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Podcast title	Roche NimbleGen Webinar Series
Website URL	http://www.nimblegen.com/news/...
Description	The Roche NimbleGen Webinar Series is a forum for researchers to present their work on the leading edge of genomics. Learn how the creative efforts of prominant researchers, combined with the power of NimbleGen high-resolution, customizable oligonucleotide arrays, is is advancing our understanding at the nexus of regulatory biology and genomics.
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Category	Science & Medicine
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Episodes
1. Audio: Introducing the High-Resolution, High-Sensitivity NimbleGen 2.1M DNA Methylation Arrays download (audio/x-mp3, 28.80Mb) Description:
2. Video: Introducing the High-Resolution, High-Sensitivity NimbleGen 2.1M DNA Methylation Arrays download (video/x-m4v, 52.37Mb) Description:
3. Audio: NimbleGen Sequence Capture Using the HD2 Platform: Exome Capture Made Easy download (audio/x-mp3, 27.17Mb) Description:
4. Video: NimbleGen Sequence Capture Using the HD2 Platform: Exome Capture Made Easy download (video/x-m4v, 49.02Mb) Description:
5. Audio: Application of NimbleGen Sequence Capture to Complex Plant Genomes download (audio/x-mp3, 23.94Mb) Description:
6. Video: Application of NimbleGen Sequence Capture to Complex Plant Genomes download (video/x-m4v, 23.33Mb) Description:
7. Audio: Whole Genome Analysis of DNA Copy Number Variation in Dogs download (audio/x-mp3, 9.83Mb) Description:
8. Video: Whole Genome Analysis of DNA Copy Number Variation in Dogs download (video/x-m4v, 18.70Mb) Description:
9. Audio: Copy Number Variation in Low Copy Repeat-Rich Regions of the Genome: How Much is There and What Does it Take to Measure It? download (audio/x-mp3, 32.27Mb) Description:
10. Video: Copy Number Variation in Low Copy Repeat-Rich Regions of the Genome: How Much is There and What Does it Take to Measure It? download (video/x-m4v, 33.08Mb) Description:
11. Audio: Distinct Chromatin Modifications at Enhancers Correlate with Cell Type-Specific Gene Expression in the Human Genome download (audio/x-mp3, 21.91Mb) Description:
12. Video: Distinct Chromatin Modifications at Enhancers Correlate with Cell Type-Specific Gene Expression in the Human Genome download (video/x-m4v, 22.64Mb) Description:
13. Audio: Discovery of Human Genetic Variations with Sequence Capture Technology download (audio/x-mp3, 17.63Mb) Description:
14. Video: Discovery of Human Genetic Variations with Sequence Capture Technology download (video/x-m4v, 18.36Mb) Description:
15. Audio: Introducing NimbleGen HD2 Arrays for High-Resolution ChIP-chip Analysis download (audio/x-mp3, 25.06Mb) Description:
16. Video: Introducing NimbleGen HD2 Arrays for High-Resolution ChIP-chip Analysis download (video/x-m4v, 46.05Mb) Description:
17. Audio: High-Throughput Detection of Exonic Copy-Number Changes Using NimbleGen Oligonucleotide-Based CGH Array Technology download (audio/x-mp3, 8.33Mb) Description:
18. Video: High-Throughput Detection of Exonic Copy-Number Changes Using NimbleGen Oligonucleotide-Based CGH Array Technology download (video/x-m4v, 26.31Mb) Description:
19. Audio: High-Throughput Approaches for DNA Methylation Profiling download (audio/x-mp3, 12.95Mb) Description:
20. Video: High-Throughput Approaches for DNA Methylation Profiling download (video/x-m4v, 28.48Mb) Description:
21. Audio: Sequence Capture for Medical Sequencing download (audio/x-mp3, 8.36Mb) Description:
22. Video: Sequence Capture for Medical Sequencing download (video/x-m4v, 18.25Mb) Description:
23. Audio: Using Microarrays to Capture Megabases of Sequence or Hundreds of Thousands of Human Exons for Next Generation Sequencing download (audio/x-mp3, 21.97Mb) Description:
24. Video: Using Microarrays to Capture Megabases of Sequence or Hundreds of Thousands of Human Exons for Next Generation Sequencing download (video/x-m4v, 47.54Mb) Description:
25. Audio: Genomic Analyses of Gene Regulation by Poly(ADP-Ribose) Polymerase-1 and Histone H1 download (audio/x-mp3, 19.84Mb) Description:
26. Video: Genomic Analyses of Gene Regulation by Poly(ADP-Ribose) Polymerase-1 and Histone H1 download (video/x-m4v, 42.81Mb) Description:
27. Audio: Integrated Epigenomic Analyses of Neuronal MeCP2 Reveal a Role for Long-Range Interaction with Active Genes download (audio/x-mp3, 27.93Mb) Description:
28. Video: Integrated Epigenomic Analyses of Neuronal MeCP2 Reveal a Role for Long-Range Interaction with Active Genes download (video/x-m4v, 60.88Mb) Description:
29. Audio: Direct Genomic Selection by Microarray Hybridization for High-Throughput Sequencing download (audio/x-mp3, 11.96Mb) Description:
30. Video: Direct Genomic Selection by Microarray Hybridization for High-Throughput Sequencing download (video/x-m4v, 26.16Mb) Description:
31. Audio: Insights into the Evolutionary Significance of Whole Genome Duplications Provided by Populus Expression Arrays download (audio/x-mp3, 11.45Mb) Description:
32. Video: Insights into the Evolutionary Significance of Whole Genome Duplications Provided by Populus Expression Arrays download (video/x-m4v, 26.25Mb) Description:
33. Audio: Duplicate gene expression evolution in cotton download (audio/x-mp3, 12.46Mb) Description:
34. Video: Duplicate gene expression evolution in cotton download (video/x-m4v, 27.25Mb) Description:
35. Audio: Genome-Scale Targeted Sequencing and Expression Analysis in Duplicated Genomes download (audio/x-mp3, 35.87Mb) Description:
36. Video: Genome-Scale Targeted Sequencing and Expression Analysis in Duplicated Genomes download (video/x-m4v, 75.44Mb) Description:
37. Audio: Genome Architecture and Genomic Disease: A Targeted Approach to Disease Discovery download (audio/x-mp3, 48.32Mb) Description: Genomic disorders are conditions that result from recurrent rearrangement of DNA caused by unequal crossing over between duplicated genomic sequences. Most studies of genomic disorders have focused on patients with cognitive disability and/or peripheral nervous system defects. In an effort to broaden the phenotypic spectrum of this disease model, we assessed 155 autopsy samples from fetuses with well-defined developmental pathologies in regions predisposed to recurrent rearrangement by array CGH. We found that 6% of fetal material showed evidence of microdeletion or microduplication, One of the microdeletions, identified in a fetus with multicystic dysplastic kidneys, encompasses the TCF2 gene on 17q12, previously shown to be mutated in maturity-onset diabetes as well as a subset of pediatric renal abnormalities. Fine-scale mapping with custom oligonucleotide arrays of the breakpoints in different patient cohorts reveals a recurrent 1.5 Mb de novo deletion in individuals with phenotypes ranging from congenital renal abnormalities to maturity-onset diabetes of the young type 5. Array analysis also reveals significant copy number and structural variation at the breakpoints. The 17q12 microdeletion is the first genomic disorder associated with diabetes and accounts for a significant proportion of previously unexplained pediatric renal disease.
38. Video: Genome Architecture and Genomic Disease: A Targeted Approach to Disease Discovery download (video/x-m4v, 52.10Mb) Description: Genomic disorders are conditions that result from recurrent rearrangement of DNA caused by unequal crossing over between duplicated genomic sequences. Most studies of genomic disorders have focused on patients with cognitive disability and/or peripheral nervous system defects. In an effort to broaden the phenotypic spectrum of this disease model, we assessed 155 autopsy samples from fetuses with well-defined developmental pathologies in regions predisposed to recurrent rearrangement by array CGH. We found that 6% of fetal material showed evidence of microdeletion or microduplication, One of the microdeletions, identified in a fetus with multicystic dysplastic kidneys, encompasses the TCF2 gene on 17q12, previously shown to be mutated in maturity-onset diabetes as well as a subset of pediatric renal abnormalities. Fine-scale mapping with custom oligonucleotide arrays of the breakpoints in different patient cohorts reveals a recurrent 1.5 Mb de novo deletion in individuals with phenotypes ranging from congenital renal abnormalities to maturity-onset diabetes of the young type 5. Array analysis also reveals significant copy number and structural variation at the breakpoints. The 17q12 microdeletion is the first genomic disorder associated with diabetes and accounts for a significant proportion of previously unexplained pediatric renal disease.
39. Audio: Demonstration of KAP1 Binding to Silenced Chromatin with Genome-wide ChIP-chip Analysis download (audio/x-mp3, 50.09Mb) Description: Methylation of lysine residues on histone H3 and H4 tails plays a key role in gene regulation, chromatin structure, and establishment and maintenance of epigenetic memory. In particular, methylation of lysines 9 or 27 of histone H3 (H3me3K9 and H3me3K27, respectively) have been associated with silenced chromatin. ChIP-chip analysis using human promoter arrays indicate that the two marks segregate differentially with the two most common types of transcription factors; H3me3K9 is highly enriched at zinc finger genes (ZNFs) and H3me3K27 is highly enriched at homeobox genes. Here we show that many promoters containing the H3me3K9 mark are also bound by the corepressor KAP1 (also known as TIF1B or TRIM28). We then performed a complete genomic analysis using a set of 38 tiling arrays, which identified ~7000 KAP1 binding sites in the entire human genome. KAP1 binding was specifically enriched at zinc finger genes. Although most KAP1 binding sites were within core promoter regions, a unique binding pattern was observed at ZNF target genes. Analysis of ChIP-chip data from promoter arrays as well as from whole genome tiling arrays will be discussed.
40. Video: Demonstration of KAP1 Binding to Silenced Chromatin with Genome-wide ChIP-chip Analysis download (video/x-m4v, 54.05Mb) Description: Methylation of lysine residues on histone H3 and H4 tails plays a key role in gene regulation, chromatin structure, and establishment and maintenance of epigenetic memory. In particular, methylation of lysines 9 or 27 of histone H3 (H3me3K9 and H3me3K27, respectively) have been associated with silenced chromatin. ChIP-chip analysis using human promoter arrays indicate that the two marks segregate differentially with the two most common types of transcription factors; H3me3K9 is highly enriched at zinc finger genes (ZNFs) and H3me3K27 is highly enriched at homeobox genes. Here we show that many promoters containing the H3me3K9 mark are also bound by the corepressor KAP1 (also known as TIF1B or TRIM28). We then performed a complete genomic analysis using a set of 38 tiling arrays, which identified ~7000 KAP1 binding sites in the entire human genome. KAP1 binding was specifically enriched at zinc finger genes. Although most KAP1 binding sites were within core promoter regions, a unique binding pattern was observed at ZNF target genes. Analysis of ChIP-chip data from promoter arrays as well as from whole genome tiling arrays will be discussed.
41. Audio: NimbleGen ASHG 2007 Genetics and Epigeneitcs Workshop, Complete Program download (audio/x-mp3, 76.01Mb) Description: Human Genetics and Epigenetics: High-Definition Analysis of: DNA Copy Number Variation in Autism, Application of CGH Arrays in Clinical Diagnostics and Expression Regulation by Non-Coding RNAs
42. Video: NimbleGen ASHG 2007 Genetics and Epigeneitcs Workshop, Complete Program download (video/x-m4v, 84.44Mb) Description: Human Genetics and Epigenetics: High-Definition Analysis of: DNA Copy Number Variation in Autism, Application of CGH Arrays in Clinical Diagnostics and Expression Regulation by Non-Coding RNAs
43. Audio: A Large-Scale Study of de novo Copy Number Variation in Autism download (audio/x-mp3, 32.98Mb) Description: New methods for detecting changes in DNA copy number (CNVs) have begun to shed new light on genetic risk factors for Autism Spectrum Disorders. What these studies have shown is that large scale deletions and duplications of gene are a significant contributor to genetic risk, and furthermore that CNV risk factors are frequently the result of spontaneous germline mutation. Our findings raise the hypothesis that much the sporadic nature of autism due to spontaneous mutations. Spontaneous CNVs have been detected at many loci throughout the genome, and no single locus has been shown to account more than 1% of cases. These data are consistent with the notion that there are many genes in the genome that, when altered, can produce a similar disease phenotype. We hypothesize that the features of autism (impaired social interaction, difficulty with communication, and restricted interests and behaviors) owe there "commonality" to the fact that the diverse set of genes involved participate in a common biological network.
44. Video: A Large-Scale Study of de novo Copy Number Variation in Autism download (video/x-m4v, 36.72Mb) Description: New methods for detecting changes in DNA copy number (CNVs) have begun to shed new light on genetic risk factors for Autism Spectrum Disorders. What these studies have shown is that large scale deletions and duplications of gene are a significant contributor to genetic risk, and furthermore that CNV risk factors are frequently the result of spontaneous germline mutation. Our findings raise the hypothesis that much the sporadic nature of autism due to spontaneous mutations. Spontaneous CNVs have been detected at many loci throughout the genome, and no single locus has been shown to account more than 1% of cases. These data are consistent with the notion that there are many genes in the genome that, when altered, can produce a similar disease phenotype. We hypothesize that the features of autism (impaired social interaction, difficulty with communication, and restricted interests and behaviors) owe there "commonality" to the fact that the diverse set of genes involved participate in a common biological network.
45. Audio: Silencing Chromatin from a Distance with Large ncRNAs download (audio/x-mp3, 21.21Mb) Description: Large Noncoding RNAs (ncRNA) are becoming a distinguishing feature of the Metazoan genomes, but their functional roles are poorly understood. Here we describe a novel type of ncRNA termed HOTAIR that is 2.2. Kb RNA, has 5 spliced exons, a poly A tail and a 5’ meC cap, yet has no potential to code a sensible amino-acid sequence. HOTAIR is encoded antisense to the human HOXC cluster at the exact juncture of a 40 Kb domain of heterochromatin and a 60 Kb domain of euchromatin. However, HOTAIR doesn’t serve to regulate this boundary; Remarkably HOTAIR affects the global epigenetic state of the HOXD cluster located on a separate chromosome. HOTAIR binds the Polycomb Repressive Complex 2 (PRC2) and is required for PRC2 occupancy and histone H3 lysine-27 trimethylation of HOXD locus. Thus, transcription of ncRNA may demarcate chromosomal domains of gene silencing at a distance; these results have broad implications for gene regulation in development and disease states.
46. Video: Silencing Chromatin from a Distance with Large ncRNAs download (video/x-m4v, 23.10Mb) Description: Large Noncoding RNAs (ncRNA) are becoming a distinguishing feature of the Metazoan genomes, but their functional roles are poorly understood. Here we describe a novel type of ncRNA termed HOTAIR that is 2.2. Kb RNA, has 5 spliced exons, a poly A tail and a 5’ meC cap, yet has no potential to code a sensible amino-acid sequence. HOTAIR is encoded antisense to the human HOXC cluster at the exact juncture of a 40 Kb domain of heterochromatin and a 60 Kb domain of euchromatin. However, HOTAIR doesn’t serve to regulate this boundary; Remarkably HOTAIR affects the global epigenetic state of the HOXD cluster located on a separate chromosome. HOTAIR binds the Polycomb Repressive Complex 2 (PRC2) and is required for PRC2 occupancy and histone H3 lysine-27 trimethylation of HOXD locus. Thus, transcription of ncRNA may demarcate chromosomal domains of gene silencing at a distance; these results have broad implications for gene regulation in development and disease states.
47. Audio: Application of CGH Arrays for DNA Diagnostics download (audio/x-mp3, 21.85Mb) Description: Molecular methods used in DNA diagnostic laboratories to detect single exon or large deletions and duplications in a single gene involve multiplex PCR amplification, quantitative PCR, Southern blotting, MLPA, DOVAM-S and SCAIP. These methods are time consuming, laborious and do not accurately detect all mutations. We have developed a high resolution approach using CGH arrays to comprehensively detect single exon or large deletions and duplications mutations. One of the biggest challenges in genetic testing is evaluation of analytical and clinical validity for each genetic test. We describe here for the first time the development, design and validation of CGH arrays for detecting single exon or large deletions and duplications in autosomal and X-linked disease associated genes in a DNA diagnostic laboratory. The CGH arrays can be easily adopted in the clinical molecular testing laboratories and is a rapid and very cost effective approach to screen single exon or large deletions and duplications.
48. Video: Application of CGH Arrays for DNA Diagnostics download (video/x-m4v, 24.47Mb) Description: Molecular methods used in DNA diagnostic laboratories to detect single exon or large deletions and duplications in a single gene involve multiplex PCR amplification, quantitative PCR, Southern blotting, MLPA, DOVAM-S and SCAIP. These methods are time consuming, laborious and do not accurately detect all mutations. We have developed a high resolution approach using CGH arrays to comprehensively detect single exon or large deletions and duplications mutations. One of the biggest challenges in genetic testing is evaluation of analytical and clinical validity for each genetic test. We describe here for the first time the development, design and validation of CGH arrays for detecting single exon or large deletions and duplications in autosomal and X-linked disease associated genes in a DNA diagnostic laboratory. The CGH arrays can be easily adopted in the clinical molecular testing laboratories and is a rapid and very cost effective approach to screen single exon or large deletions and duplications.
49. Audio: Gene Silencing by Large, Non-coding RNAs: The Regulatory Role of HOTAIR analyzed with ChIP-chip and Tiling Expression Analysis download (audio/x-mp3, 59.57Mb) Description: Large Noncoding RNAs (ncRNA) are becoming a distinguishing feature of the Metazoan genomes, but their functional roles are poorly understood. Here we describe a novel type of ncRNA termed HOTAIR that is 2.2. Kb RNA, has 5 spliced exons, a poly A tail and a 5’ meC cap, yet has no potential to code a sensible amino-acid sequence. HOTAIR is encoded antisense to the human HOXC cluster at the exact juncture of a 40 Kb domain of heterochromatin and a 60 Kb domain of euchromatin. However, HOTAIR doesn’t serve to regulate this boundary; Remarkably HOTAIR affects the global epigenetic state of the HOXD cluster located on a separate chromosome. HOTAIR binds the Polycomb Repressive Complex 2 (PRC2) and is required for PRC2 occupancy and histone H3 lysine-27 trimethylation of HOXD locus. Thus, transcription of large ncRNA may demarcate chromosomal domains of gene silencing from a distance. We further discuss RNA labeling optimizations, platform comparisons and the integration of ChIP-Chip and RNA expression on high-resolution DNA tiling arrays that were critical for our discovery of HOTAIR. Together, these results demonstrate the power of integrative genomics in elucidating the biological roles of large ncRNAs.
50. Video: Gene Silencing by Large, Non-coding RNAs: The Regulatory Role of HOTAIR analyzed with ChIP-chip and Tiling Expression Analysis download (video/x-m4v, 64.73Mb) Description: Large Noncoding RNAs (ncRNA) are becoming a distinguishing feature of the Metazoan genomes, but their functional roles are poorly understood. Here we describe a novel type of ncRNA termed HOTAIR that is 2.2. Kb RNA, has 5 spliced exons, a poly A tail and a 5’ meC cap, yet has no potential to code a sensible amino-acid sequence. HOTAIR is encoded antisense to the human HOXC cluster at the exact juncture of a 40 Kb domain of heterochromatin and a 60 Kb domain of euchromatin. However, HOTAIR doesn’t serve to regulate this boundary; Remarkably HOTAIR affects the global epigenetic state of the HOXD cluster located on a separate chromosome. HOTAIR binds the Polycomb Repressive Complex 2 (PRC2) and is required for PRC2 occupancy and histone H3 lysine-27 trimethylation of HOXD locus. Thus, transcription of large ncRNA may demarcate chromosomal domains of gene silencing from a distance. We further discuss RNA labeling optimizations, platform comparisons and the integration of ChIP-Chip and RNA expression on high-resolution DNA tiling arrays that were critical for our discovery of HOTAIR. Together, these results demonstrate the power of integrative genomics in elucidating the biological roles of large ncRNAs.
51. Audio: Assaying Gene Expression Using NimbleChip Multiplex Microarrays: Taking Advantage of High-Throughput Sample Analysis download (audio/x-mp3, 27.00Mb) Description: Microarray analysis is a powerful tool for quantifying genome-wide changes in gene expression. To facilitate wider application of microarray data in biomedical research and promote the use of microarray analysis in diagnostic and regulatory fields, it is important that data obtained using this technology is accurate and reliable. As such, we evaluated the performance of NimbleGen gene expression microarrays using standard RNA samples recently used by the Microarray Quality Control Consortium, a project established to evaluate the reproducibility and quality of data obtained using microarrays from multiple suppliers. Here we show high inter- array reproducibility was achieved for both the 1-plex and 4-plex expression microarrays, demonstrating the reliability of NimbleChip microarray data. We also show a high concordance between data obtained from NimbleChip microarray analysis and data from TaqMan analysis, the current gold standard for mRNA level quantitation, indicating the accuracy of NimbleChip microarray data in assessing gene expression values.
52. Video: Assaying Gene Expression Using NimbleChip Multiplex Microarrays: Taking Advantage of High-Throughput Sample Analysis download (video/x-m4v, 29.29Mb) Description: Microarray analysis is a powerful tool for quantifying genome-wide changes in gene expression. To facilitate wider application of microarray data in biomedical research and promote the use of microarray analysis in diagnostic and regulatory fields, it is important that data obtained using this technology is accurate and reliable. As such, we evaluated the performance of NimbleGen gene expression microarrays using standard RNA samples recently used by the Microarray Quality Control Consortium, a project established to evaluate the reproducibility and quality of data obtained using microarrays from multiple suppliers. Here we show high inter- array reproducibility was achieved for both the 1-plex and 4-plex expression microarrays, demonstrating the reliability of NimbleChip microarray data. We also show a high concordance between data obtained from NimbleChip microarray analysis and data from TaqMan analysis, the current gold standard for mRNA level quantitation, indicating the accuracy of NimbleChip microarray data in assessing gene expression values.
53. Audio: Genome-Wide Distribution, Sequence Determinant and Evolution of CTCF Binding download (audio/x-mp3, 41.15Mb) Description: Insulator elements affect gene expression by preventing the spread of heterochromatin and restricting transcriptional enhancers from activation of unrelated promoters. In vertebrates, insulator's function requires association with the CCCTC-binding factor (CTCF), a protein that recognizes long and diverse nucleotide sequences. While insulators are critical in gene regulation, only a few have been reported. Here, we describe 13,804 CTCF-binding sites in potential insulators of the human genome, discovered experimentally in primary human fibroblasts. Most of these sequences are located far from the transcriptional start sites, with their distribution strongly correlated with genes. The majority of them fit to a consensus motif highly conserved and suitable for predicting possible insulators driven by CTCF in other vertebrate genomes. In addition, CTCF localization is largely invariant across different cell types. Our results provide a resource for investigating insulator function and possible other general and evolutionarily conserved activities of CTCF sites.
54. Video: Genome-Wide Distribution, Sequence Determinant and Evolution of CTCF Binding download (video/x-m4v, 44.99Mb) Description: Insulator elements affect gene expression by preventing the spread of heterochromatin and restricting transcriptional enhancers from activation of unrelated promoters. In vertebrates, insulator's function requires association with the CCCTC-binding factor (CTCF), a protein that recognizes long and diverse nucleotide sequences. While insulators are critical in gene regulation, only a few have been reported. Here, we describe 13,804 CTCF-binding sites in potential insulators of the human genome, discovered experimentally in primary human fibroblasts. Most of these sequences are located far from the transcriptional start sites, with their distribution strongly correlated with genes. The majority of them fit to a consensus motif highly conserved and suitable for predicting possible insulators driven by CTCF in other vertebrate genomes. In addition, CTCF localization is largely invariant across different cell types. Our results provide a resource for investigating insulator function and possible other general and evolutionarily conserved activities of CTCF sites.
55. Audio: NimbleGen ESHG 2007 Workshop - Full Program download (audio/x-mp3, 69.62Mb) Description:
56. Video: NimbleGen ESHG 2007 Workshop - Full Program download (video/x-m4v, 76.43Mb) Description:
57. Audio: Towards a Comprehensive Map of Copy Number Variation in the Human Genome download (audio/x-mp3, 20.21Mb) Description: Copy number variation (CNV) in the genome is extensive and yet is grossly under-ascertained. The resolution of CNV detection of most current technology platforms is approximately 50kb, and yet copy number variation two orders of magnitude smaller than this is likely to go undetected by exon resequencing. Furthermore, we know that smaller CNVs are far more numerous than larger CNVs, and so improved CNV detection resolution can be expected to dramatically increase the numbers of known CNVs. We present preliminary data from our project to detect all common CNVs (with minor allele frequencies of 5% of more) of length 500bp or greater by performing array-based comparative genome hybridisation on oligonucleotide arrays that tile across the assayable portions of the human genome.
58. Video: Towards a Comprehensive Map of Copy Number Variation in the Human Genome download (video/x-m4v, 22.87Mb) Description: Copy number variation (CNV) in the genome is extensive and yet is grossly under-ascertained. The resolution of CNV detection of most current technology platforms is approximately 50kb, and yet copy number variation two orders of magnitude smaller than this is likely to go undetected by exon resequencing. Furthermore, we know that smaller CNVs are far more numerous than larger CNVs, and so improved CNV detection resolution can be expected to dramatically increase the numbers of known CNVs. We present preliminary data from our project to detect all common CNVs (with minor allele frequencies of 5% of more) of length 500bp or greater by performing array-based comparative genome hybridisation on oligonucleotide arrays that tile across the assayable portions of the human genome.
59. Audio: Mapping Promoter DNA Methylation in Mammalian Genomes Using Oligonucleotide Arrays download (audio/x-mp3, 20.93Mb) Description: DNA methylation at cytosines residues can mediate epigenetic gene silencing and is often perturbed in cancer cells. To gain insight into the function of DNA methylation at promoters and its impact on gene expression, we measure DNA methylation at all human promoters using Methylated DNA Immunoprecipitation (MeDIP) coupled with high density oligonucleotide arrays. We find CpG-poor promoters hypermethylated in somatic cells, which does not preclude their activity. This methylation is present in gametes and results in evolutionary loss of CpG dinucleotides, as measured by divergence between humans and primates. In contrast, strong CpG island promoters are mostly unmethylated, even when inactive. Weak CpG island promoters are distinct, as they are preferential targets for de novo methylation in somatic cells. Notably, most germline-specific genes gain promoter DNA methylation during somatic development, suggesting additional functional selection. These results show that promoter structure and gene function are major predictors of DNA methylation states.
60. Video: Mapping Promoter DNA Methylation in Mammalian Genomes Using Oligonucleotide Arrays download (video/x-m4v, 22.87Mb) Description: DNA methylation at cytosines residues can mediate epigenetic gene silencing and is often perturbed in cancer cells. To gain insight into the function of DNA methylation at promoters and its impact on gene expression, we measure DNA methylation at all human promoters using Methylated DNA Immunoprecipitation (MeDIP) coupled with high density oligonucleotide arrays. We find CpG-poor promoters hypermethylated in somatic cells, which does not preclude their activity. This methylation is present in gametes and results in evolutionary loss of CpG dinucleotides, as measured by divergence between humans and primates. In contrast, strong CpG island promoters are mostly unmethylated, even when inactive. Weak CpG island promoters are distinct, as they are preferential targets for de novo methylation in somatic cells. Notably, most germline-specific genes gain promoter DNA methylation during somatic development, suggesting additional functional selection. These results show that promoter structure and gene function are major predictors of DNA methylation states.
61. Audio: MIRA-Assisted Microarrays for DNA Methylation Analysis and Cancer Diagnosis download (audio/x-mp3, 49.26Mb) Description: Alterations in DNA methylation patterns occur in every type of human cancer and are considered a hallmark of malignant transformation. Most notable is the cancer-associated hypermethylation of CpG-rich sequences, the so-called CpG islands, which are often found near the 5 ends and promoters of genes. This CpG island methylation represents a positive signal that can be used to distinguish malignant tissue from normal tissue. Thus, characterization of CpG island hypermethylation has become a valuable tool for cancer detection and diagnosis. Besides looking at individual genes, an even greater potential lies in the characterization of genome-wide changes of DNA methylation patterns in tumors. It is likely that tumor-type and tumor-subtype-specific DNA methylation patterns exist and can be exploited for the classification of cancers, their response to therapy and their metastatic potential, and thus may have predictive value. Various methods for genome-wide analysis of DNA methylation have been developed. In this presentation, we will focus on the methylated-CpG island recovery assay (MIRA), which has been used in combination with microarray analysis to map CpG island methylation across cancer genomes.
62. Video: MIRA-Assisted Microarrays for DNA Methylation Analysis and Cancer Diagnosis download (audio/x-m4v, 53.57Mb) Description: Alterations in DNA methylation patterns occur in every type of human cancer and are considered a hallmark of malignant transformation. Most notable is the cancer-associated hypermethylation of CpG-rich sequences, the so-called CpG islands, which are often found near the 5 ends and promoters of genes. This CpG island methylation represents a positive signal that can be used to distinguish malignant tissue from normal tissue. Thus, characterization of CpG island hypermethylation has become a valuable tool for cancer detection and diagnosis. Besides looking at individual genes, an even greater potential lies in the characterization of genome-wide changes of DNA methylation patterns in tumors. It is likely that tumor-type and tumor-subtype-specific DNA methylation patterns exist and can be exploited for the classification of cancers, their response to therapy and their metastatic potential, and thus may have predictive value. Various methods for genome-wide analysis of DNA methylation have been developed. In this presentation, we will focus on the methylated-CpG island recovery assay (MIRA), which has been used in combination with microarray analysis to map CpG island methylation across cancer genomes.
63. Audio: Microarray Mediated Whole-Genome Comparison of the Distribution of RNA Polymerase with the Transcript Map in Escherichia coli download (audio/x-mp3, 41.82Mb) Description: A single RNA polymerase is responsible for all transcription in the bacterium Escherichia coli. We have investigated how the genome-wide distribution of this RNA polymerase relates to the level of transcription. Using ChIP-chip we determined the genome-wide association of RNA polymerase. We also determined an unbiased transcript map from the same cells. We identified many novel, non-coding RNAs, including intergenic and intragenic sense and antisense RNAs. Interestingly, there is not a perfect relationship between the distribution of RNA polymerase and the level of transcription. At most transcribed regions RNA polymerase associates with promoters at a much higher level than with coding sequences. Strikingly, almost a quarter of all promoters that bind RNA polymerase are not detectably transcribed. We propose that RNA polymerase is "poised" at these promoters, ready to transcribe the corresponding gene under the appropriate environmental condition.
64. Video: Microarray Mediated Whole-Genome Comparison of the Distribution of RNA Polymerase with the Transcript Map in Escherichia coli download (audio/x-m4v, 44.73Mb) Description: A single RNA polymerase is responsible for all transcription in the bacterium Escherichia coli. We have investigated how the genome-wide distribution of this RNA polymerase relates to the level of transcription. Using ChIP-chip we determined the genome-wide association of RNA polymerase. We also determined an unbiased transcript map from the same cells. We identified many novel, non-coding RNAs, including intergenic and intragenic sense and antisense RNAs. Interestingly, there is not a perfect relationship between the distribution of RNA polymerase and the level of transcription. At most transcribed regions RNA polymerase associates with promoters at a much higher level than with coding sequences. Strikingly, almost a quarter of all promoters that bind RNA polymerase are not detectably transcribed. We propose that RNA polymerase is "poised" at these promoters, ready to transcribe the corresponding gene under the appropriate environmental condition.
65. Audio: Part I: A novel genomic disorder affecting neurobehavioral development; fine mapping of rearrangements involving complex low copy repeats on chromosome 10q download (audio/x-mp3, 30.08Mb) Description: We are interested in the genetic underpinnings of behavioral disorders in children. We describe three families with recurrent deletions affecting a region of chromosome 10q that produces a range of language and behavioral deficits. These deletions are in a region with a high density of large low copy repeats (LCRs), suggesting these features of genomic architecture are involved in the production and frequency of these chromosome rearrangements. We have employed NimbleGen oligonucleotide arrays to fine-map these deletions, even those located within LCR elements. Affected genes in this interval include NRG3, GRID1 and PTEN, a tumor suppressor and lipid phosphatase. PTEN mutations have been associated with a subset of autistic children, suggesting signaling regulated by this growth regulator may be involved in autism spectrum disorder.
66. Video: Part I: A novel genomic disorder affecting neurobehavioral development; fine mapping of rearrangements involving complex low copy repeats on chromosome 10q download (audio/x-m4v, 38.84Mb) Description: We are interested in the genetic underpinnings of behavioral disorders in children. We describe three families with recurrent deletions affecting a region of chromosome 10q that produces a range of language and behavioral deficits. These deletions are in a region with a high density of large low copy repeats (LCRs), suggesting these features of genomic architecture are involved in the production and frequency of these chromosome rearrangements. We have employed NimbleGen oligonucleotide arrays to fine-map these deletions, even those located within LCR elements. Affected genes in this interval include NRG3, GRID1 and PTEN, a tumor suppressor and lipid phosphatase. PTEN mutations have been associated with a subset of autistic children, suggesting signaling regulated by this growth regulator may be involved in autism spectrum disorder.
67. Audio: Part II: Using Drosophila to model disruptions of PTEN-TSC-TOR signaling on synapse assembly and behavior download (audio/x-mp3, 30.24Mb) Description: A second project explores the function of PTEN and other components of this important growth regulatory pathway in neural development, using Drosophila as our model system. We document that the PTEN-TSC-TOR signaling pathway is critical for both axon guidance and synapse assembly. Hyperactivation of this pathway can be genetically or pharmacologically separated from growth effects, yet still produce disruption of neural development, indicating this signaling system has growth-independent roles in neural development. We have also documented behavioral deficits in adult flies with modest activation of this pathway in the nervous system, suggesting Drosophila could provide a useful model for tuberous sclerosis complex.
68. Video: Part II: Using Drosophila to model disruptions of PTEN-TSC-TOR signaling on synapse assembly and behavior download (audio/x-m4v, 38.62Mb) Description: A second project explores the function of PTEN and other components of this important growth regulatory pathway in neural development, using Drosophila as our model system. We document that the PTEN-TSC-TOR signaling pathway is critical for both axon guidance and synapse assembly. Hyperactivation of this pathway can be genetically or pharmacologically separated from growth effects, yet still produce disruption of neural development, indicating this signaling system has growth-independent roles in neural development. We have also documented behavioral deficits in adult flies with modest activation of this pathway in the nervous system, suggesting Drosophila could provide a useful model for tuberous sclerosis complex.
69. Audio: Detection of Microdeletion and Microduplication Disorders Using Ultra-High Resolution array CGH download (audio/x-mp3, 23.52Mb) Description: This is the audio of a presentation by Blake Ballif of Signature Genomic Laboratories at the NimbleGen workshop at ACMG 2007 in Nashville, TN, on the use of NimbleGen Array CGH to analyze very small genomic amplifications and deletions.
70. Video: Detection of Microdeletion and Microduplication Disorders Using Ultra-High Resolution array CGH download (audio/x-m4v, 26.32Mb) Description: This is the video and audio of a presentation by Blake Ballif of Signature Genomic Laboratories at the NimbleGen workshop at ACMG 2007 in Nashville, TN, on the use of NimbleGen Array CGH to analyze very small genomic amplifications and deletions.
71. Audio: Efficient High-Resolution Deletion Discovery in Caenorhabditis elegans by Array Comparative Genomic Hybridization download (audio/x-mp3, 31.03Mb) Description: We have developed array Comparative Genomic Hybridization for Caenorhabditis elegans as a means of screening for novel induced deletions in this organism. We designed three microarrays consisting of overlapping 50mer probes to annotated exons and micro-RNAs, the first with probes to chromosomes X and II, the second with probes to chromosome II alone, and a third to the entire genome. These arrays were used to reliably detect both a large (50Kb) multigene deletion and a small (1Kb) single-gene deletion in homozygous and heterozygous samples. In one case, a deletion breakpoint was resolved to fewer than 50bp. In an experiment designed to identify new mutations we used the X:II and II arrays to detect deletions associated with lethal mutants on chromosome II. One is an 8Kb deletion targeting the ast-1 gene on chromosome II and another is a 141bp deletion in the gene C06A8.1. Others span large sections of the chromosome, up to 750Kb. As a further application of array Comparative Genomic Hybridization in C. elegans we used the whole-genome array to detect the extensive natural gene content variation (almost 2%) between the N2 Bristol strain and the strain CB4856, a strain isolated in Hawaii and JU258, a strain isolated in Madeira.
72. Video: Efficient High-Resolution Deletion Discovery in Caenorhabditis elegans by Array Comparative Genomic Hybridization download (audio/x-m4v, 33.80Mb) Description: We have developed array Comparative Genomic Hybridization for Caenorhabditis elegans as a means of screening for novel induced deletions in this organism. We designed three microarrays consisting of overlapping 50mer probes to annotated exons and micro-RNAs, the first with probes to chromosomes X and II, the second with probes to chromosome II alone, and a third to the entire genome. These arrays were used to reliably detect both a large (50Kb) multigene deletion and a small (1Kb) single-gene deletion in homozygous and heterozygous samples. In one case, a deletion breakpoint was resolved to fewer than 50bp. In an experiment designed to identify new mutations we used the X:II and II arrays to detect deletions associated with lethal mutants on chromosome II. One is an 8Kb deletion targeting the ast-1 gene on chromosome II and another is a 141bp deletion in the gene C06A8.1. Others span large sections of the chromosome, up to >750Kb. As a further application of array Comparative Genomic Hybridization in C. elegans we used the whole-genome array to detect the extensive natural gene content variation (almost 2%) between the N2 Bristol strain and the strain CB4856, a strain isolated in Hawaii and JU258, a strain isolated in Madeira.
73. Audio: Using High-Resolution ChIP-chip to Model Chromatin Signatures of Promoters and Enhancers in the Human Genome download (audio/x-mp3, 48.51Mb) Description: Eukaryotic gene transcription is accompanied by acetylation and methylation of nucleosomes near promoters, but the locations and roles of histone modifications elsewhere in the genome remain unclear. We determined the chromatin modification states in high resolution along 30 Mb of the human genome and found that active promoters are marked by trimethylation of Lys4 of histone H3 (H3K4), whereas enhancers are marked by monomethylation, but not trimethylation, of H3K4. We developed computational algorithms using these distinct chromatin signatures to identify new regulatory elements, predicting over 200 promoters and 400 enhancers within the 30-Mb region. This approach accurately predicted the location and function of independently identified regulatory elements with high sensitivity and specificity and uncovered a novel functional enhancer for the carnitine transporter SLC22A5 (OCTN2). Our results give insight into the connections between chromatin modifications and transcriptional regulatory activity and provide a new tool for the functional annotation of the human genome.
74. Video: Using High-Resolution ChIP-chip to Model Chromatin Signatures of Promoters and Enhancers in the Human Genome download (audio/x-m4v, 52.80Mb) Description: Eukaryotic gene transcription is accompanied by acetylation and methylation of nucleosomes near promoters, but the locations and roles of histone modifications elsewhere in the genome remain unclear. We determined the chromatin modification states in high resolution along 30 Mb of the human genome and found that active promoters are marked by trimethylation of Lys4 of histone H3 (H3K4), whereas enhancers are marked by monomethylation, but not trimethylation, of H3K4. We developed computational algorithms using these distinct chromatin signatures to identify new regulatory elements, predicting over 200 promoters and 400 enhancers within the 30-Mb region. This approach accurately predicted the location and function of independently identified regulatory elements with high sensitivity and specificity and uncovered a novel functional enhancer for the carnitine transporter SLC22A5 (OCTN2). Our results give insight into the connections between chromatin modifications and transcriptional regulatory activity and provide a new tool for the functional annotation of the human genome.
75. Audio: High-Resolution Mapping of Copy-Number Variants Genome-Wide with Array CGH download (audio/x-mp3, 29.51Mb) Description: Submicroscopic (less than 2 Mb) segmental DNA copy number changes are a recently recognized source of genetic variability between individuals. The biological consequences of copy number variants (CNVs) are largely undefined. In some cases, CNVs that cause gene dosage effects have been implicated in phenotypic variation. CNVs have been detected in diverse species, including mice and humans. Published studies in mice have been limited by resolution and strain selection. We chose to study 21 well-characterized inbred mouse strains that are the focus of an international effort to measure, catalog, and disseminate phenotype data. We performed comparative genomic hybridization using long oligomer arrays to characterize CNVs in these strains. This technique increased the resolution of CNV detection by more than an order of magnitude over previous methodologies. The CNVs range in size from 21 to 2,002 kb. Clustering strains by CNV profile recapitulates aspects of the known ancestry of these strains. Most of the CNVs (77.5%) contain annotated genes, and many (47.5%) colocalize with previously mapped segmental duplications in the mouse genome. We demonstrate that this technique can identify copy number differences associated with known polymorphic traits. The phenotype of previously uncharacterized strains can be predicted based on their copy number at these loci. Annotation of CNVs in the mouse genome combined with sequence-based analysis provides an important resource that will help define the genetic basis of complex traits.
76. Video: High-Resolution Mapping of Copy-Number Variants Genome-Wide with Array CGH download (audio/x-m4v, 32.47Mb) Description: Submicroscopic (less than 2 Mb) segmental DNA copy number changes are a recently recognized source of genetic variability between individuals. The biological consequences of copy number variants (CNVs) are largely undefined. In some cases, CNVs that cause gene dosage effects have been implicated in phenotypic variation. CNVs have been detected in diverse species, including mice and humans. Published studies in mice have been limited by resolution and strain selection. We chose to study 21 well-characterized inbred mouse strains that are the focus of an international effort to measure, catalog, and disseminate phenotype data. We performed comparative genomic hybridization using long oligomer arrays to characterize CNVs in these strains. This technique increased the resolution of CNV detection by more than an order of magnitude over previous methodologies. The CNVs range in size from 21 to 2,002 kb. Clustering strains by CNV profile recapitulates aspects of the known ancestry of these strains. Most of the CNVs (77.5%) contain annotated genes, and many (47.5%) colocalize with previously mapped segmental duplications in the mouse genome. We demonstrate that this technique can identify copy number differences associated with known polymorphic traits. The phenotype of previously uncharacterized strains can be predicted based on their copy number at these loci. Annotation of CNVs in the mouse genome combined with sequence-based analysis provides an important resource that will help define the genetic basis of complex traits.
77. Audio: Genome-Wide DNA Methylation Analysis with Immunoprecipitation and Tiling DNA Microarrays download (audio/x-mp3, 41.76Mb) Description:
78. Video: Genome-Wide DNA Methylation Analysis with Immunoprecipitation and Tiling DNA Microarrays download (audio/x-m4v, 43.59Mb) Description:
79. Audio: NimbleGen ASHG 2006 Workshop - Full Program download (audio/x-mp3, 78.86Mb) Description:
80. Video: NimbleGen ASHG 2006 Workshop - Full Program download (video/x-m4v, 82.71Mb) Description:
81. Audio: ASHG 2006 Presentation: The Discovery and Characterization of Genomic Disorders with High-Resolution Array CGH download (audio/x-mp3, 25.98Mb) Description:
82. Video: ASHG 2006 Presentation: The Discovery and Characterization of Genomic Disorders with High-Resolution Array CGH download (video/x-m4v, 41.75Mb) Description:
83. Audio: Cytosine Methylation Dynamics in Development and Disease download (audio/x-mp3, 25.09Mb) Description:
84. Video: Cytosine Methylation Dynamics in Development and Disease download (video/x-m4v, 26.18Mb) Description:
85. Audio: ChIP-Chip'ing Away at the Functions of Proteins Mutated in Genetic Syndromes download (audio/x-mp3, 19.29Mb) Description:
86. Video: ChIP-Chip'ing Away at the Functions of Proteins Mutated in Genetic Syndromes download (video/x-m4v, 20.20Mb) Description:
87. Audio: A High-Resolution Method to Identify DNase I Hypersensitive Sites Using Tiled Microarrays download (audio/x-mp3, 27.73Mb) Description:
88. Video: A High-Resolution Method to Identify DNase I Hypersensitive Sites Using Tiled Microarrays download (video/x-m4v, 28.94Mb) Description:
89. Audio: Genome-Wide Mapping of Transcriptional Regulatory Elements in Mammalian Cells download (audio/x-mp3, 30.74Mb) Description:
90. Video: Genome-Wide Mapping of Transcriptional Regulatory Elements in Mammalian Cells download (video/x-m4v, 32.09Mb) Description:
91. Audio: Identifying Antibiotic Resistance and Other Adaptive Mutations in Helicobacter pylori using NimbleGen CGS Technology download (audio/x-mp3, 21.07Mb) Description:
92. Video: Identifying Antibiotic Resistance and Other Adaptive Mutations in Helicobacter pylori using NimbleGen CGS Technology download (video/x-m4v, 22.21Mb) Description: