A5020468831- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Animal Genetics and Reproduction
- Chronic Obstructive Pulmonary Disease (COPD) Research
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Genetics, Bioinformatics, and Biomedical Research
- Hearing, Cochlea, Tinnitus, Genetics
- Machine Learning in Bioinformatics
- Melanoma and MAPK Pathways
- Molecular Biology Techniques and Applications
- Vestibular and auditory disorders
- Protein Structure and Dynamics
- Ubiquitin and proteasome pathways
- Ear Surgery and Otitis Media
- Genetic and Kidney Cyst Diseases
- Renal and related cancers
- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- Adipose Tissue and Metabolism
- Genetic Syndromes and Imprinting
- Chromosomal and Genetic Variations
- Erythrocyte Function and Pathophysiology
University of Alabama at Birmingham
2020-2025
University of Massachusetts Chan Medical School
2016-2024
Institute of Molecular Medicine
2017
University of Miami
2010-2013
Dr. John T. Macdonald Foundation
2010-2013
University College London
1978-2009
Queen Mary University of London
2005-2007
Genomics England
2002-2004
Wellcome Trust
1999-2004
Medical Research Council
2003-2004
The compact genome of Fugu rubripes has been sequenced to over 95% coverage, and more than 80% the assembly is in multigene-sized scaffolds. In this 365-megabase vertebrate genome, repetitive DNA accounts for less one-sixth sequence, gene loci occupy about one-third genome. As with human are not evenly distributed, but clustered into sparse dense regions. Some “giant” genes were observed that had average coding sequence sizes spread genomic lengths significantly larger those their orthologs....
In addition to protein coding sequence, the human genome contains a significant amount of regulatory DNA, identification which is proving somewhat recalcitrant both in silico and functional methods. An approach that has been used with some success comparative sequence analysis, whereby equivalent genomic regions from different organisms are compared order identify similarities differences. general, between highly divergent imply constraint. We have whole-genome comparison humans pufferfish,...
Identification of the pathogenic mutations underlying autosomal recessive nonsyndromic hearing loss (ARNSHL) is difficult, since causative in 39 different genes have so far been reported. After excluding most common ARNSHL gene, GJB2, via Sanger sequencing, we performed whole-exome sequencing (WES) 30 individuals from 20 unrelated multiplex consanguineous families with ARNSHL. Agilent SureSelect Human All Exon 50 Mb kits and an Illumina Hiseq2000 instrument were used. An average 93%, 84% 73%...
Abstract Objective: Charcot‐Marie‐Tooth (CMT) disease comprises a large number of genetically distinct forms inherited peripheral neuropathies. The relative uniform phenotypes in many patients with CMT make it difficult to decide which the over 35 known genes are affected given patient. Genetic testing decision trees therefore broadly based on small major subtypes (eg, CMT1, CMT2) and observed mutation frequency for genes. Since conventional genetic is expensive rare not being tested at all....
Despite the ever-increasing throughput and steadily decreasing cost of next generation sequencing (NGS), whole genome humans is still not a viable option for majority genetics laboratories. This particularly true in case complex disease studies, where large sample sets are often required to achieve adequate statistical power. To fully leverage potential NGS technology on sets, several methods have been developed selectively enrich regions interest. Enrichment reduces both monetary...
Alternative pre-mRNA splicing expands the complexity of transcriptome and controls isoform-specific gene expression. Whether alternative contributes to metabolic regulation is largely unknown. Here we investigated contribution development diet-induced obesity. We found that obesity-induced changes in adipocyte expression include splicing. Bioinformatics analysis associated part this program with sequence specific NOVA factors. This conclusion was confirmed by studies mice deficiency...
Disordered proteins need to be expressed carry out specified functions; however, their accumulation in the cell can potentially cause major problems through protein misfolding and aggregation. Gene expression levels, mRNA decay rates, microRNA (miRNA) targeting ubiquitination have critical roles degradation disposal of human transcripts. Here, we describe a study examining these features gain insights into regulation disordered proteins. In comparison with ordered proteins, greater...
Oncogenomic studies indicate that copy number variation (CNV) alters genes involved in tumor progression; however, identification of specific driver affected by CNV has been difficult, as these rearrangements are often contained large chromosomal intervals among several bystander genes. Here, we addressed this problem and identified a CNV-targeted oncogene performing comparative oncogenomics human zebrafish melanomas. We determined the gene encoding growth differentiation factor 6 (GDF6),...
Lipogenesis requires coordinated expression of genes for fatty acid, phospholipid, and triglyceride synthesis. Transcription factors, such as SREBP-1 (Sterol regulatory element binding protein), may be activated in response to feedback mechanisms linking gene activation levels metabolites the pathways. SREBPs can regulated membrane cholesterol we also found that low phosphatidylcholine (a methylated phospholipid) led SBP-1/SREBP-1 maturation C. elegans or mammalian models. To identify...
ST6Gal-I, an enzyme upregulated in numerous malignancies, adds α2-6-linked sialic acids to select membrane receptors, thereby modulating receptor signaling and cell phenotype. In this study, we investigated ST6Gal-I's role epithelial mesenchymal transition (EMT) using the Suit2 pancreatic cancer line, which has low endogenous ST6Gal-I limited metastatic potential, along with two Suit2-derived subclones, S2-013 S2-LM7AA, have ST6Gal-I. RNA-Seq results suggested that subclones had greater...
We have generated and analyzed >50,000 shotgun clones from 1059 Fugu cosmid clones. All sequences been minimally edited searched against protein DNA databases. These data are all displayed on a searchable, publicly available web site at http://fugu.hgmp.mrc.ac.uk/ . With an average of 50 reads per cosmid, this is virtually nonredundant sequence skimming, covering 30%–50% each clone. This essentially random set covers nearly 25 Mb (>6%) the genome forms basis series whole analyses which...
Whole exome sequencing provides unprecedented opportunities to identify causative DNA variants in rare Mendelian disorders. Finding the responsible mutation via traditional methods families with hearing loss is difficult due a high degree of genetic heterogeneity. In this study we combined autozygosity mapping and whole family 3 affected children having nonsyndromic born consanguineous parents. Two novel missense homozygous variants, c.508C>A (p.H170N) GIPC3 c.1328C>T (p.T443M) ZNF57, were...
Breast cancer is the most commonly diagnosed malignancy in women. Analysis of breast genomic DNA indicates frequent loss-of-function mutations components cJUN NH2-terminal kinase (JNK) signaling pathway. Since JNK can promote cell proliferation by activating AP1 transcription factor, this apparent association reduced with tumor development was unexpected. We examined effect deficiency murine epithelium. Loss caused instability and cancer. Moreover, widespread early neoplasia rapid formation...
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, which lacks effective therapies. Here, we demonstrate that transcription factor, homeobox C6 (HOXC6), overexpressed in most PDACs, and its inhibition blocks PDAC tumor growth metastasis. HOXC6 transcriptionally activates tumor-promoting kinase MSK1 suppresses tumor-inhibitory protein PPP2R2B PDAC. HOXC6-induced suppression causes mammalian target rapamycin (mTOR) pathway activation, facilitates growth. Also,...
The identities and frequencies of MYO15A mutations associated with hearing loss in different populations remained largely unknown. We screened the gene for 104 unrelated multiplex consanguineous Turkish families autosomal recessive nonsyndromic sensorineural using autozygosity mapping. screening 10 mapped to DFNB3 locus revealed five previously unreported mutations: p.Y289X (1 family), p.V1400M p.S1481P p.R1937TfsX10 (3 families), p.S3335AfsX121 (2 families). Recurrent were conserved...
Gld2, a noncanonical cytoplasmic poly(A) polymerase, interacts with the RNA binding protein CPEB1 to mediate polyadenylation-induced translation in dendrites of cultured hippocampal neurons. Depletion Gld2 from hippocampus leads deficit long-term potentiation evoked by theta burst stimulation. At least mouse liver and human primary fibroblasts, also 3′ monoadenylates thereby stabilizes specific miRNAs, which enhance mRNA translational silencing eventual destruction. These results suggest...