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Tennessen JA Bigham AW O'Connor TD Fu W Kenny EE Gravel S McGee S Do R Liu X Jun G Kang HM Jordan D Leal SM Gabriel S Rieder MJ Abecasis G Altshuler D Nickerson DA Boerwinkle E Sunyaev S Bustamante CD Bamshad MJ Akey JM;Broad GO;Seattle GO;NHLBI Exome Sequencing Project 《Science (New York, N.Y.)》2012,337(6090):64-69
As a first step toward understanding how rare variants contribute to risk for complex diseases, we sequenced 15,585 human protein-coding genes to an average median depth of 111× in 2440 individuals of European (n = 1351) and African (n = 1088) ancestry. We identified over 500,000 single-nucleotide variants (SNVs), the majority of which were rare (86% with a minor allele frequency less than 0.5%), previously unknown (82%), and population-specific (82%). On average, 2.3% of the 13,595 SNVs each person carried were predicted to affect protein function of ~313 genes per genome, and ~95.7% of SNVs predicted to be functionally important were rare. This excess of rare functional variants is due to the combined effects of explosive, recent accelerated population growth and weak purifying selection. Furthermore, we show that large sample sizes will be required to associate rare variants with complex traits. 相似文献
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Kenny EE Timpson NJ Sikora M Yee MC Moreno-Estrada A Eng C Huntsman S Burchard EG Stoneking M Bustamante CD Myles S 《Science (New York, N.Y.)》2012,336(6081):554
Naturally blond hair is rare in humans and found almost exclusively in Europe and Oceania. Here, we identify an arginine-to-cysteine change at a highly conserved residue in tyrosinase-related protein 1 (TYRP1) as a major determinant of blond hair in Solomon Islanders. This missense mutation is predicted to affect catalytic activity of TYRP1 and causes blond hair through a recessive mode of inheritance. The mutation is at a frequency of 26% in the Solomon Islands, is absent outside of Oceania, represents a strong common genetic effect on a complex human phenotype, and highlights the importance of examining genetic associations worldwide. 相似文献
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D E Kenny 《Journal of zoo and wildlife medicine》1999,30(3):383-388
A survey was mailed to 72 institutions in the USA requesting information on Salmonella spp. cultures in black rhinoceroses (Diceros bicornis), white rhinoceroses (Ceratotherium simum), and Indian rhinoceroses (Rhinoceros unicornis). Sixty-one institutions responded (85% return rate), with seven reporting positive cultures (11% prevalence rate; 10% if survey nonresponders had negative cultures). There were 17 positive cultures from 16 different animals, with nine different serotypes of Salmonella and 2 additional cultures identified to the group level. 相似文献
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Walz PH Grooms DL Bell TG Kaiser L Baker JC Brock KV 《American journal of veterinary research》2005,66(10):1738-1742
OBJECTIVE: To determine whether viral involvement with platelets obtained from cattle persistently infected (PI) with bovine viral diarrhea virus (BVDV) is associated with altered platelet function or decreased platelet counts. SAMPLE POPULATION: Platelets obtained from 8 cattle PI with BVDV and 6 age-, sex-, and breed-matched uninfected control cattle. PROCEDURE: Manual platelet counts were determined, and platelet function was assessed through optical aggregometry by use of the aggregation agonists ADP and platelet-activating factor. Identification of BVDV in serum and preparations of purified platelets was determined by use of virus isolation tests. RESULTS: No significant difference in platelet counts was detected between cattle PI with BVDV and control cattle. In response to the aggregation agonists, maximum aggregation percentage and slope of the aggregation curve were not significantly different between cattle PI with BVDV and control cattle. We isolated BVDV from serum of all PI cattle and from purified platelets of 6 of 8 PI cattle, but BVDV was not isolated from serum or platelets of control cattle. CONCLUSIONS AND CLINICAL RELEVANCE: Isolation of BVDV from platelets in the peripheral circulation of cattle immunotolerant to BVDV does not result in altered platelet function or decreases in platelet counts. 相似文献
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PCR analysis was used to determine the prevalence of tick-transmitted infections in 120 systemically ill dogs and 60 cats recruited over a period of three months from 52 veterinary practices in the UK. The animals had not travelled outside the UK and had one or more of the following clinical criteria: acute or recurrent pyrexia, anaemia and/or thrombocytopenia, polyarthritis/muscle pain, splenomegaly/lymphadenopathy, and intraocular inflammation with systemic signs. Blood samples from the animals were tested for the presence of DNA from Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum by using simple PCR targeting. B. burgdorferi sensu lato was detected in five dogs and two cats, and A. phagocytophilum was detected in one dog and one cat. These results provide the first molecular evidence of naturally occurring B. burgdorferi sensu lato infection in cats in the UK and confirm that A. phagocytophilum infection is present in cats. There were no statistically significant associations between the infections and the clinical signs shown by the dogs and cats. 相似文献
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Sanchirico JN Stoffle R Broad K Talaue-McManus L 《Science (New York, N.Y.)》2003,301(5629):47-9; author reply 47-9