Hi Brad, We are looking at this data now. Someone will contact you off-list with more information.
-- Brooke Rhead UCSC Genome Bioinformatics Group On 10/6/11 10:56 AM, Quade, Bradley Joseph,M.D.,Ph.D. wrote: > Dear UCSC Genome Informatics Group, > > > > I am writing to you to inquire about including a data track on the Genome > Browser from the Developmental Genome Anatomy Project (http://dgap.harvard.edu > <http://dgap.harvard.edu/> ). > > > > The Developmental Genome Anatomy Project (DGAP) is a NIH-funded program > project > based in four Harvard Medical School laboratories (Drs. Cynthia Morton, James > Gusella, Richard Maas, and Brad Quade). Our goal is to identify genes > important > for human development and our strategy is based on identifying humans with > congenital abnormalities (birth defects) and chromosomal rearrangements. We > essentially use these naturally occurring "human knock-out experiements" > collected from around the U.S. and globe to find new developmentally important > genes and, over time, annotate the functional/developmental genome, without > any > of the biases inherent in analyzing large populations or families. Using such > rearrangements as positional markers, we identify candidate genes by mapping > those rearrangements with a variety of methods from FISH to whole genome > sequencing, study temporal and tissue-specific expression of candidate genes > near the chromosomal breakpoints, look for corresponding point mutations in > chromosomally normal, affected individuals, and in selected cases, develop > animal models that reproduces the human phenotype. To date, we now have > collected well over 200 hundred cases, and with the inclusion of genome-level > sequencing, the rate that we are able to identify candidate genes has grown > tremendously! > > > > Over the last five years, we have used Genome Browser custom tracts to share > our > results (including extensive unpublished data). For example, here is a link > to > a case page: http://www.bwhpathology.org/DGAP/LookUpCase.aspx?case=097&chr=X > <http://www.bwhpathology.org/DGAP/LookUpCase.aspx?case=097&chr=X> . This page > has some summary information about each case, as well as links to PDFs with > more > detailed information and candidate gene mapping information (using the Genome > Browser!). Other pages on our web site allow DGAP database searches by > phenotypic information or chromosomal location. > > > > I am in the process of updating the architecture of our web site to > accommodate > the faster pace of data production (primarily due to genome sequencing). With > this effort, it is a good time to inquire about creating a DGAP tract directly > on Genome Browser, probably within the Phenotype and Disease Association > cluster > of tracks. We know that there is substantial interest in the scientific and > medical genetics communities based on our broad effort to collect DGAP cases. > We also know that the NIH and our peer reviewers think that this would be a > great way to make our data, of which a substantial fraction is unpublished or > pre-publication, more accessible to a wider number of investigators. We also > believe that it would enhance the Genome Browser by adding another rich source > of functional, developmentally relevant annotation. > > > > I will be attending the ASHG 61st annual meeting / 12th International Congress > of Human Genetics in Montreal next week (Tues., Oct. 11- Friday, Oct 14). > Perhaps it would be possible to meet and discuss this proposal in person? > Also, > the DGAP group has a project-wide poster presentation next Friday afternoon > (abstract 1270F, text pasted below in rust color). Come check us out! > > > > I look forward to exploring this exciting opportunity for collaboration > further! > > > > Sincerely, > > > > Brad Quade > > > > Bradley J. Quade, M.D., Ph.D. > > Associate Professor of Pathology (Harvard Medical School) > > Division of Women's and Perinatal Pathology > > Department of Pathology > > Brigham and Women's Hospital > > 75 Francis Street > > Boston, MA 02115 > > mailto:[email protected]<mailto:[email protected]> > > Tel: (617) 732-5475 > > Fax: (617) 738-6996 > > Administrative Assistant: > > Amanda Wild > > mailto:[email protected]<mailto:[email protected]> > > Tel: (617) 732-7980 > > Fax: (617) 738-6996 > > > > 1270F > > The Developmental Genome Anatomy Project (DGAP): Annotating the Genome by > Cytogenetic and Sequencing Approaches. > > A.M. Lindgren1, M.E. Talkowski2,3, C. Hanscom2, C. Chiang2, C. Ernst2,3, S. > Ahsan1, B.B. Currall1, L. Yuan1, S. Lachke4, I. Saadi4, D.J. Harris5, R.L. > Maas4, B.J. Quade1, J.F. Gusella2,3, C.C. Morton1. 1) Depts. of Ob/Gyn and > Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; > 2) > Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA; > 3) Depts. of Genetics and Neurology, Harvard Medical School, Boston, MA; 4) > Dept. of Medicine, Brigham and Women's Hospital, Harvard Medical School, > Boston, > MA; 5) Children's Hospital Boston, Harvard Medical School, Boston, MA. > > The Developmental Genome Anatomy Project (DGAP, dgap.harvard.edu) is a > collaborative endeavor to identify genes critical in human development and > disease. Balanced chromosomal rearrangements are the biological resource for > gene discovery in DGAP as they may indicate the location of disrupted or > dysregulated genes that lead to an abnormal phenotype. DGAP analyzes the > correlation between genotype and phenotype through FISH-based breakpoint > localization, various sequencing methods, candidate gene identification and > functional analysis in model organisms. Of 235 cases enrolled to date, > breakpoints are FISH mapped in 88 cases, 116 of which are localized to a > single > clone. Seventy-six breakpoint sequences are determined in 36 cases and 57 > disrupted genes identified for which 24 animal models have been evaluated. > Notable cases under active investigation include DGAP100 > [46,X,t(X;5)(p11.3;q35.2)], a nonverbal 16 year-old female with septo-optic > dysplasia, cleft palate, severe myopia, neuromuscular scoliosis, hearing > impairment, and a history of seizures. KDM6A, a histone 3 lysine 27 > demethylase, > is disrupted at Xp11.3, and qRT-PCR reveals ~50% reduction in KDM6A expression > compared to control lymphoblast cell lines, suggesting haploinsufficiency of > KDM6A is pathogenetic in the phenotype. Zebrafish knockdowns are underway and > preliminary analyses show craniofacial anomalies. DGAP120 > [46,XY,t(6;11)(q24.3;q21)] is a 12 year-old male with low-to-mid frequency > sensorineural hearing loss, intermittent exotropia and craniofacial defects; > C6ORF103 is disrupted at 6q24.3. DGAP191 [46,XY,t(5;7)(q14.3;q21.3)], a 3 > year-old male, has sensorineural hearing loss, mental retardation, hypotonia > and > seizures. Although no genes are directly disrupted, the 5q14.3 breakpoint is > ~500 kb upstream of MEF2C and the 7q21.3 breakpoint is 2.86 kb upstream of > COL1A2. Normal expression of MEF2C and over-expression of COL1A2, as > determined > by qRT-PCR, suggest dysregulation of COL1A2 as etiologic in the phenotype. > Chromosomal rearrangements remain a rich resource for identifying genes and > regulatory elements underlying human disease and traits. In conjunction with > development of affordable sequencing methods, the study of balanced chromosome > rearrangements in phenotypically abnormal individuals is imperative in rapid > annotation of the human genome. > > > > > > The information in this e-mail is intended only for the person to whom it is > addressed. If you believe this e-mail was sent to you in error and the e-mail > contains patient information, please contact the Partners Compliance HelpLine > at > http://www.partners.org/complianceline . If the e-mail was sent to you in > error > but does not contain patient information, please contact the sender and > properly > dispose of the e-mail. > > > _______________________________________________ > Genome maillist - [email protected] > https://lists.soe.ucsc.edu/mailman/listinfo/genome _______________________________________________ Genome maillist - [email protected] https://lists.soe.ucsc.edu/mailman/listinfo/genome
