Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity

Autor: Sumeet A. Khetarpal, Maria Samuel, Khan Shah Zaman, Khalid Mahmood, Saba Akhtar, Daniel J. Rader, Kevin Trindade, Shahid Abbas, Syed Nadeem Hasan Rizvi, Zia Yaqoob, Pradeep Natarajan, Faisal Majeed, Syed Zahed Rasheed, Asif Rasheed, Benjamin Weisburd, Atif Imran, Nadeem Hayat Mallick, Namrata Gupta, Daniel G. MacArthur, John Danesh, Kaitlin E. Samocha, Hong-Hee Won, Madiha Ishaq, Wei Zhao, Mozzam Zaidi, Mohammad Ishaq, Anis Memon, Anne H. O’Donnell-Luria, Nadeem Qamar, Eric S. Lander, Fazal-ur-Rehman Memon, Irina M. Armean, Konrad J. Karczewski, Tahir Saghir, Ronald M. Krauss, Megan L. Mucksavage, Philippe M. Frossard, Naveeduddin Ahmed, Stacey Gabriel, Danish Saleheen, Sekar Kathiresan, Ron Do, Mark J. Daly
Přispěvatelé: Danesh, John [0000-0003-1158-6791], Apollo - University of Cambridge Repository
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
DNA Mutational Analysis
Myocardial Infarction
Coronary Disease
medicine.disease_cause
Cohort Studies
Consanguinity
Gene Frequency
Pakistan
Exome
Neuregulins
Genetics
Mutation
Multidisciplinary
Homozygote
Fasting
Middle Aged
Postprandial Period
Circadian Rhythm
3. Good health
Pedigree
Phenotype
Female
Sodium-Hydrogen Exchangers
Offspring
General Science & Technology
Sodium-Hydrogen Antiporter
Biology
Article
03 medical and health sciences
medicine
Humans
Cytochrome P450 Family 2
Gene
Allele frequency
Gene knockout
Triglycerides
Genetic Association Studies
Apolipoprotein C-III
Interleukin-8
Phosphoproteins
Dietary Fats
Reverse Genetics
Minor allele frequency
030104 developmental biology
Genes
1-Alkyl-2-acetylglycerophosphocholine Esterase
RNA Splice Sites
Gene Deletion
Zdroj: Nature, vol 544, iss 7649
Nature
Popis: A major goal of biomedicine is to understand the function of every gene in the human genome.1 Loss-of-function (LoF) mutations can disrupt both copies of a given gene in humans and phenotypic analysis of such ‘human knockouts’ can provide insight into gene function. Consanguineous unions are more likely to result in offspring who carry LoF mutations in a homozygous state. In Pakistan, consanguinity rates are notably high.2 Here, we sequenced the protein-coding regions of 10,503 adult participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS) designed to understand the determinants of cardiometabolic diseases in South Asians.3 We identified individuals carrying predicted LoF (pLoF) mutations in the homozygous state, and performed phenotypic analysis involving >200 biochemical and disease traits. We enumerated 49,138 rare (
Databáze: OpenAIRE
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