Multifactorial Susceptibility to Common Diseases: common and rare variants Walter Bodmer and Carolina Bonilla

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1 Multifactorial Susceptibility to Common Diseases: common and rare variants Walter Bodmer and Carolina Bonilla Supplementary Table 1. Distribution of mutation types in BRCA1 and BRCA2 A. BRCA1 mutation types by clinical significance (%) Mutation type Significant Not significant Unknown 3 UTR UTR Frameshift In-frame deletion/insertion Intervening sequence Missense Nonsense Splice Synonymous Total a B. BRCA2 mutation types by clinical significance (%) Mutation type Significant Not significant Unknown 3 UTR UTR Frameshift In-frame deletion/insertion Intervening sequence Missense Nonsense Splice Synonymous Total a Data were obtained from the Breast Cancer Information Core (BIC) database and updated using recent classification of variants of unknown significance (VUS) as neutral or pathogenic according to the literature (see Supplementary Note). a Number of mutations.

2 Supplementary Note A. References used in Figure Ahituv, N. et al. Medical sequencing at the extremes of human body mass. Am. J. Hum. Genet. 80, Alrasadi, K., Ruel, I., Marcil, M. & Genest, J. Functional mutations of the ABCA1 gene in subjects of French-Canadian descent with HDL deficiency. Atherosclerosis 188, (2006). 3. Ayala-Lugo, R. et al. Variation in optineurin (OPTN) allele frequencies between and within populations. Mol. Vis. 13, Beleza-Meireles, A. et al. FGFR2, FGF8, FGF10 and BMP7 as candidate genes for hypospadias. Eur. J. Hum. Genet. 15, Bernstein, J. et al. Population-based estimates of breast cancer risks associated with ATM gene variants c.7271t>g and c t>g (IVS10-6T>G) from the Breast Cancer Family Registry. Hum. Mutat. 27, (2006). 6. Bleyl, S. et al. Candidate genes for congenital diaphragmatic hernia from animal models: sequencing of FOG2 and PDGFRalpha reveals rare variants in diaphragmatic hernia patients. Eur. J. Hum. Genet. 15, Buch, S. et al. A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease. Nat. Genet. 39, Cao, W. et al. Analysis of genetic variants of the poly(adp-ribose) polymerase-1 gene in breast cancer in French patients. Mutat. Res. 632, Castellvi-Bel, S. et al. Association of the ARLTS1 Cys148Arg variant with sporadic and familial colorectal cancer. Carcinogenesis 28, Cohen, J. et al. Multiple rare variants in NPC1L1 associated with reduced sterol absorption and plasma low-density lipoprotein levels. Proc. Natl. Acad. Sci. USA 103, (2006). 11. Colebatch, A. et al. The role of MYH and microsatellite instability in the development of sporadic colorectal cancer. Br. J. Cancer 95, (2006). 12. Cox, A. et al. A common coding variant in CASP8 is associated with breast cancer risk. Nat. Genet. 39, Daugherty, S. et al. Variants in the alpha-methylacyl-coa racemase gene and the association with advanced distal colorectal adenoma. Cancer Epidemiol. Biomarkers Prev. 16, Easton, D. et al. Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447, Erkko, H. et al. A recurrent mutation in PALB2 in Finnish cancer families. Nature 446, Fernandez, L. et al. MC1R: three novel variants identified in a malignant melanoma association study in the Spanish population. Carcinogenesis 28,

3 17. Frayling, T. Genome-wide association studies provide new insights into type 2 diabetes aetiology. Nat. Rev. Genet. 8, Freedman, M. et al. Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men. Proc. Natl. Acad. Sci. USA 103, (2006). 19. Frikke-Schmidt, R., Nordestgaard, B., Jensen, G. & Tybjaerg-Hansen, A. Genetic variation in ABC transporter A1 contributes to HDL cholesterol in the general population. J. Clin. Invest. 114, (2004). 20. Garcia-Closas, M. et al. Large-scale evaluation of candidate genes identifies associations between VEGF polymorphisms and bladder cancer risk. PLoS Genet. 3, e Gayther, S. et al. Tagging single nucleotide polymorphisms in cell cycle control genes and susceptibility to invasive epithelial ovarian cancer. Cancer Res 67, Gregory, S. et al. Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat. Genet. 39, Gudmundsson, J. et al. Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24. Nat. Genet. 39, Gudmundsson, J. et al. Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nat. Genet. 39, Haiman, C. et al. Multiple regions within 8q24 independently affect risk for prostate cancer. Nat. Genet. 39, Hakonarson, H. et al. A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene. Nature 448, Haugarvoll, K. et al. Variants in the LRRK1 gene and susceptibility to Parkinson's disease in Norway. Neurosci Lett. 416, Jain, M. et al. Role of BCL2 (ala43thr), CCND1 (G870A) and FAS (A-670G) polymorphisms in modulating the risk of developing esophageal cancer. Cancer Detect. Prev. 31, Johnson, N. et al. Counting potentially functional variants in BRCA1, BRCA2 and ATM predicts breast cancer susceptibility. Hum. Mol. Genet. 16, Kang, D. et al. Functional variant of manganese superoxide dismutase (SOD2 V16A) polymorphism is associated with prostate cancer risk in the prostate, lung, colorectal, and ovarian cancer study. Cancer Epidemiol. Biomarkers Prev. 16, Kokko, A. et al. EPHB2 germline variants in patients with colorectal cancer or hyperplastic polyposis. BMC Cancer 6, 145 (2006). 32. Kotowski, I. et al. A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol. Am. J. Hum. Genet. 78, (2006). 33. Levin, A., Ray, A., Zuhlke, K., Douglas, J. & Cooney, K. Association between germline variation in the FHIT gene and prostate cancer in Caucasians and African Americans. Cancer Epidemiol. Biomarkers Prev. 16, Lindstrôm, S. et al. Germ-line genetic variation in the key androgen-regulating genes androgen receptor, cytochrome P450, and steroid-5-alpha-reductase type 2 is important for prostate cancer development. Cancer Res. 66, (2006).

4 35. Liu, Y., Zhang, Q., Qian, N. & Zhou, R. Relationship between LAPTM4B gene polymorphism and susceptibility of gastric cancer. Ann. Oncol. 18, Lowe, C. et al. Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes. Nat. Genet. 39, Lundmark, F. et al. Variation in interleukin 7 receptor alpha chain (IL7R) influences risk of multiple sclerosis. Nat. Genet. 39, Marçais, C. et al. Apoa5 Q139X truncation predisposes to late-onset hyperchylomicronemia due to lipoprotein lipase impairment. J. Clin. Invest. 115, (2005). 39. Miyake, Y. et al. Genetic variants in PCSK9 in the Japanese population: rare genetic variants in PCSK9 might collectively contribute to plasma LDL cholesterol levels in the general population. Atherosclerosis 196, (2008). 40. Nagase, H. et al. Screening for germ-line mutations in familial adenomatous polyposis patients: 61 new patients and a summary of 150 unrelated patients. Hum. Mutat. 1, (1992). 41. Nathanson, K., Antin-Ozerkis, D., Couch, F. & Weber, B. I1307K APC variant in non-ashkenazi Jewish women affected with breast cancer. Am. J. Med. Genet. 85, (1999). 42. Orlow, I. et al. CDKN2A germline mutations in individuals with cutaneous malignant melanoma. J. Invest. Dermatol. 127, Pedemonte, S. et al. Novel germline APC variants in patients with multiple adenomas. Genes Chromosomes Cancer 22, (1998). 44. Romeo, S. et al. Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL. Nat. Genet. 39, Rudd, M. et al. Variants in the GH-IGF axis confer susceptibility to lung cancer. Genome Res. 16, (2006). 46. Sandhu, M. et al. Common variants in WFS1 confer risk of type 2 diabetes. Nat. Genet. 39, Sandilands, A. et al. Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema. Nat. Genet. 39, Schumacher, F. et al. A common 8q24 variant in prostate and breast cancer from a large nested case-control study. Cancer Res. 67, Severi, G. et al. The common variant rs on chromosome 8q24 and prostate cancer risk: results from an Australian population-based case-control study. Cancer Epidemiol. Biomarkers Prev. 16, Siddiq, A. et al. Single nucleotide polymorphisms in the neuropeptide Y2 receptor (NPY2R) gene and association with severe obesity in French white subjects. Diabetologia 50, Sladek, R. et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445, Song, H. et al. Tagging single nucleotide polymorphisms in the BRIP1 gene and susceptibility to breast and ovarian cancer. PLoS ONE 2, e268

5 53. Stevens, V. et al. Association of polymorphisms in one-carbon metabolism genes and postmenopausal breast cancer incidence. Cancer Epidemiol. Biomarkers Prev. 16, Sun, T. et al. A six-nucleotide insertion-deletion polymorphism in the CASP8 promoter is associated with susceptibility to multiple cancers. Nat. Genet. 39, Suuriniemi, M. et al. Confirmation of a positive association between prostate cancer risk and a locus at chromosome 8q24. Cancer Epidemiol. Biomarkers Prev. 16, Tomlinson, I. et al. A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q Nat. Genet. 39, Tommiska, J. et al. ATM variants and cancer risk in breast cancer patients from Southern Finland. BMC Cancer 6, 209 (2006). 58. Wang, L. et al. Two common chromosome 8q24 variants are associated with increased risk for prostate cancer. Cancer Res. 67, Wang, X. et al. Truncating variants in p53aip1 disrupting DNA damage-induced apoptosis are associated with prostate cancer risk. Cancer Res. 66, (2006). 60. Webb, E. et al. Search for low penetrance alleles for colorectal cancer through a scan of 1467 non-synonymous SNPs in 2575 cases and 2707 controls with validation by kin-cohort analysis of first-degree relatives. Hum. Mol. Genet. 15, (2006). 61. Winkelmann, J. et al. Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nat. Genet. 39, Yeager, M. et al. Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat. Genet. 39, Zeggini, E. et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316, Zhou, X. et al. Definition of candidate low risk APC alleles in a Swedish population. Int. J. Cancer 110, (2004).

6 B. References used in Supplementary Table Abkevich, V. et al. Analysis of missense variation in human BRCA1 in the context of interspecific sequence variation. J. Med. Genet. 41, (2004). 2. Bonatti, F. et al. RNA-based analysis of BRCA1 and BRCA2 gene alterations. Cancer Genet. Cytogenet. 170, (2006). 3. Carvalho, M. et al. Determination of cancer risk associated with germ line BRCA1 missense variants by functional analysis. Cancer Res. 67, Chen, X. et al. Intronic alterations in BRCA1 and BRCA2: effect on mrna splicing fidelity and expression. Hum. Mutat. 27, (2006). 5. Chenevix-Trench, G. et al. Genetic and histopathologic evaluation of BRCA1 and BRCA2 DNA sequence variants of unknown clinical significance. Cancer Res. 66, (2006). 6. Goldgar, D. et al. Integrated evaluation of DNA sequence variants of unknown clinical significance: application to BRCA1 and BRCA2. Am. J. Hum. Genet. 75, (2004). 7. Hammet, F. et al. Is BRCA2 c.9079 G > A a predisposing variant for early onset breast cancer? Breast Cancer Res Treat 8. Karchin, R., Monteiro, A., Tavtigian, S., Carvalho, M. & Sali, A. Functional impact of missense variants in BRCA1 predicted by supervised learning. PLoS Comput. Biol. 3, e26 9. Maillet, P., Chappuis, P., Khoshbeen-Boudal, M., Sciretta, V. & Sappino, A. Twenty-three novel BRCA1 and BRCA2 sequence variations identified in a cohort of Swiss breast and ovarian cancer families. Cancer Genet. Cytogenet. 169, (2006). 10. Mathe, E. et al. Computational approaches for predicting the biological effect of p53 missense mutations: a comparison of three sequence analysis based methods. Nucleic Acids Res. 34, (2006). 11. Osorio, A. et al. Classification of missense variants of unknown significance in BRCA1 based on clinical and tumor information. Hum. Mutat. 28, Phelan, C. et al. Classification of BRCA1 missense variants of unknown clinical significance. J. Med. Genet. 42, (2005). 13. Simard, J. et al. Evaluation of BRCA1 and BRCA2 mutation prevalence, risk prediction models and a multistep testing approach in French-Canadian families with high risk of breast and ovarian cancer. J. Med. Genet. 44, Tavtigian, S. et al. Comprehensive statistical study of 452 BRCA1 missense substitutions with classification of eight recurrent substitutions as neutral. J. Med. Genet. 43, (2006). 15. Tavtigian, S., Samollow, P., de Silva, D. & Thomas, A. An analysis of unclassified missense substitutions in human BRCA1. Fam. Cancer 5, (2006). 16. Wu, K. et al. Functional evaluation and cancer risk assessment of BRCA2 unclassified variants. Cancer Res 65, (2005).