Experience using conventional compared to ancestry-based population descriptors in clinical genomics laboratories

Authors: Hatchell, Kathryn E. ^{1, ∗}, Poll, Sarah R. ¹, Russell, Emily M. ¹, Williams, Trevor J. ¹, Ellsworth, Rachel E. ¹, Facio, Flavia M. ¹, Aguilar, Sienna ¹, Esplin, Edward D. ¹, Popejoy, Alice B. ^{2, 3}, Nussbaum, Robert L. ⁴, Aradhya, Swaroop ^{5, 6}

Source: In The American Journal of Human Genetics 6 March 2025 112(3):481-491

Considerations for reporting variants in novel candidate genes identified during clinical genomic testing

Authors: Abouhala, Siwaar, Albert, Jessica, Almalvez, Miguel, Alvarez, Raquel, Amin, Mutaz, Anderson, Peter, Aradhya, Swaroop, Ashley, Euan, Assimes, Themistocles, Auriga, Light, Austin-Tse, Christina, Bamshad, Mike, Barseghyan, Hayk, Baxter, Samantha, Behera, Sairam, Beheshti, Shaghayegh, Bejerano, Gill, Berger, Seth, Bernstein, Jon, Best, Sabrina, Blankenmeister, Benjamin, Blue, Elizabeth, Boerwinkle, Eric, Bonkowski, Emily, Bonner, Devon, Boone, Philip, Bornhorst, Miriam, Brand, Harrison, Buckingham, Kati, Calame, Daniel, Carter, Jennefer, Casadei, Silvia, Chadwick, Lisa, Chavez, Clarisa, Chen, Ziwei, Chinn, Ivan, Chong, Jessica, Coban-Akdemir, Zeynep, Cohen, Andrea J., Conner, Sarah, Conomos, Matthew, Coveler, Karen, Cui, Ya Allen, Currin, Sara, Daber, Robert, Dardas, Zain, Davis, Colleen, Dawood, Moez, de Dios, Ivan, de Esch, Celine, Delaney, Meghan, Delot, Emmanuele, DiTroia, Stephanie, Doddapaneni, Harsha, Du, Haowei, Duan, Ruizhi, Dugan-Perez, Shannon, Duong, Nhat, Duyzend, Michael, Eichler, Evan, Emami, Sara, Fraser, Jamie, Fusaro, Vincent, Galey, Miranda, Ganesh, Vijay, Garcia, Brandon, Garimella, Kiran, Gibbs, Richard, Gifford, Casey, Ginsburg, Amy, Goddard, Page, Gogarten, Stephanie, Gogate, Nikhita, Gordon, William, Gorzynski, John E., Greenleaf, William, Grochowski, Christopher, Groopman, Emily, Sousa, Rodrigo Guarischi, Gudmundsson, Sanna, Gulati, Ashima, Hall, Stacey, Harvey, William, Hawley, Megan, Heavner, Ben, Horike-Pyne, Martha, Hu, Jianhong, Huang, Yongqing, Hwang, James, Jarvik, Gail, Jensen, Tanner, Jhangiani, Shalini, Jimenez-Morales, David, Jin, Christopher, Saad, Ahmed K., Kahn-Kirby, Amanda, Kain, Jessica, Kaur, Parneet, Keehan, Laura, Knoblach, Susan, Ko, Arthur, Kundaje, Anshul, Kundu, Soumya, Lancaster, Samuel M., Larsson, Katie, Lee, Arthur, Lemire, Gabrielle, Lewis, Richard, Li, Wei, Li, Yidan, Liu, Pengfei, LoTempio, Jonathan, Lupski, James (Jim), Ma, Jialan, MacArthur, Daniel, Mahmoud, Medhat, Malani, Nirav, Mangilog, Brian, Marafi, Dana, Marmolejos, Sofia, Marten, Daniel, Martinez, Eva, Marvin, Colby, Marwaha, Shruti, Mastrorosa, Francesco Kumara, Matalon, Dena, May, Susanne, McGee, Sean, Meador, Lauren, Mefford, Heather, Mendez, Hector Rodrigo, Miller, Alexander, Miller, Danny E., Mitani, Tadahiro, Montgomery, Stephen, Moyses, Mariana, Munderloh, Chloe, Muzny, Donna, Nelson, Sarah, Nguyen, Thuy-mi P., Nguyen, Jonathan, Nussbaum, Robert, Nykamp, Keith, O'Callaghan, William, O'Heir, Emily, O'Leary, Melanie, Olsen, Jeren, Osei-Owusu, Ikeoluwa, O'Donnell-Luria, Anne, Padhi, Evin, Pais, Lynn, Pan, Miao, Panchal, Piyush, Patterson, Karynne, Payne, Sheryl, Pehlivan, Davut, Petrowski, Paul, Pham, Alicia, Pitsava, Georgia, Podesta, Astaria`Sara, Ponce, Sarah, Porter, Elizabeth, Posey, Jennifer, Prosser, Jaime, Quertermous, Thomas, Rai, Archana, Ramani, Arun, Rehm, Heidi, Reuter, Chloe, Reuter, Jason, Richardson, Matthew, Rivera-Munoz, Andres, Rubio, Oriane, Sabo, Aniko, Salani, Monica, Samocha, Kaitlin, Sanchis-Juan, Alba, Savage, Sarah, Scott, Evette, Scott, Stuart, Sedlazeck, Fritz, Shah, Gulalai, Shojaie, Ali, Singh, Mugdha, Smith, Kevin, Smith, Josh, Snow, Hana, Snyder, Michael, Socarras, Kayla, Starita, Lea, Stark, Brigitte, Stenton, Sarah, Stergachis, Andrew, Stilp, Adrienne, Sutton, V. Reid, Tai, Jui-Cheng, Talkowski, Michael (Mike), Tise, Christina, Tong, Catherine (Cat), Tsao, Philip, Ungar, Rachel, VanNoy, Grace, Vilain, Eric, Voutos, Isabella, Walker, Kim, Wei, Chia-Lin, Weisburd, Ben, Weiss, Jeff, Wellington, Chris, Weng, Ziming, Westheimer, Emily, Wheeler, Marsha, Wheeler, Matthew, Wiel, Laurens, Wilson, Michael, Wojcik, Monica, Wong, Quenna, Xiao, Changrui, Yadav, Rachita, Yi, Qian, Yuan, Bo, Zhao, Jianhua, Zhen, Jimmy, Zhou, Harry, Chong, Jessica X., Berger, Seth I., Smith, Erica, Calame, Daniel G., Hawley, Megan H., Rivera-Munoz, E. Andres, Bamshad, Michael J., Rehm, Heidi L.

Source: In Genetics in Medicine October 2024 26(10)

A Systematic Method for Detecting Abnormal mRNA Splicing and Assessing Its Clinical Impact in Individuals Undergoing Genetic Testing for Hereditary Cancer Syndromes

Authors: Kamps-Hughes, Nick, Carlton, Victoria E.H., Fresard, Laure, Osazuwa, Steve, Starks, Elizabeth, Vincent, John J., Albritton, Sarah, Nussbaum, Robert L., Nykamp, Keith

Source: Journal of molecular diagnostics. 25(3):156-167

Availability: http://explore.bl.uk/primo_library/libweb/action/display.do?tabs=detailsTab&gathStatTab=true&ct=display&fn=search&doc=ETOCvdc_100183970394.0x000001&indx=1&recIds=ETOCvdc_100183970394.0x000001

Systematically testing human HMBS missense variants to reveal mechanism and pathogenic variation

Authors: van Loggerenberg, Warren, Sowlati-Hashjin, Shahin, Weile, Jochen, Hamilton, Rayna, Chawla, Aditya, Sheykhkarimli, Dayag, Gebbia, Marinella, Kishore, Nishka, Frésard, Laure, Mustajoki, Sami, Pischik, Elena, Di Pierro, Elena, Barbaro, Michela, Floderus, Ylva, Schmitt, Caroline, Gouya, Laurent, Colavin, Alexandre, Nussbaum, Robert, Friesema, Edith C.H., Kauppinen, Raili, To-Figueras, Jordi, Aarsand, Aasne K., Desnick, Robert J., Garton, Michael, Roth, Frederick P.

Source: In The American Journal of Human Genetics 5 October 2023 110(10):1769-1786

Efficacy of National Comprehensive Cancer Network Guidelines in Identifying Pathogenic Germline Variants Among Unselected Patients with Prostate Cancer: The PROCLAIM Trial

Authors: Shore, Neal, Gazi, Mukaram, Pieczonka, Christopher, Heron, Sean, Modh, Rishi, Cahn, David, Belkoff, Laurence H., Berger, Aaron, Mazzarella, Brian, Veys, Joseph, Idom, Charles, Morris, David, Jayram, Gautam, Engelman, Alexander, Bukkapatnam, Raviender, Dato, Paul, Bevan-Thomas, Richard, Cornell, Robert, Wise, David R., Hardwick, Mary Kay, Hernandez, Ryan D., Rojahn, Susan, Layman, Paige, Hatchell, Kathryn E., Heald, Brandie, Nussbaum, Robert L., Nielsen, Sarah M., Esplin, Edward D.

Source: In European Urology Oncology October 2023 6(5):477-483

Beyond the exome: What’s next in diagnostic testing for Mendelian conditions

Authors: Abouhala, Siwaar, Albert, Jessica, Almalvez, Miguel, Alvarez, Raquel, Amin, Mutaz, Anderson, Peter, Aradhya, Swaroop, Ashley, Euan, Assimes, Themistocles, Auriga, Light, Austin-Tse, Christina, Bamshad, Mike, Barseghyan, Hayk, Baxter, Samantha, Behera, Sairam, Beheshti, Shaghayegh, Bejerano, Gill, Berger, Seth, Bernstein, Jon, Best, Sabrina, Blankenmeister, Benjamin, Blue, Elizabeth, Boerwinkle, Eric, Bonkowski, Emily, Bonner, Devon, Boone, Philip, Bornhorst, Miriam, Bozkurt-Yozgatli, Tugce, Brand, Harrison, Buckingham, Kati, Calame, Daniel, Casadei, Silvia, Chadwick, Lisa, Chavez, Clarisa, Chen, Ziwei, Chinn, Ivan, Chong, Jessica, Coban-Akdemir, Zeynep, Cohen, Andrea J., Conner, Sarah, Conomos, Matthew, Coveler, Karen, Cui, Ya Allen, Currin, Sara, Daber, Robert, Dardas, Zain, Davis, Colleen, Dawood, Moez, de Dios, Ivan, de Esch, Celine, Delaney, Meghan, Délot, Emmanuèle, DiTroia, Stephanie, Doddapaneni, Harsha, Du, Haowei, Duan, Ruizhi, Dugan-Perez, Shannon, Duong, Nhat, Duyzend, Michael, Eichler, Evan, Emami, Sara, Fatih, Jawid, Fraser, Jamie, Fusaro, Vincent, Galey, Miranda, Ganesh, Vijay, Garimella, Kiran, Gibbs, Richard, Gifford, Casey, Ginsburg, Amy, Goddard, Pagé, Gogarten, Stephanie, Gogate, Nikhita, Gordon, William, Gorzynski, John E., Greenleaf, William, Grochowski, Christopher, Groopman, Emily, Guarischi Sousa, Rodrigo, Gudmundsson, Sanna, Gulati, Ashima, Guo, Daniel, Hale, Walker, Hall, Stacey, Harvey, William, Hawley, Megan, Heavner, Ben, Herman, Isabella, Horike-Pyne, Martha, Hu, Jianhong, Huang, Yongqing, Hwang, James, Jarvik, Gail, Jensen, Tanner, Jhangiani, Shalini, Jimenez-Morales, David, Jin, Christopher, Saad, Ahmed K., Kahn-Kirby, Amanda, Kain, Jessica, Kaur, Parneet, Keehan, Laura, Knoblach, Susan, Ko, Arthur, Kohler, Jennefer, Kundaje, Anshul, Kundu, Soumya, Lancaster, Samuel M., Larsson, Katie, Lemire, Gabrielle, Lewis, Richard, Li, Wei, Li, Yidan, Liu, Pengfei, LoTempio, Jonathan, Lupski, James, Ma, Jialan, MacArthur, Daniel, Mahmoud, Medhat, Malani, Nirav, Mangilog, Brian, Marafi, Dana, Marmolejos, Sofia, Marten, Daniel, Martinez, Eva, Marvin, Colby, Marwaha, Shruti, Kumara Mastrorosa, Francesco, Matalon, Dena, May, Susanne, McGee, Sean, Meador, Lauren, Mefford, Heather, Rodrigo Mendez, Hector, Miller, Alexander, Miller, Danny E., Mitani, Tadahiro, Montgomery, Stephen, Moussa, Hala Mohamed, Moyses, Mariana, Munderloh, Chloe, Muzny, Donna, Nelson, Sarah, Neu, Matthew B., Nguyen, Jonathan, Nguyen, Thuy-mi P., Nussbaum, Robert, Nykamp, Keith, O'Callaghan, William, O'Heir, Emily, O'Leary, Melanie, Olsen, Jeren, Osei-Owusu, Ikeoluwa, O'Donnell-Luria, Anne, Padhi, Evin, Pais, Lynn, Pan, Miao, Panchal, Piyush, Patterson, Karynne, Payne, Sheryl, Pehlivan, Davut, Petrowski, Paul, Pham, Alicia, Pitsava, Georgia, Podesta, Astaria, Ponce, Sarah, Posey, Jennifer, Prosser, Jaime, Quertermous, Thomas, Rai, Archana, Ramani, Arun, Rehm, Heidi, Reuter, Chloe, Reuter, Jason, Richardson, Matthew, Rivera-Munoz, Andres, Rubio, Oriane, Sabo, Aniko, Salani, Monica, Samocha, Kaitlin, Sanchis-Juan, Alba, Savage, Sarah, Scott, Stuart, Scott, Evette, Sedlazeck, Fritz, Shah, Gulalai, Shojaie, Ali, Singh, Mugdha, Smith, Josh, Smith, Kevin, Snow, Hana, Snyder, Michael, Socarras, Kayla, Starita, Lea, Stark, Brigitte, Stenton, Sarah, Stergachis, Andrew, Stilp, Adrienne, Sundaram, Laksshman, Sutton, V. Reid, Tai, Jui-Cheng, Talkowski, Michael, Tise, Christina, Tong, Catherine, Tsao, Philip, Ungar, Rachel, VanNoy, Grace, Vilain, Eric, Voutos, Isabella, Walker, Kim, Weisburd, Ben, Weiss, Jeff, Wellington, Chris, Weng, Ziming, Westheimer, Emily, Wheeler, Marsha, Wheeler, Matthew, Wiel, Laurens, Wilson, Michael, Wojcik, Monica, Wong, Quenna, Wong, Issac, Xiao, Changrui, Yadav, Rachita, Yi, Qian, Yuan, Bo, Zhao, Jianhua, Zhen, Jimmy, Zhou, Harry, Wojcik, Monica H., Reuter, Chloe M., Duyzend, Michael H., Boone, Philip M., Groopman, Emily E., Délot, Emmanuèle C., Jain, Deepti, Starita, Lea M., Montgomery, Stephen B., Bamshad, Michael J., Chong, Jessica X., Wheeler, Matthew T., Berger, Seth I., Sedlazeck, Fritz J.

Source: In The American Journal of Human Genetics 3 August 2023 110(8):1229-1248

Patterns of mosaicism for sequence and copy-number variants discovered through clinical deep sequencing of disease-related genes in one million individuals

Authors: Truty, Rebecca, Rojahn, Susan, Ouyang, Karen, Kautzer, Curtis, Kennemer, Michael, Pineda-Alvarez, Daniel, Johnson, Britt, Stafford, Amanda, Basel-Salmon, Lina, Saitta, Sulagna, Slavotinek, Anne, Chandrasekharappa, Settara C., Suarez, Carlos Jose, Burnett, Leslie, Nussbaum, Robert L., Aradhya, Swaroop

Source: In The American Journal of Human Genetics 6 April 2023 110(4):551-564

Germline Cancer Susceptibility Gene Testing in Unselected Patients With Colorectal Adenocarcinoma: A Multicenter Prospective Study

Authors: Uson, Pedro L.S., Riegert-Johnson, Douglas, Boardman, Lisa, Kisiel, John, Mountjoy, Luke, Patel, Neej, Lizaola-Mayo, Blanca, Borad, Mitesh J., Ahn, Daniel, Sonbol, Mohamad B., Jones, Jeremy, Leighton, Jonathan A., Gurudu, Suryakanth, Singh, Harminder, Klint, Margaret, Kunze, Katie L., Golafshar, Michael A., Esplin, Ed D., Nussbaum, Robert L., Stewart, A. Keith, Bekaii-Saab, Tanio S., Jewel Samadder, Niloy

Source: Clinical gastroenterology and hepatology. 20(3):e508-e528

Availability: http://explore.bl.uk/primo_library/libweb/action/display.do?tabs=detailsTab&gathStatTab=true&ct=display&fn=search&doc=ETOCvdc_100155420314.0x000001&indx=1&recIds=ETOCvdc_100155420314.0x000001

Inherited TP53 Variants and Risk of Prostate Cancer

Authors: Maxwell, Kara N., Cheng, Heather H., Powers, Jacquelyn, Gulati, Roman, Ledet, Elisa M., Morrison, Casey, Le, Anh, Hausler, Ryan, Stopfer, Jill, Hyman, Sophie, Kohlmann, Wendy, Naumer, Anne, Vagher, Jennie, Greenberg, Samantha E., Naylor, Lorraine, Laurino, Mercy, Konnick, Eric Q., Shirts, Brian H., AlDubayan, Saud H., Van Allen, Eliezer M., Nguyen, Bastien, Vijai, Joseph, Abida, Wassim, Carlo, Maria I., Dubard-Gault, Marianne, Lee, Daniel J., Maese, Luke D., Mandelker, Diana, Montgomery, Bruce, Morris, Michael J., Nicolosi, Piper, Nussbaum, Robert L., Schwartz, Lauren E., Stadler, Zsofia, Garber, Judy E., Offit, Kenneth, Schiffman, Joshua D., Nelson, Peter S., Sartor, Oliver, Walsh, Michael F., Pritchard, Colin C.

Source: European urology. 81(3):243-250

Availability: http://explore.bl.uk/primo_library/libweb/action/display.do?tabs=detailsTab&gathStatTab=true&ct=display&fn=search&doc=ETOCvdc_100156431984.0x000001&indx=1&recIds=ETOCvdc_100156431984.0x000001

The genetic architecture of Plakophilin 2 cardiomyopathy

Authors: Dries, Annika M., Kirillova, Anna, Reuter, Chloe M., Garcia, John, Zouk, Hana, Hawley, Megan, Murray, Brittney, Tichnell, Crystal, Pilichou, Kalliopi, Protonotarios, Alexandros, Medeiros-Domingo, Argelia, Kelly, Melissa A., Baras, Aris, Ingles, Jodie, Semsarian, Christopher, Bauce, Barbara, Celeghin, Rudy, Basso, Cristina, Jongbloed, Jan D.H., Nussbaum, Robert L., Funke, Birgit, Cerrone, Marina, Mestroni, Luisa, Taylor, Matthew R.G., Sinagra, Gianfranco, Merlo, Marco, Saguner, Ardan M., Elliott, Perry M., Syrris, Petros, van Tintelen, J. Peter, James, Cynthia A., Haggerty, Christopher M., Parikh, Victoria N.

Source: In Genetics in Medicine October 2021 23(10):1961-1968

One in seven pathogenic variants can be challenging to detect by NGS: an analysis of 450,000 patients with implications for clinical sensitivity and genetic test implementation

Authors: Lincoln, Stephen E., Hambuch, Tina, Zook, Justin M., Bristow, Sara L., Hatchell, Kathryn, Truty, Rebecca, Kennemer, Michael, Shirts, Brian H., Fellowes, Andrew, Chowdhury, Shimul, Klee, Eric W., Mahamdallie, Shazia, Cleveland, Megan H., Vallone, Peter M., Ding, Yan, Seal, Sheila, DeSilva, Wasanthi, Tomson, Farol L., Huang, Catherine, Garlick, Russell K., Rahman, Nazneen, Salit, Marc, Kingsmore, Stephen F., Ferber, Matthew J., Aradhya, Swaroop, Nussbaum, Robert L.

Source: In Genetics in Medicine September 2021 23(9):1673-1680

Shifting landscapes of human MTHFR missense-variant effects

Authors: Weile, Jochen, Kishore, Nishka, Sun, Song, Maaieh, Ranim, Verby, Marta, Li, Roujia, Fotiadou, Iosifina, Kitaygorodsky, Julia, Wu, Yingzhou, Holenstein, Alexander, Bürer, Céline, Blomgren, Linnea, Yang, Shan, Nussbaum, Robert, Rozen, Rima, Watkins, David, Gebbia, Marinella, Kozich, Viktor, Garton, Michael, Froese, D. Sean, Roth, Frederick P.

Source: In The American Journal of Human Genetics 1 July 2021 108(7):1283-1300

Spectrum of splicing variants in disease genes and the ability of RNA analysis to reduce uncertainty in clinical interpretation

Authors: Truty, Rebecca, Ouyang, Karen, Rojahn, Susan, Garcia, Sarah, Colavin, Alexandre, Hamlington, Barbara, Freivogel, Mary, Nussbaum, Robert L., Nykamp, Keith, Aradhya, Swaroop

Source: In The American Journal of Human Genetics 1 April 2021 108(4):696-708

Challenges in providing residual risks in carrier testing

Authors: Nussbaum, Robert Luke, Slotnick, Robert Nathan, Risch, Neil J.

Source: Prenatal diagnosis. 41(9):1049-1056

Availability: http://explore.bl.uk/primo_library/libweb/action/display.do?tabs=detailsTab&gathStatTab=true&ct=display&fn=search&doc=ETOCvdc_100127394249.0x000001&indx=1&recIds=ETOCvdc_100127394249.0x000001

Hereditary Cancer Risk Using a Genetic Chatbot Before Routine Care Visits

Authors: Nazareth, Shivani, Hayward, Laura, Simmons, Emilie, Snir, Moran, Hatchell, Kathryn E., Rojahn, Susan, Slotnick, Robert Nathan, Nussbaum, Robert L.

Source: Obstetrics and gynecology. 138(6):860-870

Availability: http://explore.bl.uk/primo_library/libweb/action/display.do?tabs=detailsTab&gathStatTab=true&ct=display&fn=search&doc=ETOCvdc_100191856715.0x000001&indx=1&recIds=ETOCvdc_100191856715.0x000001

Management of Secondary Genomic Findings

Authors: Katz, Alexander E., Nussbaum, Robert L., Solomon, Benjamin D., Rehm, Heidi L., Williams, Marc S., Biesecker, Leslie G.

Source: In The American Journal of Human Genetics 2 July 2020 107(1):3-14

Applications of artificial intelligence in clinical laboratory genomics

Authors: Aradhya, Swaroop, Facio, Flavia M., Metz, Hillery, Manders, Toby, Colavin, Alexandre, Kobayashi, Yuya, Nykamp, Keith, Johnson, Britt, Nussbaum, Robert L.

Source: American journal of medical genetics.Part C.Seminars in medical genetics. 193(3)

Availability: http://explore.bl.uk/primo_library/libweb/action/display.do?tabs=detailsTab&gathStatTab=true&ct=display&fn=search&doc=ETOCvdc_100194907366.0x000001&indx=1&recIds=ETOCvdc_100194907366.0x000001

Cover Image, Volume 193, Number 3, September 2023

Authors: Aradhya, Swaroop, Facio, Flavia M., Metz, Hillery, Manders, Toby, Colavin, Alexandre, Kobayashi, Yuya, Nykamp, Keith, Johnson, Britt, Nussbaum, Robert L.

Source: American journal of medical genetics.Part C.Seminars in medical genetics. 193(3)

Availability: http://explore.bl.uk/primo_library/libweb/action/display.do?tabs=detailsTab&gathStatTab=true&ct=display&fn=search&doc=ETOCvdc_100194907349.0x000001&indx=1&recIds=ETOCvdc_100194907349.0x000001

Pathogenic germ line variants in a prospective multicenter cohort of patients with multiple myeloma

Authors: Wiedmeier-Nutor, Julia Erin ¹, Golafshar, Michael A. ², Kunze, Katie L. ², Esplin, Edward D. ³, Nussbaum, Robert L. ³, Jessen, Erik ⁴, Heald, Brandie ³, Stewart, A. Keith ⁵, Samadder, N. Jewel ^{6, 7, ∗}, Bergsagel, P. Leif ^{1, 7}, Fonseca, Rafael ^{1, 7}

Source: In Blood Neoplasia February 2025 2(1)

Chapter 12 - Genomics of human neurological disorders

Authors: Nussbaum, Robert L.

Source: In Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease, Seventh Edition Edition: Seventh Edition. 2025:173-185