Durbin, Richard and van Heel, David A}
}
