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1. Integrative Annotation of Variants from 1092 Humans: Application to Cancer Genomics

Author

Broad Institute of MIT and Harvard, Khurana, Ekta, Fu, Yao, Colonna, Vincenza, Mu, Xinmeng Jasmine, Kang, Hyun Min, Lappalainen, Tuuli, Sboner, Andrea, Lochovsky, Lucas, Chen, Jieming, Harmanci, Arif, Das, Jishnu, Abyzov, Alexej, Balasubramanian, Suganthi, Beal, Kathryn, Chakravarty, Dimple, Challis, Daniel, Chen, Yuan, Clarke, Declan, Clarke, Laura, Cunningham, Fiona, Evani, Uday S., Flicek, Paul, Fragoza, Robert, Garrison, Erik, Gibbs, Richard, Gümüş, Zeynep H., Herrero, Javier, Kitabayashi, Naoki, Kong, Yong, Lage, Kasper, Liluashvili, Vaja, Lipkin, Steven M., MacArthur, Daniel G., Marth, Gabor, Muzny, Donna, Pers, Tune H., Ritchie, Graham R. S., Rosenfeld, Jeffrey A., Sisu, Cristina, Wei, Xiaomu, Wilson, Michael, Xue, Yali, Yu, Fuli, Dermitzakis, Emmanouil T., Yu, Haiyuan, Rubin, Mark A., Tyler-Smith, Chris, Gerstein, Mark, Broad Institute of MIT and Harvard, Khurana, Ekta, Fu, Yao, Colonna, Vincenza, Mu, Xinmeng Jasmine, Kang, Hyun Min, Lappalainen, Tuuli, Sboner, Andrea, Lochovsky, Lucas, Chen, Jieming, Harmanci, Arif, Das, Jishnu, Abyzov, Alexej, Balasubramanian, Suganthi, Beal, Kathryn, Chakravarty, Dimple, Challis, Daniel, Chen, Yuan, Clarke, Declan, Clarke, Laura, Cunningham, Fiona, Evani, Uday S., Flicek, Paul, Fragoza, Robert, Garrison, Erik, Gibbs, Richard, Gümüş, Zeynep H., Herrero, Javier, Kitabayashi, Naoki, Kong, Yong, Lage, Kasper, Liluashvili, Vaja, Lipkin, Steven M., MacArthur, Daniel G., Marth, Gabor, Muzny, Donna, Pers, Tune H., Ritchie, Graham R. S., Rosenfeld, Jeffrey A., Sisu, Cristina, Wei, Xiaomu, Wilson, Michael, Xue, Yali, Yu, Fuli, Dermitzakis, Emmanouil T., Yu, Haiyuan, Rubin, Mark A., Tyler-Smith, Chris, and Gerstein, Mark

Abstract

Interpreting variants, especially noncoding ones, in the increasing number of personal genomes is challenging. We used patterns of polymorphisms in functionally annotated regions in 1092 humans to identify deleterious variants; then we experimentally validated candidates. We analyzed both coding and noncoding regions, with the former corroborating the latter. We found regions particularly sensitive to mutations ("ultrasensitive") and variants that are disruptive because of mechanistic effects on transcription-factor binding (that is, " motif-breakers"). We also found variants in regions with higher network centrality tend to be deleterious. Insertions and deletions followed a similar pattern to single-nucleotide variants, with some notable exceptions (e.g., certain deletions and enhancers). On the basis of these patterns, we developed a computational tool (FunSeq), whose application to ∼90 cancer genomes reveals nearly a hundred candidate noncoding drivers.

Published
2020

2. Estimating survival in patients with gastrointestinal cancers and brain metastases: An update of the graded prognostic assessment for gastrointestinal cancers (GI-GPA).

Author

Sperduto, Paul W, Sperduto, Paul W, Fang, Penny, Li, Jing, Breen, William, Brown, Paul D, Cagney, Daniel, Aizer, Ayal, Yu, James B, Chiang, Veronica, Jain, Supriya, Gaspar, Laurie E, Myrehaug, Sten, Sahgal, Arjun, Braunstein, Steve, Sneed, Penny, Cameron, Brent, Attia, Albert, Molitoris, Jason, Wu, Cheng-Chia, Wang, Tony JC, Lockney, Natalie A, Beal, Kathryn, Parkhurst, Jessica, Buatti, John M, Shanley, Ryan, Lou, Emil, Tandberg, Daniel D, Kirkpatrick, John P, Shi, Diana, Shih, Helen A, Chuong, Michael, Saito, Hirotake, Aoyama, Hidefumi, Masucci, Laura, Roberge, David, Mehta, Minesh P, Sperduto, Paul W, Sperduto, Paul W, Fang, Penny, Li, Jing, Breen, William, Brown, Paul D, Cagney, Daniel, Aizer, Ayal, Yu, James B, Chiang, Veronica, Jain, Supriya, Gaspar, Laurie E, Myrehaug, Sten, Sahgal, Arjun, Braunstein, Steve, Sneed, Penny, Cameron, Brent, Attia, Albert, Molitoris, Jason, Wu, Cheng-Chia, Wang, Tony JC, Lockney, Natalie A, Beal, Kathryn, Parkhurst, Jessica, Buatti, John M, Shanley, Ryan, Lou, Emil, Tandberg, Daniel D, Kirkpatrick, John P, Shi, Diana, Shih, Helen A, Chuong, Michael, Saito, Hirotake, Aoyama, Hidefumi, Masucci, Laura, Roberge, David, and Mehta, Minesh P

Abstract

BackgroundPatients with gastrointestinal cancers and brain metastases (BM) represent a unique and heterogeneous population. Our group previously published the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for patients with GI cancers (GI-GPA) (1985-2007, n = 209). The purpose of this study is to update the GI-GPA based on a larger contemporary database.MethodsAn IRB-approved consortium database analysis was performed using a multi-institutional (18), multi-national (3) cohort of 792 patients with gastrointestinal (GI) cancers, with newly-diagnosed BM diagnosed between 1/1/2006 and 12/31/2017. Survival was measured from date of first treatment for BM. Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios. These factors were incorporated into the updated GI-GPA.ResultsMedian survival (MS) varied widely by primary site and other prognostic factors. Four significant factors (KPS, age, extracranial metastases and number of BM) were used to formulate the updated GI-GPA. Overall MS for this cohort remains poor; 8 months. MS by GPA was 3, 7, 11 and 17 months for GPA 0-1, 1.5-2, 2.5-3.0 and 3.5-4.0, respectively. >30% present in the worst prognostic group (GI-GPA of ≤1.0).ConclusionsBrain metastases are not uncommon in GI cancer patients and MS varies widely among them. This updated GI-GPA index improves our ability to estimate survival for these patients and will be useful for therapy selection, end-of-life decision-making and stratification for future clinical trials. A user-friendly, free, on-line app to calculate the GPA score and estimate survival for an individual patient is available at brainmetgpa.com.

Published
2019

3. Estimating survival in patients with gastrointestinal cancers and brain metastases: An update of the graded prognostic assessment for gastrointestinal cancers (GI-GPA).

Author

Sperduto, Paul W, Sperduto, Paul W, Fang, Penny, Li, Jing, Breen, William, Brown, Paul D, Cagney, Daniel, Aizer, Ayal, Yu, James B, Chiang, Veronica, Jain, Supriya, Gaspar, Laurie E, Myrehaug, Sten, Sahgal, Arjun, Braunstein, Steve, Sneed, Penny, Cameron, Brent, Attia, Albert, Molitoris, Jason, Wu, Cheng-Chia, Wang, Tony JC, Lockney, Natalie A, Beal, Kathryn, Parkhurst, Jessica, Buatti, John M, Shanley, Ryan, Lou, Emil, Tandberg, Daniel D, Kirkpatrick, John P, Shi, Diana, Shih, Helen A, Chuong, Michael, Saito, Hirotake, Aoyama, Hidefumi, Masucci, Laura, Roberge, David, Mehta, Minesh P, Sperduto, Paul W, Sperduto, Paul W, Fang, Penny, Li, Jing, Breen, William, Brown, Paul D, Cagney, Daniel, Aizer, Ayal, Yu, James B, Chiang, Veronica, Jain, Supriya, Gaspar, Laurie E, Myrehaug, Sten, Sahgal, Arjun, Braunstein, Steve, Sneed, Penny, Cameron, Brent, Attia, Albert, Molitoris, Jason, Wu, Cheng-Chia, Wang, Tony JC, Lockney, Natalie A, Beal, Kathryn, Parkhurst, Jessica, Buatti, John M, Shanley, Ryan, Lou, Emil, Tandberg, Daniel D, Kirkpatrick, John P, Shi, Diana, Shih, Helen A, Chuong, Michael, Saito, Hirotake, Aoyama, Hidefumi, Masucci, Laura, Roberge, David, and Mehta, Minesh P

Abstract

BackgroundPatients with gastrointestinal cancers and brain metastases (BM) represent a unique and heterogeneous population. Our group previously published the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for patients with GI cancers (GI-GPA) (1985-2007, n = 209). The purpose of this study is to update the GI-GPA based on a larger contemporary database.MethodsAn IRB-approved consortium database analysis was performed using a multi-institutional (18), multi-national (3) cohort of 792 patients with gastrointestinal (GI) cancers, with newly-diagnosed BM diagnosed between 1/1/2006 and 12/31/2017. Survival was measured from date of first treatment for BM. Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios. These factors were incorporated into the updated GI-GPA.ResultsMedian survival (MS) varied widely by primary site and other prognostic factors. Four significant factors (KPS, age, extracranial metastases and number of BM) were used to formulate the updated GI-GPA. Overall MS for this cohort remains poor; 8 months. MS by GPA was 3, 7, 11 and 17 months for GPA 0-1, 1.5-2, 2.5-3.0 and 3.5-4.0, respectively. >30% present in the worst prognostic group (GI-GPA of ≤1.0).ConclusionsBrain metastases are not uncommon in GI cancer patients and MS varies widely among them. This updated GI-GPA index improves our ability to estimate survival for these patients and will be useful for therapy selection, end-of-life decision-making and stratification for future clinical trials. A user-friendly, free, on-line app to calculate the GPA score and estimate survival for an individual patient is available at brainmetgpa.com.

Published
2019

4. Survival and prognostic factors in patients with gastrointestinal cancers and brain metastases: have we made progress?

Author

Sperduto, Paul W, Sperduto, Paul W, Fang, Penny, Li, Jing, Breen, William, Brown, Paul D, Cagney, Daniel, Aizer, Ayal, Yu, James, Chiang, Veronica, Jain, Supriya, Gaspar, Laurie E, Myrehaug, Sten, Sahgal, Arjun, Braunstein, Steve, Sneed, Penny, Cameron, Brent, Attia, Albert, Molitoris, Jason, Wu, Cheng-Chia, Wang, Tony JC, Lockney, Natalie, Beal, Kathryn, Parkhurst, Jessica, Buatti, John M, Shanley, Ryan, Lou, Emil, Tandberg, Daniel D, Kirkpatrick, John P, Shi, Diana, Shih, Helen A, Chuong, Michael, Saito, Hirotake, Aoyama, Hidefumi, Masucci, Laura, Roberge, David, Mehta, Minesh P, Sperduto, Paul W, Sperduto, Paul W, Fang, Penny, Li, Jing, Breen, William, Brown, Paul D, Cagney, Daniel, Aizer, Ayal, Yu, James, Chiang, Veronica, Jain, Supriya, Gaspar, Laurie E, Myrehaug, Sten, Sahgal, Arjun, Braunstein, Steve, Sneed, Penny, Cameron, Brent, Attia, Albert, Molitoris, Jason, Wu, Cheng-Chia, Wang, Tony JC, Lockney, Natalie, Beal, Kathryn, Parkhurst, Jessica, Buatti, John M, Shanley, Ryan, Lou, Emil, Tandberg, Daniel D, Kirkpatrick, John P, Shi, Diana, Shih, Helen A, Chuong, Michael, Saito, Hirotake, Aoyama, Hidefumi, Masucci, Laura, Roberge, David, and Mehta, Minesh P

Abstract

The literature describing the prognosis of patients with gastrointestinal (GI) cancers and brain metastases (BM) is sparse. Our group previously published a prognostic index, the Graded Prognostic Assessment (GPA) for GI cancer patients with BM, based on 209 patients diagnosed from 1985-2005. The purpose of this analysis is to identify prognostic factors for GI cancer patients with newly diagnosed BM in a larger contemporary cohort. A multi-institutional retrospective IRB-approved database of 792 GI cancer patients with new BM diagnosed from 1/1/2006 to 12/31/2016 was created. Demographic data, clinical parameters, and treatment were correlated with survival and time from primary diagnosis to BM (TPDBM). Kaplan-Meier median survival (MS) estimates were calculated and compared with log-rank tests. The MS from time of first treatment for BM for the prior and current cohorts were 5 and 8 months, respectively (P < 0.001). Eight prognostic factors (age, stage, primary site, resection of primary tumor, Karnofsky Performance Status (KPS), extracranial metastases, number of BM and Hgb were found to be significant for survival, in contrast to only one (KPS) in the prior cohort. In this cohort, the most common primary sites were rectum (24%) and esophagus (23%). Median TPDBM was 22 months. Notably, 37% (267/716) presented with poor prognosis (GPA 0-1.0). Although little improvement in overall survival in this cohort has been achieved in recent decades, survival varies widely and multiple new prognostic factors were identified. Future work will translate these factors into a prognostic index to facilitate clinical decision-making and stratification of future clinical trials.

Published
2019

5. Characterizing Mutational Signatures in Human Cancer Cell Lines Reveals Episodic APOBEC Mutagenesis

Author

Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas, Universidade de Santiago de Compostela. Departamento de Zooloxía, Xenética e Antropoloxía Física, Petljak, Mia, Alexandrov, Ludmil B., Brammeld, Jonathan S., Price, Stacey, Wedge, David C., Grossmann, Sebastian, Dawson, Kevin J., Ju, Young Seok, Ioro, Francesco, Castro Tubío, José Manuel, Koh, Ching Chiek, Georgakopoulos Soares, Ilias, Rodríguez Martín, Bernardo, Otlu, Burçak, O'Meara, Sarah, Butler, Adam P., Menzies, Andrew, Bhosle, Shriram G., Raine, Keiran, Jones, David R., Teague, Jon W., Beal, Kathryn, Latimer, Calli, O'Neill, Laura, Zamora Berna, Jorge Aurelio, Anderson, Elizabeth, Patel, Nikita, Maddison, Mark, Ng, Bee Ling, Graham, Jennifer, Garnett, Mathew J., McDermott, Ultan, Nik Zainal, Serena, Campbell, Peter J., Stratton, Michael R., Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas, Universidade de Santiago de Compostela. Departamento de Zooloxía, Xenética e Antropoloxía Física, Petljak, Mia, Alexandrov, Ludmil B., Brammeld, Jonathan S., Price, Stacey, Wedge, David C., Grossmann, Sebastian, Dawson, Kevin J., Ju, Young Seok, Ioro, Francesco, Castro Tubío, José Manuel, Koh, Ching Chiek, Georgakopoulos Soares, Ilias, Rodríguez Martín, Bernardo, Otlu, Burçak, O'Meara, Sarah, Butler, Adam P., Menzies, Andrew, Bhosle, Shriram G., Raine, Keiran, Jones, David R., Teague, Jon W., Beal, Kathryn, Latimer, Calli, O'Neill, Laura, Zamora Berna, Jorge Aurelio, Anderson, Elizabeth, Patel, Nikita, Maddison, Mark, Ng, Bee Ling, Graham, Jennifer, Garnett, Mathew J., McDermott, Ultan, Nik Zainal, Serena, Campbell, Peter J., and Stratton, Michael R.

Abstract

Multiple signatures of somatic mutations have beenidentified in cancer genomes. Exome sequences of1,001 human cancer cell lines and 577 xenograftsrevealed most common mutational signatures,indicating past activity of the underlying processes,usually in appropriate cancer types. To investigateongoing patterns of mutational-signature genera-tion, cell lines were cultured for extended periodsand subsequently DNA sequenced. Signatures ofdiscontinued exposures, including tobacco smokeand ultraviolet light, were not generatedin vitro. Sig-natures of normal and defective DNA repair and repli-cation continued to be generated at roughly stablemutation rates. Signatures of APOBEC cytidinedeaminase DNA-editing exhibited substantial fluctu-ations in mutation rate over time with episodic burstsof mutations. The initiating factors for the burstsare unclear, although retrotransposon mobilizationmay contribute. The examined cell lines constitutea resource of live experimental models of mutationalprocesses, which potentially retain patterns ofactivity and regulation operative in primary humancancers

Published
2019

6. Effect of Targeted Therapies on Prognostic Factors, Patterns of Care, and Survival in Patients With Renal Cell Carcinoma and Brain Metastases.

Author

Sperduto, Paul W, Sperduto, Paul W, Deegan, Brian J, Li, Jing, Jethwa, Krishan R, Brown, Paul D, Lockney, Natalie, Beal, Kathryn, Rana, Nitesh G, Attia, Albert, Tseng, Chia-Lin, Sahgal, Arjun, Shanley, Ryan, Sperduto, William A, Lou, Emil, Zahra, Amir, Buatti, John M, Yu, James B, Chiang, Veronica, Molitoris, Jason K, Masucci, Laura, Roberge, David, Shi, Diana D, Shih, Helen A, Olson, Adam, Kirkpatrick, John P, Braunstein, Steve, Sneed, Penny, Mehta, Minesh P, Sperduto, Paul W, Sperduto, Paul W, Deegan, Brian J, Li, Jing, Jethwa, Krishan R, Brown, Paul D, Lockney, Natalie, Beal, Kathryn, Rana, Nitesh G, Attia, Albert, Tseng, Chia-Lin, Sahgal, Arjun, Shanley, Ryan, Sperduto, William A, Lou, Emil, Zahra, Amir, Buatti, John M, Yu, James B, Chiang, Veronica, Molitoris, Jason K, Masucci, Laura, Roberge, David, Shi, Diana D, Shih, Helen A, Olson, Adam, Kirkpatrick, John P, Braunstein, Steve, Sneed, Penny, and Mehta, Minesh P

Abstract

PurposeTo identify prognostic factors, define evolving patterns of care, and the effect of targeted therapies in a larger contemporary cohort of renal cell carcinoma (RCC) patients with new brain metastases (BM).Methods and materialsA multi-institutional retrospective institutional review board-approved database of 711 RCC patients with new BM diagnosed from January 1, 2006, to December 31, 2015, was created. Clinical parameters and treatment were correlated with median survival and time from primary diagnosis to BM. Multivariable analyses were performed.ResultsThe median survival for the prior/present cohorts was 9.6/12 months, respectively (P < .01). Four prognostic factors (Karnofsky performance status, extracranial metastases, number of BM, and hemoglobin b) were significant for survival after the diagnosis of BM. Of the 6 drug types studied, only cytokine use after BM was associated with improved survival. The use of whole-brain radiation therapy declined from 50% to 22%, and the use of stereotactic radiosurgery alone increased from 46% to 58%. Nonneurologic causes of death were twice as common as neurologic causes.ConclusionsAdditional prognostic factors refine prognostication in this larger contemporary cohort. Patterns of care have changed, and survival of RCC patients with BM has improved over time. The reasons for this improvement in survival remain unknown but may relate to more aggressive use of local brain metastasis therapy and a wider array of systemic treatment options for those patients with progressive extracranial tumor.

Published
2018

7. Estimating survival for renal cell carcinoma patients with brain metastases: an update of the Renal Graded Prognostic Assessment tool.

Author

Sperduto, Paul W, Sperduto, Paul W, Deegan, Brian J, Li, Jing, Jethwa, Krishan R, Brown, Paul D, Lockney, Natalie, Beal, Kathryn, Rana, Nitesh G, Attia, Albert, Tseng, Chia-Lin, Sahgal, Arjun, Shanley, Ryan, Sperduto, William A, Lou, Emil, Zahra, Amir, Buatti, John M, Yu, James B, Chiang, Veronica, Molitoris, Jason K, Masucci, Laura, Roberge, David, Shi, Diana D, Shih, Helen A, Olson, Adam, Kirkpatrick, John P, Braunstein, Steve, Sneed, Penny, Mehta, Minesh P, Sperduto, Paul W, Sperduto, Paul W, Deegan, Brian J, Li, Jing, Jethwa, Krishan R, Brown, Paul D, Lockney, Natalie, Beal, Kathryn, Rana, Nitesh G, Attia, Albert, Tseng, Chia-Lin, Sahgal, Arjun, Shanley, Ryan, Sperduto, William A, Lou, Emil, Zahra, Amir, Buatti, John M, Yu, James B, Chiang, Veronica, Molitoris, Jason K, Masucci, Laura, Roberge, David, Shi, Diana D, Shih, Helen A, Olson, Adam, Kirkpatrick, John P, Braunstein, Steve, Sneed, Penny, and Mehta, Minesh P

Abstract

BackgroundBrain metastases are a common complication of renal cell carcinoma (RCC). Our group previously published the Renal Graded Prognostic Assessment (GPA) tool. In our prior RCC study (n = 286, 1985-2005), we found marked heterogeneity and variation in outcomes. In our recent update in a larger, more contemporary cohort, we identified additional significant prognostic factors. The purpose of this study is to update the original Renal-GPA based on the newly identified prognostic factors.MethodsA multi-institutional retrospective institutional review board-approved database of 711 RCC patients with new brain metastases diagnosed from January 1, 2006 to December 31, 2015 was created. Clinical parameters and treatment were correlated with survival. A revised Renal GPA index was designed by weighting the most significant factors in proportion to their hazard ratios and assigning scores such that the patients with the best and worst prognoses would have a GPA of 4.0 and 0.0, respectively.ResultsThe 4 most significant factors were Karnofsky performance status, number of brain metastases, extracranial metastases, and hemoglobin. The overall median survival was 12 months. Median survival for GPA groups 0-1.0, 1.5-2.0, 2.5-3, and 3.5-4.0 (% n = 25, 27, 30 and 17) was 4, 12, 17, and 35 months, respectively.ConclusionThe updated Renal GPA is a user-friendly tool that will help clinicians and patients better understand prognosis, individualize clinical decision making and treatment selection, provide a means to compare retrospective literature, and provide more robust stratification of future clinical trials in this heterogeneous population. To simplify use of this tool in daily practice, a free online application is available at brainmetgpa.com.

Published
2018

8. Multicenter, Phase 1, Dose Escalation Study of Hypofractionated Stereotactic Radiation Therapy With Bevacizumab for Recurrent Glioblastoma and Anaplastic Astrocytoma.

Author

Clarke, Jennifer, Clarke, Jennifer, Neil, Elizabeth, Terziev, Robert, Gutin, Philip, Barani, Igor, Kaley, Thomas, Lassman, Andrew B, Chan, Timothy A, Yamada, Josh, DeAngelis, Lisa, Ballangrud, Ase, Young, Robert, Panageas, Katherine S, Beal, Kathryn, Omuro, Antonio, Clarke, Jennifer, Clarke, Jennifer, Neil, Elizabeth, Terziev, Robert, Gutin, Philip, Barani, Igor, Kaley, Thomas, Lassman, Andrew B, Chan, Timothy A, Yamada, Josh, DeAngelis, Lisa, Ballangrud, Ase, Young, Robert, Panageas, Katherine S, Beal, Kathryn, and Omuro, Antonio

Abstract

PurposeTo establish the maximum tolerated dose of a 3-fraction hypofractionated stereotactic reirradiation schedule when delivered with concomitant bevacizumab to treat recurrent high-grade gliomas.Methods and materialsPatients with recurrent high-grade glioma with Karnofsky performance status ≥60, history of standard fractionated initial radiation, tumor volume at recurrence ≤40 cm3, and absence of brainstem or corpus callosum involvement were eligible. A standard 3+3 phase 1 dose escalation trial design was utilized, with dose-limiting toxicities defined as any grade 3 to 5 toxicities possibly, probably, or definitely related to radiation. Bevacizumab was given at a dose of 10 mg/kg every 2 weeks. Hypofractionated stereotactic reirradiation was initiated after 2 bevacizumab doses, delivered in 3 fractions every other day, starting at 9 Gy per fraction.ResultsA total of 3 patients were enrolled at the 9 Gy × 3 dose level cohort, 5 in the 10 Gy × 3 cohort, and 7 in the 11 Gy × 3 cohort. One dose-limiting toxicity of grade 3 fatigue and cognitive deterioration possibly related to hypofractionated stereotactic reirradiation was observed in the 11 Gy × 3 cohort, and this dose was declared the maximum tolerated dose in combination with bevacizumab. Although no symptomatic radionecrosis was observed, substantial treatment-related effects and necrosis were observed in resected specimens. The intent-to-treat median overall survival was 13 months.ConclusionsReirradiation using a 3-fraction schedule with bevacizumab support is feasible and reasonably well tolerated. Dose-escalation was possible up to 11 Gy × 3, which achieves a near doubling in the delivered biological equivalent dose to normal brain, in comparison with our previous 6 Gy × 5 schedule. Promising overall survival warrants further investigation.

Published
2017

9. Estimating Survival in Melanoma Patients With Brain Metastases: An Update of the Graded Prognostic Assessment for Melanoma Using Molecular Markers (Melanoma-molGPA).

Author

Sperduto, Paul W, Sperduto, Paul W, Jiang, Wen, Brown, Paul D, Braunstein, Steve, Sneed, Penny, Wattson, Daniel A, Shih, Helen A, Bangdiwala, Ananta, Shanley, Ryan, Lockney, Natalie A, Beal, Kathryn, Lou, Emil, Amatruda, Thomas, Sperduto, William A, Kirkpatrick, John P, Yeh, Norman, Gaspar, Laurie E, Molitoris, Jason K, Masucci, Laura, Roberge, David, Yu, James, Chiang, Veronica, Mehta, Minesh, Sperduto, Paul W, Sperduto, Paul W, Jiang, Wen, Brown, Paul D, Braunstein, Steve, Sneed, Penny, Wattson, Daniel A, Shih, Helen A, Bangdiwala, Ananta, Shanley, Ryan, Lockney, Natalie A, Beal, Kathryn, Lou, Emil, Amatruda, Thomas, Sperduto, William A, Kirkpatrick, John P, Yeh, Norman, Gaspar, Laurie E, Molitoris, Jason K, Masucci, Laura, Roberge, David, Yu, James, Chiang, Veronica, and Mehta, Minesh

Abstract

PurposeTo update the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for a markedly heterogeneous patient population, patients with melanoma and brain metastases, using a larger, more current cohort, including molecular markers.MethodsThe original Melanoma-GPA is based on data from 483 patients whose conditions were diagnosed between 1985 and 2005. This is a multi-institutional retrospective database analysis of 823 melanoma patients with newly diagnosed brain metastases from January 1, 2006, to December 31, 2015. Multivariable analyses identified significant prognostic factors, which were weighted and included in the updated index (Melanoma-molGPA). Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios to design the updated Melanoma-molGPA in which scores of 4.0 and 0.0 are associated with the best and worst prognoses, as with all of the diagnosis-specific GPA indices. Log-rank tests were used to compare adjacent classes.ResultsThere were 5 significant prognostic factors for survival (age, Karnofsky performance status [KPS], extracranial metastases [ECM], number of brain metastases, and BRAF status), whereas only KPS and the number of brain metastases were significant in the original Melanoma-GPA. Median survival improved from 6.7 to 9.8 months between the 2 treatment eras, and the median survival times for patients with Melanoma-molGPA of 0 to 1.0, 1.5 to 2.0, 2.5 to 3.0, and 3.5 to 4.0 were 4.9, 8.3, 15.8, and 34.1 months (P<.0001 between each adjacent group).ConclusionsSurvival and our ability to estimate survival in melanoma patients with brain metastases has improved significantly. The updated Melanoma-molGPA, a user-friendly tool to estimate survival, will facilitate clinical decision making regarding whether and which treatment is appropriate and will also be useful for stratification of future clinical trials. To further simplify use, a free online/smart phone app is availabl

Published
2017

10. The Prognostic Value of BRAF, C-KIT, and NRAS Mutations in Melanoma Patients With Brain Metastases.

Author

Sperduto, Paul W, Sperduto, Paul W, Jiang, Wen, Brown, Paul D, Braunstein, Steve, Sneed, Penny, Wattson, Daniel A, Shih, Helen A, Bangdiwala, Ananta, Shanley, Ryan, Lockney, Natalie A, Beal, Kathryn, Lou, Emil, Amatruda, Thomas, Sperduto, William A, Kirkpatrick, John P, Yeh, Norman, Gaspar, Laurie E, Molitoris, Jason K, Masucci, Laura, Roberge, David, Yu, James, Chiang, Veronica, Mehta, Minesh, Sperduto, Paul W, Sperduto, Paul W, Jiang, Wen, Brown, Paul D, Braunstein, Steve, Sneed, Penny, Wattson, Daniel A, Shih, Helen A, Bangdiwala, Ananta, Shanley, Ryan, Lockney, Natalie A, Beal, Kathryn, Lou, Emil, Amatruda, Thomas, Sperduto, William A, Kirkpatrick, John P, Yeh, Norman, Gaspar, Laurie E, Molitoris, Jason K, Masucci, Laura, Roberge, David, Yu, James, Chiang, Veronica, and Mehta, Minesh

Abstract

PurposeBrain metastases are a common problem in patients with melanoma, but little is known about the effect of gene mutations on survival in these patients.Methods and materialsWe created a retrospective multi-institutional database of 823 patients with melanoma and brain metastases diagnosed between 2006 and 2015. Clinical parameters, gene mutation status (BRAF, C-KIT, NRAS), and treatment were correlated with survival. Treatment patterns and outcomes were compared with a prior era (1985-2005).ResultsBRAF status was known in 584 of 823 patients (71%). BRAF, NRAS, and C-KIT mutations were present in 51%, 22%, and 11% of tested patients, respectively. The median time from primary diagnosis to brain metastasis was 32 months, and overall median survival (MS) from the time of initial treatment of brain metastases was 10 months. MS for BRAF-positive and BRAF-negative patients was 13 months and 9 months, respectively (P=.02). There was no significant difference in MS in patients with or without NRAS or C-KIT mutations. The time from primary diagnosis to brain metastasis did not vary by mutation and was not associated with survival after the diagnosis of brain metastases. MS for the 1985 to 2005 and 2006 to 2015 cohorts was 6.7 months and 10.0 months, respectively (P<.01). Reflecting treatment-trend changes, use of whole-brain radiation therapy decreased from 48% to 26% during this period. Among BRAF-positive patients, 71% received targeted BRAF and/or MEK inhibitors and 57% received some combination of targeted therapy, chemotherapy, and/or immunotherapy.ConclusionsFor melanoma patients with brain metastases, BRAF-positive patients survive longer than BRAF-negative patients and overall survival has improved from 1985-2005 to 2006-2015.

Published
2017

11. The Effect of Gene Alterations and Tyrosine Kinase Inhibition on Survival and Cause of Death in Patients With Adenocarcinoma of the Lung and Brain Metastases.

Author

Sperduto, Paul W, Sperduto, Paul W, Yang, T Jonathan, Beal, Kathryn, Pan, Hubert, Brown, Paul D, Bangdiwala, Ananta, Shanley, Ryan, Yeh, Norman, Gaspar, Laurie E, Braunstein, Steve, Sneed, Penny, Boyle, John, Kirkpatrick, John P, Mak, Kimberley S, Shih, Helen A, Engelman, Alex, Roberge, David, Arvold, Nils D, Alexander, Brian, Awad, Mark M, Contessa, Joseph, Chiang, Veronica, Hardie, John, Ma, Daniel, Lou, Emil, Sperduto, William, Mehta, Minesh P, Sperduto, Paul W, Sperduto, Paul W, Yang, T Jonathan, Beal, Kathryn, Pan, Hubert, Brown, Paul D, Bangdiwala, Ananta, Shanley, Ryan, Yeh, Norman, Gaspar, Laurie E, Braunstein, Steve, Sneed, Penny, Boyle, John, Kirkpatrick, John P, Mak, Kimberley S, Shih, Helen A, Engelman, Alex, Roberge, David, Arvold, Nils D, Alexander, Brian, Awad, Mark M, Contessa, Joseph, Chiang, Veronica, Hardie, John, Ma, Daniel, Lou, Emil, Sperduto, William, and Mehta, Minesh P

Abstract

PurposeLung cancer remains the most common cause of both cancer mortality and brain metastases (BM). The purpose of this study was to assess the effect of gene alterations and tyrosine kinase inhibition (TKI) on median survival (MS) and cause of death (CoD) in patients with BM from lung adenocarcinoma (L-adeno).MethodsA multi-institutional retrospective database of patients with L-adeno and newly diagnosed BM between 2006 and 2014 was created. Demographics, gene alterations, treatment, MS, and CoD were analyzed. The treatment patterns and outcomes were compared with those in prior trials.ResultsOf 1521 L-adeno patients, 816 (54%) had known alteration status. The gene alteration rates were 29%, 10%, and 26% for EGFR, ALK, and KRAS, respectively. The time from primary diagnosis to BM for EGFR-/+ was 10/15 months (P=.02) and for ALK-/+ was 10/20 months (P<.01), respectively. The MS for the group overall (n=1521) was 15 months. The MS from first treatment for BM for EGFR and ALK-, EGFR+, ALK+ were 14, 23 (P<.01), and 45 (P<.0001) months, respectively. The MS after BM for EGFR+ patients who did/did not receive TKI before BM was 17/30 months (P<.01), respectively, but the risk of death was not statistically different between TKI-naïve patients who did/did not receive TKI after the diagnosis of BM (EGFR/ALK hazard ratios: 1.06 [P=.84]/1.60 [P=.45], respectively). The CoD was nonneurologic in 82% of patients with known CoD.ConclusionEGFR and ALK gene alterations are associated with delayed onset of BM and longer MS relative to patients without these alterations. The CoD was overwhelmingly nonneurologic in patients with known CoD.

Published
2016

12. The pig X and Y Chromosomes: structure, sequence, and evolution.

Author

Skinner, Benjamin M, Sargent, Carole A, Churcher, Carol, Hunt, Toby, Herrero, Javier, Loveland, Jane E, Dunn, Matt, Louzada, Sandra, Fu, Beiyuan, Chow, William, Gilbert, James, Austin-Guest, Siobhan, Beal, Kathryn, Carvalho-Silva, Denise, Cheng, William, Gordon, Daria, Grafham, Darren, Hardy, Matt, Harley, Jo, Hauser, Heidi, Howden, Philip, Howe, Kerstin, Lachani, Kim, Ellis, Peter J.I., Kelly, Daniel, Kerry, Giselle, Kerwin, James, Ng, Bee Ling, Threadgold, Glen, Wileman, Thomas, Wood, Jonathan M D, Yang, Fengtang, Harrow, Jen, Affara, Nabeel A, Tyler-Smith, Chris, Skinner, Benjamin M, Sargent, Carole A, Churcher, Carol, Hunt, Toby, Herrero, Javier, Loveland, Jane E, Dunn, Matt, Louzada, Sandra, Fu, Beiyuan, Chow, William, Gilbert, James, Austin-Guest, Siobhan, Beal, Kathryn, Carvalho-Silva, Denise, Cheng, William, Gordon, Daria, Grafham, Darren, Hardy, Matt, Harley, Jo, Hauser, Heidi, Howden, Philip, Howe, Kerstin, Lachani, Kim, Ellis, Peter J.I., Kelly, Daniel, Kerry, Giselle, Kerwin, James, Ng, Bee Ling, Threadgold, Glen, Wileman, Thomas, Wood, Jonathan M D, Yang, Fengtang, Harrow, Jen, Affara, Nabeel A, and Tyler-Smith, Chris

Abstract

We have generated an improved assembly and gene annotation of the pig X Chromosome, and a first draft assembly of the pig Y Chromosome, by sequencing BAC and fosmid clones from Duroc animals and incorporating information from optical mapping and fiber-FISH. The X Chromosome carries 1033 annotated genes, 690 of which are protein coding. Gene order closely matches that found in primates (including humans) and carnivores (including cats and dogs), which is inferred to be ancestral. Nevertheless, several protein-coding genes present on the human X Chromosome were absent from the pig, and 38 pig-specific X-chromosomal genes were annotated, 22 of which were olfactory receptors. The pig Y-specific Chromosome sequence generated here comprises 30 megabases (Mb). A 15-Mb subset of this sequence was assembled, revealing two clusters of male-specific low copy number genes, separated by an ampliconic region including the HSFY gene family, which together make up most of the short arm. Both clusters contain palindromes with high sequence identity, presumably maintained by gene conversion. Many of the ancestral X-related genes previously reported in at least one mammalian Y Chromosome are represented either as active genes or partial sequences. This sequencing project has allowed us to identify genes--both single copy and amplified--on the pig Y Chromosome, to compare the pig X and Y Chromosomes for homologous sequences, and thereby to reveal mechanisms underlying pig X and Y Chromosome evolution.

Published
2015

13. Alignathon: a competitive assessment of whole-genome alignment methods.

Author

Earl, Dent, Earl, Dent, Nguyen, Ngan, Hickey, Glenn, Harris, Robert S, Fitzgerald, Stephen, Beal, Kathryn, Seledtsov, Igor, Molodtsov, Vladimir, Raney, Brian J, Clawson, Hiram, Kim, Jaebum, Kemena, Carsten, Chang, Jia-Ming, Erb, Ionas, Poliakov, Alexander, Hou, Minmei, Herrero, Javier, Kent, William James, Solovyev, Victor, Darling, Aaron E, Ma, Jian, Notredame, Cedric, Brudno, Michael, Dubchak, Inna, Haussler, David, Paten, Benedict, Earl, Dent, Earl, Dent, Nguyen, Ngan, Hickey, Glenn, Harris, Robert S, Fitzgerald, Stephen, Beal, Kathryn, Seledtsov, Igor, Molodtsov, Vladimir, Raney, Brian J, Clawson, Hiram, Kim, Jaebum, Kemena, Carsten, Chang, Jia-Ming, Erb, Ionas, Poliakov, Alexander, Hou, Minmei, Herrero, Javier, Kent, William James, Solovyev, Victor, Darling, Aaron E, Ma, Jian, Notredame, Cedric, Brudno, Michael, Dubchak, Inna, Haussler, David, and Paten, Benedict

Abstract

Multiple sequence alignments (MSAs) are a prerequisite for a wide variety of evolutionary analyses. Published assessments and benchmark data sets for protein and, to a lesser extent, global nucleotide MSAs are available, but less effort has been made to establish benchmarks in the more general problem of whole-genome alignment (WGA). Using the same model as the successful Assemblathon competitions, we organized a competitive evaluation in which teams submitted their alignments and then assessments were performed collectively after all the submissions were received. Three data sets were used: Two were simulated and based on primate and mammalian phylogenies, and one was comprised of 20 real fly genomes. In total, 35 submissions were assessed, submitted by 10 teams using 12 different alignment pipelines. We found agreement between independent simulation-based and statistical assessments, indicating that there are substantial accuracy differences between contemporary alignment tools. We saw considerable differences in the alignment quality of differently annotated regions and found that few tools aligned the duplications analyzed. We found that many tools worked well at shorter evolutionary distances, but fewer performed competitively at longer distances. We provide all data sets, submissions, and assessment programs for further study and provide, as a resource for future benchmarking, a convenient repository of code and data for reproducing the simulation assessments.

Published
2014

14. The draft genomes of soft-shell turtle and green sea turtle yield insights into the development and evolution of the turtle-specific body plan

Author

Wang, Zhuo, Pascual-Anaya, Juan, Zadissa, Amonida, Li, Wenqi, Niimura, Yoshihito, Huang, Zhiyong, Li, Chunyi, White, Simon, Xiong, Zhiqiang, Fang, Dongming, Wang, Bo, Ming, Yao, Chen, Yan, Zheng, Yuan, Kuraku, Shigehiro, Pignatelli, Miguel, Herrero, Javier, Beal, Kathryn, Nozawa, Masafumi, Li, Qiye, Wang, Juan, Zhang, Hongyan, Yu, Lili, Shigenobu, Shuji, Wang, Junyi, Liu, Jiannan, Flicek, Paul, Searle, Steve, Wang, Jun, Kuratani, Shigeru, Yin, Ye, Aken, Bronwen, Zhang, Guojie, Irie, Naoki, Wang, Zhuo, Pascual-Anaya, Juan, Zadissa, Amonida, Li, Wenqi, Niimura, Yoshihito, Huang, Zhiyong, Li, Chunyi, White, Simon, Xiong, Zhiqiang, Fang, Dongming, Wang, Bo, Ming, Yao, Chen, Yan, Zheng, Yuan, Kuraku, Shigehiro, Pignatelli, Miguel, Herrero, Javier, Beal, Kathryn, Nozawa, Masafumi, Li, Qiye, Wang, Juan, Zhang, Hongyan, Yu, Lili, Shigenobu, Shuji, Wang, Junyi, Liu, Jiannan, Flicek, Paul, Searle, Steve, Wang, Jun, Kuratani, Shigeru, Yin, Ye, Aken, Bronwen, Zhang, Guojie, and Irie, Naoki

Published
2013

15. The draft genomes of soft-shell turtle and green sea turtle yield insights into the development and evolution of the turtle-specific body plan

Author

Wang, Zhuo, Pascual-Anaya, Juan, Zadissa, Amonida, Li, Wenqi, Niimura, Yoshihito, Huang, Zhiyong, Li, Chunyi, White, Simon, Xiong, Zhiqiang, Fang, Dongming, Wang, Bo, Ming, Yao, Chen, Yan, Zheng, Yuan, Kuraku, Shigehiro, Pignatelli, Miguel, Herrero, Javier, Beal, Kathryn, Nozawa, Masafumi, Li, Qiye, Wang, Juan, Zhang, Hongyan, Yu, Lili, Shigenobu, Shuji, Wang, Junyi, Liu, Jiannan, Flicek, Paul, Searle, Steve, Wang, Jun, Kuratani, Shigeru, Yin, Ye, Aken, Bronwen, Zhang, Guojie, Irie, Naoki, Wang, Zhuo, Pascual-Anaya, Juan, Zadissa, Amonida, Li, Wenqi, Niimura, Yoshihito, Huang, Zhiyong, Li, Chunyi, White, Simon, Xiong, Zhiqiang, Fang, Dongming, Wang, Bo, Ming, Yao, Chen, Yan, Zheng, Yuan, Kuraku, Shigehiro, Pignatelli, Miguel, Herrero, Javier, Beal, Kathryn, Nozawa, Masafumi, Li, Qiye, Wang, Juan, Zhang, Hongyan, Yu, Lili, Shigenobu, Shuji, Wang, Junyi, Liu, Jiannan, Flicek, Paul, Searle, Steve, Wang, Jun, Kuratani, Shigeru, Yin, Ye, Aken, Bronwen, Zhang, Guojie, and Irie, Naoki

Published
2013

16. The draft genomes of soft-shell turtle and green sea turtle yield insights into the development and evolution of the turtle-specific body plan

Author

Wang, Zhuo, Pascual-Anaya, Juan, Zadissa, Amonida, Li, Wenqi, Niimura, Yoshihito, Huang, Zhiyong, Li, Chunyi, White, Simon, Xiong, Zhiqiang, Fang, Dongming, Wang, Bo, Ming, Yao, Chen, Yan, Zheng, Yuan, Kuraku, Shigehiro, Pignatelli, Miguel, Herrero, Javier, Beal, Kathryn, Nozawa, Masafumi, Li, Qiye, Wang, Juan, Zhang, Hongyan, Yu, Lili, Shigenobu, Shuji, Wang, Junyi, Liu, Jiannan, Flicek, Paul, Searle, Steve, Wang, Jun, Kuratani, Shigeru, Yin, Ye, Aken, Bronwen, Zhang, Guojie, Irie, Naoki, Wang, Zhuo, Pascual-Anaya, Juan, Zadissa, Amonida, Li, Wenqi, Niimura, Yoshihito, Huang, Zhiyong, Li, Chunyi, White, Simon, Xiong, Zhiqiang, Fang, Dongming, Wang, Bo, Ming, Yao, Chen, Yan, Zheng, Yuan, Kuraku, Shigehiro, Pignatelli, Miguel, Herrero, Javier, Beal, Kathryn, Nozawa, Masafumi, Li, Qiye, Wang, Juan, Zhang, Hongyan, Yu, Lili, Shigenobu, Shuji, Wang, Junyi, Liu, Jiannan, Flicek, Paul, Searle, Steve, Wang, Jun, Kuratani, Shigeru, Yin, Ye, Aken, Bronwen, Zhang, Guojie, and Irie, Naoki

Published
2013

17. The draft genomes of soft-shell turtle and green sea turtle yield insights into the development and evolution of the turtle-specific body plan

Author

Wang, Zhuo, Pascual-Anaya, Juan, Zadissa, Amonida, Li, Wenqi, Niimura, Yoshihito, Huang, Zhiyong, Li, Chunyi, White, Simon, Xiong, Zhiqiang, Fang, Dongming, Wang, Bo, Ming, Yao, Chen, Yan, Zheng, Yuan, Kuraku, Shigehiro, Pignatelli, Miguel, Herrero, Javier, Beal, Kathryn, Nozawa, Masafumi, Li, Qiye, Wang, Juan, Zhang, Hongyan, Yu, Lili, Shigenobu, Shuji, Wang, Junyi, Liu, Jiannan, Flicek, Paul, Searle, Steve, Wang, Jun, Kuratani, Shigeru, Yin, Ye, Aken, Bronwen, Zhang, Guojie, Irie, Naoki, Wang, Zhuo, Pascual-Anaya, Juan, Zadissa, Amonida, Li, Wenqi, Niimura, Yoshihito, Huang, Zhiyong, Li, Chunyi, White, Simon, Xiong, Zhiqiang, Fang, Dongming, Wang, Bo, Ming, Yao, Chen, Yan, Zheng, Yuan, Kuraku, Shigehiro, Pignatelli, Miguel, Herrero, Javier, Beal, Kathryn, Nozawa, Masafumi, Li, Qiye, Wang, Juan, Zhang, Hongyan, Yu, Lili, Shigenobu, Shuji, Wang, Junyi, Liu, Jiannan, Flicek, Paul, Searle, Steve, Wang, Jun, Kuratani, Shigeru, Yin, Ye, Aken, Bronwen, Zhang, Guojie, and Irie, Naoki

Published
2013

18. The draft genomes of soft-shell turtle and green sea turtle yield insights into the development and evolution of the turtle-specific body plan

Author

Wang, Zhuo, Pascual-Anaya, Juan, Zadissa, Amonida, Li, Wenqi, Niimura, Yoshihito, Huang, Zhiyong, Li, Chunyi, White, Simon, Xiong, Zhiqiang, Fang, Dongming, Wang, Bo, Ming, Yao, Chen, Yan, Zheng, Yuan, Kuraku, Shigehiro, Pignatelli, Miguel, Herrero, Javier, Beal, Kathryn, Nozawa, Masafumi, Li, Qiye, Wang, Juan, Zhang, Hongyan, Yu, Lili, Shigenobu, Shuji, Wang, Junyi, Liu, Jiannan, Flicek, Paul, Searle, Steve, Wang, Jun, Kuratani, Shigeru, Yin, Ye, Aken, Bronwen, Zhang, Guojie, Irie, Naoki, Wang, Zhuo, Pascual-Anaya, Juan, Zadissa, Amonida, Li, Wenqi, Niimura, Yoshihito, Huang, Zhiyong, Li, Chunyi, White, Simon, Xiong, Zhiqiang, Fang, Dongming, Wang, Bo, Ming, Yao, Chen, Yan, Zheng, Yuan, Kuraku, Shigehiro, Pignatelli, Miguel, Herrero, Javier, Beal, Kathryn, Nozawa, Masafumi, Li, Qiye, Wang, Juan, Zhang, Hongyan, Yu, Lili, Shigenobu, Shuji, Wang, Junyi, Liu, Jiannan, Flicek, Paul, Searle, Steve, Wang, Jun, Kuratani, Shigeru, Yin, Ye, Aken, Bronwen, Zhang, Guojie, and Irie, Naoki

Published
2013

19. A high-resolution map of human evolutionary constraint using 29 mammals

Author

Lindblad-Toh, Kerstin, Garber, Manuel, Zuk, Or, Lin, Michael F., Parker, Brian J., Washietl, Stefan, Kheradpour, Pouya, Ernst, Jason, Jordan, Gregory, Mauceli, Evan, Ward, Lucas D., Lowe, Craig B., Holloway, Alisha K., Clamp, Michele, Gnerre, Sante, Alfoeldi, Jessica, Beal, Kathryn, Chang, Jean, Clawson, Hiram, Cuff, James, Di Palma, Federica, Fitzgerald, Stephen, Flicek, Paul, Guttman, Mitchell, Hubisz, Melissa J., Jaffe, David B., Jungreis, Irwin, Kent, W. James, Kostka, Dennis, Lara, Marcia, Martins, Andre L., Massingham, Tim, Moltke, Ida, Raney, Brian J., Rasmussen, Matthew D., Robinson, Jim, Stark, Alexander, Vilella, Albert J., Wen, Jiayu, Xie, Xiaohui, Zody, Michael C., Worley, Kim C., Kovar, Christie L., Muzny, Donna M., Gibbs, Richard A., Warren, Wesley C., Mardis, Elaine R., Weinstock, George M., Wilson, Richard K., Birney, Ewan, Margulies, Elliott H., Herrero, Javier, Green, Eric D., Haussler, David, Siepel, Adam, Goldman, Nick, Pollard, Katherine S., Pedersen, Jakob S., Lander, Eric S., Kellis, Manolis, Lindblad-Toh, Kerstin, Garber, Manuel, Zuk, Or, Lin, Michael F., Parker, Brian J., Washietl, Stefan, Kheradpour, Pouya, Ernst, Jason, Jordan, Gregory, Mauceli, Evan, Ward, Lucas D., Lowe, Craig B., Holloway, Alisha K., Clamp, Michele, Gnerre, Sante, Alfoeldi, Jessica, Beal, Kathryn, Chang, Jean, Clawson, Hiram, Cuff, James, Di Palma, Federica, Fitzgerald, Stephen, Flicek, Paul, Guttman, Mitchell, Hubisz, Melissa J., Jaffe, David B., Jungreis, Irwin, Kent, W. James, Kostka, Dennis, Lara, Marcia, Martins, Andre L., Massingham, Tim, Moltke, Ida, Raney, Brian J., Rasmussen, Matthew D., Robinson, Jim, Stark, Alexander, Vilella, Albert J., Wen, Jiayu, Xie, Xiaohui, Zody, Michael C., Worley, Kim C., Kovar, Christie L., Muzny, Donna M., Gibbs, Richard A., Warren, Wesley C., Mardis, Elaine R., Weinstock, George M., Wilson, Richard K., Birney, Ewan, Margulies, Elliott H., Herrero, Javier, Green, Eric D., Haussler, David, Siepel, Adam, Goldman, Nick, Pollard, Katherine S., Pedersen, Jakob S., Lander, Eric S., and Kellis, Manolis

Abstract

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering similar to 4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for similar to 60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate-and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.

Published
2011
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20. A high-resolution map of human evolutionary constraint using 29 mammals.

Author

Lindblad-Toh, Kerstin, Lindblad-Toh, Kerstin, Garber, Manuel, Zuk, Or, Lin, Michael F, Parker, Brian J, Washietl, Stefan, Kheradpour, Pouya, Ernst, Jason, Jordan, Gregory, Mauceli, Evan, Ward, Lucas D, Lowe, Craig B, Holloway, Alisha K, Clamp, Michele, Gnerre, Sante, Alföldi, Jessica, Beal, Kathryn, Chang, Jean, Clawson, Hiram, Cuff, James, Di Palma, Federica, Fitzgerald, Stephen, Flicek, Paul, Guttman, Mitchell, Hubisz, Melissa J, Jaffe, David B, Jungreis, Irwin, Kent, W James, Kostka, Dennis, Lara, Marcia, Martins, Andre L, Massingham, Tim, Moltke, Ida, Raney, Brian J, Rasmussen, Matthew D, Robinson, Jim, Stark, Alexander, Vilella, Albert J, Wen, Jiayu, Xie, Xiaohui, Zody, Michael C, Broad Institute Sequencing Platform and Whole Genome Assembly Team, Baldwin, Jen, Bloom, Toby, Chin, Chee Whye, Heiman, Dave, Nicol, Robert, Nusbaum, Chad, Young, Sarah, Wilkinson, Jane, Worley, Kim C, Kovar, Christie L, Muzny, Donna M, Gibbs, Richard A, Baylor College of Medicine Human Genome Sequencing Center Sequencing Team, Cree, Andrew, Dihn, Huyen H, Fowler, Gerald, Jhangiani, Shalili, Joshi, Vandita, Lee, Sandra, Lewis, Lora R, Nazareth, Lynne V, Okwuonu, Geoffrey, Santibanez, Jireh, Warren, Wesley C, Mardis, Elaine R, Weinstock, George M, Wilson, Richard K, Genome Institute at Washington University, Delehaunty, Kim, Dooling, David, Fronik, Catrina, Fulton, Lucinda, Fulton, Bob, Graves, Tina, Minx, Patrick, Sodergren, Erica, Birney, Ewan, Margulies, Elliott H, Herrero, Javier, Green, Eric D, Haussler, David, Siepel, Adam, Goldman, Nick, Pollard, Katherine S, Pedersen, Jakob S, Lander, Eric S, Kellis, Manolis, Lindblad-Toh, Kerstin, Lindblad-Toh, Kerstin, Garber, Manuel, Zuk, Or, Lin, Michael F, Parker, Brian J, Washietl, Stefan, Kheradpour, Pouya, Ernst, Jason, Jordan, Gregory, Mauceli, Evan, Ward, Lucas D, Lowe, Craig B, Holloway, Alisha K, Clamp, Michele, Gnerre, Sante, Alföldi, Jessica, Beal, Kathryn, Chang, Jean, Clawson, Hiram, Cuff, James, Di Palma, Federica, Fitzgerald, Stephen, Flicek, Paul, Guttman, Mitchell, Hubisz, Melissa J, Jaffe, David B, Jungreis, Irwin, Kent, W James, Kostka, Dennis, Lara, Marcia, Martins, Andre L, Massingham, Tim, Moltke, Ida, Raney, Brian J, Rasmussen, Matthew D, Robinson, Jim, Stark, Alexander, Vilella, Albert J, Wen, Jiayu, Xie, Xiaohui, Zody, Michael C, Broad Institute Sequencing Platform and Whole Genome Assembly Team, Baldwin, Jen, Bloom, Toby, Chin, Chee Whye, Heiman, Dave, Nicol, Robert, Nusbaum, Chad, Young, Sarah, Wilkinson, Jane, Worley, Kim C, Kovar, Christie L, Muzny, Donna M, Gibbs, Richard A, Baylor College of Medicine Human Genome Sequencing Center Sequencing Team, Cree, Andrew, Dihn, Huyen H, Fowler, Gerald, Jhangiani, Shalili, Joshi, Vandita, Lee, Sandra, Lewis, Lora R, Nazareth, Lynne V, Okwuonu, Geoffrey, Santibanez, Jireh, Warren, Wesley C, Mardis, Elaine R, Weinstock, George M, Wilson, Richard K, Genome Institute at Washington University, Delehaunty, Kim, Dooling, David, Fronik, Catrina, Fulton, Lucinda, Fulton, Bob, Graves, Tina, Minx, Patrick, Sodergren, Erica, Birney, Ewan, Margulies, Elliott H, Herrero, Javier, Green, Eric D, Haussler, David, Siepel, Adam, Goldman, Nick, Pollard, Katherine S, Pedersen, Jakob S, Lander, Eric S, and Kellis, Manolis

Abstract

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.

Published
2011

21. Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development

Author

Renfree, Marilyn B., Papenfuss, Anthony T., Deakin, Janine E., Lindsay, James, Heider, Thomas, Belov, Katherine, Rens, Willem, Waters, Paul D., Pharo, Elizabeth A., Shaw, Geoff, Wong, Emily S. W., Gibbs, Richard A, Cooper, Desmond W, Speed, Terence P, Fujiyama, Asao, Graves, Jennifer A. M., O'Neill, Rachel J., Pask, Andrew J., Forrest, Susan M., Worley, Kim C., Lefèvre, Christophe M., Nicholas, Kevin R., Kuroki, Yoko, Wakefield, Matthew J., Zenger, Kyall R., Wang, Chenwei, Ferguson-Smith, Malcolm, Nicholas, Frank W., Hickford, Danielle, Yu, Hongshi, Short, Kirsty R., Siddle, Hannah V., Frankenberg, Stephen R., Chew, Keng, Menzies, Brandon R., Stringer, Jessica M., Suzuki, Shunsuke, Hore, Timothy A., Delbridge, Margaret L., Mohammadi, Amir, Schneider, Nanette Y., Hu, Yanqiu, O'Hara, William, Al Nadaf, Shafagh, Wu, Chen, Feng, Zhi-Ping, Cocks, Benjamin G., Wang, Jianghui, Flicek, Paul, Searle, Stephen M. J., Fairley, Susan, Beal, Kathryn, Herrero, Javier, Carone, Dawn M., Suzuki, Yutaka, Sugano, Sumio, Toyoda, Atsushi, Sakaki, Yoshiyuki, Kondo, Shinji, Nishida, Yuichiro, Tatsumoto, Shoji, Mandiou, Ion, Hsu, Arthur, McColl, Kaighin A., Lansdell, Benjamin, Weinstock, George, Kuczek, Elizabeth, McGrath, Annette, Wilson, Peter, Men, Artem, Hazar-Rethinam, Mehlika, Hall, Allison, Davis, John, Wood, David, Williams, Sarah, Sundaravadanam, Yogi, Muzny, Donna M, Jhangiani, Shalini N, Lewis, Lora R, Morgan, Margaret B, Okwuonu, Geoffrey O, Ruiz, San, Santibanez, Jireh, Nazareth, Lynne, Cree, Andrew, Fowler, Gerald, Kovar, Christie L, Dinh, Huyen H, Joshi, Vandita, Jing, Chyn, Lara, Fremiet, Thornton, Rebecca, Chen, Lei, Deng, Jixin, Liu, Yue, Shen, Joshua Y, Song, Xing-Zhi, Edson, Janette, Troon, Carmen, Thomas, Daniel, Stephens, Amber, Yapa, Lankesha, Levchenko, Tanya, Renfree, Marilyn B., Papenfuss, Anthony T., Deakin, Janine E., Lindsay, James, Heider, Thomas, Belov, Katherine, Rens, Willem, Waters, Paul D., Pharo, Elizabeth A., Shaw, Geoff, Wong, Emily S. W., Gibbs, Richard A, Cooper, Desmond W, Speed, Terence P, Fujiyama, Asao, Graves, Jennifer A. M., O'Neill, Rachel J., Pask, Andrew J., Forrest, Susan M., Worley, Kim C., Lefèvre, Christophe M., Nicholas, Kevin R., Kuroki, Yoko, Wakefield, Matthew J., Zenger, Kyall R., Wang, Chenwei, Ferguson-Smith, Malcolm, Nicholas, Frank W., Hickford, Danielle, Yu, Hongshi, Short, Kirsty R., Siddle, Hannah V., Frankenberg, Stephen R., Chew, Keng, Menzies, Brandon R., Stringer, Jessica M., Suzuki, Shunsuke, Hore, Timothy A., Delbridge, Margaret L., Mohammadi, Amir, Schneider, Nanette Y., Hu, Yanqiu, O'Hara, William, Al Nadaf, Shafagh, Wu, Chen, Feng, Zhi-Ping, Cocks, Benjamin G., Wang, Jianghui, Flicek, Paul, Searle, Stephen M. J., Fairley, Susan, Beal, Kathryn, Herrero, Javier, Carone, Dawn M., Suzuki, Yutaka, Sugano, Sumio, Toyoda, Atsushi, Sakaki, Yoshiyuki, Kondo, Shinji, Nishida, Yuichiro, Tatsumoto, Shoji, Mandiou, Ion, Hsu, Arthur, McColl, Kaighin A., Lansdell, Benjamin, Weinstock, George, Kuczek, Elizabeth, McGrath, Annette, Wilson, Peter, Men, Artem, Hazar-Rethinam, Mehlika, Hall, Allison, Davis, John, Wood, David, Williams, Sarah, Sundaravadanam, Yogi, Muzny, Donna M, Jhangiani, Shalini N, Lewis, Lora R, Morgan, Margaret B, Okwuonu, Geoffrey O, Ruiz, San, Santibanez, Jireh, Nazareth, Lynne, Cree, Andrew, Fowler, Gerald, Kovar, Christie L, Dinh, Huyen H, Joshi, Vandita, Jing, Chyn, Lara, Fremiet, Thornton, Rebecca, Chen, Lei, Deng, Jixin, Liu, Yue, Shen, Joshua Y, Song, Xing-Zhi, Edson, Janette, Troon, Carmen, Thomas, Daniel, Stephens, Amber, Yapa, Lankesha, and Levchenko, Tanya

Abstract

BACKGROUND We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution.

Published
2011

22. A high-resolution map of human evolutionary constraint using 29 mammals.

Author

Lindblad-Toh, Kerstin, Lindblad-Toh, Kerstin, Garber, Manuel, Zuk, Or, Lin, Michael F, Parker, Brian J, Washietl, Stefan, Kheradpour, Pouya, Ernst, Jason, Jordan, Gregory, Mauceli, Evan, Ward, Lucas D, Lowe, Craig B, Holloway, Alisha K, Clamp, Michele, Gnerre, Sante, Alföldi, Jessica, Beal, Kathryn, Chang, Jean, Clawson, Hiram, Cuff, James, Di Palma, Federica, Fitzgerald, Stephen, Flicek, Paul, Guttman, Mitchell, Hubisz, Melissa J, Jaffe, David B, Jungreis, Irwin, Kent, W James, Kostka, Dennis, Lara, Marcia, Martins, Andre L, Massingham, Tim, Moltke, Ida, Raney, Brian J, Rasmussen, Matthew D, Robinson, Jim, Stark, Alexander, Vilella, Albert J, Wen, Jiayu, Xie, Xiaohui, Zody, Michael C, Broad Institute Sequencing Platform and Whole Genome Assembly Team, Baldwin, Jen, Bloom, Toby, Chin, Chee Whye, Heiman, Dave, Nicol, Robert, Nusbaum, Chad, Young, Sarah, Wilkinson, Jane, Worley, Kim C, Kovar, Christie L, Muzny, Donna M, Gibbs, Richard A, Baylor College of Medicine Human Genome Sequencing Center Sequencing Team, Cree, Andrew, Dihn, Huyen H, Fowler, Gerald, Jhangiani, Shalili, Joshi, Vandita, Lee, Sandra, Lewis, Lora R, Nazareth, Lynne V, Okwuonu, Geoffrey, Santibanez, Jireh, Warren, Wesley C, Mardis, Elaine R, Weinstock, George M, Wilson, Richard K, Genome Institute at Washington University, Delehaunty, Kim, Dooling, David, Fronik, Catrina, Fulton, Lucinda, Fulton, Bob, Graves, Tina, Minx, Patrick, Sodergren, Erica, Birney, Ewan, Margulies, Elliott H, Herrero, Javier, Green, Eric D, Haussler, David, Siepel, Adam, Goldman, Nick, Pollard, Katherine S, Pedersen, Jakob S, Lander, Eric S, Kellis, Manolis, Lindblad-Toh, Kerstin, Lindblad-Toh, Kerstin, Garber, Manuel, Zuk, Or, Lin, Michael F, Parker, Brian J, Washietl, Stefan, Kheradpour, Pouya, Ernst, Jason, Jordan, Gregory, Mauceli, Evan, Ward, Lucas D, Lowe, Craig B, Holloway, Alisha K, Clamp, Michele, Gnerre, Sante, Alföldi, Jessica, Beal, Kathryn, Chang, Jean, Clawson, Hiram, Cuff, James, Di Palma, Federica, Fitzgerald, Stephen, Flicek, Paul, Guttman, Mitchell, Hubisz, Melissa J, Jaffe, David B, Jungreis, Irwin, Kent, W James, Kostka, Dennis, Lara, Marcia, Martins, Andre L, Massingham, Tim, Moltke, Ida, Raney, Brian J, Rasmussen, Matthew D, Robinson, Jim, Stark, Alexander, Vilella, Albert J, Wen, Jiayu, Xie, Xiaohui, Zody, Michael C, Broad Institute Sequencing Platform and Whole Genome Assembly Team, Baldwin, Jen, Bloom, Toby, Chin, Chee Whye, Heiman, Dave, Nicol, Robert, Nusbaum, Chad, Young, Sarah, Wilkinson, Jane, Worley, Kim C, Kovar, Christie L, Muzny, Donna M, Gibbs, Richard A, Baylor College of Medicine Human Genome Sequencing Center Sequencing Team, Cree, Andrew, Dihn, Huyen H, Fowler, Gerald, Jhangiani, Shalili, Joshi, Vandita, Lee, Sandra, Lewis, Lora R, Nazareth, Lynne V, Okwuonu, Geoffrey, Santibanez, Jireh, Warren, Wesley C, Mardis, Elaine R, Weinstock, George M, Wilson, Richard K, Genome Institute at Washington University, Delehaunty, Kim, Dooling, David, Fronik, Catrina, Fulton, Lucinda, Fulton, Bob, Graves, Tina, Minx, Patrick, Sodergren, Erica, Birney, Ewan, Margulies, Elliott H, Herrero, Javier, Green, Eric D, Haussler, David, Siepel, Adam, Goldman, Nick, Pollard, Katherine S, Pedersen, Jakob S, Lander, Eric S, and Kellis, Manolis

Abstract

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.

Published
2011

23. Multi-Platform Next-Generation Sequencing of the Domestic Turkey (Meleagris gallopavo): Genome Assembly and Analysis

Author

Dalloul, Rami A., Long, Julie A., Zimin, Aleksey V., Aslam, Luqman, Beal, Kathryn, Blomberg, Le Ann, Bouffard, Pascal, Burt, David W., Crasta, Oswald, Crooijmans, Richard P. M. A., Cooper, Kristal, Coulombe, Roger A., De, Supriyo, Delany, Mary E., Dodgson, Jerry B., Dong, Jennifer J., Evans, Clive, Frederickson, Karin M., Flicek, Paul, Florea, Liliana, Folkerts, Otto, Groenen, Martien A. M., Harkins, Tim T., Herrero, Javier, Hoffmann, Steve, Megens, Hendrik-Jan, Jiang, Andrew, de Jong, Pieter, Kaiser, Pete, Kim, Heebal, Kim, Kyu-Won, Kim, Sungwon, Langenberger, David, Lee, Mi-Kyung, Lee, Taeheon, Mane, Shrinivasrao P., Marcais, Guillaume, Marz, Manja, McElroy, Audrey P., Modise, Thero, Nefedov, Mikhail, Notredame, Cédric, Paton, Ian R., Payne, William S., Pertea, Geo, Prickett, Dennis, Puiu, Daniela, Qioa, Dan, Raineri, Emanuele, Ruffier, Magali, Salzberg, Steven L., Schatz, Michael C., Scheuring, Chantel, Schmidt, Carl J., Schroeder, Steven, Searle, Stephen M. J., Smith, Edward J., Smith, Jacqueline, Sonstegard, Tad S., Stadler, Peter F., Tafer, Hakim, Tu, Zhijian Jake, Van Tassell, Curtis P., Vilella, Albert J., Williams, Kelly P., Yorke, James A., Zhang, Liqing, Zhang, Hong-Bin, Zhang, Xiaojun, Zhang, Yang, Reed, Kent M., Dalloul, Rami A., Long, Julie A., Zimin, Aleksey V., Aslam, Luqman, Beal, Kathryn, Blomberg, Le Ann, Bouffard, Pascal, Burt, David W., Crasta, Oswald, Crooijmans, Richard P. M. A., Cooper, Kristal, Coulombe, Roger A., De, Supriyo, Delany, Mary E., Dodgson, Jerry B., Dong, Jennifer J., Evans, Clive, Frederickson, Karin M., Flicek, Paul, Florea, Liliana, Folkerts, Otto, Groenen, Martien A. M., Harkins, Tim T., Herrero, Javier, Hoffmann, Steve, Megens, Hendrik-Jan, Jiang, Andrew, de Jong, Pieter, Kaiser, Pete, Kim, Heebal, Kim, Kyu-Won, Kim, Sungwon, Langenberger, David, Lee, Mi-Kyung, Lee, Taeheon, Mane, Shrinivasrao P., Marcais, Guillaume, Marz, Manja, McElroy, Audrey P., Modise, Thero, Nefedov, Mikhail, Notredame, Cédric, Paton, Ian R., Payne, William S., Pertea, Geo, Prickett, Dennis, Puiu, Daniela, Qioa, Dan, Raineri, Emanuele, Ruffier, Magali, Salzberg, Steven L., Schatz, Michael C., Scheuring, Chantel, Schmidt, Carl J., Schroeder, Steven, Searle, Stephen M. J., Smith, Edward J., Smith, Jacqueline, Sonstegard, Tad S., Stadler, Peter F., Tafer, Hakim, Tu, Zhijian Jake, Van Tassell, Curtis P., Vilella, Albert J., Williams, Kelly P., Yorke, James A., Zhang, Liqing, Zhang, Hong-Bin, Zhang, Xiaojun, Zhang, Yang, and Reed, Kent M.

Abstract

A synergistic combination of two next-generation sequencing platforms with a detailed comparative BAC physical contig map provided a cost-effective assembly of the genome sequence of the domestic turkey (Meleagris gallopavo). Heterozygosity of the sequenced source genome allowed discovery of more than 600,000 high quality single nucleotide variants. Despite this heterozygosity, the current genome assembly (,1.1 Gb) includes 917 Mb of sequence assigned to specific turkey chromosomes. Annotation identified nearly 16,000 genes, with 15,093 recognized as protein coding and 611 as non-coding RNA genes. Comparative analysis of the turkey, chicken, and zebra finch genomes, and comparing avian to mammalian species, supports the characteristic stability of avian genomes and identifies genes unique to the avian lineage. Clear differences are seen in number and variety of genes of the avian immune system where expansions and novel genes are less frequent than examples of gene loss. The turkey genome sequence provides resources to further understand the evolution of vertebrate genomes and genetic variation underlying economically important quantitative traits in poultry. This integrated approach may be a model for providing both gene and chromosome level assemblies of other species with agricultural, ecological, and evolutionary interest.

Published
2010
Full Text
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24. Multi-Platform Next-Generation Sequencing of the Domestic Turkey (Meleagris gallopavo): Genome Assembly and Analysis

Author

Dalloul, Rami A., Long, Julie A., Zimin, Aleksey V., Aslam, Luqman, Beal, Kathryn, Blomberg, Le Ann, Bouffard, Pascal, Burt, David W., Crasta, Oswald, Crooijmans, Richard P. M. A., Cooper, Kristal, Coulombe, Roger A., De, Supriyo, Delany, Mary E., Dodgson, Jerry B., Dong, Jennifer J., Evans, Clive, Frederickson, Karin M., Flicek, Paul, Florea, Liliana, Folkerts, Otto, Groenen, Martien A. M., Harkins, Tim T., Herrero, Javier, Hoffmann, Steve, Megens, Hendrik-Jan, Jiang, Andrew, de Jong, Pieter, Kaiser, Pete, Kim, Heebal, Kim, Kyu-Won, Kim, Sungwon, Langenberger, David, Lee, Mi-Kyung, Lee, Taeheon, Mane, Shrinivasrao P., Marcais, Guillaume, Marz, Manja, McElroy, Audrey P., Modise, Thero, Nefedov, Mikhail, Notredame, Cédric, Paton, Ian R., Payne, William S., Pertea, Geo, Prickett, Dennis, Puiu, Daniela, Qioa, Dan, Raineri, Emanuele, Ruffier, Magali, Salzberg, Steven L., Schatz, Michael C., Scheuring, Chantel, Schmidt, Carl J., Schroeder, Steven, Searle, Stephen M. J., Smith, Edward J., Smith, Jacqueline, Sonstegard, Tad S., Stadler, Peter F., Tafer, Hakim, Tu, Zhijian Jake, Van Tassell, Curtis P., Vilella, Albert J., Williams, Kelly P., Yorke, James A., Zhang, Liqing, Zhang, Hong-Bin, Zhang, Xiaojun, Zhang, Yang, Reed, Kent M., Dalloul, Rami A., Long, Julie A., Zimin, Aleksey V., Aslam, Luqman, Beal, Kathryn, Blomberg, Le Ann, Bouffard, Pascal, Burt, David W., Crasta, Oswald, Crooijmans, Richard P. M. A., Cooper, Kristal, Coulombe, Roger A., De, Supriyo, Delany, Mary E., Dodgson, Jerry B., Dong, Jennifer J., Evans, Clive, Frederickson, Karin M., Flicek, Paul, Florea, Liliana, Folkerts, Otto, Groenen, Martien A. M., Harkins, Tim T., Herrero, Javier, Hoffmann, Steve, Megens, Hendrik-Jan, Jiang, Andrew, de Jong, Pieter, Kaiser, Pete, Kim, Heebal, Kim, Kyu-Won, Kim, Sungwon, Langenberger, David, Lee, Mi-Kyung, Lee, Taeheon, Mane, Shrinivasrao P., Marcais, Guillaume, Marz, Manja, McElroy, Audrey P., Modise, Thero, Nefedov, Mikhail, Notredame, Cédric, Paton, Ian R., Payne, William S., Pertea, Geo, Prickett, Dennis, Puiu, Daniela, Qioa, Dan, Raineri, Emanuele, Ruffier, Magali, Salzberg, Steven L., Schatz, Michael C., Scheuring, Chantel, Schmidt, Carl J., Schroeder, Steven, Searle, Stephen M. J., Smith, Edward J., Smith, Jacqueline, Sonstegard, Tad S., Stadler, Peter F., Tafer, Hakim, Tu, Zhijian Jake, Van Tassell, Curtis P., Vilella, Albert J., Williams, Kelly P., Yorke, James A., Zhang, Liqing, Zhang, Hong-Bin, Zhang, Xiaojun, Zhang, Yang, and Reed, Kent M.

Abstract

A synergistic combination of two next-generation sequencing platforms with a detailed comparative BAC physical contig map provided a cost-effective assembly of the genome sequence of the domestic turkey (Meleagris gallopavo). Heterozygosity of the sequenced source genome allowed discovery of more than 600,000 high quality single nucleotide variants. Despite this heterozygosity, the current genome assembly (,1.1 Gb) includes 917 Mb of sequence assigned to specific turkey chromosomes. Annotation identified nearly 16,000 genes, with 15,093 recognized as protein coding and 611 as non-coding RNA genes. Comparative analysis of the turkey, chicken, and zebra finch genomes, and comparing avian to mammalian species, supports the characteristic stability of avian genomes and identifies genes unique to the avian lineage. Clear differences are seen in number and variety of genes of the avian immune system where expansions and novel genes are less frequent than examples of gene loss. The turkey genome sequence provides resources to further understand the evolution of vertebrate genomes and genetic variation underlying economically important quantitative traits in poultry. This integrated approach may be a model for providing both gene and chromosome level assemblies of other species with agricultural, ecological, and evolutionary interest.

Published
2010
Full Text
View/download PDF

25. Multi-Platform Next-Generation Sequencing of the Domestic Turkey (Meleagris gallopavo): Genome Assembly and Analysis

Author

Dalloul, Rami A., Long, Julie A., Zimin, Aleksey V., Aslam, Luqman, Beal, Kathryn, Blomberg, Le Ann, Bouffard, Pascal, Burt, David W., Crasta, Oswald, Crooijmans, Richard P. M. A., Cooper, Kristal, Coulombe, Roger A., De, Supriyo, Delany, Mary E., Dodgson, Jerry B., Dong, Jennifer J., Evans, Clive, Frederickson, Karin M., Flicek, Paul, Florea, Liliana, Folkerts, Otto, Groenen, Martien A. M., Harkins, Tim T., Herrero, Javier, Hoffmann, Steve, Megens, Hendrik-Jan, Jiang, Andrew, de Jong, Pieter, Kaiser, Pete, Kim, Heebal, Kim, Kyu-Won, Kim, Sungwon, Langenberger, David, Lee, Mi-Kyung, Lee, Taeheon, Mane, Shrinivasrao P., Marcais, Guillaume, Marz, Manja, McElroy, Audrey P., Modise, Thero, Nefedov, Mikhail, Notredame, Cédric, Paton, Ian R., Payne, William S., Pertea, Geo, Prickett, Dennis, Puiu, Daniela, Qioa, Dan, Raineri, Emanuele, Ruffier, Magali, Salzberg, Steven L., Schatz, Michael C., Scheuring, Chantel, Schmidt, Carl J., Schroeder, Steven, Searle, Stephen M. J., Smith, Edward J., Smith, Jacqueline, Sonstegard, Tad S., Stadler, Peter F., Tafer, Hakim, Tu, Zhijian Jake, Van Tassell, Curtis P., Vilella, Albert J., Williams, Kelly P., Yorke, James A., Zhang, Liqing, Zhang, Hong-Bin, Zhang, Xiaojun, Zhang, Yang, Reed, Kent M., Dalloul, Rami A., Long, Julie A., Zimin, Aleksey V., Aslam, Luqman, Beal, Kathryn, Blomberg, Le Ann, Bouffard, Pascal, Burt, David W., Crasta, Oswald, Crooijmans, Richard P. M. A., Cooper, Kristal, Coulombe, Roger A., De, Supriyo, Delany, Mary E., Dodgson, Jerry B., Dong, Jennifer J., Evans, Clive, Frederickson, Karin M., Flicek, Paul, Florea, Liliana, Folkerts, Otto, Groenen, Martien A. M., Harkins, Tim T., Herrero, Javier, Hoffmann, Steve, Megens, Hendrik-Jan, Jiang, Andrew, de Jong, Pieter, Kaiser, Pete, Kim, Heebal, Kim, Kyu-Won, Kim, Sungwon, Langenberger, David, Lee, Mi-Kyung, Lee, Taeheon, Mane, Shrinivasrao P., Marcais, Guillaume, Marz, Manja, McElroy, Audrey P., Modise, Thero, Nefedov, Mikhail, Notredame, Cédric, Paton, Ian R., Payne, William S., Pertea, Geo, Prickett, Dennis, Puiu, Daniela, Qioa, Dan, Raineri, Emanuele, Ruffier, Magali, Salzberg, Steven L., Schatz, Michael C., Scheuring, Chantel, Schmidt, Carl J., Schroeder, Steven, Searle, Stephen M. J., Smith, Edward J., Smith, Jacqueline, Sonstegard, Tad S., Stadler, Peter F., Tafer, Hakim, Tu, Zhijian Jake, Van Tassell, Curtis P., Vilella, Albert J., Williams, Kelly P., Yorke, James A., Zhang, Liqing, Zhang, Hong-Bin, Zhang, Xiaojun, Zhang, Yang, and Reed, Kent M.

Abstract

A synergistic combination of two next-generation sequencing platforms with a detailed comparative BAC physical contig map provided a cost-effective assembly of the genome sequence of the domestic turkey (Meleagris gallopavo). Heterozygosity of the sequenced source genome allowed discovery of more than 600,000 high quality single nucleotide variants. Despite this heterozygosity, the current genome assembly (,1.1 Gb) includes 917 Mb of sequence assigned to specific turkey chromosomes. Annotation identified nearly 16,000 genes, with 15,093 recognized as protein coding and 611 as non-coding RNA genes. Comparative analysis of the turkey, chicken, and zebra finch genomes, and comparing avian to mammalian species, supports the characteristic stability of avian genomes and identifies genes unique to the avian lineage. Clear differences are seen in number and variety of genes of the avian immune system where expansions and novel genes are less frequent than examples of gene loss. The turkey genome sequence provides resources to further understand the evolution of vertebrate genomes and genetic variation underlying economically important quantitative traits in poultry. This integrated approach may be a model for providing both gene and chromosome level assemblies of other species with agricultural, ecological, and evolutionary interest.

Published
2010
Full Text
View/download PDF

26. Multi-Platform Next-Generation Sequencing of the Domestic Turkey (Meleagris gallopavo): Genome Assembly and Analysis

Author

Animal and Poultry Sciences, Biochemistry, Computer Science, Fralin Life Sciences Institute, Dalloul, Rami A., Long, Julie A., Zimin, Aleksey V., Aslam, Luqman, Beal, Kathryn, Blomberg, Le Ann, Bouffard, Pascal, Burt, David W., Crasta, Oswald, Crooijmans, Richard P. M. A., Cooper, Kristal, Coulombe, Roger A., De, Supriyo, Delany, Mary E., Dodgson, Jerry B., Dong, Jennifer J., Evans, Clive, Frederickson, Karin M., Flicek, Paul, Florea, Liliana, Folkerts, Otto, Groenen, Martien A. M., Harkins, Tim T., Herrero, Javier, Hoffmann, Steve, Megens, Hendrik-Jan, Jiang, Andrew, de Jong, Pieter, Kaiser, Pete, Kim, Heebal, Kim, Kyu-Won, Kim, Sungwon, Langenberger, David, Lee, Mi-Kyung, Lee, Taeheon, Mane, Shrinivasrao P., Marcais, Guillaume, Marz, Manja, McElroy, Audrey P., Modise, Thero, Nefedov, Mikhail, Notredame, Cédric, Paton, Ian R., Payne, William S., Pertea, Geo, Prickett, Dennis, Puiu, Daniela, Qioa, Dan, Raineri, Emanuele, Ruffier, Magali, Salzberg, Steven L., Schatz, Michael C., Scheuring, Chantel, Schmidt, Carl J., Schroeder, Steven, Searle, Stephen M. J., Smith, Edward J., Smith, Jacqueline, Sonstegard, Tad S., Stadler, Peter F., Tafer, Hakim, Tu, Zhijian Jake, Van Tassell, Curtis P., Vilella, Albert J., Williams, Kelly P., Yorke, James A., Zhang, Liqing, Zhang, Hong-Bin, Zhang, Xiaojun, Zhang, Yang, Reed, Kent M., Animal and Poultry Sciences, Biochemistry, Computer Science, Fralin Life Sciences Institute, Dalloul, Rami A., Long, Julie A., Zimin, Aleksey V., Aslam, Luqman, Beal, Kathryn, Blomberg, Le Ann, Bouffard, Pascal, Burt, David W., Crasta, Oswald, Crooijmans, Richard P. M. A., Cooper, Kristal, Coulombe, Roger A., De, Supriyo, Delany, Mary E., Dodgson, Jerry B., Dong, Jennifer J., Evans, Clive, Frederickson, Karin M., Flicek, Paul, Florea, Liliana, Folkerts, Otto, Groenen, Martien A. M., Harkins, Tim T., Herrero, Javier, Hoffmann, Steve, Megens, Hendrik-Jan, Jiang, Andrew, de Jong, Pieter, Kaiser, Pete, Kim, Heebal, Kim, Kyu-Won, Kim, Sungwon, Langenberger, David, Lee, Mi-Kyung, Lee, Taeheon, Mane, Shrinivasrao P., Marcais, Guillaume, Marz, Manja, McElroy, Audrey P., Modise, Thero, Nefedov, Mikhail, Notredame, Cédric, Paton, Ian R., Payne, William S., Pertea, Geo, Prickett, Dennis, Puiu, Daniela, Qioa, Dan, Raineri, Emanuele, Ruffier, Magali, Salzberg, Steven L., Schatz, Michael C., Scheuring, Chantel, Schmidt, Carl J., Schroeder, Steven, Searle, Stephen M. J., Smith, Edward J., Smith, Jacqueline, Sonstegard, Tad S., Stadler, Peter F., Tafer, Hakim, Tu, Zhijian Jake, Van Tassell, Curtis P., Vilella, Albert J., Williams, Kelly P., Yorke, James A., Zhang, Liqing, Zhang, Hong-Bin, Zhang, Xiaojun, Zhang, Yang, and Reed, Kent M.

Abstract

A synergistic combination of two next-generation sequencing platforms with a detailed comparative BAC physical contig map provided a cost-effective assembly of the genome sequence of the domestic turkey (Meleagris gallopavo). Heterozygosity of the sequenced source genome allowed discovery of more than 600,000 high quality single nucleotide variants. Despite this heterozygosity, the current genome assembly (,1.1 Gb) includes 917 Mb of sequence assigned to specific turkey chromosomes. Annotation identified nearly 16,000 genes, with 15,093 recognized as protein coding and 611 as non-coding RNA genes. Comparative analysis of the turkey, chicken, and zebra finch genomes, and comparing avian to mammalian species, supports the characteristic stability of avian genomes and identifies genes unique to the avian lineage. Clear differences are seen in number and variety of genes of the avian immune system where expansions and novel genes are less frequent than examples of gene loss. The turkey genome sequence provides resources to further understand the evolution of vertebrate genomes and genetic variation underlying economically important quantitative traits in poultry. This integrated approach may be a model for providing both gene and chromosome level assemblies of other species with agricultural, ecological, and evolutionary interest.

Published
2010

27. Multi-Platform Next-Generation Sequencing of the Domestic Turkey (Meleagris gallopavo): Genome Assembly and Analysis

Author

Animal and Poultry Sciences, Biochemistry, Computer Science, Fralin Life Sciences Institute, Dalloul, Rami A., Long, Julie A., Zimin, Aleksey V., Aslam, Luqman, Beal, Kathryn, Blomberg, Le Ann, Bouffard, Pascal, Burt, David W., Crasta, Oswald, Crooijmans, Richard P. M. A., Cooper, Kristal, Coulombe, Roger A., De, Supriyo, Delany, Mary E., Dodgson, Jerry B., Dong, Jennifer J., Evans, Clive, Frederickson, Karin M., Flicek, Paul, Florea, Liliana, Folkerts, Otto, Groenen, Martien A. M., Harkins, Tim T., Herrero, Javier, Hoffmann, Steve, Megens, Hendrik-Jan, Jiang, Andrew, de Jong, Pieter, Kaiser, Pete, Kim, Heebal, Kim, Kyu-Won, Kim, Sungwon, Langenberger, David, Lee, Mi-Kyung, Lee, Taeheon, Mane, Shrinivasrao P., Marcais, Guillaume, Marz, Manja, McElroy, Audrey P., Modise, Thero, Nefedov, Mikhail, Notredame, Cédric, Paton, Ian R., Payne, William S., Pertea, Geo, Prickett, Dennis, Puiu, Daniela, Qioa, Dan, Raineri, Emanuele, Ruffier, Magali, Salzberg, Steven L., Schatz, Michael C., Scheuring, Chantel, Schmidt, Carl J., Schroeder, Steven, Searle, Stephen M. J., Smith, Edward J., Smith, Jacqueline, Sonstegard, Tad S., Stadler, Peter F., Tafer, Hakim, Tu, Zhijian Jake, Van Tassell, Curtis P., Vilella, Albert J., Williams, Kelly P., Yorke, James A., Zhang, Liqing, Zhang, Hong-Bin, Zhang, Xiaojun, Zhang, Yang, Reed, Kent M., Animal and Poultry Sciences, Biochemistry, Computer Science, Fralin Life Sciences Institute, Dalloul, Rami A., Long, Julie A., Zimin, Aleksey V., Aslam, Luqman, Beal, Kathryn, Blomberg, Le Ann, Bouffard, Pascal, Burt, David W., Crasta, Oswald, Crooijmans, Richard P. M. A., Cooper, Kristal, Coulombe, Roger A., De, Supriyo, Delany, Mary E., Dodgson, Jerry B., Dong, Jennifer J., Evans, Clive, Frederickson, Karin M., Flicek, Paul, Florea, Liliana, Folkerts, Otto, Groenen, Martien A. M., Harkins, Tim T., Herrero, Javier, Hoffmann, Steve, Megens, Hendrik-Jan, Jiang, Andrew, de Jong, Pieter, Kaiser, Pete, Kim, Heebal, Kim, Kyu-Won, Kim, Sungwon, Langenberger, David, Lee, Mi-Kyung, Lee, Taeheon, Mane, Shrinivasrao P., Marcais, Guillaume, Marz, Manja, McElroy, Audrey P., Modise, Thero, Nefedov, Mikhail, Notredame, Cédric, Paton, Ian R., Payne, William S., Pertea, Geo, Prickett, Dennis, Puiu, Daniela, Qioa, Dan, Raineri, Emanuele, Ruffier, Magali, Salzberg, Steven L., Schatz, Michael C., Scheuring, Chantel, Schmidt, Carl J., Schroeder, Steven, Searle, Stephen M. J., Smith, Edward J., Smith, Jacqueline, Sonstegard, Tad S., Stadler, Peter F., Tafer, Hakim, Tu, Zhijian Jake, Van Tassell, Curtis P., Vilella, Albert J., Williams, Kelly P., Yorke, James A., Zhang, Liqing, Zhang, Hong-Bin, Zhang, Xiaojun, Zhang, Yang, and Reed, Kent M.

Abstract

A synergistic combination of two next-generation sequencing platforms with a detailed comparative BAC physical contig map provided a cost-effective assembly of the genome sequence of the domestic turkey (Meleagris gallopavo). Heterozygosity of the sequenced source genome allowed discovery of more than 600,000 high quality single nucleotide variants. Despite this heterozygosity, the current genome assembly (,1.1 Gb) includes 917 Mb of sequence assigned to specific turkey chromosomes. Annotation identified nearly 16,000 genes, with 15,093 recognized as protein coding and 611 as non-coding RNA genes. Comparative analysis of the turkey, chicken, and zebra finch genomes, and comparing avian to mammalian species, supports the characteristic stability of avian genomes and identifies genes unique to the avian lineage. Clear differences are seen in number and variety of genes of the avian immune system where expansions and novel genes are less frequent than examples of gene loss. The turkey genome sequence provides resources to further understand the evolution of vertebrate genomes and genetic variation underlying economically important quantitative traits in poultry. This integrated approach may be a model for providing both gene and chromosome level assemblies of other species with agricultural, ecological, and evolutionary interest.

Published
2010

28. Multi-Platform Next-Generation Sequencing of the Domestic Turkey (Meleagris gallopavo): Genome Assembly and Analysis

Author

Animal and Poultry Sciences, Biochemistry, Computer Science, Fralin Life Sciences Institute, Dalloul, Rami A., Long, Julie A., Zimin, Aleksey V., Aslam, Luqman, Beal, Kathryn, Blomberg, Le Ann, Bouffard, Pascal, Burt, David W., Crasta, Oswald, Crooijmans, Richard P. M. A., Cooper, Kristal, Coulombe, Roger A., De, Supriyo, Delany, Mary E., Dodgson, Jerry B., Dong, Jennifer J., Evans, Clive, Frederickson, Karin M., Flicek, Paul, Florea, Liliana, Folkerts, Otto, Groenen, Martien A. M., Harkins, Tim T., Herrero, Javier, Hoffmann, Steve, Megens, Hendrik-Jan, Jiang, Andrew, de Jong, Pieter, Kaiser, Pete, Kim, Heebal, Kim, Kyu-Won, Kim, Sungwon, Langenberger, David, Lee, Mi-Kyung, Lee, Taeheon, Mane, Shrinivasrao P., Marcais, Guillaume, Marz, Manja, McElroy, Audrey P., Modise, Thero, Nefedov, Mikhail, Notredame, Cédric, Paton, Ian R., Payne, William S., Pertea, Geo, Prickett, Dennis, Puiu, Daniela, Qioa, Dan, Raineri, Emanuele, Ruffier, Magali, Salzberg, Steven L., Schatz, Michael C., Scheuring, Chantel, Schmidt, Carl J., Schroeder, Steven, Searle, Stephen M. J., Smith, Edward J., Smith, Jacqueline, Sonstegard, Tad S., Stadler, Peter F., Tafer, Hakim, Tu, Zhijian Jake, Van Tassell, Curtis P., Vilella, Albert J., Williams, Kelly P., Yorke, James A., Zhang, Liqing, Zhang, Hong-Bin, Zhang, Xiaojun, Zhang, Yang, Reed, Kent M., Animal and Poultry Sciences, Biochemistry, Computer Science, Fralin Life Sciences Institute, Dalloul, Rami A., Long, Julie A., Zimin, Aleksey V., Aslam, Luqman, Beal, Kathryn, Blomberg, Le Ann, Bouffard, Pascal, Burt, David W., Crasta, Oswald, Crooijmans, Richard P. M. A., Cooper, Kristal, Coulombe, Roger A., De, Supriyo, Delany, Mary E., Dodgson, Jerry B., Dong, Jennifer J., Evans, Clive, Frederickson, Karin M., Flicek, Paul, Florea, Liliana, Folkerts, Otto, Groenen, Martien A. M., Harkins, Tim T., Herrero, Javier, Hoffmann, Steve, Megens, Hendrik-Jan, Jiang, Andrew, de Jong, Pieter, Kaiser, Pete, Kim, Heebal, Kim, Kyu-Won, Kim, Sungwon, Langenberger, David, Lee, Mi-Kyung, Lee, Taeheon, Mane, Shrinivasrao P., Marcais, Guillaume, Marz, Manja, McElroy, Audrey P., Modise, Thero, Nefedov, Mikhail, Notredame, Cédric, Paton, Ian R., Payne, William S., Pertea, Geo, Prickett, Dennis, Puiu, Daniela, Qioa, Dan, Raineri, Emanuele, Ruffier, Magali, Salzberg, Steven L., Schatz, Michael C., Scheuring, Chantel, Schmidt, Carl J., Schroeder, Steven, Searle, Stephen M. J., Smith, Edward J., Smith, Jacqueline, Sonstegard, Tad S., Stadler, Peter F., Tafer, Hakim, Tu, Zhijian Jake, Van Tassell, Curtis P., Vilella, Albert J., Williams, Kelly P., Yorke, James A., Zhang, Liqing, Zhang, Hong-Bin, Zhang, Xiaojun, Zhang, Yang, and Reed, Kent M.

Abstract

A synergistic combination of two next-generation sequencing platforms with a detailed comparative BAC physical contig map provided a cost-effective assembly of the genome sequence of the domestic turkey (Meleagris gallopavo). Heterozygosity of the sequenced source genome allowed discovery of more than 600,000 high quality single nucleotide variants. Despite this heterozygosity, the current genome assembly (,1.1 Gb) includes 917 Mb of sequence assigned to specific turkey chromosomes. Annotation identified nearly 16,000 genes, with 15,093 recognized as protein coding and 611 as non-coding RNA genes. Comparative analysis of the turkey, chicken, and zebra finch genomes, and comparing avian to mammalian species, supports the characteristic stability of avian genomes and identifies genes unique to the avian lineage. Clear differences are seen in number and variety of genes of the avian immune system where expansions and novel genes are less frequent than examples of gene loss. The turkey genome sequence provides resources to further understand the evolution of vertebrate genomes and genetic variation underlying economically important quantitative traits in poultry. This integrated approach may be a model for providing both gene and chromosome level assemblies of other species with agricultural, ecological, and evolutionary interest.

Published
2010

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