Project description:MYB Binding: Protein 1 A (MYBBP1A) is hemizygous in a majority of PDAC due to chromosome 17p deletion which also affects TP53. We generated isogenic homozygous and hemizygous MYBBP1A knockout cell lines to elucidate MYBBP1A function in cancer. As the function of MYBBP1A at the chromatin is unclear, we performed MYBBP1A ChIPseq in MYBBP1A wild-type and hemizygous cells. Surprisingly, despite the hemizygous cells expressing decreased MYBBP1A expression, the whole genome binding profile is largely similar compared to MYBBP1A wild-type cells.
Project description:Background: Sepsis, a leading cause of morbidity and mortality, is not a homogeneous disease but rather a syndrome encompassing many heterogeneous pathophysiologies. Patient factors including genetics predispose to poor outcomes, though current clinical characterizations fail to identify those at greatest risk of progression and mortality. Results: The Community Acquired Pneumonia and Sepsis Outcome Diagnostic study enrolled 1,152 subjects with suspected sepsis. We sequenced peripheral blood RNA of 129 representative subjects with systemic inflammatory response syndrome (SIRS) or sepsis (infection with SIRS), including 78 sepsis survivors and 28 sepsis nonsurvivors, who had previously undergone plasma proteomic and metabolomic profiling. The expression of 338 genes differed between subjects with SIRS and those with sepsis, primarily reflective of immune activation in sepsis. The expression of 1,238 genes differed with sepsis outcome: Nonsurvivors had lower expression of many immune function-related genes. Functional genetic variants associated with sepsis mortality were sought based on a common disease â rare variant hypothesis. VPS9D1, whose expression was increased in sepsis survivors, had a higher burden of missense variants in sepsis survivors, and these were associated with altered expression of 3,799 genes, primarily reflecting Golgi and endosome biology. Conclusions: Host response in sepsis survivors â activation of immune response-related genes â was muted in sepsis nonsurvivors. The association of sepsis survival with robust immune response and presence of missense variants in VPS9D1 warrants replication and further functional studies. We sequenced peripheral blood RNA of 129 representative subjects with systemic inflammatory response syndrome (SIRS, n=23) or sepsis (infection with SIRS), including 78 sepsis survivors and 28 sepsis nonsurvivors, who had previously undergone plasma proteomic and metabolomic profiling.
Project description:We report on the analyses of four unrelated patients with de novo, overlapping, hemizygous deletions of the long arm of chromosome 10. These include two small terminal deletions (10q26.2 to 10qter), a larger terminal deletion (10q26.12 to 10qter), and an interstitial deletion (10q25.3q26.13). Single nucleotide polymorphism (SNP) studies (Illumina 550 K) established that these deletions resulted in the hemizygous loss of approximately 6.1, approximately 6.1, approximately 12.5, and approximately 7.0 Mb respectively. Additionally, these data establish that Patients 1, 2, and 3 share common, distal, hemizygous deleted regions of 6.09 Mb containing 37 RefSeq genes. Patients 3 and 4 share a 2.52 Mb deleted region corresponding to the proximal deleted region of Patient 3 and the distal deleted region of Patient 4. This common, hemizygous region contains 20 RefSeq genes including two H6 family homeobox genes (HMX2 and HMX3). Based on previous reports that Hmx2/Hmx3 knockout mice have vestibular anomalies, we propose that hemizygous deletions of HMX2 and HMX3 are responsible for the inner ear malformations observed from CT images, vestibular dysfunction, and congenital sensorineural hearing loss found in Patients 3 and 4.
Project description:We report on the analyses of four unrelated patients with de novo, overlapping, hemizygous deletions of the long arm of chromosome 10. These include two small terminal deletions (10q26.2 to 10qter), a larger terminal deletion (10q26.12 to 10qter), and an interstitial deletion (10q25.3q26.13). Single nucleotide polymorphism (SNP) studies (Illumina 550 K) established that these deletions resulted in the hemizygous loss of approximately 6.1, approximately 6.1, approximately 12.5, and approximately 7.0 Mb respectively. Additionally, these data establish that Patients 1, 2, and 3 share common, distal, hemizygous deleted regions of 6.09 Mb containing 37 RefSeq genes. Patients 3 and 4 share a 2.52 Mb deleted region corresponding to the proximal deleted region of Patient 3 and the distal deleted region of Patient 4. This common, hemizygous region contains 20 RefSeq genes including two H6 family homeobox genes (HMX2 and HMX3). Based on previous reports that Hmx2/Hmx3 knockout mice have vestibular anomalies, we propose that hemizygous deletions of HMX2 and HMX3 are responsible for the inner ear malformations observed from CT images, vestibular dysfunction, and congenital sensorineural hearing loss found in Patients 3 and 4. Four cases were identified as having hemizygous 10q deletions through g-banding. These were analyzed with SNP microarrays as well as parents (controls) for cases 1 and 4.