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(12) United States Patent (10) Patent No.: US 8,229,677 B2 Braun Et Al

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(12) United States Patent (10) Patent No.: US 8,229,677 B2 Braun Et Al US00822.9677B2 (12) United States Patent (10) Patent No.: US 8,229,677 B2 Braun et al. (45) Date of Patent: *Jul. 24, 2012 (54) METHODS FOR GENERATING DATABASES s A A. 3. St.SOn et al.1 SERENERS 4,568,6494,562,639 A 2/19861/1986 McElroyBertoglio-Matte 4,640,835. A 2f1987 Shimizu et al. (75) Inventors: Andreas Braun, San Diego, CA (US); 4,656,127 A 4/1987 Mundy Hubert Koster, La Jolla, CA (US); Dirk 4,670,417 A 6, 1987 Iwasaki et al. Van den Boom, La Jolla, CA (US); Ping 2.3 A 28, Mills et al. Yip, San Diego, CA (US); Charles 4,722,848.ww- A 2/1988 PaolettiUS et al. Rodi, Del Mar, CA (US); Liyan He, 4,791,192 A 12/1988 Nakagawa et al. Chandler, AZ (US); Norman Chiu, San 4,826,360 A 5/1989. Iwasawa et al. Diego, CA (US); Christiane Jurinke, La 4,851,018 A 7, 1989 LaZZari et al. Jolla, CA (US) 4,981,957 A 1/1991 Lebleu et al. s 4,987,071 A 1/1991 Cech et al. 4,988,617 A 1/1991 Landegren et al. (73) Assignee: Sequenom, Inc., San Diego, CA (US) 4,998,617 A 3/1991 Ladd, Jr. et al. 5,013,830 A 5/1991 Ohtsuka et al. (*) Notice: Subject to any disclaimer, the term of this 5,024,939 A 6, 1991 Gorman patent is extended or adjusted under 35 59.5% A R E. SE t al. U.S.C. 154(b) by 0 days. W was atfield et al. 5,118,800 A 6/1992 Smith et al. This patent is Subject to a terminal dis- 5,118,937 A 6/1992 Hillenkamp et al. claimer 5,122,342 A 6/1992 McCulloch et al. 5,128,448 A 7, 1992 Danho 5,149,797 A 9, 1992 Pederson et al. (21) Appl. No.: 12/643,933 5,166,315 A 1 1/1992 Summerton et al. 5,175,430 A 12/1992 Enke et al. (22) Filed: Dec. 21, 2009 5,185,444 A 2, 1993 Summerton et al. 5,214,134 A 5/1993 Weis et al. (65) Prior Publication Data 5,216,141 A 6/1993 Benner US 2010/0292.930 A1 Nov. 18, 2010 (Continued) Related U.S. Application Data FOREIGN PATENT DOCUMENTS EP O296781 6, 1988 (60) Continuation of application No. 10/273.321, filed on (Continued) Oct. 15, 2002, now Pat. No. 7,668,658, which is a division of application No. 09/687,483, filed on Oct. OTHER PUBLICATIONS 13, 2000, now abandoned, which is a continuation-in-part of application No. 09/663,968, Roses (Annals of the NY Academy of Science (1998) vol. 855; pp. filed on Sep. 19, 2000, now Pat. No. 7,917,301. 738-743).* Shaw et al. (Genome Research (1998) vol. 8, pp. 111-123).* (60) al applits NE s p3. Sherry et al. (Genome Research (1999) vol. 9: pp. 677-679).* s proV1S1onal app ication o, oU.41 1, s Halushka et al. (Nature Genetics Jul. 1999, vol. 22, pp. 239-247).* filed on Jul. 10, 2000, provisional application No. A Practical Guide to Molecular Cloning, Book: Perbal B. John Wiley 60/159,176, filed on Oct. 13, 1999. & Sons, New York, 1984. Aebersold and Mann, Nature 422:198-207 (2003). (51) Int. Cl. Ahern (The Scientist. vol. 9, No. 15, p. 20, Jul. 1995). G06F 9/00 (2011.01) Ali et al., “The Akinase anchoring protein is required for mediating CI2O I/68 (2006.01) the effect of protein kinase a on ROMK1 channels'. Proc. Natl. Acad. GOIN 24/00 (2006.01) Sci.,95:10274-10278 (1998). (52) U.S. Cl. ............................ 702/19:436/173; 435/6.1 Alto N.M., et al., “Bioinformatic design of A-kinase anchoring pro (58) Field of Classification Search ........................ None tein-in silico: A potent and selective peptide antagonist of type II See application file for complete search history. protein kinase Aanchoring.” PNAS 100:8, Apr. 15, 2003 pp. 4445 4450. (56) References Cited (Continued) U.S. PATENT DOCUMENTS Primary Examiner — Lori A Clow 3,645,090 A 2f1972 Mochizuki et al. 3,687,808 A 8, 1972 Merigan, Jr. et al. (74) Attorney, Agent, or Firm — Grant Anderson LLP 3,817,837 A 6, 1974 Rubenstein et al. 3,850,752 A 11/1974 Schuurs et al. (57) ABSTRACT 3,939,350 A 2f1976 Kronicket al. 3,940,475 A 2f1976 Gross Processes and methods for creating a database of genomic 3.996,345 A 12/1976 Ullman et al. samples from healthy human donors, methods that use the 4,076,982 A 2f1978 Ritter et al. database to identify and correlate polymorphic genetic mark 4,179,337 A 12/1979 Davis et al. 4,275,149 A 6, 1981 Litman et al. ers and other markers with diseases and conditions are pro 4,277.437 A 7, 1981 Maggio vided. 4,301,144. A 11, 1981 Iwashita et al. 4,366,241 A 12/1982 Tom et al. 17 Claims, 51 Drawing Sheets US 8,229,677 B2 Page 2 U.S. PATENT DOCUMENTS 5,714,330 2, 1998 Brenner et al. 5,777,324 7, 1998 Hillenkamp 5,220,007 6, 1993 Pederson et al. 5,786,146 7, 1998 Herman et al. 5,235,033 8, 1993 Summerton et al. 5,786.464 7, 1998 Seed et al. 5,256,775 10, 1993 Froehler 5,795,714 8, 1998 Cantor et al. 5,257, 175 10, 1993 Skelton et al. 5,807,693 9, 1998 Scott et al. 5,259,044 11, 1993 Isono et al. 5,834,189 11, 1998 Stevens et al. 5,264,562 11, 1993 Matteucci 5,837,832 11, 1998 Chee et al. 5,264,564 11, 1993 Matteucci 5,843,669 12, 1998 Kaiser et al. 5,270,170 12, 1993 Schatz et al. 5,851,765 12, 1998 Köster 5,273,718 12, 1993 Sköld et al. 5,853,979 12, 1998 Green et al. 5,283,173 2, 1994 Fields et al. 5,856,092 1/1999 Dale et al. 5,319,080 6, 1994 Leumann 5,858,659 1/1999 Sapolsky et al. 5,338,665 8, 1994 Schatz et al. 5,858,705 1/1999 Wei et al. 5,354,934 10, 1994 Pitt et al. 5,869,242 2, 1999 Kamb 5,363.885 11, 1994 McConnell et al. 5,869,275 2, 1999 Huang 5,366,878 11, 1994 Pederson et al. 5,871,911 2, 1999 Dahlberg et al. 5,393,878 2, 1995 Leumann 5,871,945 2, 1999 Lockerbie et al. 5,403,711 4, 1995 Walder et al. 5,872,003 2, 1999 Köster 5,405,938 4, 1995 Summerton et al. 5,874.283 2, 1999 Harrington et al. 5.434,257 7, 1995 Matteucci et al. 5,876,934 3, 1999 Duthie et al. 5,436,150 7, 1995 Chandrasegaran 5,885,841 3, 1999 Higgs, Jr. et al. 5.439,797 8, 1995 Tsien et al. 5,888,795 3, 1999 Hamilton 5.440,119 8, 1995 Labowsky 5,900,481 5, 1999 Lough et al. 5,446,137 8, 1995 Maag et al. 5,902,723 5, 1999 Dower et al. 5.453,613 9, 1995 Gray et al. 5,908,755 6, 1999 Kumar et al. 5,466,677 11, 1995 Baxter et al. 5,912,118 6, 1999 Ansorge et al. 5,466,786 11, 1995 Buhr et al. 5,925,525 7, 1999 Fodor et al. 5,470,967 11, 1995 Huie et al. 5,928,870 7, 1999 Lapidus et al. 5,474,796 12, 1995 Brennan 5,928,906 7, 1999 Köster et al. 5,489,677 2, 1996 Sanghvi et al. 5,928,952 7, 1999 Hutchins et al. 5,491,133 2, 1996 Walder et al. 5,952,174 9, 1999 Nikiforov et al. 5.492,806 2, 1996 Drmanac et al. 5,952, 176 9, 1999 McCarthy et al. 5,498,545 3, 1996 Vestal 5,975.492 11, 1999 Brenes 5,503.980 4, 1996 Cantor 5,976,802 11, 1999 Ansorge et al. 5,506,137 4, 1996 Mathur et al. 5,976,806 11, 1999 Mahajan et al. 5,514,785 5, 1996 Van Ness et al. 5,981, 186 11, 1999 Gabe et al. 5,519,134 5, 1996 Acevedo et al. 5,985,214 11, 1999 Stylli et al. 5,525,464 6, 1996 Drmanac et al. 5.998,143 12, 1999 Ellis et al. 5,536,649 T. 1996 Fraiser et al. 6,004,744 12, 1999 Goelet et al. 5,541,307 T. 1996 Cook et al. 6,011,013 1, 2000 Carr et al. 5,547,835 8, 1996 Köster 6,013,431 1, 2000 Söderlund et al. 5,561.225 10, 1996 Maddry et al. 6,017,693 1, 2000 Yates, III et al. 5,565,350 10, 1996 Kmiec 6,017,702 1, 2000 Lee et al. 5,567,811 10, 1996 Misiura et al. 6,017,704 1, 2000 Herman et al. 5,571,676 11, 1996 Shuber 6,018,041 1, 2000 Drmanac et al. 5,576.427 11, 1996 Cook et al. 6,020,122 2, 2000 Okasinski et al. 5,580,732 12, 1996 Grossman et al. 6,022,688 2, 2000 Jurinke et al. 5,591,722 1/1997 Montgomery et al. 6,024925 2, 2000 Little et al. 5,593,826 1/1997 Fung et al.
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