Power of deep, all-exon resequencing for discovery of human trait genes

Proceedings of the National Academy of Sciences of the United States of America

Volumn 106, Issue 10, 2009, Pages 3871-3876

  Kryukov, Gregory V ^a   Shpunt, Alexander ^a,b   Stamatoyannopoulos, John A ^c   Sunyaev, Shamil R ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^c UNIVERSITY OF WASHINGTON   (United States)

Author keywords

Association studies; Polymorphism; Rare variants; Sequencing

Indexed keywords

MELANOCORTIN 4 RECEPTOR;

ALAGILLE SYNDROME; ARTICLE; ASIAN; COMPUTER SIMULATION; EXON; GENE FREQUENCY; GENE MAPPING; GENE MUTATION; GENETIC ASSOCIATION; GENETIC DRIFT; GENETIC POLYMORPHISM; HAPLOTYPE; HUMAN; OBESITY; PHENOTYPIC VARIATION; POPULATION GENETICS; POPULATION MODEL; PRIORITY JOURNAL; QUANTITATIVE TRAIT; SAMPLE SIZE; SINGLE NUCLEOTIDE POLYMORPHISM;

CHROMOSOME MAPPING; COMPUTER SIMULATION; DEMOGRAPHY; EXONS; GENE FREQUENCY; GENETIC VARIATION; HUMANS; META-ANALYSIS AS TOPIC; MODELS, GENETIC; MUTATION, MISSENSE; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE; QUANTITATIVE TRAIT, HERITABLE; RECEPTOR, MELANOCORTIN, TYPE 4; SELECTION (GENETICS); SEQUENCE ANALYSIS, DNA;

EID: 62649084535     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.0812824106     Document Type: Article

References (47)

1. Couzin J, Kaiser J (2007) Genome-wide association. Closing the net on common disease genes. Science 316:820-822.
2. Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447:661-678.
3. Frayling TM (2007) Genome-wide association studies provide new insights into type 2 diabetes aetiology. Nat Rev Genet 8:657-662.
4. Cohen JC, et al. (2004) Multiple rare alleles contribute to low plasma levels of HDL cholesterol. Science 305:869-872.
5. Kotowski IK, et al. (2006) A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol. Am J Hum Genet 78:410-422.
6. Romeo S, et al. (2007) Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL. Nat Genet 39:513-516.
7. Riley BM, et al. (2007) Impaired FGF signaling contributes to cleft lip and palate. Proc Natl Acad Sci USA 104:4512-4517.
8. Ahituv N, et al. (2007) Medical sequencing at the extremes of human body mass. Am J Hum Genet 80:779-791.
9. Morgenthaler S, Thilly WG (2007) A strategy to discover genes that carry multi-allelic or mono-allelic risk for common diseases: A cohort allelic sums test (CAST). Mutat Res 615, 28-56.
10. Hirschhorn JN, Altshuler D (2002) Once and again-issues surrounding replication in genetic association studies. J Clin Endocrinol Metab 87:4438-4441.
11. Eyre-Walker A, Keightley PD (2007) The distribution of fitness effects of new mutations. Nat Rev Genet 8:610-618.
12. Kryukov GV, Pennacchio LA, Sunyaev SR (2007) Most rare missense alleles are deleterious in humans: Implications for complex disease and association studies. Am J Hum Genet 80:727-739.
13. Yampolsky LY, Kondrashov FA, Kondrashov AS (2005) Distribution of the strength of selection against amino acid replacements in human proteins. Hum Mol Genet 14:3191-3201.
14. Eyre-Walker A, Woolfit M, Phelps T (2006) The distribution of fitness effects of new deleterious amino acid mutations in humans. Genetics 173:891-900.
15. Ohta T (1973) Slightly deleterious mutant substitutions in evolution. Nature 246:96-98.
16. Kondrashov AS (2003) Direct estimates of human per nucleotide mutation rates at 20 loci causing Mendelian diseases. Hum Mutat 21:12-27.
17. Adams AM, Hudson RR (2004) Maximum-likelihood estimation of demographic parameters using the frequency spectrum of unlinked single-nucleotide polymorphisms. Genetics 168:1699-1712.
18. Evans SN, Shvets Y, Slatkin M (2007) Non-equilibrium theory of the allele frequency spectrum. Theor Popul Biol 71:109-119.
19. Griffiths RC (2003) The frequency spectrum of a mutation, and its age, in a general diffusion model. Theor Popul Biol 64:241-251.
20. Ammerman AJ, Cavalli-Sforza LL (1984) The Neolithic Transition and the Genetics of Populations in Europe (Princeton Univ Press, Princeton, NJ).
21. Marth GT, Czabarka E, Murvai J, Sherry ST (2004) The allele frequency spectrum in genome-wide human variation data reveals signals of differential demographic history in three large world populations. Genetics 166:351-372.
22. Williamson SH, et al. (2005) Simultaneous inference of selection and population growth from patterns of variation in the human genome. Proc Natl Acad Sci USA 102:7882-7887.
23. Schaffner SF, et al. (2005) Calibrating a coalescent simulation of human genome sequence variation. Genome Res 15:1576-1583.
24. Voight BF, et al. (2005) Interrogating multiple aspects of variation in a full resequencing data set to infer human population size changes. Proc Natl Acad Sci USA 102:18508-18513.
25. Keinan A, Mullikin JC, Patterson N, Reich D (2007) Measurement of the human allele frequency spectrum demonstrates greater genetic drift in East Asians than in Europeans. Nat Genet 39:1251-1255.
26. Loewe L, Charlesworth B (2006) Inferring the distribution of mutational effects on fitness in Drosophila. Biol Lett 2:426-430.
27. Cole TR, Hughes HE (1994) Sotos syndrome: A study of the diagnostic criteria and natural history. J Med Genet 31:20-32.
28. Rovner AJ, et al. (2002) Rethinking growth failure in Alagille syndrome: The role of dietary intake and steatorrhea. J Pediatr Gastroenterol Nutr 35:495-502.
29. Moura B, et al. (2006) Bone mineral density in Marfan syndrome. A large case-control study. Joint Bone Spine 73:733-735.
30. Brown MS, Goldstein JL (1986) A receptor-mediated pathway for cholesterol homeostasis. Science 232:34-47.
31. Spirin V, et al. (2007) Common single-nucleotide polymorphisms act in concert to affect plasma levels of high-density lipoprotein cholesterol. Am J Hum Genet 81:1298-1303.
32. Li B, Leal SM (2008) Methods for detecting associations with rare variants for common diseases: Application to analysis of sequence data. Am J Hum Genet 83:311-321.
33. Hinney A, et al. (2006) Prevalence, spectrum, and functional characterization of melanocortin-4 receptor gene mutations in a representative population-based sample and obese adults from Germany. J Clin Endocrinol Metab 91:1761-1769.
34. Larsen LH, et al. (2005) Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity. J Clin Endocrinol Metab 90:219-224.
35. Hinney A, et al. (2003) Melanocortin-4 receptor gene: Case-control study and transmission disequilibrium test confirm that functionally relevant mutations are compatible with a major gene effect for extreme obesity. J Clin Endocrinol Metab 88:4258-4267.
36. Pritchard JK (2001) Are rare variants responsible for susceptibility to complex diseases? Am J Hum Genet 69:124-137.
37. Reich DE, Lander ES (2001) On the allelic spectrum of human disease. Trends Genet 17:502-510.
38. Pritchard JK, Cox NJ (2002) The allelic architecture of human disease genes: Common disease-common variant.or not? Hum Mol Genet 11:2417-2423.
39. Ahituv N, et al. (2007) Deletion of ultraconserved elements yields viable mice. PLoS Biol 5:e234.
40. Kryukov GV, Schmidt S, Sunyaev S (2005) Small fitness effect of mutations in highly conserved non-coding regions. Hum Mol Genet 14:2221-2229.
41. Keightley PD, Kryukov GV, Sunyaev S, Halligan DL, Gaffney DJ (2005) Evolutionary constraints in conserved nongenic sequences of mammals. Genome Res 15:1373-1378.
42. Chen CT, Wang JC, Cohen BA (2007) The strength of selection on ultraconserved elements in the human genome. Am J Hum Genet 80:692-704.
43. Ewens W (2004) Mathematical Population Genetics I. Theoretical Introduction (Springer, Heidelberg).
44. Kimura M (1955) Solution of a process of random genetic drift with a continuous model. Proc Natl Acad Sci USA 41:144-150.
45. Kimura M (1964) Diffusion models in population genetics. J Appl Prob 1:177-232.
46. Joyce P, Tavaré S (1995) The distribution of rare alleles. J Math Biol 33:602-618.
47. Myers S, Fefferman C, Patterson N (2008) Can one learn history from the allelic spectrum? Theor Popul Biol 73:342-348.