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1. Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families

Author

Bailey-Wilson Joan E, Childs Erica J, Cropp Cheryl D, Schaid Daniel J, Xu Jianfeng, Camp Nicola J, Cannon-Albright Lisa A, Farnham James M, George Asha, Powell Isaac, Carpten John D, Giles Graham G, Hopper John L, Severi Gianluca, English Dallas R, Foulkes William D, Mæhle Lovise, Møller Pål, Eeles Rosalind, Easton Douglas, Guy Michelle, Edwards Steve, Badzioch Michael D, Whittemore Alice S, Oakley-Girvan Ingrid, Hsieh Chih-Lin, Dimitrov Latchezar, Stanford Janet L, Karyadi Danielle M, Deutsch Kerry, McIntosh Laura, Ostrander Elaine A, Wiley Kathleen E, Isaacs Sarah D, Walsh Patrick C, Thibodeau Stephen N, McDonnell Shannon K, Hebbring Scott, Lange Ethan M, Cooney Kathleen A, Tammela Teuvo LJ, Schleutker Johanna, Maier Christiane, Bochum Sylvia, Hoegel Josef, Grönberg Henrik, Wiklund Fredrik, Emanuelsson Monica, Cancel-Tassin Geraldine, Valeri Antoine, Cussenot Olivier, and Isaacs William B

Subjects
Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. Methods Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. Results Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2–3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded. Conclusions Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2–3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.

Published
2012
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2. Low-pass sequencing for microbial comparative genomics

Author

Kennedy Sean, Pan Min, Deutsch Kerry, Baliga Nitin S, Glusman Gustavo, Roach Jared, Goo Young Ah, DasSarma Shiladitya, Victor Ng Wailap, and Hood Leroy

Subjects
Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background We studied four extremely halophilic archaea by low-pass shotgun sequencing: (1) the metabolically versatile Haloarcula marismortui; (2) the non-pigmented Natrialba asiatica; (3) the psychrophile Halorubrum lacusprofundi and (4) the Dead Sea isolate Halobaculum gomorrense. Approximately one thousand single pass genomic sequences per genome were obtained. The data were analyzed by comparative genomic analyses using the completed Halobacterium sp. NRC-1 genome as a reference. Low-pass shotgun sequencing is a simple, inexpensive, and rapid approach that can readily be performed on any cultured microbe. Results As expected, the four archaeal halophiles analyzed exhibit both bacterial and eukaryotic characteristics as well as uniquely archaeal traits. All five halophiles exhibit greater than sixty percent GC content and low isoelectric points (pI) for their predicted proteins. Multiple insertion sequence (IS) elements, often involved in genome rearrangements, were identified in H. lacusprofundi and H. marismortui. The core biological functions that govern cellular and genetic mechanisms of H. sp. NRC-1 appear to be conserved in these four other halophiles. Multiple TATA box binding protein (TBP) and transcription factor IIB (TFB) homologs were identified from most of the four shotgunned halophiles. The reconstructed molecular tree of all five halophiles shows a large divergence between these species, but with the closest relationship being between H. sp. NRC-1 and H. lacusprofundi. Conclusion Despite the diverse habitats of these species, all five halophiles share (1) high GC content and (2) low protein isoelectric points, which are characteristics associated with environmental exposure to UV radiation and hypersalinity, respectively. Identification of multiple IS elements in the genome of H. lacusprofundi and H. marismortui suggest that genome structure and dynamic genome reorganization might be similar to that previously observed in the IS-element rich genome of H. sp. NRC-1. Identification of multiple TBP and TFB homologs in these four halophiles are consistent with the hypothesis that different types of complex transcriptional regulation may occur through multiple TBP-TFB combinations in response to rapidly changing environmental conditions. Low-pass shotgun sequence analyses of genomes permit extensive and diverse analyses, and should be generally useful for comparative microbial genomics.

Published
2004

7. A combined genomewide linkage scan of 1,233 families for prostate cancer-susceptibility genes conducted by the International Consortium for Prostate Cancer Genetics

Author

Xu, Jianfeng, Dimitrov, Latchezar, Chang, Bao-Li, Adams, Tamara S., Turner, Aubrey R., Meyers, Deborah A., Eeles, Rosalind A., Easton, Douglas F., Foulkes, William D., Simard, Jacques, Giles, Graham G., Hopper, John L., Mahle, Lovise, Moller, Pal, Bishop, Tim, Evans, Chris, Edwards, Steve, Meitz, Julia, Bullock, Sarah, Hope, Questa, Hsieh, Chih-lin, Halpern, Jerry, Balise, Raymond N., Oakley-Girvan, Ingrid, Whittemore, Alice S., Ewing, Charles M., Gielzak, Marta, Isaacs, Sarah D., Walsh, Patrick C., Wiley, Kathleen E., Isaacs, William B., Thibodeau, Stephen N., McDonnell, Shannon K., Cunningham, Julie M., Zarfas, Katherine E., Hebbring, Scott, Schaid, Daniel J., Friedrichsen, Danielle M., Deutsch, Kerry, Kolb, Suzanne, Badzioch, Michael, Jarvik, Gail P., Janer, Marta, Hood, Leroy, Ostrander, Elaine A., Stanford, Janet L., Lange, Ethan M., Beebe-Dimmer, Jennifer L., Mohai, Caroline E., Cooney, Kathleen A., Ikonen, Tarja, Baffoe-Bonnie, Agnes, Fredriksson, Henna, Matikainen, Mika P., Tammela, Teuvo LJ, Bailey-Wilson, Joan, Schleutker, Johanna, Maier, Christiane, Herkommer, Kathleen, Hoegel, Josef J., Vogel, Walther, Paiss, Thomas, Wiklund, Fredrik, Emanuelsson, Monica, Stenman, Elisabeth, Jonsson, Bjorn-Anders, Gronberg, Henrik, Camp, Nicola J., Farnham, James, Cannon-Albright, Lisa A., and Seminara, Daniela

Subjects
Prostate cancer -- Genetic aspects, Human genetics -- Research, Biological sciences
Published
2005

8. Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG

Author

Lu, Lingyi, Cancel-Tassin, Geraldine, Valeri, Antoine, Cussenot, Olivier, Lange, Ethan M., Cooney, Kathleen A., Farnham, James M., Camp, Nicola J., Cannon-Albright, Lisa A., Tammela, Teuvo L.J., Schleutker, Johanna, Hoegel, Josef, Herkommer, Kathleen, Maier, Christiane, Vogel, Walther, Wiklund, Fredrik, Emanuelsson, Monica, Grönberg, Henrik, Wiley, Kathleen E., Isaacs, Sarah D., Walsh, Patrick C., Helfand, Brian T., Kan, Donghui, Catalona, William J., Stanford, Janet L., FitzGerald, Liesel M., Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A., Thibodeau, Stephen N., McDonnell, Shannon K., Hebbring, Scott, Schaid, Daniel J., Whittemore, Alice S., Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Powell, Isaac, Bailey-Wilson, Joan E., Cropp, Cheryl D., Simpson, Claire, Carpten, John D., Seminara, Daniela, Zheng, Lilly S., Xu, Jianfen, Giles, Graham G., Severi, Gianluca, Hopper, John L., English, Dallas R., Foulkes, William D., Maehle, Lovise, Moller, Pal, Badzioch, Michael D., Edwards, Steve, Guy, Michelle, Eeles, Ros, Easton, Douglas, and Isaacs, William B.

Published
2012
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9. Family-based association analysis of 42 hereditary prostate cancer families identifies the Apolipoprotein L3 region on chromosome 22q12 as a risk locus

Author

Johanneson, Bo, McDonnell, Shannon K., Karyadi, Danielle M., Quignon, Pascale, McIntosh, Laura, Riska, Shaun M., FitzGerald, Liesel M., Johnson, Gregory, Deutsch, Kerry, Williams, Gabrielle, Tillmans, Lori S., Stanford, Janet L., Schaid, Daniel J., Thibodeau, Stephen N., and Ostrander, Elaine A.

Published
2010
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10. Genome-Wide Linkage Analysis of 1,233 Prostate Cancer Pedigrees From the International Consortium for Prostate Cancer Genetics Using Novel sum LINK and sum LOD Analyses

Author

Christensen, Bryce G., Baffoe-Bonnie, Agnes B., George, Asha, Powell, Isaac, Bailey-Wilson, Joan E., Carpten, John D., Giles, Graham G., Hopper, John L., Severi, Gianluca, English, Dallas R., Foulkes, William D., Maehle, Lovise, Moller, Pal, Eeles, Ros, Easton, Douglas, Badzioch, Michael D., Whittemore, Alice S., Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Xu, Jianfeng, Stanford, Janet L., Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A., Wiley, Kathleen E., Isaacs, Sarah D., Walsh, Patrick C., Isaacs, William B., Thibodeau, Stephen N., McDonnell, Shannon K., Hebbring, Scott, Schaid, Daniel J., Lange, Ethan M., Cooney, Kathleen A., Tammela, Teuvo L.J., Schleutker, Johanna, Paiss, Thomas, Maier, Christiane, Grönberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, Farnham, James M., Cannon-Albright, Lisa A., and Camp, Nicola J.

Published
2010
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12. Compelling evidence for a prostate cancer gene at 22q12.3 by the International Consortium for Prostate Cancer Genetics

Author

Camp, Nicola J., Cannon-Albright, Lisa A., Farnham, James M., Baffoe-Bonnie, Agnes B., George, Asha, Powell, Isaac, Bailey-Wilson, Joan E., Carpten, John D., Giles, Graham G., Hopper, John L., Severi, Gianluca, English, Dallas R., Foulkes, William D., Maehle, Lovise, Moller, Pal, Eeles, Ros, Easton, Douglas, Badzioch, Michael D., Whittemore, Alice S., Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Xu, Jianfeng, Stanford, Janet L., Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A., Wiley, Kathleen E., Isaacs, Sarah D., Walsh, Patrick C., Thibodeau, Stephen N., McDonnell, Shannon K., Hebbring, Scott, Schaid, Daniel J., Lange, Ethan M., Cooney, Kathleen A., Tammela, Teuvo L.J., Schleutker, Johanna, Paiss, Thomas, Maier, Christiane, Grönberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, and Isaacs, William B.

Published
2007

16. Abstract 1679: Neoepitope screening in colorectal cancer patients by custom exome panel profiling somatic mutations

Author

Venkatramanan, Raghavee, primary, Deutsch, Kerry, additional, Golez, Inah, additional, Shroff, Pallavi, additional, Seale, Spencer, additional, Ralph, Brendan, additional, Dow, Sally., additional, Anderson, Evan, additional, Tahir, Saman, additional, Malge, Anjali, additional, Braastad, Corey, additional, and Anderson, Steven, additional

Published
2019
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17. Abstract 3418: Cross-comparison of targeted gene expression technologies for patient stratification

Author

Venkatramanan, Raghavee, primary, Saloranta, Tuuli, additional, Golez, Inah, additional, Swanson, Elliot, additional, Kruse, Kimberly, additional, Satele, Vickie, additional, Tahir, Saman, additional, Dow, Sally, additional, Anderson, Evan, additional, Hudson, Briana, additional, Chee, Spencer, additional, Deutsch, Kerry, additional, Anderson, Steve, additional, Lo, Fang Yin, additional, and Madan, Anup, additional

Published
2018
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20. Abstract 104: Investigation of genetic architecture of multiple myeloma by next generation sequencing

Author

Deutsch, Kerry, primary, Lo, Fang Yin, additional, Olson, Claire, additional, Austin, Sharon, additional, Howard, Kellie, additional, Leonti, Amanda, additional, Maassel, Lindsey, additional, Subia, Christopher, additional, Saloranta, Tuuli, additional, Christopherson, Nicole, additional, Shiji, Kathryn, additional, Patil, Shradha, additional, Schwartz, Stuart, additional, Papenhausen, Peter, additional, Anderson, Steven, additional, and Madan, Anup, additional

Published
2016
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21. Abstract 498: Meta-analysis of genomic aberrations identified in CTCs andctDNA in triple negative breast cancer

Author

Howard, Kellie, primary, Austin, Sharon, additional, Lo, Fang Yin, additional, Ramirez, Arturo, additional, Boles, Debbie, additional, Pruitt, John, additional, Mahen, Elisabeth, additional, Collins, Heather, additional, Leonti, Amanda, additional, Maassel, Lindsey, additional, Subia, Christopher, additional, Saloranta, Tuuli, additional, Christopherson, Nicole, additional, Deutsch, Kerry, additional, Stilwell, Jackie, additional, Kaldjian, Eric, additional, Dorschner, Michael, additional, Blau, Sibel, additional, Blau, Anthony, additional, Eisenberg, Marcia, additional, Anderson, Steven, additional, and Madan, Anup, additional

Published
2016
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22. Abstract 3946: Stratification of metastatic colorectal cancer patients using DNA and RNA sequencing and in-silico prediction of tumor antigens for consideration in immunotherapy

Author

Lo, FangYin, primary, Austin, Sharon, additional, Howard, Kellie, additional, McWhorter, Mollie, additional, Collins, Heather, additional, Leonti, Amanda, additional, Maassel, Lindsey, additional, Subia, Christopher, additional, Saloranta, Tuuli, additional, Christopherson, Nicole, additional, Shiji, Kathryn, additional, Patil, Shradha, additional, Tahir, Saman, additional, Dow, Sally, additional, Anderson, Evan, additional, Oblad, Jon, additional, Deutsch, Kerry, additional, Yeatman, Timothy, additional, Anderson, Steven, additional, and Madan, Anup, additional

Published
2016
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23. Abstract 4436: Synergistic effects of promoter associated DNA methylation and genetic alterations to better understand oncogenic gene expression profiles

Author

Olson, Claire, primary, Lo, Fang Yin, additional, Deutsch, Kerry, additional, Austin, Sharon, additional, Howard, Kellie, additional, Leonti, Amanda, additional, Maassel, Lindsey, additional, Subia, Christopher, additional, Saloranta, Tuuli, additional, Christopherson, Nicole, additional, Shiji, Kathryn, additional, Patil, Shradha, additional, Anderson, Steven, additional, and Madan, Anup, additional

Published
2016
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24. Comparative analysis of various targeted enrichment methodologies to identify actionable mutations in lung cancer.

Author

Madan, Anup, primary, Howard, Kellie, additional, Lo, Fang Yin, additional, Austin, Sharon, additional, Leonti, Amanda, additional, Maassel, Lindsey, additional, Subia, Christopher, additional, Saloranta, Tuuli, additional, Heying, Nicole, additional, Shiji, Kathryn, additional, Patil, Shradha, additional, Tahir, Saman, additional, Dow, Sally, additional, Anderson, Evan, additional, Oblad, Jon, additional, Deutsch, Kerry, additional, and Anderson, Steven, additional

Published
2016
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25. Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families

Author

Bailey-Wilson, Joan E, Childs, Erica J, Cropp, Cheryl D, Schaid, Daniel J, Xu, Jianfeng, Camp, Nicola J, Cannon-Albright, Lisa A, Farnham, James M, George, Asha, Powell, Isaac, Carpten, John D, Giles, Graham G, Hopper, John L, Severi, Gianluca, English, Dallas R, Foulkes, William D, Mæhle, Lovise, Møller, Pål, Eeles, Rosalind, Easton, Douglas, Guy, Michelle, Edwards, Steve, Badzioch, Michael D, Whittemore, Alice S, Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Stanford, Janet L, Karyadi, Danielle M, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A, Wiley, Kathleen E, Isaacs, Sarah D, Walsh, Patrick C, Thibodeau, Stephen N, McDonnell, Shannon K, Hebbring, Scott, Lange, Ethan M, Cooney, Kathleen A, Tammela, Teuvo LJ, Schleutker, Johanna, Maier, Christiane, Bochum, Sylvia, Hoegel, Josef, Grönberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, Cancel-Tassin, Geraldine, Valeri, Antoine, Cussenot, Olivier, Isaacs, William B, International Consortium for Prostate Cancer Genetics, Easton, Douglas [0000-0003-2444-3247], and Apollo - University of Cambridge Repository

Subjects
Male, Chromosomes, Human, X, Genetic Linkage, Humans, Prostatic Neoplasms, Alleles, Genome-Wide Association Study, Microsatellite Repeats
Abstract

BACKGROUND: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. METHODS: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. RESULTS: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded. CONCLUSIONS: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.

Published
2012

26. Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG

Author

Kan, Donghui, Tammela, Teuvo L.J., Maier, Christiane, Vogel, Walther, Cancel-Tassin, Geraldine, Isaacs, Sarah D., Valeri, Antoine, Farnham, James M., Thibodeau, Stephen N., Hoegel, Josef, Wiley, Kathleen E., Ostrander, Elaine A., Helfand, Brian T., McIntosh, Laura, Deutsch, Kerry, Lange, Ethan M., Camp, Nicola J., Johanneson, Bo, Cussenot, Olivier, Herkommer, Kathleen, Catalona, William J., Cannon-Albright, Lisa A., Emanuelsson, Monica, Walsh, Patrick C., McDonnell, Shannon K., FitzGerald, Liesel M., Wiklund, Fredrik, Stanford, Janet L., Lu, Lingyi, Schleutker, Johanna, Cooney, Kathleen A., and Grönberg, Henrik

Abstract

In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer remains largely incomplete. In a previous microsatellite-based linkage scan of 1233 prostate cancer (PC) families, we identified suggestive evidence for linkage (i.e. LOD≥1.86) at 5q12, 15q11, 17q21, 22q12, and two loci on 8p, with additional regions implicated in subsets of families defined by age at diagnosis, disease aggressiveness, or number of affected members.

Published
2012
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27. Abstract 1609: Comprehensive multi-omic analysis of circulating tumor cells isolated from a metastatic triple-negative breast cancer patient to identify pathogenic genomic aberrations

Author

Howard, Kellie, primary, Austin, Sharon, additional, Ramirez, Arturo, additional, Ritter, Leila, additional, Boles, Debbie, additional, Cox, James, additional, Lo, Fang Yin, additional, Deutsch, Kerry, additional, Subia, Christopher, additional, Saloranta, Tuuli, additional, Heying, Nicole, additional, Collins, Heather, additional, Leonti, Amanda, additional, Maassel, Lindsey, additional, Stilwell, Jackie, additional, Kaldjian, Eric, additional, Dorschner, Michael, additional, Blau, Anthony, additional, Eisenberg, Marcia, additional, Anderson, Steven, additional, and Madan, Anup, additional

Published
2015
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28. Abstract 4842: Pharmacodynamic stratification of metastatic colorectal cancer patients using genomic datasets

Author

Austin, Sharon, primary, Lo, Fang Yin, additional, Howard, Kellie, additional, McWhorter, Mollie, additional, Collins, Heather, additional, Leonti, Amanda, additional, Maassel, Lindsey, additional, Subia, Christopher, additional, Saloranta, Tuuli, additional, Heying, Nicole, additional, Ritter, Leila, additional, Deutsch, Kerry, additional, Cox, James, additional, Anderson, Steven, additional, Madan, Anup, additional, and Yeatman, Timothy, additional

Published
2015
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29. Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for prostate cancer Genetics using novel sumLINK and sumLOD analyses

Author

Hsieh, Chih-Lin, Oakley-Girvan, Ingrid, Easton, Douglas, Severi, Gianluca, Thibodeau, Stephen N., Whittemore, Alice S., Eeles, Ros, Powell, Isaac, Moller, Pal, Giles, Graham G., Foulkes, William D., McIntosh, Laura, Bailey-Wilson, Joan E., Hopper, John L., Deutsch, Kerry, Isaacs, Sarah D., Dimitrov, Latchezar, Isaacs, William B., Johanneson, Bo, Walsh, Patrick C., English, Dallas R., Wiley, Kathleen E., Christensen, G. Bryce, Xu, Jianfeng, Maehle, Lovise, McDonnell, Shannon K., Stanford, Janet L., Baffoe-Bonnie, Agnes B., George, Asha, Badzioch, Michael D., Carpten, John D., and Ostrander, Elaine A.

Abstract

Prostate cancer is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity.

Published
2010
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30. Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for prostate cancer Genetics using novel sumLINK and sumLOD analyses.

Author

Christensen, G Bryce, Baffoe-Bonnie, Agnes B, George, Asha, Powell, Isaac, Bailey-Wilson, Joan E, Carpten, John D, Giles, Graham G, Hopper, John L, Severi, Gianluca, English, Dallas R, Foulkes, William D, Maehle, Lovise, Moller, Pal, Eeles, Ros, Easton, Douglas, Badzioch, Michael D, Whittemore, Alice S, Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Xu, Jianfeng, Stanford, Janet L, Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A, Wiley, Kathleen E, Isaacs, Sarah D, Walsh, Patrick C, Isaacs, William B, Thibodeau, Stephen N, McDonnell, Shannon K, Hebbring, Scott, Schaid, Daniel J, Lange, Ethan M, Cooney, Kathleen A, Tammela, Teuvo L J, Schleutker, Johanna, Paiss, Thomas, Maier, Christiane, Grönberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, Farnham, James M, Cannon-Albright, Lisa A, Camp, Nicola J, Christensen, G Bryce, Baffoe-Bonnie, Agnes B, George, Asha, Powell, Isaac, Bailey-Wilson, Joan E, Carpten, John D, Giles, Graham G, Hopper, John L, Severi, Gianluca, English, Dallas R, Foulkes, William D, Maehle, Lovise, Moller, Pal, Eeles, Ros, Easton, Douglas, Badzioch, Michael D, Whittemore, Alice S, Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Xu, Jianfeng, Stanford, Janet L, Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A, Wiley, Kathleen E, Isaacs, Sarah D, Walsh, Patrick C, Isaacs, William B, Thibodeau, Stephen N, McDonnell, Shannon K, Hebbring, Scott, Schaid, Daniel J, Lange, Ethan M, Cooney, Kathleen A, Tammela, Teuvo L J, Schleutker, Johanna, Paiss, Thomas, Maier, Christiane, Grönberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, Farnham, James M, Cannon-Albright, Lisa A, and Camp, Nicola J

Abstract

BACKGROUND: Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. METHODS: We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. RESULTS: Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genome-wide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11-q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive PC pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9 cM. CONCLUSIONS: Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk PC pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify PC predisposition genes. Prostate (c) 2010 Wiley-Liss, Inc.

Published
2010
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31. Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for prostate cancer Genetics using novel sumLINK and sumLOD analyses

Author

University of Michigan ICPCG Group ; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, University of Michigan ICPCG Group ; University of Michigan, Ann Arbor, Michigan, University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah ; Division of Genetic Epidemiology, University of Utah School of Medicine, 391, Chipeta Way, Suite D, Salt Lake City, UT 84108., African American Hereditary Prostate Cancer ICPCG Group ; Fox Chase Cancer Center, Philadelphia, Pennsylvania ; National Human Genome Research Institute, NIH, Bethesda, Maryland, African American Hereditary Prostate Cancer ICPCG Group ; Fox Chase Cancer Center, Philadelphia, Pennsylvania, African American Hereditary Prostate Cancer ICPCG Group ; Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, African American Hereditary Prostate Cancer ICPCG Group ; National Human Genome Research Institute, NIH, Bethesda, Maryland, African American Hereditary Prostate Cancer ICPCG Group ; Translational Genomics Research Institute, Genetic Basis of Human Disease Research Division, Phoenix, Arizona, ACTANE Consortium ICPCG Group ; Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Australia, ACTANE Consortium ICPCG Group ; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia, ACTANE Consortium ICPCG Group ; Department of Oncology, McGill University, Montreal, Quebec, Canada, ACTANE Consortium ICPCG Group ; The Norwegian Radium Hospital, Oslo, Norway, ACTANE Consortium ICPCG Group ; Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Surrey, UK, ACTANE Consortium ICPCG Group ; Cancer Research UK Genetic Epidemiology Unit, Cambridge, UK, ACTANE Consortium ICPCG Group ; Division of Medical Genetics, University of Washington Medical Center, Seattle, Washington, BC/CA/HI ICPCG Group ; Department of Health Research and Policy, Stanford School of Medicine, Stanford, California ; Stanford Comprehensive Cancer Center, Stanford School of Medicine, Stanford, California, BC/CA/HI ICPCG Group ; Stanford Comprehensive Cancer Center, Stanford School of Medicine, Stanford, California, BC/CA/HI ICPCG Group ; Department of Urology and Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California, Data Coordinating Center for the ICPCG and Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, FHCRC ICPCG Group ; Fred Hutchinson Cancer Research Center, Divisions of Public Health Sciences, Seattle, Washington, FHCRC ICPCG Group ; Cancer Genetics Branch, National Institutes of Health, Bethesda, Maryland, FHCRC ICPCG Group ; Institute for Systems Biology, Seattle, Washington, Johns Hopkins University ICPCG Group and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, Mayo Clinic ICPCG Group and Mayo Clinic, Rochester, Minnesota, University of Tampere ICPCG Group, University of Tampere and Tampere University Hospital, Tampere, Finland, University of Ulm ICPCG Group ; Department of Urology, University of Ulm, Ulm, Germany, University of Ulm ICPCG Group ; Institute of Human Genetics, University of Ulm, Ulm, Germany, University of Ume?? ICPCG Group ; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, University of Ume?? ICPCG Group ; Oncologic Centre, Ume?? University, Ume??, Sweden, University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah, Christensen, G. Bryce, Baffoe-Bonnie, Agnes B., George, Asha, Powell, Isaac, Bailey-Wilson, Joan E., Carpten, John D., Giles, Graham G., Hopper, John L., Severi, Gianluca, English, Dallas R., Foulkes, William D., Maehle, Lovise, Moller, Pal, Eeles, Ros, Easton, Douglas, Badzioch, Michael D., Whittemore, Alice S., Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Xu, Jianfeng, Stanford, Janet L., Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A., Wiley, Kathleen E., Isaacs, Sarah D., Walsh, Patrick C., Isaacs, William B., Thibodeau, Stephen N., McDonnell, Shannon K., Hebbring, Scott, Schaid, Daniel J., Lange, Ethan M., Cooney, Kathleen A., Tammela, Teuvo L. J., Schleutker, Johanna, Paiss, Thomas, Maier, Christiane, Gr??nberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, Farnham, James M., Cannon-Albright, Lisa A., Camp, Nicola J., University of Michigan ICPCG Group ; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, University of Michigan ICPCG Group ; University of Michigan, Ann Arbor, Michigan, University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah ; Division of Genetic Epidemiology, University of Utah School of Medicine, 391, Chipeta Way, Suite D, Salt Lake City, UT 84108., African American Hereditary Prostate Cancer ICPCG Group ; Fox Chase Cancer Center, Philadelphia, Pennsylvania ; National Human Genome Research Institute, NIH, Bethesda, Maryland, African American Hereditary Prostate Cancer ICPCG Group ; Fox Chase Cancer Center, Philadelphia, Pennsylvania, African American Hereditary Prostate Cancer ICPCG Group ; Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, African American Hereditary Prostate Cancer ICPCG Group ; National Human Genome Research Institute, NIH, Bethesda, Maryland, African American Hereditary Prostate Cancer ICPCG Group ; Translational Genomics Research Institute, Genetic Basis of Human Disease Research Division, Phoenix, Arizona, ACTANE Consortium ICPCG Group ; Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Australia, ACTANE Consortium ICPCG Group ; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia, ACTANE Consortium ICPCG Group ; Department of Oncology, McGill University, Montreal, Quebec, Canada, ACTANE Consortium ICPCG Group ; The Norwegian Radium Hospital, Oslo, Norway, ACTANE Consortium ICPCG Group ; Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Surrey, UK, ACTANE Consortium ICPCG Group ; Cancer Research UK Genetic Epidemiology Unit, Cambridge, UK, ACTANE Consortium ICPCG Group ; Division of Medical Genetics, University of Washington Medical Center, Seattle, Washington, BC/CA/HI ICPCG Group ; Department of Health Research and Policy, Stanford School of Medicine, Stanford, California ; Stanford Comprehensive Cancer Center, Stanford School of Medicine, Stanford, California, BC/CA/HI ICPCG Group ; Stanford Comprehensive Cancer Center, Stanford School of Medicine, Stanford, California, BC/CA/HI ICPCG Group ; Department of Urology and Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California, Data Coordinating Center for the ICPCG and Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, FHCRC ICPCG Group ; Fred Hutchinson Cancer Research Center, Divisions of Public Health Sciences, Seattle, Washington, FHCRC ICPCG Group ; Cancer Genetics Branch, National Institutes of Health, Bethesda, Maryland, FHCRC ICPCG Group ; Institute for Systems Biology, Seattle, Washington, Johns Hopkins University ICPCG Group and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, Mayo Clinic ICPCG Group and Mayo Clinic, Rochester, Minnesota, University of Tampere ICPCG Group, University of Tampere and Tampere University Hospital, Tampere, Finland, University of Ulm ICPCG Group ; Department of Urology, University of Ulm, Ulm, Germany, University of Ulm ICPCG Group ; Institute of Human Genetics, University of Ulm, Ulm, Germany, University of Ume?? ICPCG Group ; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, University of Ume?? ICPCG Group ; Oncologic Centre, Ume?? University, Ume??, Sweden, University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah, Christensen, G. Bryce, Baffoe-Bonnie, Agnes B., George, Asha, Powell, Isaac, Bailey-Wilson, Joan E., Carpten, John D., Giles, Graham G., Hopper, John L., Severi, Gianluca, English, Dallas R., Foulkes, William D., Maehle, Lovise, Moller, Pal, Eeles, Ros, Easton, Douglas, Badzioch, Michael D., Whittemore, Alice S., Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Xu, Jianfeng, Stanford, Janet L., Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A., Wiley, Kathleen E., Isaacs, Sarah D., Walsh, Patrick C., Isaacs, William B., Thibodeau, Stephen N., McDonnell, Shannon K., Hebbring, Scott, Schaid, Daniel J., Lange, Ethan M., Cooney, Kathleen A., Tammela, Teuvo L. J., Schleutker, Johanna, Paiss, Thomas, Maier, Christiane, Gr??nberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, Farnham, James M., Cannon-Albright, Lisa A., and Camp, Nicola J.

Abstract

BACKGROUND Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. METHODS We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. RESULTS Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genome-wide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11???q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive PC pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9???cM. CONCLUSIONS Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk PC pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify PC predisposition genes. Prostate 70: 735???744, 2010. ?? 2010 Wiley-Liss, Inc.

Published
2010

32. Compelling evidence for a prostate cancer gene at 22q12.3 by the International Consortium for Prostate Cancer Genetics.

Author

Camp, Nicola J, Cannon-Albright, Lisa A, Farnham, James M, Baffoe-Bonnie, Agnes B, George, Asha, Powell, Isaac, Bailey-Wilson, Joan E, Carpten, John D, Giles, Graham G, Hopper, John L, Severi, Gianluca, English, Dallas R, Foulkes, William D, Maehle, Lovise, Moller, Pal, Eeles, Ros, Easton, Douglas, Badzioch, Michael D, Whittemore, Alice S, Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Xu, Jianfeng, Stanford, Janet L, Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A, Wiley, Kathleen E, Isaacs, Sarah D, Walsh, Patrick C, Thibodeau, Stephen N, McDonnell, Shannon K, Hebbring, Scott, Schaid, Daniel J, Lange, Ethan M, Cooney, Kathleen A, Tammela, Teuvo L J, Schleutker, Johanna, Paiss, Thomas, Maier, Christiane, Grönberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, Isaacs, William B, Camp, Nicola J, Cannon-Albright, Lisa A, Farnham, James M, Baffoe-Bonnie, Agnes B, George, Asha, Powell, Isaac, Bailey-Wilson, Joan E, Carpten, John D, Giles, Graham G, Hopper, John L, Severi, Gianluca, English, Dallas R, Foulkes, William D, Maehle, Lovise, Moller, Pal, Eeles, Ros, Easton, Douglas, Badzioch, Michael D, Whittemore, Alice S, Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Xu, Jianfeng, Stanford, Janet L, Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A, Wiley, Kathleen E, Isaacs, Sarah D, Walsh, Patrick C, Thibodeau, Stephen N, McDonnell, Shannon K, Hebbring, Scott, Schaid, Daniel J, Lange, Ethan M, Cooney, Kathleen A, Tammela, Teuvo L J, Schleutker, Johanna, Paiss, Thomas, Maier, Christiane, Grönberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, and Isaacs, William B

Published
2007
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34. Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for prostate cancer Genetics using novel sumLINK and sumLOD analyses

Author

Christensen, G. Bryce, primary, Baffoe‐Bonnie, Agnes B., additional, George, Asha, additional, Powell, Isaac, additional, Bailey‐Wilson, Joan E., additional, Carpten, John D., additional, Giles, Graham G., additional, Hopper, John L., additional, Severi, Gianluca, additional, English, Dallas R., additional, Foulkes, William D., additional, Maehle, Lovise, additional, Moller, Pal, additional, Eeles, Ros, additional, Easton, Douglas, additional, Badzioch, Michael D., additional, Whittemore, Alice S., additional, Oakley‐Girvan, Ingrid, additional, Hsieh, Chih‐Lin, additional, Dimitrov, Latchezar, additional, Xu, Jianfeng, additional, Stanford, Janet L., additional, Johanneson, Bo, additional, Deutsch, Kerry, additional, McIntosh, Laura, additional, Ostrander, Elaine A., additional, Wiley, Kathleen E., additional, Isaacs, Sarah D., additional, Walsh, Patrick C., additional, Isaacs, William B., additional, Thibodeau, Stephen N., additional, McDonnell, Shannon K., additional, Hebbring, Scott, additional, Schaid, Daniel J., additional, Lange, Ethan M., additional, Cooney, Kathleen A., additional, Tammela, Teuvo L.J., additional, Schleutker, Johanna, additional, Paiss, Thomas, additional, Maier, Christiane, additional, Grönberg, Henrik, additional, Wiklund, Fredrik, additional, Emanuelsson, Monica, additional, Farnham, James M., additional, Cannon‐Albright, Lisa A., additional, and Camp, Nicola J., additional

Published
2010
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35. Genetic mapping at 3-kilobase resolution reveals inositol 1,4,5-triphosphate receptor 3 as a risk factor for type 1 diabetes in Sweden

Author

Roach, Jared C., Deutsch, Kerry, Li, Sarah, Siegel, Andrew F., Bekris, Lynn M., Einhaus, Derek C., Sheridan, Colleen M., Glusman, Gustavo, Hood, Leroy, Lernmark, Ake, and Janer, Marta

Subjects
Type 1 diabetes -- Genetic aspects, Type 1 diabetes -- Diagnosis, Chromosome mapping -- Research, Nucleotide sequencing -- Research, Inositol -- Risk factors, Inositol -- Research, Biological sciences
Abstract

Genetic mapping for type 1 diabetes (T1D) was performed using single-nucleotide polymorphism (SNP) markers in the 4.4-Mb human major histocompatibility complex (MHC) locus in a survey of Swedish T1D cases and controls. A peak of association within the inositol 1,4,5-triphosphate receptor 3 gene (ITPR3) is identified in the region centromeric to the MHC, and the estimated population-attributable risk suggests that variation within ITPR3 reflects an important contribution to T1D in Sweden.

Published
2006

36. Fine mapping of familial prostate cancer families narrows the interval for a susceptibility locus on chromosome 22q12.3 to 1.36 Mb

Author

Johanneson, Bo, primary, McDonnell, Shannon K., additional, Karyadi, Danielle M., additional, Hebbring, Scott J., additional, Wang, Liang, additional, Deutsch, Kerry, additional, McIntosh, Laura, additional, Kwon, Erika M., additional, Suuriniemi, Miia, additional, Stanford, Janet L., additional, Schaid, Daniel J., additional, Ostrander, Elaine A., additional, and Thibodeau, Stephen N., additional

Published
2007
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37. Low-pass sequencing for microbial comparative genomics

Author

Goo, Young Ah, primary, Roach, Jared, additional, Glusman, Gustavo, additional, Baliga, Nitin S, additional, Deutsch, Kerry, additional, Pan, Min, additional, Kennedy, Sean, additional, DasSarma, Shiladitya, additional, Victor Ng, Wailap, additional, and Hood, Leroy, additional

Published
2004
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38. Genomic scan of 254 hereditary prostate cancer families

Author

Janer, Marta, primary, Friedrichsen, Danielle M., additional, Stanford, Janet L., additional, Badzioch, Michael D., additional, Kolb, Suzanne, additional, Deutsch, Kerry, additional, Peters, Mette A., additional, Goode, Ellen L., additional, Welti, Russ, additional, DeFrance, Hawkins B., additional, Iwasaki, Lori, additional, Li, Sarah, additional, Hood, Leroy, additional, Ostrander, Elaine A., additional, and Jarvik, Gail P., additional

Published
2003
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39. Low-pass sequencing for microbial comparative genomics.

Author

Young Ah Goo, Roach, Jared, Glusman, Gustavo, Baliga, Nitin S., Deutsch, Kerry, Min Pan, Kennedy, Sean, DasSarma, Shiladitya, Ng, Wailap Victor, and Hood, Leroy

Subjects
NUCLEOTIDE sequence, ARCHAEBACTERIA, MICROBIAL genomes, HALOBACTERIUM, HALOPHILIC microorganisms, MICROBIAL genetics
Abstract

Background: We studied four extremely halophilic archaea by low-pass shotgun sequencing: (1) the metabolically versatile Haloarcula marismortui; (2) the non-pigmented Natrialba asiatica; (3) the psychrophile Halorubrum lacusprofundi and (4) the Dead Sea isolate Halobaculum gomorrense. Approximately one thousand single pass genomic sequences per genome were obtained. The data were analyzed by comparative genomic analyses using the completed Halobacterium sp. NRC-1 genome as a reference. Low-pass shotgun sequencing is a simple, inexpensive, and rapid approach that can readily be performed on any cultured microbe. Results: As expected, the four archaeal halophiles analyzed exhibit both bacterial and eukaryotic characteristics as well as uniquely archaeal traits. All five halophiles exhibit greater than sixty percent GC content and low isoelectric points (pI) for their predicted proteins. Multiple insertion sequence (IS) elements, often involved in genome rearrangements, were identified in H. lacusprofundi and H. marismortui. The core biological functions that govern cellular and genetic mechanisms of H. sp. NRC-1 appear to be conserved in these four other halophiles. Multiple TATA box binding protein (TBP) and transcription factor IIB (TFB) homologs were identified from most of the four shotgunned halophiles. The reconstructed molecular tree of all five halophiles shows a large divergence between these species, but with the closest relationship being between H. sp. NRC-1 and H. lacusprofundi. Conclusion: Despite the diverse habitats of these species, all five halophiles share (1) high GC content and (2) low protein isoelectric points, which are characteristics associated with environmental exposure to UV radiation and hypersalinity, respectively. Identification of multiple IS elements in the genome of H. lacusprofundi and H. marismortui suggest that genome structure and dynamic genome reorganization might be similar to that previously observed in the IS-element rich genome of H. sp. NRC-1. Identification of multiple TBP and TFB homologs in these four halophiles are consistent with the hypothesis that different types of complex transcriptional regulation may occur through multiple TBP-TFB combinations in response to rapidly changing environmental conditions. Low-pass shotgun sequence analyses of genomes permit extensive and diverse analyses, and should be generally useful for comparative microbial genomics. [ABSTRACT FROM AUTHOR]

Published
2004
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40. Pooled genome linkage scan of aggressive prostate cancer: results from the International Consortium for Prostate Cancer Genetics.

Author

Schaid DJ, McDonnell SK, Zarfas KE, Cunningham JM, Hebbring S, Thibodeau SN, Eeles RA, Easton DF, Foulkes WD, Simard J, Giles GG, Hopper JL, Mahle L, Moller P, Badzioch M, Bishop DT, Evans C, Edwards S, Meitz J, Bullock S, Hope Q, Guy M, Hsieh CL, Halpern J, Balise RR, Oakley-Girvan I, Whittemore AS, Xu J, Dimitrov L, Chang BL, Adams TS, Turner AR, Meyers DA, Friedrichsen DM, Deutsch K, Kolb S, Janer M, Hood L, Ostrander EA, Stanford JL, Ewing CM, Gielzak M, Isaacs SD, Walsh PC, Wiley KE, Isaacs WB, Lange EM, Ho LA, Beebe-Dimmer JL, Wood DP, Cooney KA, Seminara D, Ikonen T, Baffoe-Bonnie A, Fredriksson H, Matikainen MP, Tammela TL, Bailey-Wilson J, Schleutker J, Maier C, Herkommer K, Hoegel JJ, Vogel W, Paiss T, Wiklund F, Emanuelsson M, Stenman E, Jonsson BA, Grönberg H, Camp NJ, Farnham J, Cannon-Albright LA, Catalona WJ, Suarez BK, and Roehl KA

Subjects
Black or African American genetics, Aged, Chromosome Mapping, Family Health, Female, Genetic Heterogeneity, Genetic Predisposition to Disease ethnology, Genotype, Humans, International Cooperation, Lod Score, Male, Microsatellite Repeats, Middle Aged, Pedigree, Prostatic Neoplasms ethnology, White People genetics, Genetic Linkage, Genome, Human, Prostatic Neoplasms genetics
Abstract

While it is widely appreciated that prostate cancers vary substantially in their propensity to progress to a life-threatening stage, the molecular events responsible for this progression have not been identified. Understanding these molecular mechanisms could provide important prognostic information relevant to more effective clinical management of this heterogeneous cancer. Hence, through genetic linkage analyses, we examined the hypothesis that the tendency to develop aggressive prostate cancer may have an important genetic component. Starting with 1,233 familial prostate cancer families with genome scan data available from the International Consortium for Prostate Cancer Genetics, we selected those that had at least three members with the phenotype of clinically aggressive prostate cancer, as defined by either high tumor grade and/or stage, resulting in 166 pedigrees (13%). Genome-wide linkage data were then pooled to perform a combined linkage analysis for these families. Linkage signals reaching a suggestive level of significance were found on chromosomes 6p22.3 (LOD = 3.0), 11q14.1-14.3 (LOD = 2.4), and 20p11.21-q11.21 (LOD = 2.5). For chromosome 11, stronger evidence of linkage (LOD = 3.3) was observed among pedigrees with an average at diagnosis of 65 years or younger. Other chromosomes that showed evidence for heterogeneity in linkage across strata were chromosome 7, with the strongest linkage signal among pedigrees without male-to-male disease transmission (7q21.11, LOD = 4.1), and chromosome 21, with the strongest linkage signal among pedigrees that had African American ancestry (21q22.13-22.3; LOD = 3.2). Our findings suggest several regions that may contain genes which, when mutated, predispose men to develop a more aggressive prostate cancer phenotype. This provides a basis for attempts to identify these genes, with potential clinical utility for men with aggressive prostate cancer and their relatives.

Published
2006
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